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PRINCIPLES    OF 
HUMAN    PHYSIOLOGY 


PRINCIPLES    OF 
HUMAN    PHYSIOLOGY 


ERNEST    H.    STARLING 

C.M.G.,    F.R.S. 

M.D.,    HON.    SC.D.    (CAMBRIDGE    AND    DUBLIN),    F.R.C.P. 

JODRELL    PROFESSOR   OF    PHYSIOLOGY    IN    UNIVERSITY   COLLEGE,    LONDON 


THE    CHAPTER    ON    THE    SENSE    ORGANS    REVISED    AND 
LARGELY    REWRITTEN    BY 

H.  HARTRIDGE,  M.A.,  M.B.  Cantab. 


THIRD   EDIT  I  OS 
With  jj<j  Illustrations,  10  in  Colour 


PHILADELPHIA 

LEA    &    FEBIGER 

706    SANSOM    STREET 
1920 


Printed  in  Great   Britain. 


QT3f 
Si  X 


:  J.0 


W-m  I 


PREFACE  TO  THE  THIRD   EDITION 

Even  during  the  five  years  of  war.  which  have  elapsed  since  the  appear- 
ance of  the  last  edition,  physiology  has  continued  to  advance,  and  I  have 
had,  in  revising  this  work,  to  introduce  a  number  of  alterations,  especially 
in  the  latter  half,  in  order  to  make  the  presentation  of  the  material  more 
in  accord  with  our  actual  knowledge.  The  chief  changes  affect  the  section 
on  Sense  Organs,  which  has  been  revised  and  largely  rewritten  by  Dr.  H. 
Hartridge,  who  is  entirely  responsible  for  the  Section  on  Vision,  which 
is  quite  new.  The  fifty  pages  increase  in  the  size  of  the  book  is  due  entirely 
to  the  more  adequate  treatment  of  this  subject  which  I  have  secured 
by  Dr.  Hartridge's  co-operation,  room  having  been  found  for  the  other 
additions  to  the  work  by  corresponding  omissions. 

In  the  preparation  of  this  edition  I  have  received  valuable  aid  from 
my  wife,  who  undertook  not  only  the  whole  burden  of  proof  correcting 
but  also  the  arrangement  of  the  index.  I  am  also  much  indebted  to  many 
friends,  known  and  unknown,  who  have  pointed  out  mistakes  and  omissions 
in  previous  editions.  I  shall  be  glad  to  receive  any  suggestions  as  to  points 
in  which  this  text-book  may  be  made  more  useful  to  students. 

ERNEST   H.  STARLING. 
University  College.  London, 

March   1920. 


PREFACE  TO  THE   FIRST  EDITION 

Physiology,  though  dealing  with  the  phenomena  of  living  organisms, 
has  to  use  the  same  tools,  whether  material  or  intellectual,  as  the  sciences  of 
physics  and  chemistry.  Any  advances  which  are  made  in  these  sciences 
not  only  increase  our  powers  of  attack  upon  physiological  problems  but  at 
the  same  time  alter  the  intellectual  standpoint  from  which  we  view  them. 
On  the  other  hand,  the  investigation  of  the  phenomena  of  living  beings 
is  continually  attracting  our  attention  and  that  of  workers  in  the  other 
branches  of  science  to  unexplored  regions  in  physics  and  chemistry.  This 
mutual  stimulation  and  co-operation  among  the  different  sciences  have  as 
their  result  a  continual  modification  of  our  attitude  with  regard  to  the 
fundamental  problems  of  physiology.  The  present  time  has  seemed  to  me, 
therefore,  fitting  for  the  production  of  a  text-book  which,  while  not  neglecting 
the  data  of  physiology,  should  lay  special  stress  on  the  significance  of  these 
data,  and  attempt  to  weave  them  into  a  fabric  representing  the  principles 
which  are  guiding  physiologists  and  physicians  of  the  present  day  in  their 
endeavours  to  extend  the  bounds  of  the  known  and  to  increase  their 
powers  of  control  over  the  functions  of  living  organisms. 

In  a  science  such  as  physiology,  based  on  so  wide  a  discipline  and  with  so 
diverse  a  technique,  it  is  almost  impossible  for  any  one  man  to  attain  to  a 
personal  acquaintance  with  all  its  branches.  In  the  present  book  I  have 
therefore  not  hesitated  to  avail  myself  of  the  work  of  masters  of  the  science 
in  fields  which  I  had  not  myself  explored.  Thus,  in  the  physiology  of  the 
nervous  system,  which  has  been  transformed  and  built  up  on  a  new  basis 
by  the  researches  of  Sherrington,  I  have  endeavoured  to  follow  this  author 
as  closely  as  possible.  I  am  also  deeply  sensible  of  my  obligations  to 
the  writings  of  Tigerstedt,  Leathes,  and  Lusk  on  general  metabolism,  of 
Abderhalden  and  Plimmer  on  physiological  chemistry,  of  Bayliss  on  general 
physiology,  as  well  as  to  various  authors  of  articles  m  the  Ergebnisse  der 
Physiologic,  in  Nagel's  Handbuch  der  Physiologie,  and  in  Dr.  L.  E.  Hill's 
Recent  and  Further  Advances  in  Physiology. 

Although  I  have  endeavoured  to  confine  my  demands  on  the  previous 
knowledge  of  the  student  within  the  narrowest  possible  limits,  I  should 
recommend  him  in  every  case  to  read  some  primer  on  physiology  in  order  to 
obtain  a  bird's  eye  view  of  the  subject  before  beginning  the  study  of  this 
work.  He  will  then  be  able  to  vary  the  order  of  chapters  in  this  book 
according  to  the  part  of  physiology  which  he  is  hearing  about  in  his  lectures 
or  working  at  in  his  practical  classes.     Those  of  my  readers  who  are  entirely 


viii  PREFACE 

unacquainted  with  physiology  might  do  well  on   a   first    perusal  to  omii 
Book  I.,  dealing  with  the  general  concepts  of  the  science. 

I  have  deemed  it  a  hopeless  and  indeed  a  useless  task  to  give  any  full 
account  of  the  multifarious  methods  employed  in  the  experimental  investi- 
gation of  the  different  organs  of  the  body.  In  most  cases  I  have  consigned 
to  small  type  a  description  of  one  or  two  typical  methods,  which  would 
suffice  to  show  how  the  questions  may  be  approached  from  the  experimental 

side. 

Throughout  the  work  I  have  sought  to  show  that  the  only  foundation 
for  rational  therapeutics  is  the  proper  understanding  of  the  working  of  the 
healthy  body.  Until  we  know  more  about  the  physiology  of  nutrition, 
quacks  will  thrive  and  food  faddists  abound.  Ignorance  of  physiology 
tends  to  make  a  medical  man  as  credulous  as  his  patients  and  almost  as 
easily  beguiled  by  the  specious  puffings  of  the  advertising  druggist.  I  trust 
therefore  that  the  following  pages  will  be  found  of  value  not  only  to  the 
candidate  for  a  university  degree  but  also  to  the  practitioner  of  medicine  in 
equipping  him  for  his  struggle  against  the  factors  of  disease. 

In  the  selection  of  diagrams  for  the  illustration  of  this  book  I  am  especially 
indebted  to  Professor  Schafer  and  to  his  publishers,  Messrs.  Longmans, 
for  the  permission  to  make  use  of  a  large  number  from  Quain's  Anatomy 
and  from  Schafer's  Essentials  of  Histology.  I  must  also  express  my  obli- 
gation to  Professor  Wilson  for  the  use  of  certain  figures  from  his  admirable 
work  on  the  cell,  to  the  publishers  of  Cunningham's  Anatomy,  and  to  many 
physiological  friends,  especially  to  Dr.  Mott  and  Dr.  Gordon  Holmes,  for 
the  use  of  original  diagrams.  The  index  was  kindly  made  for  me  by  Mr. 
Lovatt  Evans. 

ERNEST  H.  STARLING. 
University  College,  London, 

May  I'-UJ. 


CONTENTS 


CHAPTER    I 

PAGE 

INTRODUCTION 1 

BOOK   I 
GENERAL   PHYSIOLOGY 

GHAPTER    II 
THE  STRUCTURAL  BASIS  OF  THE  BODY  .         .         .         .13 

CHAPTER    III 
THE  MATERIAL  BASIS  OF  THE  BODY 

SECTION 

I.     The  Elementary  Constituents  of  Living  Cells     . 


II.  The  Proximate  Constituents  of  the  Animal  Body 

III.  The  Fats 

IV.  The  Carbohydrates         

V.  The  Proteins  ....... 

VI.  The  Mechanism  of  Organic  Synthesis   . 


in    Living    Matter. 


36 
45 
53 
59 
'71 
107 


CHAPTER    IV 
THE  ENERGETIC  BASIS  OF  THE  BODY 
I.    The  Energy  of  Molecules  in  Solution  .         .         .         .121 

II.     The  Passage   of  Water  and  Dissolved  Substances  across 
Membranes  ..... 

III.  The  Properties  of  Colloids  . 

IV.  The    Mechanism    of    Chemical    Changes 

Ferments     ..... 
V.    Electrical  Changes  in  Living  Tissues 


129 
137 


152 
169 


BOOK   II 
THE   MECHANISMS   OF   MOVEMENT   AND   SENSATION 

CHAPTER    V 
THE  CONTRACTILE  TISSUES 
I.     The  Structure  of  Voluntary  Muscle    .....     177 

II.     The  Excitation  of  Muscle     .......     185 

III.     The  Mechanical  Changes  that  a  Muscle  undergoes  when  it 

Contracts    ..........     194 


\ 


CONTENTS 

CHAPTER    V    (continued) 



JV.  The  Conditions  affecting  the  Mechanical  Response  of  a 
Muscle   ........ 

V.  The  Chemical  Changes  in  Muscle 

VI.  The  Production  of  Heat  ix  Muscle 

VII.  Electrical  Chances  in  Muscle 

VIII.  The  Intimate  Nature  of  Muscular  Contraction 

IX.  Voluntary  Contraction      ..... 

X.  Other  Forms  of  Contractile  Tissue 


THE  SPINAL  CORD  ■ 
VI.    Structure  of  the  Spinal  Cord 
VII.    The  Spinal  Cord  as  a  Reflex  Centre 
VIII.    The  Mechanism  of  Co-ordinated  Movements 
IX.     Trophic  Functions  of  the  Cord 
X.     The  Spinal  Cord  as  a  Conductor 


205 
212 
219 
224 
234 
239 
243 


CHAPTER    VI 
NERVE   FIBRES  (CONDUCTING  TISSUES) 

I.     The  Structure  of  Nerve  Fibres       .         ...         .         ■  250 

II.    Propagation  along  Nerve  Fibres 253 

III.  Events  accompanying  the  Passage  of  a  Nervous  Impulse  256 

IV.  Conditions  affecting  the  Passage  of  a  Nervous  Impulse  258 
V.     The  Excitation  of  Nerve  Fibres      .....  262 

VI.     The  Conditions  which  Determine  Electrical  Stimulation  270 

VII.     The  Neuro-Muscular  Junction 275 

VIII.    Polarisation  Phenomena  in  Nerve   .....  280 

IX.     The  Nature  of  the  Excitatory  Process  ....  284 

CHAPTER    VII 
THE  CENTRAL  NERVOUS  SYSTEM 

I.     The  Evolution  and  Significance  of  the  Nervous  System  288 

II.     The  Nervous  System  of  Vertebrates       ....  297 

III.  General  Characteristics  of  Reflex  Actions    .         .         .  303 

IV.  Nature  of  the  Connection  between  Neurons  .         .  307 
V.     Functions  of  the  Nerve  Cell  ......  312 


315 
322 
338 
349 
351 


THE   BRAIN 

XI.    The  Structure  of  the  Brain  Stem   .....  361 

XII.     The  Functions  of  the  Brain  Stem 390 

XIII.  The  Functions  of  the  Cerebellum  .....  395 

XIV.  Visual  Reflexes 405 

XV.    Summary  of  the  Connections  and  Functions  of  the  Cranial 

Nerves 409 


CONTENTS 


CHAPTER    VII    (continued) 
THE   CEREBRAL   HEMISPHERES 

General  Structural  Arrangements  of  the  Cerebrum     . 

XVII.    The  Functions  of  the  Cerebral  Hemispheres 

The  Nutritive  and  Vascular  Arrangements  of  the  Central 
Nervous  System      ........ 


SECTION 

XVI. 


XVIII. 


PAGE 

415 
433 


461 


THE  AUTONOMIC   SYSTEM 
XIX.     The  Visceral  or  Autonomic  Nervous  System 


46G 


PART 
I. 


CHAPTER    VIII 
THE  SENSE  OEGANS 

Introduction     .........  478 

II.    Vision  (by'  H.  Hartridge)           .         .         .         .         .         .  486 

SECTION 

1.  Properties  of  Light,  Colour  and  the  Spectrum    .  486 

2.  Orbital  Cavity  and  its  Contents  ....  493 

3.  Ey'eball,  its  Histology.    Pupil  Reflex          .         .  500 

4.  Nutrition  and  Protection  of  the  Eyeball    .         .  514 

5.  Optical  Media  of  Eye,  and  Accommodation  .         .  519 

6.  Optical  properties  and  Defects  of  the  Eyes        .  529 

7.  Retina,  its  Histology  and  Phytsiologyt  .         .         .  540 

8.  Response  to  Light  and  Colour      ....  555 

9.  Subjective  Phenomena  of  Vision    ....  566 

10.  Defects  of  Vision  and  their  Detection         .         .  577 

11.  Duplex  Theory'  and  Hypotheses  of  Colour  Vision  583 

12.  Binocular  and  Stereoscopic  Vision        .         .         .  588 

III.  Hearing ■ 595 

SECTION  • 

1.  Properties  of  Sound       ......  595 

2.  The  External,  Middle  and  Internal  Ear      .         .  600 

3.  Hypothesis    of    Audition,    and    Appreciation     of 

Direction     .         .         .         .         .         .         .         .611 

IV.  Voice  and  Speech 618 

V.     Cutaneous  Sensations        . 026 

VI.     Taste  and  Smell 639 

VII.    Sensations  of  Movement  and  Position      ....  646 

VIII.    Labyrinthine  Sensations 651 


CONTENTS 

BOOK    III 

THE   MECHANISMS   OF   NUTRITION 


SECTION 
I. 


CHAPTER    IX 
THE   EXCHANGES   OF   MATTER  AND   ENERGY   IN   THE 
BODY   (GENERAL  METABOLISM) 
Methods  employed  in  Determining:  the  Total  Exchanges 


of  the  Body  ....... 

II.     Metabolism  during  Starvation 

III.  The  Effect  of  Food  on  Metabolism 

IV.  The  Effect  of  Muscular  Work  on  Metabolism 
V.     The  Significance  of  the  Foodstuffs 

VI.     The  Normal  Diet  of  Man  .... 


660 
670 
677 
683 
688 
695 


CHAPTER    X 

THE  PHYSIOLOGY  OF  DIGESTION 

Changes  undergone  by  the  Foodstuffs  in  the  Alimentary 
Canal      .... 
I.     Digestion  in  the  Mouth    . 
II.     The  Passage  of  Food  from  the  Mou' 

III.  Digestion  in  the  Stomach 

IV.  The  Movements  of  the  Stomach 
V.     The  Pancreatic  Juice 

VI.  The  Liver  and  Bile 

VII.  The  Intestinal  Juice 

VIII.  Functions  of  the  Large  Intestine 

IX.  Movements  of  the  Intestines    . 

X.  The  Absorption  of  the  Foodstuffs 

XL  The  F^ces  .... 


703 

706 

ITH  TO  THE 

Stomach 

721 
728 
742 
748 
759 
764 
768 
771 
779 
799 

CHAPTER    XI 
THE  HISTORY  OF  THE  FOODSTUFFS 
I.     Protein  Metabolism  ...... 

II.     Nuclein  or  Purine  Metabolism 

III.  The  History  of  Fat  in  the  Body     . 

IV.  The  Metabolism  of  Carbohydrates  . 


SOI 
818 
826 
839 


CONTENTS 

CHAPTER,  XII 
THE  BLOOD 

ECTION  '       . 

General  Characters  of  the  Blood 

I.     The  White  Blood  Corpuscles    . 
II.     The  Red  Blood  Corpuscles 
ITT.     The  Blood  Platelets 
TV.     The  Coagulation  op  the  Blood 

V.     The  Quantity  and  Composition  of  the  Blood  in  Man 


PAGE 

853 

856 
861 
879 
882 
897 


CHAPTER    XIII 
THE   PHYSIOLOGY   OP   THE   CIRCULATION 

I.     General  Features  of  the  Circulation      ....     913 
II.     The  Blood  Pressure  at  Different  Parts  of  the  Vascular 

Circuit 919 

III.  The  Velocity  of  the  Blood  at  Different  Parts  of  the 

Vascular  System 931 

IV.  The  Mechanism  of  the  Heart  Pump  ....     935 
V.     The  Flow  of  Blood  through  the  Arteries      .         .         .     962 

VI.     The  Flow  of  Blood  in  the  Veins     .         .         .         .         .  976 

VII.     The  Pulmonary  Circulation      ......  979 

VIII.     The  Causation  of  the  Heart  Beat  .....  982 

IX.    The  Nervous  Regulation  of  the  Heart  ....  1012 

X.     The  Nervous  Control  of  the  Blood  Vessels  .         .         .  1025 

XI^/The  Circulatory  Changes  during  Muscular  Exercise     .  1051 
XII.     The  Influence  on  the  Circulation  of  Variations  in  the 

Total  Quantity  of  Blood      ......  1058 

CHAPTER    XIV 
LYMPH  AND  TISSUE  FLUIDS 1061 

CHAPTER    XV 
THE   DEFENCE   OF   THE   ORGANISM  AGAINST   INFECTION 
I.     The  Cellular  Mechanisms  of  Defence      ....   1070 
II.     The  Chemical  Mechanisms  of  Defence      ....   1079 

CHAPTER    XVI 
RESPIRATION 

I.     The  Mechanics  of  the  Respiratory  Movements        .         .   1088 
II.     The  Chemistry  of  Respiration  .....   1100 

TIL     The  Regulation  of  the  Respiratory  Movements      .         .    1126 
IV.     The    Effects    on    Respiration    of    Changes    in    the    Ah: 

Breathed        .         .         .         .         .         .         .         .         .1148 

V.     The  Mechanisms  of  Oxidation   in  the  Tissues  .         .   1155 


xiv  CONTENTS 

CHAPTER    XVI] 
RENAL   EXCRETION 

SIXTH'S  PAGB 

I.    The  Composition  and  Characters  of  the  Urine  .  1160 

II.    The  Secretion  of  Urine   .......  1181 

III.     The  Physiology  of  Micturition 1205 

CHAPTER    XVIII 
THE   SKIN    AND   THE   SKIN   GLANDS 1216 

CHAPTER    XIX 
THE  TEMPERATURE  OP  THE  BODY  AND  ITS  REGULATION   .    1219 

CHAPTER    XX 
THE  DUCTLESS  GLANDS       ....:...  1230 

BOOK    IV 

REPRODUCTION 

CHAPTER    XXI 

THE  PHYSIOLOGY  OF  REPRODUCTION 

SECTION 

I.     The  Essential  Features  of  the  Sexual  Process      .         .   1251 


II.  Development  and  Heredity 

III.  Reproduction  in  Man 

IV.  Pregnancy'  and  Parturition 

V.  The  Secretion  and  Properties  of  Milk 


lXhKX 


1264 
1269 
1282 
1289 

1299 


CHAPTER   I 

INTRODUCTION 

Physiology  in  its  widest  sense  signifies  the  study  of  the  phenomena  pre- . 
sented  by  living  organisms,  the  classification  of  these  phenomena,  and  the 
recognition  of  their  sequence  and  relative  significance.  Such  a  range  would 
include  many  studies  which  are  not  generally  grouped  under  the  term 
physiology,  and  would  in  fact  correspond  to  the  comprehensive  science  of 
biology.  Thus  the  study  of  the  relations  of  living  beings  to  one  another  and 
to  their  surroundings  is  the  special  object  of  the  science  of  cecology.  The 
aims  of  physiology  in  its  restricted  sense  are  the  description,  analysis,  and 
classification  of  the  phenomena  presented  by  the  isolated  organism,  the 
allocation  of  every  function  to  its  appropriate  organ,  and  the  study  of  the 
conditions  and  mechanisms  which  determine  each  function. 

The  fundamental  phenomena  of  life  are  essentially  identical  throughout 
the  whole  series  of  living  organisms.  This  continuity  of  function  is  the 
necessary  correlation  of  the  continuity  of  descent,  which  brings  into  relation 
all  members  of  the  animal  and  vegetable  kingdoms.  No  living  organism 
can  therefore  be  regarded  as  outside  the  sphere  of  our  investigations.  The 
interest  of  mankind  in  this  subject  was,  however,  naturally  awakened  in 
connection  with  his  own  body,  and  the  science,  growing  up  as  ancillary  and 
preliminary  to  medical  studies,  has  always  taken  man  as  its  chief  type  of 
study.  In  the  present  work  the  elucidation  of  the  functions  of  man  will 
also  be  our  first  concern,  and  this  for  two  reasons.  In  the  first  place, 
in  physiology,  as  in  all  other  sciences,  the  motive  of  man's  activity  is  his 
social  instinct  to  increase  the  power  of  his  race  in  the  struggle  for  existence, 
by  the  acquisition  of  control,  either  over  the  external  forces  of  nature, 
which  may  be  turned  to  his  own  benefit,  or  over  the  factors,  intrinsic  and 
extrinsic,  which  tend  to  his  enfeeblement  or  extirpation  by  disease  and  death. 
Consciously  or  unconsciously,  all  our  researches  on  physiology,  whether  on 
the  higher  animals  or  on  the  lowest  protozoa,  have  the  welfare  of  man  as 
their  ultimate  object.  In  the  second  place,  the  choice  of  the  higher  animals 
as  our  chief  objects  of  study  receives  justification  from  the  fact  that  whereas 
morphology,  or  the  science  of  structure,  must  proceed  from  the  lowest  to 
the  highest  organisation,  the  science  of  function  presents  its  problems  in 
then-  simplest  form  in  the  most  highly  differentiated  organisms.  In  the 
unicellular  animal  all  the  essential  functions  which  we  associate  with  living 
beings  are  carried  out,  often  simultaneously,  in  one  little  speck  of  proto- 
plasm.    An  analysis  of  these  functions,  the  determination  of  their,condit:'ons 

1  1 


2  PHYSIOLOGY 

and  mechanism,  is  oh  vim  i  sly  impossible  under  such  circumstances.  It  is  only 
when,  as  in  the  higher  animals,  one  part  of  the  living  body  is  differentiated 
into  an  organ  which  lias  one  function  and  one  function  only  as  the  outlet 
for  its  activities,  that  it  becomes  possible  to  peer  into  the  details  of  the 
function  with  some  chance  of  discovering  its  ultimate  mechanism. 

Our  especial  preoccupation  with  the  physiology  of  man  will  not  prevent 
our  employment  of  examples  from  any  part  of  the  animal  or  vegetable 
kingdom,  when  light  can  he  thrown  by  their  study  on  fundamental  physio- 
logical phenomena  common  to  the  whole  of  the  living  world.  In  many 
cases  such  a  study  will  enable  us  to  separate  the  essential  features  in  a 
process  from  those  which  have  been  added  as  auxiliary,  with  increasing 
complexity  of  the  structures  concerned. 

What  are  the  fundamental  phenomena  which  are  wrapt  up  in  our  con- 
ception of  living  beings  ?  When  dealing  with  the  higher  animals,  we  are 
inclined  to  lav  greater  stress  on  the  phenomena  involving  a  discharge  of 
energy.  Thus  we  should  say  that  a  man  was  alive  if  his  body  were  warm 
and  if  he  were  presenting  spontaneous  movements,  such  as  those  of  respira- 
tion or  of  the  heart.  The  life  of  a  man  in  the  ordinary  sense  of  the  term  is 
made  up  of  those  movements  which  place  him  in  relationship  with  his  environ- 
ment. For  the  production  of  these  movements,  as  for  the  maintenance  of  a 
constant  body-temperature,  a  continual  expenditure  of  energy  is  necessary. 
Experience  teaches  us  that  these  movements  come  to  an  end  in  the  absence 
of  food  or  of  oxygen,  and  that  an  increased  call  on  the  energies  of  the  body 
must  always  be  met  by  a  corresponding  increase  in  the  air  and  in  the  food 
supplied.  Two  further  processes  must  therefore  be  included  among  those 
making  up  our  conception  of  life,  viz.  the  function  of  assimilation  (the 
taking  in  and  digestion  of  food),  and  the  function  of  respiration,  in  which 
oxygen  is  absorbed  and  carbon  dioxide  is  excreted  into  the  surrounding 
atmosphere. 

The  substances  which  make  up  our  foodstuffs  are  all  capable  of  oxidation. 
Composed  chiefly  of  carbon  and  hydrogen,  with  some  oxygen,  nitrogen,  and 
sulphur,  they  yield  on  complete  combustion  carbon  dioxide,  water  and 
small  amounts  of. ammonia  or  allied  bodies,  and  sulphates.  In  this  process 
of  oxidation  there  is  liberation  of  heat.  In  the  body  a  similar  oxidation 
occurs,  the  products  of  oxidation  being  discharged  into  the  surrounding 
medium.  An  amount  of  energy  is  thus  set  free  which  is  available  for  the 
activities  of  the  living  organism.  Before  we  can  make  any  accurate  in- 
vestigations of  the  conditions  which  determine  these  activities,  we  must 
know  whether  the  two  great  laws  of  chemistry  and  physics,  viz.  the  conser- 
vation of  mass  and  the  conservation  of  energy,  hold  good  for  the  processes 
within  the  living  body.  The  many  experiments  which  have  been  made  on 
this  point  have  decided  the  question  in  the  affirmative.  Thousands  of 
experiments  have  been  made,  both  on  man  and  on  animals,  in  which  the 
total  income  of  the  body,  viz.  food  and  oxygen,  has  been  weighed,  and 
compared  with  the  total  output,  viz.  carbon  dioxide,  water,  and  bodies 
allied  to  ammonia  (urea,  &c).     In  every  case  complete  equality  has  been 


INTRODUCTION 


obtained,  and  we  can  be  certain  that  any  matter  found  in  the  body  must 
have  been  derived  from  without.  There  is  no  creation  or  destruction  of 
matter  in  the  body. 

The  determination  of  the  equation  in  the  case  of  the  total  energy  of  the 
body  is  rather  more  difficult.  We  have,  in  the  first  place,  to  measure  the 
total  income  and  output  of  the  body,  and  to  determine  the  total  heat  which 
would  be  evolved  by  the  oxidation  of  th  9.  foodstuffs  taken  into  the  carbon 
dioxide,  water,  &c,  that  are  given  out.7  We  must  then  compare  the  figure 
so  obtained  with  the  actual  output  of  energy  by  the  body.  The  latter  can 
be  measured  in  terms  of  heat  by  placing  the  animal  inside  a  calorimeter. 
Many  practical  difficulties  arise  in  the  performance  of  the  experiment,  in 
consequence  of  the  necessity  of  providing  the  animal  with  a  constant  supply 
of  air  to  breathe,  and  of  allowing  for  the  continual  loss  of  water  by  evapora- 
tion which  is  going  on  at  the  surface  of  the  animal.  The  first  accurate 
experiments  of  this  nature  were  made  by  Eubner.  This  observer  deter- 
mined by  means  of  the  calorimeter  the  total  heat  loss  of  dogs.  In  the  same 
animals  the  material  income  and  output  of  the  body  were  measured,  and  a 
calculation  was  made  as  to  the  amount  of  energy  which  would  be  set  free 
in  the  body  by  the  processes  of  oxidation  involved  in  the  change  of  material 
observed.     The  following  Table  represents  a  summary  of  Rubner's  results  : 


Dcg.    1                  Condition  of  dog. 

Calculated 

heat 
production. 

Heat  loss  deter- 
mined calori- 
metrically. 

Duration 

of 
experiment. 

l. 

o 
3. 

4. 
5. 
6. 

8. 

Fasting  . 

Fed  with  meat 
Fed  with  fat  . 
Meat  and  fat  . 

Fed  with  meat 

Cal. 
259-3 
545-6 
329-9 
3020 
332  1 
311-6 
375-0 
683-0 

Cal. 
261  0 
528-3 
333-9 
299  1 
3300 
3310 
•    379-5 
681-3 

Days. 
5 
2 
1 
5 
12 
8 
6 

It  will  be  seen  that  the  average  difference  between  the  calculated  and 
observed  results  amounts  only  to  1  01  per  cent.- — an  amazing  agreement 
considering  the  extreme  difficulties  of  the  experimental  methods  involved. 
The  important  deduction  to  be  drawn  from  these  observations  is  that  the 
foodstuffs  which  are  oxidised  in  the  body  develop  in  this  process  exactly 
the  same  amount  of  energy  as  when  they  are  burnt  up  outside  the  body. 

From  one  aspect,  therefore,  the  animal  body  may  be  looked  upon  as  a 
machine  for  the  transformation  of  the  potential  energy  of  the  foodstuffs 
into  kinetic  energy,  represented  by  the  warmth  and  movements  of  the  body 
as  well  as  by  other  physical  changes  involved  in  vital  processes.  In  the  living 
organism  we  cannot,  however,  distinguish  between  the  source  of  energy  and 
the  machinery,  as  we  can  in  the  case  of  our  engines.  When  we  endeavour 
to  trace  the  foodstuffs  after  their   entry  into  the  body,  we  lose  sight    of 


i  PHYSIOLOGY 

them  at  the  poinl  where  they  are  built  up  to  form  apparently  an  integral 
part  of  the  living  framework.  During  activity  there  is  a  discharge  of  the 
products  of  oxidation  of  the  foodstuffs  from  this  living  matter,  which  there- 
fore becomes  reduced  in  mass.  This  reduction,  or  disintegration  of  the 
living  matter,  associated  with  activity,  is  always  followed  by  a  period  of 
increased  integration,  during  which  the  organism  grows  by  the  assimilation 
of  more  food.  Our  conception  of  life  must  therefore  involve  the  idea  of  a 
constantly  recurring  cycle  of  processes,  one  of  building  up,  repair,  or  inte- 
gration, and  the  other,  associated  with  activity,  of  destruction  or  disinte- 
gration. If  the  former  process  predominates,  we  obtain  a  steady  increase 
in  the  mass  of  the  organism,  an  increase  which  we  speak  of  as  growth,  and 
in  many  cases,  as  in  that  of  plants,  it  is  this  power  of  growth  which  we  take 
as  our  criterion  of  the  existence  of  life.  In  fact,  the  possession  by  the  green 
parts  of  plants  of  the  power  of  utilising  the  energies  of  the  sun's  rays  for  the 
integration  of  foodstuffs,  such  as  starch,  with  a  high  potential  energy,  is 
the  necessary  condition  for  the  existence  of  all  higher  forms  of  life  on  this 
earth. 

Closely  associated  with  the  property  of  growth  is  the  power  possessed 
by  all  living  organisms  of  repair,  i.e.  the  replacement  by  newly  formed 
healthy  living  material  of  parts  which  have  been  damaged  by  external 
events. 

The  process  of  growth  does  not,  in  the  individual,  proceed  indefinitely. 
At  a  certain  stage  in  its  life  every  organism  divides,  and  a  part  or  parts  of 
its  substance  are  thrown  off  to  form  new  individuals,  each  of  them  endowed 
with  the  same  properties  as  the  parent  organism,  and  destined  to  grow  until 
they  are  indistinguishable  from  the  organism  whence  the)7  were  derived.  In 
the  lowest  forms  of  life,  the  unicellular  organisms,  these  processes  of  growth 
and  division  may  go  on  imtil  brought  to  an  end  by  some  change  in  the 
environment  which  will  not  allow  the  necessary  conditions  of  life,  viz. 
assimilation  and  disintegration,  to  proceed.  In  all  the  higher  forms,  how- 
ever, after  the  process  of  reproduction  has  been  completed,  the  parent 
organism  begins  to  undergo  decay,  and  the  processes  of  assimilation  and 
repair  no  longer  keep  pace  with  those  of  destruction,  however  favourable 
the  environment,  until  finally  death  of  the  organism  takes  place. 

All  these  phenomena,  viz.  assimilation,  respiration,  activity  associated 
with  the  discharge  of  energy,  growth,  reproduction,  and  death  itself,  are 
bound  up  in  our  conception  of  life.  All  have  one  feature  in  common,  viz. 
they  are  subject  to  the  statement  that  every  living  organism  is  endowed 
with  the  power  of  adaptation.  Adaptation  may  indeed  receive  the  definitk  n 
which  Herbert  Spencer  has  applied  to  life — "  the  continuous  adjustment 
of  internal  relations  to  external  relations."  A  living  organism  may  be 
regarded  as  a  highly  unstable  system  which  tends  to  increase  itself  con- 
tinuously under  the  average  of  the  conditions  to  which  it  is  subject,  but 
undergoes  disintegration  as  a  result  of  any  variation  from  this  average. 
It  is  evident  that  the  sole  condition  for  the  survival  of  the  organism  is  that 
any  such  act  of  disintegration  shall  result  in  so  modifying  the  relation  of  the 


INTRODUCTION  5 

system  to  the  environment  that  it  is  once  more  restored  to  the  average  in 
which  assimilation  can  be  resumed.  Every  phase  of  activity  in  a  living 
being  must  be  not  only  a  necessary  sequence  of  some  antecedent  change  in 
its  environment,  but  must  be  so  adapted  to  this  change  as  to  tend  to  its  neu- 
tralisation, and  so  to  the  survival  of  the  organism.  This  is  what  is  meant 
by  '  adaptation.'  Not  only  does  it  involve  the  teleological  conception  that 
every  normal  activity  must  be  for  the  good  of  the  organism,  but  it  must 
also  apply  to  all  the  relations  of  living  beings.  It  must  therefore  be  the 
guiding  principle,  not  only  in  physiology  with  its  special  preoccupation  with 
the  internal  relations  of  the  parts  of  the  organism,  but  also  in  the  other 
branches  of  biology,  which  treat  of  the  relations  of  the  living  animal  to  its 
environment,  and  of  the  factors  which  determine  its  survival  in  the  struggle 
for  existence.  The  origin  of  new  species  and  the  succession  of  the  different 
forms  of  life  upon  this  earth  depend  on  the  varying  perfection  of  the 
mechanisms  of  adaptation. 

We  may  imagine  that  the  first  step  in  the  evolution  of  life  was  taken 
during  the  chaotic  chemical  interchanges  which  accompanied  the  cooling 
down  of  the  molten  mass  forming  the  earth,  when  some  compound  Was 
formed,  probably  with  absorption  of  heat,  endowed  with  the  property  of 
continuous  polymerisation  and  growth  at  the  expense  of  surrounding 
material.  Such  a  substance  could  continue  to  exist  only  at  the  expense  of 
the  energy  derived  from  the  surrounding  medium,  and  would  undergo 
destruction  with  any  storm}'  change  in  its  environment.  Out  of  the  many 
such  compounds  which  might  have  come  into  being,  only  such  would  survive 
in  which  the  process  of  exothermic  disintegration  tended  towards  a  condition 
of  greater  stability,  so  that  the  process  would  come  to  an  end  spontaneously, 
and  the  organism  or  compound  be  enabled  to  await  the  more  favourable 
conditions  necessary  for  the  continuance  of  its  growth.  With  the  con- 
tinued cooling  of  the  earth,  the  new  production  of  endothermic  compounds 
would  become  rarer  and  rarer  ;  and  in  all  probability  the  beginning  of  life, 
as  we  know  it,  was  the  formation  of  some  complex  substance,  analogous 
to  the  present  chlorophyll  corpuscles,  with  the  power  of  absorbing  the 
newly  penetrating  sun's  rays  and  utilising  them  for  the  endothermic  forma- 
tion of  further  unstable  compounds.  Once  given  an  unstable  system. 
such  as  we  have  imagined,  the  great  principle  laid  down  by  Darwin,  viz. 
survival  of  the  fittest,  will  suffice  to  account  for  the  production  from  it  by 
evolution  of  the  ever-increasing  variety  of  living  beings  which  have  appeared 
in  the  later  history  of  this  globe.  The  '  adaptation,'  i.e.  the  reactions  of 
the  primitive  living  material  to  changes  in  its  environment,  must  become 
ever  more  and  more  complex,  since  only  by  means  of  increasing  variety  of 
reaction  is  it  possible  to  provide  for  the  stability  of  the  system  within  greater 
and  greater  range  of  external  conditions.  The  difference  between  higher 
and  lower  forms  is  therefore  one  of  complexity  of  reaction,  or  of  range 
of   adaptation. 

In  all  the  physiological  processes  which  we  shall  study  in  the  course  of 
this  work,  adaptation  will  be  found  the  constant  and  guiding  quality.     The 


6  PHYSIOLOGY 

naked  protoplasm  of  the  Plasmodium  of  Myxomycetes,  if  placed  on  a  piece 

of  wet  blotting-paper,  will  crawl  towards  an  infusion  of  dead  leaves,  or 
away  from  a  solution  of  quinine.  It  is  the  same  property  of  adaptation, 
the  deciding  factor  in  the  struggle  for  existence,  which  impels  the  greatest 
thinkers  of  our  time  to  spend  long  years  of  toil  in  the  invention  of  the  means 
for  the  offence  and  defence  of  their  community,  or  for  the  protection  of  man- 
kind against  disease  and  death.  The  same  law  which  determines  the  down- 
ward growth  of  the  root  in  plants  is  responsible  for  the  existence  to-day  of 
all  the  sciences  of  which  mankind  is  proud. 

This  "  adjustment  of  internal  to  external  relations  "  is  possible,  however, 
only  within  strictly  defined  limits,  limits  which  increase  in  extent  with  rise 
in  the  type  of  organism,  and  in  the  complexity  of  its  powers  of  reaction. 
Some  of  these  limiting  conditions  we  shall  have  to  study  in  the  next  chapter. 
Among  the  chief  of  them  are  temperature,  and  the  presence  of  food  material 
and  of  oxygen.  At  the  present  time  the  limits  of  temperature  may  be 
placed  between  0°  and  50°  C.  Many  organisms,  however,  are  killed  by  the 
alteration  of  only  a  few  degrees  in  the  temperature  of  their  environment. 
Every  shifting  of  a  cold  or  warm  current  in  the  Atlantic,  in  consequence  of 
storms  on  the  surface,  leads  to  the  destruction  of  myriads  of  fish  and  other 
denizens  of  the  sea.  In  the  higher  animals  a  greater  stability  in  face  of  such 
changes  has  been  accomplished  by  the  development  of  a  heat-regulating 
mechanism,  so  that,  provided  sufficient  food  is  available,  the  temperature 
of  the  body  is  maintained  at  a  constant  level,  which  represents  the  optimum 
for  the  discharge  of  the  normal  functions  of  the  constituent  parts  of  the 
body.  The  presence  of  food  material  in  the  environment  of  the  living 
organism  is  a  necessary  condition  for  its  continued  existence.  In  some  cases, 
and  this  we  must  assume  to  be  the  primitive  condition,  the  food  material 
must  be  of  a  given  character  and  form  a  constant  constituent  of  the  sur- 
rounding medium.  In  the  higher  forms,  the  development  of  a  complex 
digestive  system  has  enabled  the  organism  to  utilize  many  different  kinds  of 
food,  while  the  storage  of  any  excess  of  food  as  reserve  material,  either  in 
the  form  of  fats  or  carbohydrates,  provides  for  a  constant  supply  of  food 
to  the  constituent  cells  of  the  body,  even  when  it  is  quite  wanting  in  the 
environment.  Since  plants  depend  for  their  food  in  the  first  place  on  the 
carbohydrates  produced  within  the  chlorophyll  corpuscles  out  of  the  atmo- 
spheric carbon  dioxide  by  the  energy  of  the  sun's  rays,  necessary  conditions 
for  their  existence  will  be  sunlight  and  the  presence  of  this  gas  in  the 
surrounding  atmosphere. 

One  other  necessary  condition  for  the  existence  of  life  is  the  presence  of 
water.  Although  this  substance  cannot  furnish  any  energy  to  the  complex 
molecules  of  which  the  living  matter  is  composed,  it  is  an  essential  con- 
stituent of  all  living  matter,  and  takes  part  in  all  the  changes  which  deter- 
mine the  transformations  of  matter  and  energy  in  the  organism. 

This  short  summary  of  the  chief  characteristics  of  living  beings  would 
be  incomplete  without  the  mention  of  what  is  perhaps  their  distinctive 
feature,  namely,  organisation.    Although  little  marked  in  the  lowest  members 


INTRODUCTION  "  7 

of  the  living  kingdom,  where  we  can  detect  only  a  speck  of  structureless 
material  containing  a  few  granules,  of  which  one  or  more,  in  consequent  e  of 
its  reaction  to  stains,  is  distinguished  by  the  name  of  a  nucleus,  in  the 
higher  members  this  organisation  becomes  more  and  more  marked.  This 
increased  complexity  of  organisation,  which  we  often  speak  of  as  histological 
differentiation,  runs  parallel  with  increasing  range  of  power  of  adaptation, 
and  with  increasing  efficiency  of  adaptive  reactions  attained  by  the  setting 
apart  of  special  structures  (organs)  for  the  performance  of  definite  functions. 
This  parallelism  between  the  development  of  function  and  structure  justifies 
us  in  the  assumption  generally,  though  often  only  tacitly,  made  by  physio- 
logists, that  the  structure  is  the  determining  factor  for  the  function.  We 
might  regard  the  histological  differentiation  as  representing  merely  a  con- 
tinuation of  the  increasing  molecular  complexity,  which  we  assumed  must 
accompany  and  determine  every  widening  in  the  range  of  the  adaptive 
power  of  the  organism. 

To  sum  up  : — our  objects  in  the  study  of  physiology  include  the  descrip- 
tion of  the  chief  reactions  of  the  body  to  changes  in  its  environment,  the 
analysis  of  these  reactions  into  the  simpler  reactions  cf  which  they  are  made 
up.  and  the  assignment  to  each  differentiated  structure  of  the  organism  its 
part  in  every  reaction.  We  must  determine  the  conditions  under  which 
each  reaction  takes  place,  so  that  we  may  learn  to  evoke  any  part  of  it  at 
will  by  application  of  the  appropriate  stimulus,  i.e.  by  effective  change  of 
environment. 

A  reaction  involves  expenditure  of  energy,  and  this  can  be  derived  only 
from  chemical  change  in  the  reacting  organ,  and  ultimately  from  the  dis- 
integration or  oxidation  of  the  foodstuffs.  Our  next  task  must  be,  there- 
fore, the  analysis  of  the  energetic  and  material  changes,  with  a  view  to 
determining  the  whole  sequence  of  events,  from  the  occurrence  of  the 
external  exciting  change  to  the  finished  reaction,  which  will  alter  in  the 
direction  of  protection  the  relation  of  the  organism  to  its  environment. 
In  short,  it  is  the  office  of  physiology  to  discover  the  routine  sequence  of 
events  in  the  living  organism  under  all  manner  of  conditions.  In  attacking 
this  problem  our  methods  cannot  differ  fundamentally  from  those  of  the 
physicist  and  chemist.  In  every  case  our  experiments  will  consist  in  the 
observation  and  measurement  of  movements  of  one  kind  or  another  which 
we  shall  interpret  in  terms  of  mass  or  energy.  Physiology,  if  it  could  be 
completed,  would  therefore  describe  the  how  of  every  process  in  the  body. 
It  would  state  the  sequence  of  events  and  would  summarise  these  as  so-called 
'  laws.'  These  laws  would,  however,  no  more  explain  the  phenomena 
of  life  than  does  the  '  law  of  gravitation  '  explain  the  fact  that  two  masses 
tend  to  move  towards  one  another  with  uniform  acceleration.  Nor  can  we 
hope  to  explain  physiological  phenomena  by  reference  to  the  laws  of  physics 
and  chemistry,  since  these  themselves  are  only  expressions  of  sequences, 
and  not  explanations.  With  every  growth  in  science,  however,  its  generalisa- 
tions become  wider  and  its  laws  summarise  ever  more  extensive  groups  of 
phenomena.     We  have  no  reason  for  asserting  that,  in  the  course  of  research, 


8  PHYSIOLOGY 

we  may  not  finally  succeed  in  describing  vital  phenomena  in  the  "  conceptual 
shorthand  "  *  used  by  the  physicist,  involving  his  ideal  world  of  ether,  aton 
and  molecule.  At  present  we  are  far  from  such  a  consummation.  T) 
principle  of  adaptation  is  the  only  formula  which  will  include  all  the  phen  ' 
mena  of  living  beings,  and  it  is  difficult  to  see  how  this  principle  can  b 
expressed  by  means  of  the  concepts  of  the  physicist. 

This  difficulty,  which  must  be  felt  with  greater  force  the  more  deeply  the 
physiologist  endeavours  to  peer  into  the  processes  within  the  living  cells, 
has  led  some,  even  at  the  present  day,  to  the  assumption  of  some  special 
quality  in  living  organisms  which  is  designated  as  '  vital  force  '  or  '  vital 
activity.'  Such  views  are  classified  together  under  the  term  vitalism. 
From  his  beginning  man  has  been  accustomed  to  draw  a  sharp  line  of  dis- 
tinction between  those  phenomena  which  by  their  constant  occurrence  seemed 
to  him  natural,  and  therefore  explicable,  and  those  phenomena  of  which  he 
could  not  see  the  determining  antecedent,  and  which  were  to  him,  therefore, 
anomic  and  capricious.  To  the  latter  he  set  up  graven  images,  and  not 
perceiving  his  own  springs  of  action,  endowed  them  with  a  self-determining 
personality  such  as  he  imagined  himself  to  possess.  This  procedure,  though 
possessing  certain  advantages  in  allowing  him  to  perform  his  common  duties 
free  from  the  everdurking  fear  of  supernatural  interference,  suffered  from 
the  great  drawback  that  it  fenced  off  unknown  phenomena  as  unknowable 
and  not  to  be  known.  It  has  therefore  acted  as  a  continual  check  on  the 
growth  of  man's  knowledge  and  control  of  his  environment.  Such  a  graven 
image  is  vitalism.  As  a  working  hypothesis  it  must  be  sterile.  Just  as  the 
hypothesis  of  special  creation  would  impede  all  research  into  the  relationships 
of  animals  and  plants,  so  vitalism  would  stay  the  hand  of  the  physiologist 
in  his  endeavours  to  determine  the  changes  which  occur  within  the  living 
organism.  In  many  cases,  however,  the  terms  '  vitalism  '  and  its  antithesis 
'  mechanism  '  are  used  unjustifiably.  The  production  of  energy  within  the 
body  is  due  to  the  oxidation  of  the  foodstuffs.  In  certain  functions  it  is  not 
yet  fully  established  whether  the  changes  involved  take  place  at  the  expense 
of  the  energy,  hydrostatic  pressure  or  otherwise,  of  the  fluids  outside  the 
cells,  or  whether  energy  is  supplied  to  the  process  by  the  cells  themselves 
at  the  expense  of  oxidative  or  other  changes  occurring  in  their  living  sub- 
stance. Both  views  are  possible,  but  the  adoption  of  either  by  a  physiologist 
does  not  justify  the  statement  that  he  is  a  *  vitalist,'  '  neo-vitalist,'  or 
'  mechanist.'  The  office  of  the  physiologist  is  the  determination  of  the 
changes  which  occur  in  the  living  body  and  the  establishment  of  the  causal 
nexus  (i.e.  the  routine  of  sequences)  between  them.  For  such  a  man  to 
describe  himself  as  a  vitalist  or  mechanist  is  as  germane  to  the  subject  as 
if  he  were  to  call  himself  a  Trinitarian  or  a  Plymouth  Brother. 

Throughout  this  chapter  we  have  assumed  no  necessary  dividing  line 

between  the  different  classes  of  phenomena  in  the  conceptual  universe, 

although  in  the  present  state  of  our  knowledge  we  are  far  from  being  able 

to  include  the  whole  of  them  under  the  same  general  laws.     It  might  be 

*   Karl  Pearson,  "  Grammar  of  Science,"  p.  328  et  seq.  (2nd  ed.). 


INTRODUCTION  9 

bjected  that  in  taking  up  this  attitude  we  had  left  out  of  account  one 
preme  fact,  viz.  the  existence  of  consciousness  in  ourselves.  As  a  com- 
ative  and  objective  study,  however,  physiology  is  concerned,  not  with 
study  of  consciousness,  but  with  the  conceptions  in  consciousness  of  the 
momma  presented  by  living  beings.  Consciousness,  in  fact,  we  know  only 
.1  ourselves.  From  the  actions  of  other  living  beings  similarly  organised,  we 
mfer  in  them  the  existence  of  a  similar  consciousness.  Again,  from  the  fact 
that  the  reactions  of  the  higher  mammals  are  evidently  determined,  not  by 
immediate  impressions,  but  largely  by  stored-up  impressions  of  past  stimuli, 
we  credit  them  also  with  a  certam  but  lower  degree  of  consciousness.  As 
we  descend  the  scale  of  animal  life,  evidence  of  the  existence  of  consciousness, 
as  we  know  it,  rapidly  diminishes  and  finally  disappears,  though  it  is  im- 
possible to  draw  a  sharp  line  between  those  animals  which  possess  conscious- 
ness and  those  in  which  it  is  absent.  That  it  is  a  necessary  accompaniment 
of  life  is  certainly  not  the  case.  A  man  is  living  though  he  is  asleep,  anaes- 
thetised, or  stunned,  and  it  would  be  absurd  to  speak  of  the  consciousness 
of  a  cabbage.  Consciousness  is,  in  fact,  connected  with  the  possession  of  a 
highly  developed  central  nervous  system,  and  its  activity  is  in  proportion  to 
the  complexity  of  this  system.  Since  the  brain  with  all  the  other  organs 
of  the.  body  is  derived  from  a  simple  cell,  the  fertilised  ovum,  similar  in  its 
absence  of  differentiation  to  the  lowest  organisms,  it  might  be  argued  that  all 
types  of  life  are  endowed  with  something  which  is  not  consciousness,  but 
which  has  the  potentiality  of  developing  into  consciousness.  To  such  a 
hypothetical  property  Lloyd  Morgan  has  given  the  name  '  metakinesis.'  We 
have,  however,  no  means  of  judging  of  the  presence  or  absence  of  this  hypo- 
thetical quality  and  still  less  of  determining  whether  it  is  a  property  only  of 
living  substance,  or  is  shared  also  by  the  atoms  of  so-called  dead  material. 


BOOK    I 
GENERAL   PHYSIOLOGY 


CHAPTER  II 

THE   STRUCTURAL    BASIS   OF   THE    BODY 
THE  CELL 

All  the  higher  animals  and  plants,  when  submitted  to  microscopic  examina- 
tion, are  seen  to  consist  of  structural  units  which  are  spoken  of  as  cells. 
In  each  organ  we  find  a  mass  of  these  cells  closely  resembling  one  another 
in  all  respects,  and  we  may  therefore  regard  the  function  of  any  organ  as 
the  sum  of  the  functions  of  its  constituent  cells.  Indeed,  any  given  reaction 
of  the  whole  body  is  the  resultant  of  the  reactions  of  the  unlike  cells  of  which 
the  body  is  composed.  The  cell  is  therefore  the  physiological  as  well  as  the 
structural  unit,  and  it  is  necessary  to  commence  our  study  of  the  functions  of 
the  animal  body  with  some  consideration  of  the  functions  and  reactions  which 
are  common  to  all  the  structural  units. 

This  composite  structure  is  peculiar  to  the  higher  forms  of  life.  Amongst 
the  lower  forms,  both  animal  and  vegetable,  an  immense  number  of  organisms 
consist  only  of  a  single  cell.  In  this  cell  are  represented  all  the  phenomena 
of  life,  all  the  adapted  reactions  which  we  associate  with  the  life  of  the  higher 
organisms.  That  the  unicellular  condition  represents  the  more  primitive 
stage  from  which  the  higher  organisms  have  been  evolved  in  the  course  of 
ages  is  indicated  by  the  fact  that  every  one  of  these  higher  organisms  in 
the  course  of  its  development  passes  through  a  unicellular  stage,  namely, 
the  fertilised  ovum.  We  may  assume  that  the  series  of  changes  attending 
the  development  of  the  higher  organism  from  the  egg  is  a  repetition  in  sum- 
mary of  the  changes  which  have  determined  the  evolution  of  the  species  from 
the  primitive  unicellular  type.* 

The  general  characteristics  of  the  cell  present  important  similarities, 
whether  we  are  considering  a  cell  which  forms  the  whole  of  an  organism  or  a 
cell  which  is  but  an  infinitesimal  part  of  a  highly  developed  animal. 

The  name  'cell'  was  first  applied  by  botanists  to  the  structural  units 
found  by  them  in  plant  tissues,  and  involved  therefore  the  idea  of  certain 
qualities  which  do  not  enter  into  our  present  conception  of  the  term.  A 
section  through  the  stem  of  a  growing  plant  shows  it  to  be  made  up  of  an 
aggregation  of  cells  in  the  etymological  sense  of  the  word,  i.e.  small  sacs 
bounded  by  a  wall  of  cellulose  and  containing  cell  sap.  Immediately  inside 
the  cellulose  wall  is  a  thin  layer,  the  primordial  utricle,  which  encloses  at  one 
point  a  spherical  or  oval  structure  known  as  the  nucleus.     If  the  section  be 

*  This  assumption  is  often  spoken  of  as  the  '  law  of  recapitulation.' 
13 


II 


PHYSIOLOGY 


taken  from  the  growing  rip  of  a  plant  (Fig.  1),  the  cell  sap  is  found  to  be 
wanting  and  the  cells  consist  only  of  the  substance  known  as  protoplasm, 
which  later  on  will  form  the  primordial  utricle.  This  with  a  nucleus  is 
enclosed  in  a  delicate  cellulose  wall.  The  wall  is  not  an  essential  constituent, 
since  it  is  absent  from  many  vegetable  cells  at  some  period  of  their  life  and 
from  animal  cells  generally. 

A  better  conception  of  the  essentials  of  a  cell  can  be  obtained  by  the  study 


Fig.  1.     General 


of  cells  in  the  growing  root-tip  of  the  onion,  from  a  longitudinal 

section,  enlarged  800  diameters.      (Wilson.) 
it,    non-dividing    cells,    with   chromatin -network   and    deeply    stained   nucleoli ; 
nuclei  preparing  for  division  (spireme-stage)  ;    c,  dividing  cells  showing  mitotic 
ures ;    c,  pair  of  daughter-cells  shortly  after  division. 


of  a  unicellular  animal  such  as  an  amoeba  (Fig.  2).  This  is  an  organism 
frequenting  stagnant  pools,  of  varying  size  (fromO'l  to  0"3  mm.  in  diameter), 
apparently  of  a  semi-fluid  consistence.  When  first  examined  it  is  generally 
spherical,  but  in  a  short  time  begins  to  change  its  form,  putting  out  processes 
known  as  pseudopodia.  By  shifting  the  distribution  of  its  material  among 
these  processes,  it  is  able  to  move  about  and  also  to  ingest  particles  of  food  or 
pigment  with  which  it  may  come  in  contact.  Near  its  centre  a  differentiated 
portion  can  be  distinguished  which  is  known  as  the  nucleus.  The  rest  of  the 
amoeba,  the  protoplasm  or  cytoplasm,  often  presents  further  differentiation 
into  an  outer  clear  layer  and  an  inner  finely  granular  substance.  The  latter 
may  contain  coarser  granules,  some  of  food  material,  others  apparently 
formed  in  situ  by  the  surrounding  protoplasm,  and  often  small  vacuoles 
('  contractile  vacuoles ')  which  are  continually  altering  their  size  and  serve 
to  keep  up  a  circulation  of  fluid  in  the  interstices  of  the  cytoplasm.  In  all 
cells,  whether  animal  or  vegetable,  with  which  we  are  acquainted,  this 


THE  STRUCTURAL  BASIS   OF  THE   BODY  15 

twofold  structure  is  also  found.     So  we  may  define  a  cell  as  a  small  mass  of 
protoplasm  containing  a  nucleus. 

Doubt  has  often  been  expressed  whether  a  nucleus  is  to  be  regarded  as  essential 
to  OUT  conception  of  a  cell.  In  many  of  the  lowest  forms  of  animals  and  plants,  such 
as  the  Flagellata  among  the  former  and  the  Cyanophyceae  and  Bacteria  among  the 
latter,  no  distinct  nucleus  can  be  demonstrated.  In  many  of  these  forms  the  dimen- 
sions of  the  whole  organism  are  too  minute  to  allow  of  any  definite  statement  being 


■  .  \ 

V 


■/■• 


Fig.  2.     Ammbn  protcus,  an  animal  consisting  of  a  single  naked  cell,   X280. 

(From  Sedgwick  and  Wilson's  Biology.) 
n,  the  nucleus  ;    wv,  water- vacuoles  ;   cv,  contractile,  vacuole  ;   jv.  food-vacuole. 

inndi  ns  to  the  presence  or  absence  of  nuclear  material.  In  the  larger  of  them,  how- 
ever, the  cytoplasm  of  the  cell  contains  numerous  scattered  granules  which  stain  with 
rh  in  the  same  way  as  do  the  nuclei  of  the  cells  of  higher  animals,  and  these  granules 
possess  the  resistance  to  the  action  of  certain  digestive  fluids  which  is  typical  of  nuclei. 
They  may  therefore  be  taken  as  representing  the  nucleus  in  the  higher  forms.  Even 
in  the  latter  at  certain  stages,  namely,  during  the  division  of  the  cell,  the  nucleus 
breaks  up  into  discrete  parts,  and  there  is  no  reason  fur  believing  that  such  a  scattered 
condition  of  the  nuclear  material  may  not  last  throughout  tin-  whole  life  of  the  cell. 

We  have  defined  a  cell  as  a  small  mass  of  protoplasm  containing  a  nucleus. 
Since  we  shall  have  to  use  the  term  '  protoplasm  '  on  many  occasions  in  the 
course  of  this  work,  we  must  have  a  definite  conception  of  what  we  mean 
by  it.  The  term  is  often  used  by  histologists  as  implying  a  substance  of 
certain  definite  chemical  and  staining  characters.  When  employed  by 
physiologists  it  generally  implies  any  material  which  we  can,  on  a  study  of  its 
behaviour  to  changes  in  its  environment,  regard  as  endowed  with  life. 
Huxley  has  defined  it  as  "  the  physical  basis  of  life."  Though  it  may  be  con- 
venient to  have  a  word  such  as  protoplasm  signifying  simply  '  living  material," 
it  is  important  to  remember  that  there  is  no  such  thing  as  a  single  substance 
— protoplasm.  The  reactions  of  every  cell  as  well  as  its  organisation  are  the 
resultant  of  the  molecular  structure  of  the  matter  of  which  it  is  built  up. 
The  gross  methods  of  the  chemist  show  him  that  the  composition  of  the 


L6 


PHYSIOLOGY 


'  protoplasm  '  of  the  muscle  cell  is  entirely  different  from  that  of  a  leucocyte 
or  white  blood  corpuscle.  The  finer  methods  of  the  physiologist  show  him 
that  every  sort  of  cell  in  the  body  has  its  own  manner  of  life,  its  own  pecu- 
liarities of  reaction  to  uniform  changes  in  its  surroundings.  No  individual 
will  react  in  exactly  the  same  manner  as  another  individual,  even  of  the 
same  species,  and  the  reactions  of  the  whole  organism  are  but  the  sum  of  the 

Attraction-sphere  enclosing  two  centrosomea 


— -    :    ..    .      .  ,      .-,   — — ^. 


Plasmosonie 

or  true 
nucleolus 


Lhlin  network 


Karyosome 


Plastids  lyin?  in  the 
/      cytoplasm 


Passive  bodies  (metaplasm 
or  paraplasm)  suspended 
in  the  cytoplasmic  mi  sh- 
work 


Fig.  3.     Diagram  of  a  cell.     Its  basis  consists  of  a  meshwork  containing  numerous  minute 
.  granules  (microsomes)  and  traversing  a  transparent  ground-substance.     (Wilson.) 

reactions  of  its  constituent  cells.  There  is  not  one  protoplasm  therefore,  but 
an  infinity  of  protoplasms,  and  the  use  of  the  term  can  be  justified  only  if  we 
keep  this  fact  in  mind  and  use  the  word  merely  as  a  convenient  abbreviation 
for  any  material  endowed  with  life.  Even  in  a  single  cell  there  is  more  than 
one  kind  of  protoplasm.  In  its  chemical  characters,  in  its  mode  of  life, 
and  in  its  reactions,  the  nucleus  differs  widely  from  the  cytoplasm.  Both 
are  necessary  for  the  life  of  the  cell  and  both  must  be  considered,  according  to 
our  present  ideas,  as  '  living.'  In  the  cytoplasm  itself  we  find  structures  or 
substances  which  we  must  regard  as  on  their  way  to  protoplasm  or  as  products 
of  the  breakdown  of  protoplasm  ;  but  in  many  cases  it  is  impossible  to  say 
whether  a  given  material  is  to  be  regarded  as  lifeless  or  as  reactive  living 
matter.  Even  in  a  single  cell  we  may  have  differentiation  among  its  different 
parts,  one  part  serving  for  the  process  of  digestion  while  others  are 
employed  for  the  purpose  of  locomotion.  Here  again  there  must  be  chemical 
differences,  and  therefore  different  protoplasms.  In  this  work  the  term 
protoplasm  will  be  used  in  its  broadest  sense,  namely,  as  the  physical  basis 
of  living  organisms. 

STRUCTURE  OF  THE  CELL.     In  every  cell  can  be  distinguished  the 
two  parts — nucleus  and  cytoplasm.     The  nucleus  is  generally  an  oval  or 


THE  STRUCTURAL  BASIS   OF  THE   BODY  17 

spherical  body  lying  near  the  centre  of  the  cell  and  bounded  by  a  definite 
contour  or  nuclear  membrane.  In  its  interior  it  contains  masses  or  filaments 
of  a  material  known  as  chromatin,  which  are  strung,  so  to  speak,  on  a  fine 
network  of  material  known  as  limn.  Besides  the  granules  of  chromatin, 
other  masses  are  sometimes  found  which  stain  in  a  different  manner  and  are 
called  nucleoli.  The  material  filling  up  the  meshes  of  the  network  is  the 
nuclear  sap  or  nucleoplasm.  The  cytoplasm,  which  varies  greatly  in  extent 
in  different  cells,  varies  also  in  its  appearance,  being  sometimes  homogeneous, 
sometimes  alveolar,  sometimes  granular  in  structure.  In  it  can  be  often 
distinguished  differentiated  parts  which  may  be  regarded  as  organs  of  the 
cell.  Thus  in  the  amoeba  we  have  the  contractile  vacuoles  already  men- 
tioned. In  the  green  parts  of  plants  the  cytoplasm  contains  green  granules, 
the  chloroplasts,  whose  special  function  it  is  to  assimilate  carbon  dioxide  from 
the  atmosphere,  and  by  means  of  the  energy  of  the  sun's  rays  to  convert  this 
into  starch  with  the  evolution  of  oxygen.  Other  parts  of  the  plant  have 
similar  granules,  the  leucoplasts,  whose  office  it  is  to  build  up  sugar  into 
starch,  and  it  is  possible  that  other  kinds  of  these  '  plastids  '  with  special 
chemical  functions  are  present  in  the  cytoplasm  of  many  cells.  In  addition 
to  these  cell  organs,  the  cytoplasm  may  contain  granules  which  represent 
stages  in  the  metabolism  of  the  cell  and  are  either  food  material  which  is 
being  assimilated  or  products  of  the  disintegration  of  the  protoplasm, 
formed  either  for  the  service  of  the  cell  itself  or,  in  the  case  of  the  multi- 
cellular animals,  for  the  service  of  other  cells  of  the  organism.  Others 
of  these  granules  may  represent  reserve  material,  i.e.  excess  of  nourishment 
which  has  been  put  aside  by  the  cell  in  an  insoluble  form,  to  serve  for  its 
subsequent  needs  in  times  of  scarcity. 

THE  PHYSICAL  STRUCTURE  OF  PROTOPLASM.  Owing  to  the  close 
similarities  which  exist  between  the  fundamental  properties  of  all  living 
organisms,  histologists  have  sought  to  discover  some  corresponding  uniform 
morphological  organisation  of  the  physical  basis  of  these  phenomena,  namely, 
protoplasm. 

It  is  often  impossible,  even  under  the  highest  powers  of  the  microscope, 
to  make  out  any  structure  whatsoever  in  the  cytoplasm,  which  is  spoken  of 
then  as  hyaline.  In  most  cases  examination  of  a  cell,  even  unstained,  shows 
some  differentiation  between  a  more  or  less  regular  framework  or  meshwork 
and  a  more  fluid  portion  filling  up  its  interstices,  and  these  appearances  are 
still  more  manifest  when  the  cells  have  been  fixed  by  various  hardening 
fluids.  All  the  results  obtained  in  this  manner  must  be  regarded  with  some 
suspicion,  since,  as  has  been  shown  by  Fischer  and  by  Hardy,  it  is  possible  to 
imitate  artificially  the  various  structures,  which  have  been  assigned  as 
characteristic  of  protoplasm,  by  hardening  a  homogeneous  colloidal  solution 
such  as  egg-white  by  different  methods  and  with  different  agents.  The 
theories  of  protoplasmic  structure  can  be  classified  under  three  heads  : 

1.  The  Granular  Theory  of  Altmann.  By  the  use  of  certain  hardening 
reagents,  a  dense  mass  of  spherical  or  rod-shaped  granules  may  be  demon- 
strated in  almost  all  cells  of  the  body  (Fig.  4).     These  granules  have  been 

2 


18  PHYSIOLOGY 

regarded  by  Altmann  as  bhe  elementary  particles  of  life,  and  he  locates  in 
them  the  various  vital  functions,  the  sum  of  which  makes  up  the  life  of  the 
cell.  According  to  Altmann  these  granules  can  arise  only  from  the  division  of 
pre-existing  granules,  and  he  has  formulated  the  phrase  omve  granulum  e 
granuh,  which  is  a  further  extension  of  Virchow's  sentence  omnis  cellula  e 
cellula.  It  is  probable  that  a  number  of  different  kinds  of  structures  of  vary- 
ing importance  are  included  among  Altmann's  granules.     In  some  cases  they 


Fig.  4.  ■  Section  of  liver  stained  to  show  granules.     (Altmann.) 


are  the  products  of  the  activity  of  the  cytoplasm  and,  as  in  secreting  cells, 
will  be  later  on  cast  out  with  water  and  salts  as  the  specific  secretion.  In 
other  cases  they  may  be  cell  organs  or  plastids  with  the  special  metabolic 
functions  assigned  to  all  granules  by  Altmann.  In  some  cases  no  treatment 
whatever  will  display  the  existence  of  granules. 

2.  The  Fibrillar  Theory.  By  the  employment  of  appropriate  methods 
of  hardening,  it  is  easy  in  most  cells  to  demonstrate  a  network  or  clusters 
of  fibrils  which  form,  so  to  speak,  a  denser  part  of  the  cell.  This  fibrillar 
network  has  been  named  the  '  spongioplasm  '  in  contra-distinction  to  the 
structureless  material  filling  its  meshes  known  as  '  hyaloplasm.'  A  network- 
is,  however,  one  of  the  commonest  pseudostructures  produced  in  the  coagu- 
lation of  an  albuminous  fluid  by  any  means  whatever,  and  it  is  probable 
that  in  most  cases  the  network  which  is  seen  in  hardened  cells  is  simply  an 
artefact.  Sometimes  a.  large  portion  of  the  protoplasm  may  take  a  fibrillar 
form  which  can  be  detected  even  in  the  unstained  and  unfixed  cell,  and  there 
is  no  doubt  that,  in  certain  phases  at  any  rate,  the  fibrillar  structure  of  the 
protoplasm  is  really  present. 

3.  The  Alveolar  Theory  of  Butschli.  This  theory  may  be  looked 
upon  as  corresponding  morphologically  to  the  granular  theory  of  Altmann. 
If  we  imagine  a  hyaline  protoplasm  which  is  continually  manufacturing 
metaplasmic  products  and  storing  them  up  in  its  protoplasm,  these  products 
will  be  deposited  as  spherules  gradually  increasing  in  size,  so  that  the  proto- 


THE  STRUCTURAL   BASIS   OF  THE  BODY 


19 


Fig.  5.  Diagram  o£  a  cell- 
highly  magnified.  (Schafer.) 
p,  protoplasm,  consisting  of 
hyaloplasm  and  a  network  of 
spongioplasm,  rx,  exoplasm : 
end,  endoplasm.  with  distinct 
granules  and  va  c  u  o  1  e  s  ; 
c,  double  centrosome  ;  re",  nu- 
cleus ;    «',  nucleolus. 


plasm  between  them  will  be  converted  into  alveolar  partitions  between  the 
droplets.  In  many  an  egg  cell,  where  there  is  a  growth  of  protoplasm  from 
this  building  up  of  food  into  reserve  materials,  the  development  of  such 
an  alveolar  structure  can  be  followed  in  the 
living  protoplasm,  and  such  cells  when  mature 
show  a  marked  alveolar  structure  whether  ex- 
amined fresh  or  in  the  hardened  and  stained 
condition.  Such  a  protoplasm  would  be  prac- 
tically an  emulsion  of  one  fluid  in  another,  and 
according  to  Biitschli,  artificial  emulsions,  made 
by  mixing  rancid  oil  with  sodium  carbonate 
solutions,  may  show  under  the  microscope  a 
very  close  resemblance  to  cell  protoplasm 
(Fig.  6),  and  may  even  exhibit  amceboid 
changes  of  form  in  consequence  of  the  diffusion 
currents  set  up  at  the  surface  of  the  drop 
between  its  contents  and  the  surrounding 
water.  Most  histologis'ts  are  in  accord  that 
none  of  the  above  theories  can  be  regarded  as  applicable  to  all  forms  of 
protoplasm, but  that  during  the  life  of  a  cell  its  protoplasm,  as  observed 
under  the  microscope,  maybe  either 
hyaline  and  structureless  or  may 
present  any  of  the.  structural  modi- 
fications described  above,  according 
to  its  state  of  nutrition  and  the  form 
in  which  its  metabolic  products  are 
laid  down  in  the  cell.  Of  course 
it  is  possible  that,  even  in  the 
apparently  hyaline  protoplasm,  a 
structural  differentiation  is  still  pre- 
sent, but  is.  invisible  owing  to  the 
minute  size  of  its  constituent  parts 
or  an  identity  of  refractive  index 
between  the  alveolar  walls  and  their 
contents.  The  fact  that!  every 
chemical  differentiation  occurring 
within  the  colloidal  mass  will  tend 
to  cause  differences  of  surface  ten- 
sion, and  therefore  formation  of 
droplets,  shows  that  an  alveolar 
structure,  i.e.  one  in  which  there  is 
a  large  number  of  surfaces  separat- 
ing heterogeneous  mixtures  inside 
the  cells,  must  be  of  very  common 
occurrence,  even  in  cases  where  it  is  not  detectable  under  the  microscope. 
Such  a  structure  must  be  present,  at  any  rate,  in  those  cases  where,  apart 


Fig.  6.     a.  protoplasm  of  an  epidermal  cell  of 
the  crayfish  :    it.  foam-like  appearance  of 
an  emulsion  of  olive  oil.     (Butschli.) 


20  PHYSIOLOGY 

from  tlic  existence  of  a  solid  cell  wall,  the  cell    presents   a  certain  degree 
of  rigidity  and  resistance  to  deforming  stress. 

ULTRAMICROSCOPIC  STRUCTURE  OF  PROTOPLASM.  Since  the  study  of 
the  behaviour  of  the  cell  shows  that  it  must  possess  a  much  more  complex  structure 
or  organisation  than  that  which  is  revealed  by  the  microscope,  one,  that  is  to  say, 
which  permits  of  the  spatial  differentiation  of  the  different  chemical  processes  that 
may  occur  at  one  and  the  same  time  in  the  protoplasm,  many  theories  have  been  put 
forward  of  an  ultramicroscopic  cell  structure.  Though  Spencer  in  1864  spoke  of 
physiological  units  out  of  which  protoplasm  could  be  regarded  as  made  up,  and  Darwin 
(1868)  conceived  ultramicroscopic  particles — gemmules — which  might  be  discharged 
from  every  cell  in  the  body  and,  passing  into  the  reproductive  organs,  serve  as  the 
material  basis  of  heredity,  the  first  elaborate  conception  of  such  a  structure  was  worked 
out  by  Nageli  (1884).  According  to  Nageli  all  organised  structures  are  made  up  of 
micellae,  minute  particles  arranged  in  definite  order  and  surrounded  with  water.  For 
growth  to  take  place  it  was  necessary  that  the  system  should  be  in  a  condition  of 
'  turgor,'  which  was  determined  by  the  amount  of  water  between  the  micellae.  These 
micellae  arose  in  every  case  from  the  division  of  pre-existing  micellae,  and  the  vital 
properties  of  the  protoplasm  were  to  be  regarded  as  the  sum  of  the  changes  taking 
place  in  the  individual  micellae.  Similar  conceptions  have  been  put  forward  by  numerous 
other  observers,  each  of  whom  has  applied  a  different  name  to  the  elementary  living 
particle,  such  as  '  pangene.'  '  plasome,'  '  biophor,'  '  biogen-molecule,'  and  many  others. 
The  resemblance  of  these  theories  to  that  of  Altmann  is  obvious,  though  the  latter 
regarded  the  elementary  particle  as  in  many  eases  of  microscopic  size  and  capable  of 
demonstration  by  appropriate  methods  of  staining.  That  the  cell  possesses  organs 
of  smaller  dimensions  than  itself,  which  may  give  rise  to  like  organs  by  division,  is 
shown  by  Schiinper's  observations  on  the  plastids  of  plant  cells.  These  apparently 
are  not  formed  by  a  process  of  differentiation  of  the  protoplasm,  but  are  continuous 
from  one  generation  to  another  and  are  reproduced  by  division.  There  is  no  doubt, 
however,  that  most  of  the  granules  to  be  observed  in  the  cytoplasm  are  not  of  this 
character,  but  are  elaborated  by  the  general  cytoplasm  out  of  the  foodstuffs  which  are 
supplied  to  it ;  and  though  conceptions  such  as  those  of  De  Vries  and  Verworn  are 
often  of  value  as  a  means  of  describing  certain  phenomena  in  the  life  of  the  cell  and  have 
played  a  great  part  in  the  description  of  the  phenomena  of  heredity,  they  cannot  be 
regarded  as  having  any  serious  justification  in  fact.  At  the  present  time  our  know- 
ledge of  the  properties  of  the  colloidal  and  capillary  systems,  which  must  play  so  great 
a  part  in  the  organisation  and  reactions  of  living  protoplasm,  is  much  too  meagre  to 
justify  weight  being  laid  on  any  theory  of  the  ultramicroscopic  structure  of  protoplasm 
that  oan  at  present  be  put  forward. 

One  question  which  has  been  much  discussed  relates  to  the  physical 
condition  of  protoplasm.  Is  it  to  be  regarded  as  a  viscous  fluid  or  as  a  soft 
solid  ?  The  perfect  potential  mobility  of  the  protoplasm  of  many  cells,  as 
instanced  by  the  flow  of  a  substance  of  an  amoeba  into  its  pseudopodia,  or  the 
occurrence  of  rapid  streaming  movements  in  the  threads  of  protoplasm 
found  in  many  plants,  e.g.  the  root  hairs  of  tradescantia,  indicates  a  fluid 
character  for  the  protoplasm.  Against  such  a  character  has  been  urged  the 
fact  that  in  protoplasm  we  may  have  shape,  organisation,  and  power  of 
resistance  to  deformation — qualities  which  are  generally  associated  with  the 
possession  of  solidity.  It  must  be  remembered,  however,  that  the  absence  of 
resistance  to  deformation,  which  is  characteristic  of  a  liquid,  applies  only  to 
the  internal  molecules,  and  that  the  surface  of  any  liquid  is  in  a  condition 
of  tension  which  not  only  limits  deformation,  but  presents  considerable 
resistance  to  any  enlargement  of  the  surface.     Small  water  animals  take 


THE  STRUCTURAL  BASIS  OF  THE  BODY  21 

advantage  of  this  resistance  to  run  freely  over  the  surface  of  water,  although 
their  specific  gravity  may  be  greater  than  that  of  water.  The  continued 
existence  of  protoplasm  in  a  watery  environment  shows  that  not  only  must 
its  composition  be  different  from  that  of  its  environment,  but  that  there  must 
be  a  distinct  surface  separating  the  two.  The  superficial  layers  of  the  proto- 
plasm must  therefore  be  in  a  condition  of  tension,  and  exercise  pressure  on  the 
internal  portions  of  the  cell,  which  will  tend  to  diminish  the  surface  of  the  cell 
to  the  smallest  possible  extent,  i.e.  to  bring  it  into  the  spherical  form. 

This  form  is  characteristic  of  free  cells  in  their  conditions  of  inactivity, 
and  the  smaller  the  mass  of  protoplasm,  supposing  it  to  be  homogeneous, 
the  greater  will  be  the  pressure  exerted  by  its  surface  layer  on  its  contents 
and  the  greater  resistance  will  it  present  to  deformation  of  the  spherical  form. 
A  fluid  drop,  if  suspended  in  a  fluid  with  which  it  is  immiscible,  will  present 
greater  rigidity  the  smaller  its  dimensions.  Almost  any  degree  of  rigidity 
can  also  be  imparted  to  larger  masses  of  fluid  protoplasm  if  their  interior  has 
undergone  chemical  differentiation  so  as  to  be  made  up  of  two  or  more  im- 
miscible fluids  arranged  as  droplets  within  alveoli,  as  in  Biitschli's  theory. 
In  such  a  case  every  droplet  will  present  resistance  to  deformation  and 
every  surface  will  resist  penetration  or  extension.  The  resistance  of  the 
surface  in  colloidal  fluids  is  still  further  increased  by  a  property  common  to 
all  these  fluids,  namely,  the  aggregation  in  the  surface  of  a  greater  concentra- 
tion of  the  dissolved  substance  than  is  present  in  the  underlying  fluid.  If, 
for  instance,  we  take  a  beaker  containing  egg-white  diluted  1(10  times,  and 
drop  a  steel  magnetised  needle  on  to  the  surface,  it  will  float  although  it  is 
much  heavier  than  the  fluid,  in  consequence  of  the  resistance  of  the  surface. 
If  the  needle  be  greasy  the  same  thing  will  occur  on  a  glass  of  water.  In  this 
case  the  needle  will  lie  N".  and  S.  On  the  albumen  solution,  however,  the 
needle  will  lie  in  the  position  in  which  it  has  been  dropped.  The  aggregation 
of  the  albumen  molecules  on  the  surface  of  the  fluid  is  such  that  it  is  practi- 
cally solid  and  resists  any  turning  of  the  needle.  In  consequence  of  the  sur- 
face aggregation  and  solidification  of  the  colloidal  molecules,  it  is  possible 
to  throw  out  the  greater  part  of  the  albumen  in  a  solid  form  from  a  solution 
of  this  substance,  if  it  be  shaken  up  in  a  bottle  with  a  little  air  so  as  to  make 
a  surface.  As  the  fluid  is  shaken  fresh  surfaces  are  always  being  formed,  and 
the  albumen  aggregating  in  each  of  these  surfaces  has  not  time  to  redissolve 
before  a  fresh  aggregation  -occurs  on  a  new  surface,  and  the  films  thus  pro- 
duced gradually  collect  to  form  a  solid  mass  of  insoluble  protein.  Proto- 
plasm may  be  regarded  as  essentially  fluid  in  character,  the  form  and  rigidity 
which  are  acquired  by  most  cells  being  due  to  chemical  and  physical  differen- 
tiation occurring  in  the  fluid. 

THE  SURFACE  LAYER  OF  CELLS.  Since  it  is  by  means  of  its  surface 
layer  that  the  organism  enters  into  relation  with  its  environment,  this 
layer  acquires  a  prime  importance  for  the  life  of  the  cell,  and  we  may  there- 
fore consider  here  at  greater  length  some  of  the  properties  of  this  layer,  the 
Phsmahaut,  as  it  has  been  called. 

The  superficial  layer  of  the  protoplasm  is  not  to  be  confounded  with  fchfc 


22  PHYSIOLOGY 

cell  wall.  The  latter,  which  playsagreal  pari  in  the  buildingup  of  vegetable 
tissues,  is  formed  by  a  process  of  secretion  from  the  living  protoplasm  and 
is  situated  altogether  outside  the  superficial  Plasmahavt.  The  cell  wall 
differs  considerably  in  its  chemical  composition  from  the  protoplasm  out  of 
which  it  has  been  formed.  In  most  plants  it  consists  of  cellulose,  a  substam  e 
belonging  to  the  carbohydrate  group,  and  with  a  composition  represented 
by  some  multiple  of  the  formula  CeH100B.  In  other  cells  the  wall  may  be 
built  up  from  calcium  carbonate  or  other  lime  salts,  from  silica,  from  chitin. 
In  many  cases  it  is  perforated  to  allow  the  passage  of  communicating  strands 
of  protoplasm  between  adjacent  cells.  It  is  generally  lively  permeable  to 
all  kinds  of  solutions,  and  in  this  ease  plays  no  part  in  regulating  the  inter 
changes  of  the  cell  with  the  environment. 

The  superficial  layer  of  protoplasm  represents  that  part  of  the  living 
substance  which  stands  in  immediate  relationship  to  the  environment. 
Every  change  in  the  latter  can  only  influence  the  living  cell  through  this 
layer,  and  it  is  through  this  layer  thai  substances  must  pass  on  their  wa\  into 
the  cell  for  assimilation,  or  out  of  the  cell  for  excretion.  The  retention  of  an 
individuality  by  the  cell  must  he  determined  by  chemical  and  physical 
differences  between  this  layer  and  the  surrounding  fluid.  Since  itdiffers  from 
the  rest  of  the  protoplasm  in  the  changes  to  which  it  is  subject,  it  must  also 
differ  in  its  chemical  composition,  apart  altogether  from  the  factors  which, 
as  we  saw  above,  determine  molecular  differences  between  the  surface  and  the 
interior  of  any  colloidal  solution.  On  this  account  one  must  assume  the 
existence  of  a  definite  boundary  layer  of  the  protoplasm,  even  where  it  is 
impossible  to  see  any  differentiation  between  this  layer  and  the  deeper- 
parts  under  the  highest  powers  of  the  microscope. 

A  (living)  cell,  which  leads  its  life  iir  a  liquid  environment,  must  take  up 
the  greater  part  of  its  food  material  in  the  form  of  solution,  and  it  is  the 
permeability  of  the  superficial  protoplasm  which  will  determine  the  passage 
of  food  substances  from  the  surrounding  medium  into  the  body  of  the  tell. 
The  immiscibility  of  the  protoplasm  with  the  surrounding  fluid  shows  that 
the  permeability  of  the  membrane  must  be  a  limited  one.  The  qualitative 
permeability  can  be  easily  studied  in  vegetable  cells.  These  present  within 
a  cellulose  wall  a  thin  layer  of  protoplasm  (the  primordial  utricle),  enclosing 
a  cell  sap.  If  the  root  hairs  of  tradescantia  be  immersed  in  a  10  per  cent, 
solution  of  glucose  or  in  a  2  to  3  per  cent,  solution  of  salt,  a  process  of 
flasmolysis  takes  place.  The  cell  sap  diminishes  in  amount  by  the  diffusion 
of  water  outwards  so  that  the  primordial  utricle  shrinks  (Fig.  7).  On  im- 
mersing the  cells  in  distilled  water,  water  passes  into  the  cell  sap  until  the 
further  expansion  of  the  protoplasmic  layer  is  prevented  by  the  tension  of 
the  surrounding  cell  walls.  This  behaviour  can  lie  explained  only  on  the 
assumption  that  the  protoplasm  is  impermeable  both  to  sugar  and  to  salt, 
but  is  freely  permeable  to  molecules  of  water,  i.e.  it  behaves  as  a  semi- 
permeable membrane.  Similar  experiments  can  be  made  on  animal  cells. 
The  most  convenient  for  this  purpose  are  the  red  blood  corpuscles.  These 
also  shrink  when  immersed  in  salt  solutions  with  a  greater  molecular  con- 


THE  STRUCTURAL  BASK  OF  THE  BODY 


23 


(••'titration  than  would  correspond  to  the  plasma  of  the  blood  from  which  the 
corpuscles  were  derived,  whereas  if  placed  in  weak  salt  solutions  or  distilled 
water  they  swell  up  and  burst,  discharging  their  haemoglobin  in  solution  into 
the  surrounding  fluid.  By  comparison  of  various  salts  it  is  found  that  the 
strength  of  each  salt  solution  which  is  just  necessary  to  cause  plasmolysis 
or  haemolysis,  as  the  case  may  be,  is  determined  entirely  by  its  molecular 
concentration,  i.e.  a  decinormal  solution  of  sodium  chloride  will  be  equivalent 


FlO.  7.     Vegetable  cells,  showing  varying  degrees  of  plasmolysis.     (De  Vries.) 

in  its  effect  on  the  cells  to  a  decinormal  solution  of  potassium  nitrate  or  of 
potassium  chloride.  The  impermeability  of  the  plasma  skin  does  not  apply 
to  all  dissolved  substances.  Overton  has  found  that,  whereas  this  layer  is 
practically  impermeable  to  salts,  sugars,  and  amino-acids,  it  permits  the 
easy  passage  of  monatornic  alcohols,  aldehydes,  alkaloids,  &c.  All  these 
substances  are  more  soluble  in  ether,  oil,  and  similar  media  than  they  are  in 
water.  The  passage  of  dissolved  substances  through  a  membrane  wetted 
by  the  solvent  depends  on  ths  solubility  of  these  substances  in  the  membrane, 
and  Overton  therefore  concludes  that  the  superficial  layer  of  protoplasmic 
cells  must  itself  partake  of  a  '  lipoid  '  character,  and  that  cholesterin  and 
lecithin  probably  enter  largely  into  its  composition.  Thus  only  those  aniline 
dyes  which  are  soluble  in  a  mixture  of  melted  lecithin  and  cholesterin  have 
the  property  of  penetrating  the  living  cell,  and  only  these  dyes,  such  as 
methylene  blue,  neutral  red,  can  be  used  for  intra  vitam  staining.  For  the 
same  reason  substances  which  have  the  power  of  dissolving  lecithin  and 
cholesterin,  such  as  ether  or  bile  salts,  also  act  as  haemolytic  agents,  i.e.  they 
cause  a  destruction  of  the  red  blood  cells  by  dissolving  the  superficial  layer 
which  is  necessary  for  their  preservation  from  the  solvent  effects  of  the 
surrounding  fluid.. 

The  semi-permeability  of  the  plasma  skin  can  be  altered  by  changes  in 
the  saline  concentration  or  other  factors  of  the  surrounding  medium.  Over- 
ton has  shown  that,  whereas  a  7  per  cent,  solution  of  saccharose  produces 
plasmolysis  in  living  cells,  no  plasmolysis  is  observed  if  they  are  treated  with 
a  solution  containing  3  per  cent,  methyl  alcohol  phis  7  per  cent,  cane  sugar. 
The  superficial  layer,  therefore,  is  able  to  dissolve  a  mixture  of  methyl 
alcohol  and  cane  sugar,  although  it  has  no  solvent  power  on  cane  sugar  in 


24  PHYSIOLOGY 

pure  watery  solutions.  It  is  possible  that,  in  order  to  serve  the  nutrient 
needs  of  the  cells,  more  extensive  changes  may  take  place  in  the  permeability 
of  the  surface  layer  under  limited  conditions  of  time  and  space.  There  is  no 
doubt,  for  instance,  that  dextrose,  to  which  the  surface  layer  is  apparently 
impermeable,  can  yet  serve  as  a  very  efficient  food  for  the  cell,  and  one 
might  ascribe  the  fact  that  the  cell  assimilates  only  the  food  which  it  requires 
and  no  more,  to  such  limited  changes  in  permeability.  An  important  factor 
in  the  process  of  assimilation,  at  any  rate  by  lowly  organised  cells,  must  be  the 
relative  solubility  of  the  absorbed  substances  in  the  cell  and  its  surrounding 
medium  respectively.  When  a  watery  solution  of  iodine  is  shaken  up  with 
chloroform,  the  latter  sinks  to  the  bottom,  carrying  with  it  the  greater  part 
of  the  iodine.  If  a  watery  solution  of  organic  acid  be  shaken  with  ether,  the 
latter  fluid  will  extract  the  greater  quantity  of  the  acid.  In  no  case  will  the 
extraction  be  complete,  but  there  will  be  a  definite  ratio  between  the 
amount  dissolved  by  the  ether  and  the  amount  dissolved  by  the  water,  the 
so-called  '  coefficient  of  partage,'  depending  on  the  different  solubilities  of 
the  dissolved  substance  in  the  two  menstrua.  In  the  same  way  a  mass,  of 
protoplasm  will  tend  to  absorb  from  the  surrounding  medium  and  to  con- 
centrate in  itself  all  those  substances  which  are  more  soluble  in  the  colloidal 
system  of  the  protoplasm  than  in  the  surrounding  fluid,  and  this  process  of 
absorption  may  be  carried  to  a  very  large  extent,  if  the  dissolved  substances 
meet  in  the  cell  with  any  products  of  protoplasmic  activity  with  which  they 
form  insoluble  compounds  so  that  they  are  removed  from  the  sphere  of 
action.  It  is  probably  by  such  a  process  as  this  that  w7e  may  account  for 
the  accumulation  of  calcium  or  silicon  in  such  large  quantities  in  connection 
with  the  bodies  of  various  minute  organisms. 

Whereas  assimilation  by  a  living  cell  is  ultimately  conditioned  by  the 
permeability  of  the  surface  protoplasm,  its  form  is  determined  by  the  tension 
of  this  layer.  If  the  tension  is  uniform  at  all  parts  of  the  surface  the  form  of 
the  cell  will  be  spherical.  Any  diminution  of  the  surface  tension  at  one 
point  must  tend  to  cause  a  bulging  of  the  fluid  contents  at  this  point,  just  as 
on  distending  a  rubber  tube  with  one  weak  spot  in  its  wall  this  suddenly 
gives  way  with  the  production  of  a  large  balloon,  which  rapidly  extends  in 
size  and  ruptures  unless  the  pressure  be  diminished.  Diminution  of  the  sur- 
face tension  at  one  point  of  the  cell  will  be  attended  by  a  contraction  of  all  the 
rest  of  the  surface  and  a  driving  out  of  the  contents  through  the  weak  part. 
This  process  will  not  as  a  rule  result  in  destruction  of  the  cell ;  the  resulting 
protrusion  will  be  limited  by  the  distortion  of  the  internal  alveolar  structure 
of  the  protoplasm  caused  by  any  alteration  of  the  spherical  form  of  the  cell. 
Change  of  form  in  living  structures  thus  depends  ultimately  on  alterations 
in  surface  tension,  return  to  normal  being  effected  by  the  elastic  reaction  of 
the  structural  arrangement  of  the  protoplasm.  This  point  we  shall  have  to 
consider  more  fully  when  dealing  with  muscular  contraction.  At  present 
it  is  sufficient  to  see  how  any  slight  alteration  in  the  chemical  environment, 
such  as  might  be  due  to  the  presence  of  a  particle  of  foodstuff,  may 
cause  local  variations  in  the  surface  tension  of  the  plasma-skin  and  thus 


THE  STRUCTURAL  BASIS   OF  THE  BODY  25 

result  in  the  protrusion  of  pseudopodia  and  the  ingestion  of  the  food 
particle. 

VITAL  PHENOMENA  OF  CELLS.  A.  Assimilation.  The  activity  of 
every  living  being,  whether  uni-  or  multi-cellular,  can  be  regarded  as  com- 
pounded of  two  phases,  assimilation  and  dissimilation.  By  assimilation  we 
mean  the  building  up  of  the  living  substance  at  the  expense  of  material 
obtained  from  the  external  world.  In  this  process  substances  are  formed  of 
high  potential  energy,  and  this  energy  can  be  obtained  only  at  the  expense 
either  of  energy  imparted  to  the  system  at  the  moment  of  assimilation,  as, 
e.g.  in  the  assimilation  of  carbon  from  carbon  dioxide  under  the  influence 
of  the  sun's  rays,  or  of  energy  contained  in  the  food-stuffs  themselves.  In  all 
living  organisms,  except  those  provided  with  chlorophyll  corpuscles,  it  is 
the  latter  method  which  is  adopted,  and  a  food-stuff  therefore  connotes  some 
substance  which  can  be  taken  in  by  the  cell  and  can  serve  it  as  a  source 
of  chemical  energy.  The  evolution  of  energy,  which  is  required  for  the 
movements  and  other  vital  activities  of  the  cell,  is  derived  from  a  disintegra- 
tion-or  dissimilation  of  the  protoplasm  and  is  generally  associated  with  the 
process  of  oxidation.  In  assimilation,  besides  the  building  up  of  living 
protoplasm,  there  may  also  be  a  synthesis  of  more  complex  from  less  complex 
compounds,  without  their  necessary  entry  into  the  structure  of  the  living 
molecule.  In  the  absence  of  any  definite  criteria  by  which  we  may  judge 
as  to  the  living  or  non-living  condition  of  parts  of  the  cell,  it  is  a  little 
dangerous  to  draw  any  hard-and-fast  distinction  between  these  two  sets  of 
processes.  Assimilation  requires  the  ingestion  of  food  into  the  organism,  and 
in  the  second  place  its  digestion,  i.e.  its  solution  in  the  juices  of  the  cells. 
These  two  processes  are  svicceeded,  through  stages  which  we  cannot  trace, 
by  an  actual  growth  in  the  living  material.  In  naked  cells  ingestion  may 
occur  either  at  any  part  of  the  surface,  as  in  the  amoeba,  or  at  a  specialised 
portion,  so-called  '  mouth,'  as  in  many  of  the  infusoria.  Digestion  is 
apparently  effected  in  most  cases  by  the  production  and  secretion  around  the 
ingested  food  partiele.of  solutions  containing  ferments,  i.e.  agents  which  have 
the  power  of  hydrolysing  the  different  foodstuffs  and  rendering  them  soluble. 

In  the  vast  majority  of  living  organisms  the  energy  for  their  activities 
is  derived  from  the  oxidation,  ultimately  of  the  foodstuffs,  but  immediately 
of  molecules  attached  to  the  living  protoplasm.  A  necessary  condition, 
therefore,  for  the  life  of  these  cells  is  the  presence  of  oxygen  in. the  surround- 
ing medium,  from  which  it  is  taken  up  in  the  molecular  form.  We  may 
therefore  speak  of  an  assimilation  of  oxygen  ;  but  it  is  still  a  matter  of 
dispute  whether  the  oxygen  is  built  up  as  such  in  the  living  molecule  (so-called 
intra-molecular  oxygen)  to  be  utilised  for  the  formation  of  carbon  dioxide 
when  a  discharge  of  energy  is  necessary,  or  whether  it  is  taken  in  only  at  the 
moment  when  the  combustion  of  the  carbon  and  hydrogen  constituents  of  the 
food  or  protoplasm  is  necessary  for  the  supply  of  energy.  However  this  may 
be,  products  are  formed  as  a  result  of  this  oxidation  which  are  of  no  further 
value  to  the  cell  and  are  therefore  excreted,  i.e.  turned  out  of  the  cell.  The 
chief  of  these  are  the  products  of  oxidation  of  carbon  and  hydrogen,  namely, 


20  PHYSIOLOGY 

carbon  dioxide  and  water.  There  arc  also  many  substances  resulting  from 
the  oxidation  of  the  nitrogenous  portions  of  the  protoplasm,  which  have  to 
be  excreted  in  the  solid  or  dissolved  form. 

Although  the  assimilation  of  oxygen  is  so  general  a  quality  of  living  protoplasm, 
the  presence  of  this  gas,  at  any  rate  in  the  free  form,  docs  not  sccni  to  lie  necessary 
for  all  kinds  of  life.  Thus  a  number  of  the  bacteria  arc  known  which  arc  anaerobic, 
i.e.  exist  only  in  the  absence  of  oxygen.  Examples  of  such  are  bacillus  tetanus,  and 
the  bacillus  of  malignant  oedema.  In  order  to  cultivate  them  it,  is  necessary  to  dis- 
place all  the  air  in  the  cultivating  vessels  by  means  of  a  current  of  hydrogen.  It  has 
been  supposed  thai  the  ultimate  oiirce  of  the  energy  of  these  organisms  is  also  derived 
from  a  process  of  oxidation,  and  that,  they  differ  from  other  organisms  in  being  able 
to  utilise  for  this  purpose  oxygen  which  "s  built  up  into  the  structure  of  their  food  sub- 
stances. It  is  possible,  however,  that  these  organisms  derive  the  energy  for  the  building 
up  of  their  protoplasm,  for  their  movements.  fas.,  not  from  a  process  of  oxidation  at 
all,  but  from  processes  of  disintegration  of  the  substances  which  they  utilise  as  food. 
It  is  by  such  means  that  in  all  probability  the  intestinal  worms,  fairly  highly  organised 
animals,  are  able  to  exist  in  Hie  intestine  in  a  medium  containing  no  oxygen,  but  rich 
in  carbon  dioxide.  Here  they  an-  plentifully  supplied  with  foodstuffs  and  can  afford 
to  adopt  a  wasteful  method  of  nutrition,  in  which  only  a,  small  fraction  of  the  energy 
is  obtained  which  would  be  produced  by  a  total  oxidation  of  the  food. 

B.  The  Phenomena  <</  Dissimilation.  The  activities  of  a.  living  cell 
or  organism  can  be  regarded  m  every  case  as  dependent  originally  on  en- 
vironmental chance,  ami  are  adapted  to  (his  change,  i.e.  are  of  such  a  nature 
that  they  tend  to  preserve  the  organism  intact,  to  favour  its  growth,  or  pre- 
vent its  destruction.  The  property  of  reacting  in  such  a  manner  to  changes 
in  the  environment  is  fundamental  to  all  protoplasm  and  is  spoken  of  as 
kx&itability,  anil  the  change  which  will  influence  an  organism  and  cause  a 
corresponding  adaptive  change  in  it  is  known  as  a  stimulus.  Stimuli  may  be 
of  various  kinds.  Thus  mechanical,  thermal,  chemical,  electrical  changes, 
light,  and  so  on,  may  act  as  stimuli.  The  reactions  which  they  evoke  involve 
in  every  case  chemical  changes  in  the  protoplasm,  i.e.  changes  in  the  metabol- 
ism of  the  cell.  Sometimes  this  change  may  be  assinulatory  in  character, 
leading  to  an  increased  growth  of  the  protoplasm,  or  at  any  rate  to  a  cessation 
of  dissimilation.  In  such  a  case  the  stimulus  is  spoken  of  as  inhibitory, 
because  it  diminishes  or  prevents  the  output  of  energy  by  the  organism. 
The  frequent  result  of  a  stimulus  is  an  increased  output  of  energy,  which  may 
appear  in  the  form  of  movement,  in  the  form  of  heat,  or  as  chemical  change. 

A  common  feature  of  all  dissimilatory  changes  evoked  by  the  application 
of  a  stimulus  is  that  the  energy  of  the  reaction  is  always  many  times  greater 
than  the  energy  represented  by  the  stimulus,  the  excess,  of  course,  being 
supplied  at  the  expense  of  the  potential  energy  of  the  food  material  which 
has  been  stored  up  in  or  built  up  into  the  living  protoplasm.  This  dispropor- 
tion between  stimulus  and  reaction  can  be  well  illustrated  on  an  excitatory 
tissue  such  as  muscle.  Thus  in  one  experiment  the  gastrocnemius  muscle  of  a 
frog  was  loaded  with  a  weight  of  4s  gms.  The  nerve  running  to  the  muscle 
was  placed  on  a  hard  surface  and  a  weight  of  half  a  gramme  was  allowed  to 
fall  upon  it  from  a  height  of  10  mm.  The  muscle  contracted  in  response  to 
this  mechanical  stimulus  applied  to  the  nerve  and  raised  the  weight  38  mm. 


THE  STRUCTURAL  BASIS   OF  THE  BODY  27 

In  this  case  the  wink  performed  by  the  muscle  was  48  X  3'8  =  182'4 
grm.  mm.,  while  the  potential  energy  of  the  stimulus  represented  only 
0'5  X  lO'O  =  50  grm.  mm.  Thus  the  work  performed  by  the  muscle 
was  thirty-six  times  larger  than  the  energy  of  the  stimulus  applied  to  the 
nerve. 

In  the  case  of  unicellular  organisms,  definite  classes  of  motor  reaction  to  stimulus 
have  been  described.  The  ordinary  retraction  of  a  unicellular  organism,  such  as  the 
yorticella,  in  response  to  a  touch  is  called  thigmotaxis.  Certain  cells  are  influenced 
by  gravity,  tending  to  rise  or  fall  in  the  surrounding  medium  according  to  the  conditions 
which  favour  their  existence.  .\  similar  sensitiveness  to  gravity  is  observed  in  the 
growing  parts  of  plants,  where  the  root  alwuys  grows  downwards  and  the  stem  up- 
wards. This  reaction  to  gravity  is  known  as  geolaxis,  which  is  distinguished  as  'nega- 
tive '  or  '  positive  '  respectively,  according  as  the  plant  grows  in  opposition  or  in  obedi- 
ence to  tl»'  gravitational  attraction.  If  growing  plants  be  placed  on  the  rim  of  a 
wheel  and  rotated  so  thai  the  centrifugal  force  is  greater  than  that  of  gravity,  the 
stems  all  grow  towards  the  centre  of  the  wheel  while  the  rootlets  grow  outwards.  In 
the  same  way  the  reaction  of  micro-organisms  to  light  is  known  as  photolaxis,  some 
organisms  seeking  the  light  while  others  shun  it.  Among  the  primitive  reactions  of 
cells  perhaps  the  mosl  important  in  the  life  of  higher  animals  are  those  grouped  under 
the  term  rli,  miotaxis.  The  fertilisation  of  the  ovum  in  the  prothallus  of  ferns  is  effected 
bj  the  penetration  of  the  antherozoids  produced  in  the  male  organs  at  some  little 
distance  from  the  female  organs.  It  was  shown  by  Pfeffer  that  the  movement  of 
the  antherozoids  towards  the  ova  is  effected  in  response  to  a  chemical  stimulus,  probably 
malic  acid,  since  he  found  that  antherozoids  suspended  in  a  fluid  will  always  swim 
towards  any  locality  where  there  is  a  greater  concentration  of  this  acid.  In  the  same 
«j\  aerobic  bacteria  are  attracted  by'the  presence  of  oxygen.  If  such  bacteria  are 
present  in  a  solution  with  an  alga,  on  exposure  of  the  fluid  to  light  there  is  an  evolution 
of  oxygen  by  the  green* alga,  and  a  consequent,  congregation  of  the  bacteria  round  the 
seat  of  production  of  the  oxygen.  The  movements  of  the  white  corpuscles  of  the  blood 
of  the  higher  animals  arc  also  largely  determined  by  their  chemical  sensibility,  and 
various  substances  can  be  divided  into  (a)  those  which  exercise  positive  and  (b)  those 
which  exercise  negati\e  ehemiotactic  influence  on  the  leucocytes.  Thus  the  intro- 
duction under  the  skin  of  an  animal  of  a  capillary  tube  containing  a  solution  of  sub- 
stances of  the  first  class,  aucb  as  peptone,  tissue  extracts,  or  the  chemical  products 
of  certain  bacteria,  leads  to  an  accumulation  within  the  tube  of  leucocytes  which  pass 
to  it  from  all  the  surrounding  tissues.  Other  substances,  such  as  quinine,  exert  a  nega- 
tive chemiotaxis.  Tubes  filled  with  these,  after  introduction  into  the  subcutaneous 
tissue  of  a  mammal,  will  be  found  many  hours  later  to  contain  no  leucocytes  at  all. 

THE  RELATIONS  OF  THE  NUCLEUS  TO  THE  CYTOPLASM.  The 
universal  existence  in  living  cells  of  a  differentiated  nucleus  indicates  that 
the  life  cycle  of  assimilation  and  dissimilation  must  depend  on  an  interaction 
between  the  nucleus  and  cytoplasm,  and  that  each  plays  a  distinct  part  in  the 
sum  of  the  changes  which  make  up  the  life  of  the  cell.  The  different  staining 
reactions  of  nucleus  and  cytoplasm  suggest  a  corresponding  difference  in  their 
chemical  composition,  a  suggestion  which  is  confirmed  by  analysis.  In  the 
building  up  of  protoplasm  proteins  play  an  important  part.  They  are  not 
present,  however,  as  simple  proteins,  hut  built  up  with  other  complex  bodies 
to  form  conjugated  proteins.  Whereas  in  the  cytoplasm  these  conjugated 
proteins  consist  chiefly  of  compounds  of  protein  ami  lecithin,  in  the  nucleus 
the  chief  constituents  belong  to  the  class  of  nucleo-proteins.  The  nucleo- 
proteins  are  of  varying  composition,  and  are  distinguished  chiefly  by  the 


28  PHYSIOLOGY 

large  amount  of  phosphorus  in  their  molecule.  A  nueleo-protein  can  be 
broken  down  into  nuclein  and  protein.  Nuclein  can  be  broken  down  into 
nucleic  acid  and  a  protein-like  substance,  protamine.  Nuclei  differ  among 
each  other  and  at  different  periods  of  their  existence  or  in  different  conditions 
of  activity  according  to  the  greater  or  less  amount  of  protein  which  is 


A 


V0§!$$As  D 

Fig.  8.     Nucleated  and  non-nucleated  fragments  of  Ameeba.      (Wilson  after  Hofeb.) 
A,  B.     An   Amceba  divided  into  nucleated  and  non-nucleated  halves,  five    minutes 
after  the  operation.     C,  D.  The  two  halves  after  eight  days,  each  containing  a  con- 
tractile vacuole. 

combined  with  the  nuclein.  The  latter  seems  to  be  the  essential  constituent 
of  cell  nuclei  and  to  be  present  in  only  small  quantities  in  the  cytoplasm 
The  properties  and  reactions  of  these  bodies  will  be  dealt  with  at  greater 
length  in  the  next  chapter. 

In  order  to  appreciate  the  part  played  by  the  nucleus  in  the  ordinary 
cell  processes,  we  must  study  the  behaviour  of  cells  or  parts  of  cells  deprived 
of  a  nucleus  and  compare  it  with  that  of  similar  cells  or  parts  of  cells  still 
containing  a  nucleus.  By  means  of  a  fine  needle  it  is  possible  to  divide  the 
larger  protozoa  into  two  pieces,  one  with  and  one  without  a  nucleus.  Hofer, 
experimenting  on  the  amoeba,  found  that  the  fragment  containing  the  nucleus 
quickly  regenerated  the  missing  part  and  pursued  a  normal  existence.  On 
the  other  hand,  the  non-nucleated  fragments  showed  no  signs  of  regeneration. 
They  might,  indeed,  live  as  long  as  fourteen  days  after  the  operation  (Fig.  8). 


THE  STRUCTURAL   BASIS   OF  THE   BODY 


29 


Their  movements  continued  for  a  short  time  and  then  ceased,  though  the 
pulsations  of  the  contractile  vesicle  were  but  little  affected.  The  power 
of  digestion  of  food  was  completely  lost.  Other  observers  have  shown 
that  Stentor,  an  infusorium  which  possesses  a  fragmented  nucleus,  may  be 
broken  up  into  fragments  of  all  sizes.  Nucleated  fragments  as  small  as 
one-twenty-seventh  the  volume  of  the  entire  animal  are  still  capable  of 


Fig.  9,     Regeneration  in  the  unicellular  animal  Stentor.     (From  Gruber  after  Balbiani.) 
-•1.  Animal  divided  into  three  pieces,  each  containing  a  fragment  of  the  nucleus. 
B.  The  three  fragments  shortly  afterwards.     C.  The  three  fragments  after  twenty-four 
hours,  each  regenerated  to  a  perfect  animal. 

regeneration.  The  wound  quickly  heals  and  the  special  organs — the  mouth, 
with  its  surrounding  cilia,  and  the  contractile  vacuole — are  regenerated,  but 
all  non-nucleated  fragments  quickly  perish  (Fig.  9). 

Many  similar  observations  have  shown  that  the  non-nucleated  cytoplasm, 
though  it  may  survive  for  some  time  and  perform  normal  movements  in 
response  to  stimuli,  such  as  those  of  ingestion  of  food  particles,  loses  entirely 
the  power  of  digestion,  secretion,  and  growth.  In  animals  possessing  a  shell, 
a  small  secretion  of  the  lime  salts  may  occur  on  the  surface,  but  this  process 
rapidly  comes  to  an  end  as  the  store  of  material  in  the  cytoplasm  is  exhausted. 
In  vegetable  cells  it  is  possible  to  break  up  the  protoplasm  by  means  of 
plasmolysis  into  nucleated  and  non-nucleated  parts.  The  nucleated  part 
quickly  forms  a  new  cell  wall.  The  non-nucleated  part  is  unable  to  effect 
this  formation,  and  soon  dies  unless  it  is  in  connection  with  an  adjacent 
cell  containing  a  nucleus  by  means  of  fine  threads  of  protoplasm  which 
pass  through  pores  in  the  intercellular  septa  (Fig.  10).    In  the  higher  animals 


30 


PHYSIOLOGY 


we  have,  in  the  case  of  the  nerve-cell,  an  example  of  the  necessity  of  the 
nucleus  for  growth.  Here  division  of  the  nerve  fibre  causes  degeneration  of 
the  whole  fibre  separated  from  the  cell  containing  the  nucleus,  and  regenera- 
tion of  the  fibre,  when  it  occurs,  is  effected  by  a  down-growth  of  that  part  of 
the  fibre  which  is  still  in  conned  inn  with  the  nucleus.     All  these  facts  show 


A 


C 


D 


Fig.    10.     Formation  of  membranes  by  protoplasmic  fragments  of  plasmolysed  cells. 
(Wilson  after  Townsend.) 

A.  Plasmolysed  cell,  leaf-bail  of  Cucurbita,  showing  protoplasmic  balls  connected 
by  strands.  B.  Calyx-hair  of  Gaillardia  ;  nucleated  fragment  with  membrane,  non- 
nucleated  one  naked.  C.  Root-hair  of  Marchanlia  :  all  the  fragments,  connected  by 
protoplasmic  strands,  have  formed  membranes.  />.  Leaf-hair  of  Cucurbtta ;  non- 
nucleated  fragment,  with  membrane,  connected  with  nucleated  fragment  of  adjoining 
cell. 

that  the  power  of  morphological  as  well  as  of  chemical  synthesis  depends  on 
the  presence  of  a  nucleus.  On  this  account  the  nucleus,  as  we  shall  learn 
later  on,  must  be  regarded  as  the  especial  organ  of  inheritance.  The  trans- 
mission of  the  paternal  qualities  from  one  generation  to  the  next  is  effected  by 
the  entrance  simply  of  the  nuclear  material  of  the  male  cell,  the  spermato- 
zoon, into  the  ovum.  In  the  words  of  Claude  Bernard,  "  the  functional 
phenomena  in  which  there  is  expenditure  of  energy  have  their  seat  in  the 
protoplasm  of  the  cell  (i.e.  the  cytoplasm).  The  nucleus  is  an  apparatus  for 
organic  synthesis,  an  instrument  of  production,  the  germ  of  the  cell." 

Similar  conclusions  may  be  drawn  from  a  study  of  the  changes  in  the 
nucleus  which  accompany  different  phases  in  the  activity  of  the  whole  cell. 


THE  STRUCTURAL  BASIS  OF  THE  "BODY  31 

Thus  in  growing  plant  cells  the  nucleus  is  always  situated  at  the  point  of 
most  rapid  growth.  In  the  formation  of  epidermal  cells  the  nucleus  moves 
towards  the  outer  wall  and  remains  closely  applied  to  it  so  long  as  it  is  growing 
in  thickness.  When  this  growth  is  finished  the  nucleus  moves  to  another 
part  of  the  cell.  In  the  formation  of  root  hairs  the  outgrowth  always  takes 
place  in  the  immediate  neighbourhood  of  the  nucleus,  which  is  carried  forward 
and  remains  near  the  tip  of  the  growing  hair.  The  active  growth  of  cyto- 
plasm, which  accompanies  the  activity  of 
secreting  cells,  is  always  associated  with 
changes  in  the  position  and  in  the  size  of 
the  nucleus.  Where  the  nutritive  activity 
of  the  cell  is  very  intense,  as  in  the  silk 
glands  of  various  lepidopterous  larvae,  the 
nucleus  is  found  to  be  very  large  and  much 
branched  (Fig.  II)  so  as  to  present  the 
greatest  possible  extent  of  surface  through  Flo  ,,  Branched  nucleus  from 
which    interchanges   can     go    on    between        the  spinning  gland  of  butterfly 

,  j        .      ,  larva  (Pieris).     (Korschelt.) 

nucleus  and  cytoplasm.  v         '     ( 

The  important  changes  which  the  nucleus  undergoes  in  the  process 
of  cell  division  we  shall  have  to  consider  more  fully  in  the  later  chapters 
of  this  work.  In  the  function  of  assimilation  it  is  natural  to  assume  that 
it  is  those  constituents  of  the  nucleus  which  are  peculiar  to  it  both  morpho- 
logically and  chemically,  namely,  the  chromatin  filaments,  which  are  most 
directly  concerned.  This  assumption  receives  support  from  the  changes 
which  have  been  observed  to  occur  in  these  filaments  during  various  phases 
of  nutritive  activity  of  the  cell.  The  staining  powers  of  chromatin  are  in 
direct  proportion  to  the  amount  of  nuclein  it  contains.  In  the  eggs  of  the 
shark  it  has  been  shown  that  the  chromosomes  undergo  characteristic  changes 
during  the  entire  growing  period  of  the  egg.  At  first  I  bey  are  small  and  stain 
deeply  with  ordinary  nuclear  dyes,  but  during  the  period  of  growth  they 
undergo  a  great  increase  in  size  and  at  the  same  lime  lose  their  staining 
capacity,*  their  surface  being  increased  by  the  development  of  long  threads 
which  grow  out  in  every  direction  from  the  central  axis.  As  the  egg 
approaches  its  lull  size,  the  chromosomes  diminish  in  size  and  are  finally 
reduced  to  minute  intensely  staining  bodies  which  take  part  in  the  first 
division  of  the  egg  preparatory  to  its  fertilisation  (Fig.  12).  We  must 
conclude  that  whereas  the  processes  of  destructive  metabolism  or  dissimila- 
tion, which  determine  the  activity  of  the  cell,  have  their  immediate  seat  in 
the  cytoplasm,  the  processes  of  constructive  metabolism  which  lead  to  the. 
formation  of  new  material,  to  the  chemical  and  morphological  building  up  of 
the  cell,  are  carried  out  in  or  by  the  intermediation  of  the  nucleus. 

HISTOLOGICAL   DIFFERENTIATION  OF    CELLS.      Even  within  the 

limits  of  a  single  cell,  differentiation  of  structure  can  take  place  by  the 

setting  apart  of  distinct  portions  of  the  cell  for  isolated  functions.     Thus  in 

an  organism  such  asvorticella  the  cell  is  shaped  somewhat  like  a  wine-glass, 

*  Ruckert,  citad  by  Wilson. 


32 


PHYSIOLOGY 


the  .stem  being  composed  <>f  a  spiral  contractile  fibre  which  lias  the  function 
of  withdrawing  the  rest  of  the  organism  when  necessary  towards  its  point  of 
attachment.  The  main  portion  of  the  cell  presents  at  its  free  extremity  a 
part  which  is  the  seat  of  ingestion  of  food,  and  is  therefore  spoken  of  as  the 
'  mouth.'  This  is  surrounded  by  a  circle  of  cilia  whose  function  it  is  to  set 
up  currents  in  the  surrounding  fluid  and  so  favour  the  passage  of  food  parti- 
cles towards  the  mouth.      Food  when  ingested  at  this  end  passes  only  a 


Fig.  12.     Chromosomes  of  the  germinal  vesicle  in  the  shark  Pristiniits,  at  different  periods 
drawn  to  the  same  scale.     (BtJCKEET.) 
A.  At  the  period  of  maximal  size  and  minimal  staining-capacity   (egg  3  mm.    in 
diameter).     B.  Later  period  (egg  13  mm.  in  diameter).     C.  At  the  close  of  ovarian  life, 
of  minimal  size  and  maximal  staining-power. 

short  distance  into  the  body  of  the  vorticella.  Here  fluid  is  secreted  around 
it  which  serves  for  its  digestion.  This  portion  of  the  cell  may  therefore  be 
regarded  as  the  alimentary  canal  or  stomach.  The  indigestible  residue  of  the 
food  is  excreted  in  close  proximity  to  the  mouth.  In  addition  to  these  organs 
we  have  the  usual  differentiation  of  the  protoplasm  into  an  external  and 
internal  layer,  and  the  development  within  the  protoplasm  of  contractile 
vacuoles  which  serve  to  keep  up  a  circulation  of  fluid  and  therefore  to  pass 
the  products  of  digestion  through  all  parts  of  the  cell  body.  Within  the 
limits  of  the  single  cell  which  forms  the  vorticella  we  may  therefore  speak 
of  organs  for  contraction,  for  digestion,  for  circulatiqp,  and  so  on. 

The  organs  which  are  thus  formed  in  unicellular  animals  or  plants  can  be 
divided  into  two  classes,  namely  (1)  temporary  organs,  which  are  formed  out 


THE  STRUCTURAL  BASIS  OF  THE   BODY  33 

of  a  common  structural  basis  and  can  therefore  be  replaced  at  any  time  by 
the  cytoplasm  if  destroyed.  Examples  of  such  organs  are  the  cilia,  the 
commonest  motor  apparatus  of  unicellular  organisms  ;  the  pseudopodia, 
which,  as  we  have  seen,  can  be  made  and  destroyed  at  will  ;  the  mouth  of 
animals  such  as  Volvox  or  Vorticella  ;  and  the  stinging  cells  or  nectocysts, 
which  surround  the  mouth  of  many  of  these  animals  and  serve  to  paralyse 
or  kill  the  smaller  living  organisms  brought  by  the  cilia  within  reach  in 
order  that  they  may  serve  as  food.  In  contradistinction  to  these  organs 
are  (2)  a  number  of  others  which  must  be  regarded  as  permanent.  These 
cannot  be  formed  by  differentiation  from  the  cytoplasm  of  the  cell,  but  are 
derived  by  the  division  of  pre-existing  organs  of  the  same  character,  and 
are  therefore  transmitted  from  one  generation  to  another.  As  examples  of 
such  cell-organs  may  perhaps  be  mentioned  the  nucleus,  with  its  chromo- 
somes, and  the  plastids,  of  which  the  chloroplasts  of  vegetable  cells  are  the 
most  conspicuous.  Certain  cell  organs  may  fall  into  either  class.  Thus 
the  contractile  vacuoles  are  sometimes  derived  by  the  division  of  the  pre- 
existing vacuoles  in  a  previous  generation,  at  other  times  are  certainly  formed 
out  of  the  common  cytoplasm.  The  centrosome,  a  small  particle  generally 
situated  in  the  cytoplasm,  which  plays  an  important  part  in  cell-division, 
is  generally  derived  by  the  division  of  a  pre-existing  centrosome,  but  under 
certain  conditions  and  in  some  organisms  can  be  developed  in  situ  in  the 
cytoplasm  itself. 

The  possibility  of  histological  differentiation  and  of  the  adaptation  of 
structure  to  definite  functions  becomes  much  more  pronounced  as  we  pass 
from  the  unicellular  to  the  multicellular  organisms  or  metazoa.  The  lowest 
of  the  metazoa,  such  as  the  sponges,  consist  of  little  more  than  an  aggregation 
or  colony  of  cells.  All  the  cells  are  still  bathed  with  the  outer  fluid,  and  any 
differentiation  of  structure  or  function  seems  to  be  entirely  conditioned  by 
tin-  position  of  the  cell.  In  the  ccelenterata  the  differentiation  is  already 
much  more  marked.  The  hydra,  one  of  the  simplest  of  the  group,  consists 
of  a  sac  formed  of  two  layers  of  cells  and  attached  by  a  stalk  to  some  firm 
basis.  Round  the  mouth  of  the  sac  is  a  circle  of  tentacles.  The  inner  layer, 
or  hypoblast,  represents  the  digestive  and  assimilatory  layer,  while  the 
epiblast,  or  outer  layer,  is  modified  for  the  purposes  of  protection,  of  reception 
of  stimuli,  and  of  motor  reaction.  In  the  jelly-fish  the  differentiation  of  the 
outer  layers  leads  to  the  formation  of  the  first  trace  of  a  nervous  system,  i.e. 
a  system  fitted  especially  for  the  reception  of  stimuli  and  for  their  trans- 
mission to  the  reactive  tissues,  namely,  the  muscles. 

In  all  these  classes  of  animals  the  external  medium  of  every  cell  forming 
the  organism  is  the  sea-water  or  other  medium  in  which  they  li\e.  This  can 
penetrate  through  the  interstices  between  the  cells,  and  every  cell  is  there- 
fore exposed  to  all  the  possible  variations  which  may  occur  in  the  composition 
of  the  surrounding  medium.  A  great  step  in  evolution  was  accomplished 
with  the  formation  of  the  ccelomata,  the  class  to  which  all  the  higher  animals 
belong.  In  these,  by  the  formation  of  a  body  cavity  containing  fluid,  an 
internal  medium  is  provided  for  all  the  working  cells  of  the  body.     The  com- 

3 


34  PHYSIOLOGY 

position  of  this  internal  medium  is  maintained  constant  by  tne  activity  of  the 
cells  in  contact  with  it,  and  the  stress  of  sudden  changes  in  the  chemical  com- 
position of  the  surrounding  medium  is  borne  entirely  by  the  outer  protective 
layer  of  epiblast  cells.  These  are  rendered  more  or  less  impermeable  by  the 
secretion  on  their  surfaces  of  a  cuticular  layer,  and  only  such  of  the  con- 
stituents of  the  surrounding  medium  are  allowed  to  enter  the  organism  as  can 
be  utilised  by  it  for  building  up  its  living  protoplasm.  Out  of  the  ccelom 
is  later  on  formed  a  circulatory  system  which,  by  the  circulation  of  the  ccelo- 
mic  fluid  or  of  blood  through  the  whole  body,  can  procure  a  still  more  per- 
fect uniformity  in  the  chemical  conditions  to  which  every  cell  is  exposed.  It, 
is  not  till  much  later  that  the  organism  achieves  an  independence  of  external 
conditions  of  temperature.  In  the  mammalia,  by  means  of  the  reactive 
nervous  system,  the  heat  produced  in  every  vital  activity  by  the  chemical 
changes  of  combustion  and  disintegration  is  so  balanced  against  the  heat 
lost  through  the  external  surface  to  the  environment  that  the  temperature  of 
the  internal  fluid  is  maintained  practically  constant.  One  of  the  main  results 
of  the  differentiation  of  function  and  structure  is  therefore  a  gradual  setting 
free  of  the  majority  of  the  cells  of  the  body  from  the  influence  of  variations  in 
the  environment  ;  and  in  the  highest  type  of  all  animals,  in  man,  this  inde- 
pendence of  external  conditions  is  carried  to  a  much  further  extent  by 
conscious  adaptations,  such  as  the  use  of  clothes,  dwellings,  artificial  heating, 
and  so  on. 

The  differentiation  of  the  cells  which  compose  the  organs  of  the  body  is 
determined  in  the  first  place  by  the  different  conditions  to  which  they  are 
exposed  in  virtue  of  their  positions  in  the  course  of  development.  All  the 
higher  animals  may  be  considered  as  built  in  the  form  of  a  tube,  the  external 
surface  of  which  is  modified  for  the  purpose  of  defence  and  for  adaptation  to 
changes  in  the  environment.  From  this  layer  there  are  developed  not  only 
the  protective  cuticle,  but  also  tin1  organs  of  motor  reaction,  namely,  the 
special  senses  and  the  nervous  system.  The  internal  surface  of  the  tube 
is  modified  for  purposes  of  alimentation.  From  it  are  developed  all  those 
structures  which  serve  for  the  digestion  of  the  food-stuffs,  for  their  absorption 
into  the  common  circulating  fluid,  for  their  elaboration  after  absorption,  and 
their  preparation  for  utilisation  by  other  cells  of  the  body.  Between  these 
two  surfaces  are  situated  the  supporting  tissues  of  the  body  as  well  as  the 
organs  for  the  conversion  of  the  potential  energy  of  the  body  into  motion  and 
work,  namely,  the  muscles.  Here  also  is  the  cesium  or  body  cavity,  repre- 
sented in  the  higher  animals  by  the  pleural  and  peritoneal  cavities.  The 
alimentary  canal  projects  for  a  considerable  part  of  its  course  into  this  ccelum, 
being  attached  to  the  body  wall  only  by  one  side.  From  the  ccelom  is  also 
developed  the  blood  vascular  system,  surrounded  by  contractile  and  con- 
nective cells  which  maintain  a  constant  circulation  of  the  blood  throughout 
the  body.  By  this  differentiation  the  body  becomes  divided  into  a  number 
of  organs,  each  of  which  is  composed  of  like  cells,  modified  for  a  common 
function  and  bound  together  by  connective  tissue,  the  latter  serving  also  to 
carry  the  blood-vessels  which  convey  the  common  medium  for  the  working 


THE  STRUCTURAL  BASIS  OF  THE   BODY  35 

cells.  In  the  study  of  physiology  our  task  consists,  firstly,  in  the  description 
of  the  special  part  taken  by  each  organ  in  the  general  functions  of  the  body, 
and,  secondly,  in  the  determination  of  the  limiting  conditions  of  such  func- 
tions and  of  the  physical  and  chemical  factors  which  determine  them. 
Finally,  we  have  to  endeavour  to  form  a  complete  conception  of  the  chain  of 
events  concerned  in  the  discharge  of  each  function  and  of  their  causal 
nexus. 

In  the  foregoing  lines  we  have  compared  the  higher  animal  to  a  colony 
of  cells,  and  we  often  speak  of  an  isolated  cell  of  the  body  as  if  it  were  an 
independent  elementary  organism.     A  better  term  for  such  an  aggregation  of 
cells  as  presented  by  the  higher  animals  is  not  however  '  cell  colony,'  but 
'  cell  state,'  since,  just  as  in  the  state  politic,  no  cell  is  independent  of  the 
activities  of  the  others,  but  the  autonomy  of  each  is  merged  into  the  life  of  the 
whole.     With  increasing  differentiation  there  is  increasing  division  of  func- 
tion among  the  various  members  of  the  state,  and  each  therefore  becomes 
less  and  less  fitted  for  an  independent  existence  or  for  the  discharge  of  all  its 
vital  functions.     The  more  highly  civilised  a  man  becomes  and  the  greater 
his  specialisation  in  the  work  of  the  community,  the  smaller  chance  would  he 
have  of  existing  on  a  desert  island.     Thus  the  life  of  the  organism  is  essen- 
fcially  composed  of  and  determined  by  the  reciprocal  actions  of  the  single 
elementary  parts.     It  is  evident  that,  if  the  process  of  specialisation  has  gone 
far  enough,  a  discussion  whether  each  unit  has  or  has  not  an  independent  life 
is  beside  the  mark,  since  it  cannot  possibly  exist  apart  from  the  activities  of 
the  other  cells.     Of  late  years  histologists  have  brought  forward  evidence 
which  seems  to  imply  that  an  actual  structural  interaction  exists,  in  addition 
to  the  functional  dependence  which  is  a  necessary  resultant  of  specialisation. 
Even  in  the  case  of  plant  cells  with  their  thick  cellulose  walls,  fine  bridges  of 
protoplasm  can  be  made  out  passing  from  one  cell  to  another  through  pores 
in  the  cellulose  wall.     In  animals  protoplasmic  bridges  are  known  to  exist 
joining  up  adjacent  cells  in  unstriated  muscle,  epithelium  and  cartilage 
cells,  and  in  some  nerve-cells.     The  conclusion  has  therefore  been  drawn 
that  the  morphological  unit  is  not  the  cell,  but  the  whole  organism,  and  that 
the  division  of  the  common  cytoplasm  into  cells  is  merely  a  question  of  size 
and  convenience.     There  can  be  no  doubt  that  the  determining  factor  in  the 
division  of  cells  is  their  growth  :   the  cell  divides  because  it  grows.     With 
increased  mass  of  living  substance  it  is  necessary  to  provide  for  increase  of 
surface  both  of  cytoplasm  and  of  nucleus.     Whether  all  the  tissues  of  the 
higher  animals  remain  in  structural  continuity  by  protoplasmic  bridges,  &e., 
must  be  to  us  a  matter  of  indifference,  since  all  that  is  necessary  for  the 
interdependent  working  of  the  different  cells  of  the  body  is  a   functional 
continuity,  and  this  in  the  higher   animals  is   effected  by  the  presence  of  a 
common  circulating  fluid  and   a  reactive   nervous  system  connected  by 
conducting  strands  with  all  the  cells  of  the  bodv. 


CHAPTER  III 
THE    MATERIAL    BASIS    OF    THE    BODY 

SECTION  1 

THE    ELEMENTARY  CONSTITUENTS   OF 
PROTOPLASM 

The  material  basis  of  which  living  organisms  are  built  vrp  is  derived  from 
the  surrounding  medium,  and  the  elements  which  compose  the  framework 
of  the  body  must  therefore  be  identical  with  those  found  in  the  earth's  crust. 
Not  all  the  elements  are  so  utilised  in  the  formation  of  living  matter.  Every 
living  organism  without  exception  contains  the  following  elements  :  carbon, 
hydrogen,  oxygen,  nitrogen,  sulphur,  phosphorus,  chlorine,  potassium, 
sodium,  calcium,  magnesium,  and  iron.  In  addition  to  these  twelve  elements 
others  are  found  in  certain  organisms,  sometimes  to  a  large  extent,  but  it  is 
not  known  how  far  they  are  necessary  to  the  proper  development  of  these 
organisms,  and  it  is  certain  that  they  do  not  form  an  integral  constituent 
of  all  organisms.  Of  these  elements  we  may  mention  especially  silicon, 
iodine,  fluorine,  bromine,  aluminium,  manganese,  and  copper.  Dealing  with 
the  first  class,  which  includes  those  essential  to  all  forms  of  life,  we  find  that 
their  relative  proportions  in  living  organisms  have  little  or  no  relation  to 
their  proportions  in  the  environment  of  the  organisms.  Their  presence, 
however,  in  the  latter  is  a  necessary  condition  of  life.  In  the  case  of  plants 
which  have  a  fixed  habitat  and  camiot  move  in  search  of  food,  the  growth 
of  the  plant  is  limited  by  the  amount  of  the  necessary  element  which  is 
present  in  smallest  quantities  in  the  surrounding  medium.  This  is  what  is 
meant  by  the  agriculturist's '  Law  of  the  Minimum.'  Of  the  elements  derived 
from  the  earth's  crust,  those  present  in  the  smallest  amounts  in  most  soils 
are  potassium,  nitrogen,  and  phosphorus.  The  growth  of  a  crop  in  any  given 
soil  is  determined  by  the  amount  of  that  one  of  these  three  substances  which 
is  present  in  smallest  quantities,  and  the  aim  of  agriculture  is  to  supply  to 
every  soil  the  ingredient  thus  present  in  minimal  amount. 

Carbon  forms  the  greater  part  by  weight  of  the  solid  constituents  of 
living  protoplasm.  The  proximate  constituents  of  living  organisms  are 
practically  all  carbon  compounds,  so  that  organic  chemistry,  which  was 
originally  the  chemistry  of  substances  producedrby  the  agency  of  living 
organisms,  has  come  to  be  synonymous  with  the  chemistry  of  carbon  com- 

36 


THE  ELEMENTARY  CONSTITUENTS   OF  PROTOPLASM     37 

pounds.  The  carbon  compounds  which  make  up  the  living  cell  are  com- 
bustible, i.e.  they  can  unite  with  oxygen  to  form  carbon  dioxide  with  the 
evolution  of  heat.  In  the  inorganic  world  practically  all  the  carbon  occurs 
in  a  completely  oxidised  form,  namely,  carbon  dioxide.  A  small  amount, 
4  parts  in  10,000,  is  present  in  the  atmosphere,  while  vast  quantities  are 
buried  in  the  crust  of  the  earth  as  carbonates  of  the  alkaline  earths,  &c,  in 
the  form  of  chalk  and  limestone.  In  this  condition  the  carbon  dioxide  is 
practically  removed  from  the  life  cycle,  the  whole  of  the  carbon  contained  in 
the  tissue,  of  living  beings,  whether  plant  or  animal,  being  derived  from 
the  minute  proportion  of  carbon  dioxide  present  in  the  atmosphere.  The 
energy  for  the  conversion  of  carbon  dioxide  into  the  oxidisable  forms  with 
high  potential  energy,  which  make  up  the  tissues  of  plants  and  animals,  is 
furnished  by  the  sun's  rays.  The  machine  for  the  conversion  of  the  radiant 
energy  into  the  potential  chemical  energy  of  the  carbon  compounds  is 
represented  by  the  chlorophyll  corpuscles  in  the  green  parts  of  plants.  In 
these  corpuscles,  under  the  influence  of  the  sun's  rays,  the  carbon  dioxide  of 
the  atmosphere,  together  with  water,  is  converted  into  carbohydrates,  viz. 
starch  (C6rllu05),  and  the  oxygen  liberated  in  the  process  is  set  free  into  the 
surrounding  atmosphere. 

6C02  +  5H20  =  C6H10O5  +  GO,. 

In  this  process  a  large  amount  of  energy  is  absorbed,  an  energy  which 
can  be  set  free  later  by  the  oxidation  of  the  starch  to  carbon  dioxide.  In 
the  oxidation  of  one  gramme  of  starch  about  4500  calories  are  evolved,  and 
this  represents  also  the  measure  of  the  solar  energy  which  must  be  absorbed 
by  the  chlorophyll  corpuscle  in  the  process  of  formation  of  starch  from  the 
carbon  dioxide  of  the  atmosphere.  By  this  means  the  world  of  life  is  pro- 
vided with  a  source  of  energy.  At  the  expense  of  the  energy  of  the  starch 
further  synthetic  processes  are  carried  out.  By  the  oxidation  of  a  part 
of  the  carbohydrates,  sufficient  energy  may  be  supplied  to  deoxidise  other 
portions  of  the  carbohydrates  with  the  production  of  fats.     Thus 

3C6H1206-802  =  C18H3602 

(Glucose)  (Stearic  acid) 

The  potential  energy  of  a  fat  is  still  greater  than  that  of  a  carbohydrate, 
one  gramme  of  fat  giving  on  complete  combustion  to  carbonic  acid  and 
water  as  much  as  9000  calories.  By  the  introduction  of  ammonia  groups 
(NH2)  into  the  molecules  of  fatty  acids,  amino-acids  may  be  produced,  from 
which  the  complex  proteins  are  built  up  to  form  the  chief  constituents  of  the 
living  protoplasm. 

The  synthesis  of  carbon  compounds  from  the  inert  carbon  dioxide  of 
the  atmosphere  can  be  effected  only  by  chlorophyll  corpuscles.  All  animals 
take  in  carbon,  hydrogen,  nitrogen,  oxygen,  and  sulphur  in  the  form  of  the 
carbohydrates,  fats,  and  proteins  which  have  been  built  up  in  the  living 
plants.  In  the  animal  organism  these  food-stuffs  serve  as  sources  of  energy. 
They  undergo  a  gradual  oxidation,  and  finally  leave  the  body  in  the  form  of 


38  PHYSIOLOGY 

carbon  dioxide,  water,  ammonia  or  some  related  compound,  and  sulphates. 
A  sharp  distinction  lias  therefore  often  been  drawn  between  the  metabolism 
of  plants  and  animals,  plants  being  regarded  as  essentially  assimilatory  in 
character  while  animals  are  dissimilatory,  utilising  the  stores  of  energy  which 
have  been  accumulated  by  the  plant.  There  is  however  no  definite  line 
of  demarcation.  Although,  generally  speaking,  the  green  plant  breaks  up 
carbon  dioxide,  giving  oft  oxygen  and  storing  up  carbon  compounds,  and 
the  animal  taking  in  carbon  compounds  oxidises  them  with  the  help  of  the 
oxygen  of  the  atmosphere  to  carbon  dioxide,  which  is  redischarged  into  the 
surrounding  medium  and  is  available  for  further  assimilation  by  plants,  yet 
this  process  of  respiration  is  common  to  all  living  organisms,  whether  plants 
or  animals.  In  the  green  plant  it  may  be  masked  by  the  assimilatory  process 
occurring  under  the  influence  of  the  sun's  rays,  but  in  the  dark  all  parts  of 
the  plant,  and  in  the  light  all  parts  which  are  free  from  chlorophyll,  display 
a  process  of  respiration,  i.e.  they  are  constantly  taking  up  oxygen  from  the 
atmosphere  and  using  it  for  the  oxidation  of  carbon  compounds  in  their 
tissues,  with  the  production  of  carbon  dioxide 

The  sum  total  of  the  processes  of  life  tend  therefore  to  maintain  a 
constant  proportion  of  carbon  dioxide  and  oxygen  in  the  atmosphere,  the 
decomposition  of  carbon  dioxide  by  the  green  plants  being  balanced  by  the 
oxidation  of  the  carbon  compounds  and  the  continual  discharge  of  carbon 
dioxide  by  animals.  It  is  not  certain  however  that  this  balance  will  be 
maintained  throughout  all  time.  As  Bunge  has  pointed  out,  there  are 
cosmic  factors  at  work  which  are  apparently  tending  to  cause  a  constant 
diminution  in  the  quantity  of  carbon  dioxide  in  the  atmosphere,  which  alone 
is  of  value  to  the  plant.  One  of  these  factors  is  the  variable  affinity  of  the 
silica  and  carbon  dioxide  respectively  for  the  chief  liases  of  the  earth's  crust. 
At  a  high  temperature  silica  can  displace  carbon  dioxide  from  its  compounds. 
Thus  chalk  heated  with  silica  will  give  rise  to  calcium  silicate  with  the  evolu- 
tion of  carbon  dioxide.  At  an  early  geological  epoch  therefore,  it  is  prol  >a  ble 
that  the  greater  part  of  the  silica  was  present  in  combination  with  bases  and 
that  the  proportion  of  carbon  dioxide  in  the  atmosphere  was  very  much 
higher  than  it  is  now.  At  temperatures  at  present  ruling  on  the  earth's 
surface  carbon  dioxide  is  a  stronger  acid  than  silica.  The  action  of  water 
charged  with  carbon  dioxide  on  a  silicate  is  to  cause  its  gradual  decomposi- 
tion with  the  formation  of  carbonate  and  silica.  Both  these  products,  being 
insoluble,  are  deposited  as  part  of  the  earth's  crust,  the  silica  in  the  form  of 
sandstone,  the  carbonate  as  chalk  or  limestone.  The  carbon  dioxide  is 
being  constantly  removed  by  water  from  the  atmosphere  and  being  locked 
up  in  this  way  in  the  earth's  crust,  the  process  of  separation  of  calcium  car- 
bonate being  aided  to  a  marked  extent  by  the  agency  of  living  organisms 
themselves.  The  whole  of  the  extensive  deposits  of  limestone  and  chalk 
have  been  separated  from  the  sea-water  by  the  action  of  living  organisms. 
With  the  cooling  of  the  earth's  crust  which  is  supposed  to  be  going  on,  the 
discharge  of  carbon  dioxide  by  volcanoes  must  get  less  and  less,  so  that  one 
can  conceive  a  time  when  the  whole  of  the  carbon  dioxide  will  be  bound  up 


THE  ELEMENTARY  CONSTITUENTS  OF  PROTOPLASM     39 

with  bases  in  the  earth's  crust,  and  life,  without  any  source  of  carbon,  must 
become  extinct. 

Hydrogen  exists  almost  exclusively  in  the  form  of  water.  In  this  form 
it  is  taken  up  by  plants  and  animals,  with  the  exception  of  a  small  proportion 
al  >s<  irbed  in  the  form  of  ammonia.  In  this  form  too  it  is  discharged  by  living 
organisms.  Oxygen  is  the  only  element  which,  in  all  the  higher  organisms  at 
any  rate,  is  taken  up  in  the  free  state.  It  forms  one-fifth  of  the  atmosphere 
and,  as  the  oxides  of  the  various  metals,  a  considerable  fraction  of  the  earth's 
crust.  It  takes  a  position  apart  from  the  other  food-stuffs  in  that  its 
presence  is  the  essential  condition  for  the  utilisation  of  their  potential  energy. 
In  the  living  cells  it  combines  with  the  oxidisable  compounds  formed  by  the 
agency  of  the  living  protoplasm,  with  the  production  of  carbon  dioxide  and 
water,  and  the  evolution  of  energy.  This  process  is  spoken  of  as  respira- 
tion. 

•Like  the  three  elements  we  have  already  considered,  nitrogen  is  also 
derived  directly  or  indirectly  from  the  surrounding  atmosphere.  In  conse- 
quence of  its  feeble  combining  power  for  other  elements  and  the  instability  of 
i's  compounds,  very  little  nitrogen  is  to  be  found  in  the  combined  state  in  the 
earth's  crust,  whereas  it  constitutes  four-fifths  of  the  atmospheric  gases. 
It  can  be  taken  up  by  most  plants  only  in  the  form  of  ammonia,  nitrites. 
or  nitrates.  To  animals  these  compounds  are  useless,  and  their  only 
source  of  nitrogen  is  the  protein  which  has  been  built  up  by  the  agency 
of  the  plant  cell.  Since  nitrogen  in  the  free  state  is  useless  to  nearly  all 
living  organisms,  the  existence  of  life  must  depend  on  the  amount  of  com- 
bined nitrogen  which  is  available.  In  view  of  the  small  tendency  presented 
by  this  element  to  enter  into  combination,  it  becomes  interesting  to  inquire 
into  the  source  of  the  combined  nitrogen  which  is  the  common  capita]  of  the 
living  kingdom.  There  are  certain  cosmic  factors  which  result  in  the  pro- 
duction of  combined  nitrogen.  The  passage  of  electric  sparks  or  of  the 
silent  discharge  through  moist  air  leads  to  the  production  of  ammonium 
nitrite. 

N,  +  2H20  =  NH4NO,. 

Every  thunderstorm  therefore  will  result  in  the  production  of  small  quan- 
tities of  ammonium  nitrite,  which  will  be  washed  down  with  the  rain  and 
serve  as  a  source  of  combined  nitrogen  to  the  soil.  Every  decaying  vegetable 
or  animal  tissue  serves  as  a  source  of  ammonia,  so  that  from  various  causes 
the  soil  may  contain  nitrogen  in  the  form  of  ammonia,  or  of  ammonium  nitrite. 
These  forms  of  combined  nitrogen  are  not  however  suitable  for  all  classes  of 
plants.  Most  moulds  can  assimilate  ammonia  as  ammonium  carbonate  or 
as  amino-acids  or  amines,  provided  that  they  are  supplied  at  the  same 
time  with  sugar,  the  oxidation  of  which  will  serve  them  as  a  source  of  energy. 
Some  moulds,  many  of  the  higher  plants,  and  especially  the  Graminese; 
which  include  the  food-producing  cereals,  require  then  nitrogen  in  the 
condition  of  nitrates.  It  is  necessary  therefore  that  the  ammonia  or 
nitrites  in  the  soil  shall  be  converted  into  this  highly  oxidised  form.     This 


40 


PHYSIOLOGY 


conversion  is  effected  by  a  group  of  micro-organisms.  There  are  a  number 
of  bacteria  (bacterium  nitrosomonas)  which  have  the  power  of  converting 
ammonia  into  nitrites.  Others  (bacterium  nitro- 
monas)  convert  nitrites  into  nitrates.  If  sewage 
matter  rich  in  ammonia  is  allowed  to  percolate 
through  a  cylinderpacked  with  coke  and  the  process 
be  continued  for  several  weeks,  it  is  found  after  a 
time  that  in  its  passage  through  the  filter  the  fluid 
has  lost  its  ammonia  and  contains  the  whole  of  its 
nitrogen  in  the  form  of  nitrate.  If  the  cylinder  be 
tapped  (Fig.  13)  half-way  down,  say  at  K,  the  fluid 
will  be  found  to  contain,  not  nitrates,  but  nitrites. 
In  this  conversion  the  two  kinds  of  microbes  men- 
tioned above  are  concerned.  At  the  top  of  the 
cylinder  the  nitrous  bacterium  is  present,  in  the 
bottom  of  the  cylinder  the  nitrate  bacterium  is 
present.  The  conversion  of  ammonia  into  nitrates 
by  the  agency  of  bacteria  has  been  made  the  basis 
of  a  method  of  treatment  of  sewage  which  is  now 
very  largely  employed.  These  different  bacteria 
play  an  important  part  in  all  soils  in  preparing 
them  for  the  cultivation  of  crops. 

Is  the  total  capital  of  combined  nitrogen,  which 
is  worked  over  by  these  bacteria  and  utilised  by 
the  whole  living  world,  confined  to  the  small  quanti- 
ties produced  by  atmospheric  discharges  ?  Of  late 
years  definite  evidence  has  been  brought  forward 
that  such  is  not  the  case  and  that  organisms  exist 
which  can  utilise  and  bring  into  combination  the 
free  atmospheric  nitrogen  itself.  Thus  certain  soils 
have  been  found  to  undergo  a  gradual  enriching 
in  nitrogen  although  no  nitrogenous  manure  has 
been  applied  to  them.  Winogradsky  has  shown 
that  this  fixation  of  nitrogen  by  soils  is  effected  by 
a  distinct  micro-organism. which  may  be  isolated  by 
growing  it  on  gelatinous  silica  free  from  any  trace 
of  combined  nitrogen,  so  that  the  organism  has 
to  procure  its  entire  nitrogen  from  the  atmo- 
sphere. Under  such  conditions  the  numerous  other 
micro-organisms  of  the  soil  die  of  nitrogen  starva- 
tion, and  only  the  microbe  survives  which  is  able  to  utilise  free  nitrogen. 
This  organism,  which  he  called  Clostridium  pasieurianum,  grows  well  on  sugar 
solution  if  free  from  ammonia  and  enriches  the  solution  with  combined 
nitrogen.  It  is  anaerobic,  i.e.  only  grows  in  the  absence  of  oxygen.  In  the 
soil,  where  oxygen  is  constantly  present,  it  occurs  associated  in  a  sort  of 
symbiosis  with  two  species  of  bacteria  which  are  aerobic  and  protect  it  from 


Fig.  13.  Arrangement  for 
studying  the  nitrifica- 
tion of  sewage.  (Miss 
H.  Chick.) 


THE  ELEMENTARY  CONSTITUENTS   OF   PROTOPLASM     41 


the  surrounding  oxygen.  The  mechanism  by  which  this  organism  is  able 
to  fix  free  nitrogen,  and  the  nature  of  the  first  product  of  the  assimilation  are 
not  yet  ascertained.  Such  an  assimilation  will  serve  to  the  organism  as  ;i 
source  of  energy,  since  the  application  of  heat  is  necessary  for  the  dissociation 
either  of  ammonium  nitrite  or  of  nitrous  acid  into  nitrogen  and  water,  as  is 
seen  from  the  following  equation  : 

HN02Aq.  +  308  Cal.  =  H  +  N  +  Oa  +  Aq. 
NH4N02Aq.  +  602  Cal.  =  2N  +  4H  +  20  +  Aq. 

In  addition  to  this  spontaneous  fixation  of  nitrogen  by  humus,  a  method 
has  long  been  known  to  farmers  by  which  the  fertility  of  a  soil  can  be  in- 
creased without  the  application  of  nitrogenous  manures. 
If  a  plot  of  land  is  to  be  left  fallow  it  is  a  very  usual 
custom  to  sow  it  with  some  leguminous  crop  such  as  sain- 
foin.    Careful    experiments   by  Boussingault,  Lawes  and 
Gilbert,  and  others,  have  shown  that  the  growth  of  almost 
any  leguminous  crop  in  a  soil  poor  in  nitrogen  may  result 
not  only  in  the  production  of  a  crop  containing  much  com- 
bined nitrogen,  but  also  in  an  actual  increase  of  nitrogen  in 
the  soil  from  which  the  crop  is  taken.     It  was  then  shown 
by  the  last  two  observers,  as  well  as  by  Schloesing  and 
Laurent,  that  the  power  of  a  leguminous  crop  to  enrich  the 
soil  with  nitrogen  was  dependent  on  the  presence  on  the 
roots  of  certain  small  nodules  which  had  been  described 
long  before  by  Malpighi  (Fig.  14).     They  showed  also  that 
the  production  of  these  nodules  took  place  only  as  a  result 
of  infection.     Beans  grown  in  sterilised  sand  produced  a 
plant  free  from  nodules,  which  however  grew  very  scantily 
unless  nitrogenous  manure  were  added  to  the  sand.    Such  a 
crop  derived  the  nitrogen  for   its  growth  from  the  added 
nitrogen,  the  total  amount  of  which  in  the  soil  was  there- 
fore  diminished    by  the   crop.      If  however  the  sterilised 
sand  were  treated  with  an  infusion  of   root  nodules   from 
another   plant    without    the  addition    of    any  combined    'vetch  with  nod- 
nitrogen  at  all,  the  beans  developed  nodules  on  their  roots     ules. 
and    grew    luxuriantly,    and  at  the    termination  of  their 
growth  the  soil  was  richer  in  nitrogen  than  at  the  commencement.      On 
microscopic  examination  the  protoplasm    which  makes  up  these  nodules 
is  found  to  be  swarming  with  small  rods  (Fig.  15),  and  it  was  shown  by 
Beyerinck  that  these  rods  are  bacteria  and  can  be  cultivated  in  media 
apart  altogether  from  the  plant.     We  have  thus  an  example  of  a  class  of  bac- 
teria which,  like  those  of  humus,  are  able  to  assimilate  the  free  nitrogen  of  the 
atmosphere,  but,  unlike  them,  can  only  effect  this  assimilation  in  a  condition 
of  symbiosis,  i.e.  living  in  the  growing  tissues  of  a  leguminous  plant.     Similar 
nodules  have  been  described  on  the  roots  of  other  plants  which  can  grow  in  a 


42 


PHYSIOLOGY 


soil  free  from  combined  nitrogen,  e.y.  conifers,  but  it  is  in  the  legurninosae 
that  their  presence  is  most  widespread. 

The  source  of  the  combined  nitrogen,  which  can  be  built  up  by  plants 
into  proteins  and  utilised  in  this  form  by  animals,  is  thus  not  only  the 
ammonium   nitrite   produced  by  the  agency  of   electric   discharges   in   the 


Fig 


15.     Section  of  a  root  oodiile  « >t  Doryehnium.     (Vi  u.rx.uis.) 
a.  cortical  tissue;    l>.  cells  containing   bacteria. 


atmosphere,  but  also  the  free  nitrogen  of  the  atmosphere  assimilated  by 
various  types  of  bacteria. 

Sulphur  is  found  in  all  soils  in  the  form  of  sulphates,  generally  of  lime. 
As  sulphates  it  is  taken  up  by  plants.  In  the  plant  cell  a  process  of  deoxida- 
tion  takes  place  at  the  expense  of  the  energy  derived  either  from  the  starch 
or,  in  the  case  of  bacteria,  from  other  ingredients  of  their  food-supply.  It  is 
built  up,  together  with  nitrogen,  carbon,  and  hydrogen,  to  form  sulphur 
derivatives  and  amino-acids  such  as  cystine,  and  these,  together  with  other 
amino-acids,  are  synthetised  to  form  proteins.  Practically  the  whole  of  the 
sulphur  taken  in  by  animals  is  in  the  form  of  proteins.  It  shares  the  oxida- 
tion of  the  protein  molecule  in  the  animal  body  winch  it  leaves  in  the  form  of 
sulphates.  The  output  of  sulphates  by  an  animal  can  therefore  be  regarded, 
like  the  nitrogen  output,  as  an  index  of  the  protein  metabolism.  It  is 
returned  to  the  soil  in  the  form  in  which  it  was  taken  by  the  plant,  and  the 
cycle  can  be  continuously  repeated. 

Iron,  although  forming  but  a  minute  proportion  of  the  materia]  basis' 
of  living  organisms  (the  whole  body  of  man  contains  only  six  grammes),  is 
nevertheless  indispensable  for  the  maintenance  of  life.  It  is  necessary,  for 
instance,  in  two  important  functions,  viz.  the  formation  of  chlorophyll  in  the 
green  plant  and  the  respiratory  process  in  the  higher  animals.  Although  iron 
forms  no  part  of  the  chlorophyll  molecule,  plants  grown  in  the  absence  of  this 


THE  ELEMENTARY  CONSTITUENTS   OF  PROTOPLASM     43 

substance  remain  etiolated,  but  form  chlorophyll  if  the  smallest  trace  of  iron 
is  added  to  the  soil  in  which  they  are  growing  or  even  if  the  leaves  are  wash*  d 
with  a  very  dilate  solution  of  an  iron  salt.  In  animals  iron  forms  an  essential 
constituent  of  haemoglobin,  the  red  colouring-matter  of  the  blood,  whose 
office  it  is  to  carry  oxyTgen  from  the  lungs  to  the  tissues.  It  is  probable  too 
that  the  minute  traces  of  iron  in  protoplasm  exercise  an  important  function 
in  the  processes  of  oxidation  which  are  continually  going  on.  Even  in  the 
inorganic  world  iron  plays  the  part  of  an  oxygen  carrier.  In  the  earth's 
crust  it  occurs  as  ferrous  salts  and  as  ferric  oxide.  The  ferrous  silicate,  for 
instance,  may  be  decomposed  by  water  containing  carbon  dioxide  into  silica 
and  ferrous  carbonate  ;  the  latter  then  absorbs  oxygen  from  the  atmosphere, 
liberating  carbon  dioxide  and  forming  ferric  oxide.  In  the  presence  of 
decomposing  organic  matter,  the  ferric  oxide  parts  with  its  oxygen  to  oxidise 
the  organic  substances  and  is  converted  once  more  into  ferrous  carbonate, 
and  this  may  be  decomposed  by  the  oxygen  of  the  air  as  before.  In  the 
presence  of  sulphates  and  decomposing  organic  matter,  ferrous  sulphate, 
which  is  first  formed,  undergoes  deoxidation  to  ferrous  sulphide,  and  this  may 
again  be  oxidised  to  sulphates  and  ferric  salts  on  exposure  to  the  atmosphere, 
so  that  both  the  sulphur  and  the  iron  act  as  oxygen  carriers  between  the 
atmosphere  and  the  organic  matter.  Iron  is  obtained  by  plants  from  the 
soil  as  ferrous  or  ferric  salts.  In  the  protoplasm  it  is  built  up  into  highly 
complex  organic  compounds,  and  m  this  form  is  taken  up  by  animals.  It  is 
probable  that  the  main  requirements  of  the  animal  for  iron,  which  are  very 
small,  may  be  satisfied  entirely  at  the  expense  of  these  organic  compounds, 
but  there  can  be  little  doubt  that  the  animal  can,  if  need  be,  also  utilise  the 
iron  salts  presenl  in  its  food.  The  animal  proceeds  extremely  economically 
with  its  supply  of  iron.  Any  excess  of  iron  above  that  needed  to  supply 
the  iron  lost  to  the  body  is  excreted  almost  entirely  with  the  faeces  in  the 
form  of  sulphide.  In  the  soil  this  undergoes  oxidation  and  returns  once  nunc 
to  the  form  in  which  it  was  originally  taken  up  by  the  plant. 

Phosphorus  is  absorbed  by  the  plant  as  phosphates.  In  the  cell  proto- 
plasm it  is  built  up  with  fatty  acids  and  other  organic  radicals  to  form  com- 
plex compounds  such  as  lecithin,  a  phosphorised  fat,  and  nuclein,  a  com- 
bination of  phosphorus  with  nitrogenous  bases  of  great  variety.  Both  leci- 
thin and  nuclein  are  essential  constituents  of  living  protoplasm.  Practically 
the  whole  of  the  phosphorus  income  of  animals  is  represented  by  these 
lecithin  and  nuclein  compounds.  After  absorption  into  the  animal  body  they 
are  broken  down  by  processes  of  dissociation  and  oxidation,  with  the  pro- 
duction, as  a  final  result,  of  phosphates,  which  are  excreted  with  the  urine 
or  fasces  and  return  to  the  soil. 

Chlorine,  potassium,  sodium,  calcium,  and  magnesium  are  taken  up  by 
the  plants  in  the  form  of  salts.  Although  playing  an  essential  part  in  all 
vital  processes,  they  do  not  seem  to"  be  built  up  into  organic  combination 
with  the  protein  and  other  constituents  of  the  cell  protoplasm.  They  are 
therefore  taken  up  also  by  annuals  in  the  form  of  salts,  and  as  such  are  again 
excreted  with  the  urine. 


44  PHYSIOLOGY 

Little  is  known  about  the  significance,  if  any,  of  the  other  elements  which 
I  have  mentioned  as  occasional  constituents  of  living  beings.  Silicon,  which 
is  of  universal  distribution,  is  assimilated  as  silica,  probably  in  colloidal 
solution,  and  is  distributed  in  minute  quantities  through  all  plant  and 
animal  tissues.  It  forms  a  very  large  percentage  of  the  mineral  basis  of 
grasses,  but  even  here  it  does  not  seem  to  be  indispensable,  since  these  will 
grow  in  a  medium  devoid  of  silica  as  luxuriantly  as  under  normal  conditions. 

Fluorine  is  found  in  the  enamel  of  the  teeth  and  in  minute  traces  in  other 
tissues  of  the  body. 

Bromine,  though  present  in  quantity  in  some  seaweeds,  appears  to  play 
no  part  in  the  edonomy  of  higher  animals. 

Iodine  is  found  in  large  quantities  in  many  seaweeds  and  is  present  as  an 
organic  iodine  compound  in  the  skeleton  of  certain  horny  sponges.  An 
organic  iodine  compound  is  also  found  in  the  thyroid  gland  of  the  higher 
animals,  and  may  possibly  be  the  active  principle  by  means  of  which  these 
glands  are  able  to  affect  the  nutrition  of  the  whole  body.  Iodine,  therefore, 
would  seem  to  be  an  essential  constituent  of  the  higher  animals. 

Aluminium  is  found  in  large  quantities  in  certain  lycopods.  Whether 
it  is  essential  to  their  growth  is  not  known. 

Copper  is  certainly  not  a  necessary  constituent  of  a  large  number  of 
plants  and  animals.  In  one  class,  the  cephalopods,  it  appears  to  take  the 
part  of  iron  in  the  formation  of  a  blood  pigment.  The  hsemocyanine,  which 
was  described  by  Fredericq,  plays  the  same  part  in  the  blood  of  cephalopods 
that  is  played  by  haemoglobin  in  the  blood  of  vertebrates.  When  oxidised 
it  is  of  a  blue  colour,  but  gives  off  its  oxygen  and  is  reduced  to  a  colourless 
compound  on  exposure  to  a  vacuum. 

Among  these  elementary  constituents  of  the  body,  a  definite  line  of 
demarcation  can  be  drawn  between  the  carbon  and  hydrogen  on  the  one 
hand  and  all  the  other  constituents  on  the  other.  The  first  two  elements  are 
built  up  in  a  deoxidised  form  into  the  living  structure  of  the  protoplasmic 
molecule.  The  products  of  their  complete  oxidation  are  volatile,  namely. 
carbon  dioxide  and  water,  and  leave  the  body  in  these  forms.  The  nitrogen 
set  free  by  the  breaking  down  of  the  proteins  will  pass  off  as  free  nitrogen  or 
;is  ammonia.  The  sulphuric  acid  formed  by  the  oxidation  of  the  sulphur 
combines  with  the  basis  to  form  non-volatile  salts.  We  may  therefore  divide 
t  he  ultimate  constituents  of  the  body  into  those  which  are  combustible  and 
are  driven  off  on  heating,  and  those  which  are  left  behind  as  the  ash. 


SECTION  II 

THE    PROXIMATE  CONSTITUENTS   OF   THE 
ANIMAL   BODY 

In  spite  of  the  enormous  variety  of  the  proximate  constituents  of  living 
organisms,  they  are  all  members  or  derivatives  of  three  classes  of  compounds. 
Since  living  organisms  form  the  entire  food  of  the  animal  kingdom,  a  study 
of  these  proximate  constituents  includes  the  study  of  all  the  food-stuffs. 
These  classes  are  : 

(a)  Proteins,  containing  the  elements  carbon,  hydrogen,  nitrogen,  oxygen, 
and  sulphur  ;   in  some  cases  also  phosphorus. 

(b)  Fats,  containing  carbon,  hydrogen,  and  oxygen. 

(c)  Carbohydrates,  containing  carbon,  hydrogen,  and  oxygen,  the  two 
latter  elements  being  present  in  the  proportions  in  which  they  form  water. 

THE  CHIEF   TYPES   OF   ORGANIC  COMPOUNDS   OCCURRING 
IN   THE   ANIMAL   BQDY 

The  full  consideration  of  the  various  modifications  undergone  by  these  three  classes 
of  food-stuffs  in  the  body,  especially  if  we  include  the  by-products  occurring  both 
in  plants  and  in  animal  metabolism,  involves  a  wide  knowledge  of  organic  chemistry 
which  indeed  at  its  origin  was  simply  the  chemistry  of  the  products  of  living  (i.e. 
organised)  beings.  The  most  important  substances  with  which  we  shall  have  to  deal 
belong  to  a  comparatively  restricted  number  of  groups.  For  the  convenience  of  the 
reader  a  short  summary  of  the  relationships  of  these  groups  to  one  another  and  to  the 
hydrocarbons  is  given  here. 

THE  HYDROCARBONS  (Fatty  Series).  These  form  a  continuous  homologous 
series,  and  may  be  saturated  or  unsaturated.     Examples  of  the  saturated  series  are 

CH4      methane 

C2H  6    ethane 

C3H8    propane 

C4Hj0  butane,  and  so  on, 

the  general  formula  for  the  group  being 

PnH.,n  +  2. 

These  paraffins,  the  lower  members  of  which  are  gaseous,  while  the  higher  members 
form  the  petroleum  ether,  the  heavy  petroleums,  vaseline,  and  the  paraffin  Max  with 
which  we  are  all  familiar,  are  entirely  inert  in  the  animal  body.  If  taken  with  the 
food  they  pass  through  the  alimentary  canal  unchanged.  In  order  to  render  them 
accessible  to  the  action  of  the  living  cell  they  must  first  undergo  oxidation. 

The    unsaturated    hydrocarbons    have    the    general    formulae    ^H,,,,    CnH2„_„ 

45 


46  PHYSIOLOGY 

Examples  of  the  first  two  groups  are  ethylene  CH, 

II 

CH2 
and  acetylene  CH 

III 
CH 

Derivatives  of  all  these  groups  occur  in  the  body. 

THE  ALCOHOLS.  The  first  product  of  the  oxidation  of  hydrocarbons  is  the 
series  of  bodies  known  as  the  alcohols.     Examples  of  these  are  : 

CH3OH        methyl  alcohol 

C2H6OH       ethyl 

C3H7OH      propyl  „ 

C4H9OH      butyl 

C5HuOH     amyl  „ 

C0H13OH     capryl  .,        and  so  on, 

the  general  formula  for  the  group  being 

C„H2D  +  iOH. 
In  all  these  alcohols  the  OH  group  is,  so  to  speak,  more  mobile  than  the  other  atoms 
connected  with  the  carbons,  and  can  therefore  be  replaced  by  other  substances  or 
groups  with  comparative  ease.  In  this  respect  therefore  an  alcohol  can  be  compared 
to  water  HOH  or  to  alkaline  hydroxide  NaOH  or  KOH.  The  best-known  example 
of  the  group  is  ethyl  alcohol,  the  ordinary  product  of  fermentation  of  sugar.  In  these 
alcohols  the  H  of  the  OH  group  can  be  replaced  by  Na.  Thus,  water  with  metallic 
sodium  gives  sodium  hydroxide  and  hydrogen  as  follows : 

2HOH  +  2Na  =  2NaOH  +  H2. 
In  the  same  way  alcohol  treated  with  metallic  sodium  gives  off  hydrogen,  and  the 
remaining  fluid  contains  sodium,  ethylate,  thus  : 

21   ,H5OH  +  2Na  =  2C2H5ONa  +  H, 
(sodium  ethylate) 

On  the  other  hand,  the  OH  group  may  be  replaced  by  acid  radicals.  Thus,  if  ethyl 
alcohol  be  treated  with  phosphorus  pentachloride,  ethyl  chloride  is  formed  together 
with  phosphorus  oxychloride  and  hydrochloric  acid.     Thus  : 

Et.OH  +  PC15  =  POCI3  +  HC1  +  Et.Cl 

(ethyl  chloride) 
With  concentrated  sulphuric  acid  the  reaction  is  similar  to  that  which  obtains  between 
sodium  hydrate  and  this  acid,  and  we  have  formed  ethyl  hydrogen  sulphate  and  water. 
Thus : 

Et.OH  +  H2S04  =  Et.HS04  +  HOH 

If  alcohol  be  warmed  with  acetic  acid  and  strong  sulphuric  acid,  among  the  products 
of  the  reaction  is  ethyl  acetate,  which  is  volatile,  and  therefore  passes  off.     Thus  : 

Et.OH  +  HCH3O,  =  Et.C2H302  +  HOH. 
These  compounds  of  the  hydrocarbon  group  of  the  alcohol,  such  as  methyl,  ethyl, 
propyl,  &c,  with  an  acid,  in  which  the  ethyl  takes  the  part  of  a  base,  are  known  as 
esters. 

An  ester  treated  with  an  alkali  is  decomposed  with  the  formation  of  an  alkaline 
salt  of  the  acid,  and  the  corresponding  alcohol  which,  being  volatile,  is  given  off  on 
warming  the  mixture.     Thus  : 

Et.C2H302  +  NaHO  =  NaC2H302  +  Et.OH. 

(ethyl  acetate)         (potassium  acetate)   (alcohol) 
This  process  of  decomposition  of  an  ester  with  the  formation  of  the  alkaline  salt  of  an 
acid  is  often  spoken  of  as  saponification,  i.e.  soap  formation,  though  the  term  '  soap  ' 


PROXIMATE  CONSTITUENTS   OF  THE  ANIMAL  BODY      47 

is  applied  only  to  the  compounds  of  alkalies  with  the  higher  fatty  acids.  The  series  of 
alcohols  we  have  just  dealt  with  containing  one  OH  group  replaceable  by  metals  or 
acid  radicals  are  known  as  monatomic  alcohols.  If  in  the  molecule  of  the  paraffin  two 
or  more  atoms  of  hydrogen  have  been  replaced  by  the  group  OH,  we  speak  of  diatomic 
or  polyatomic  alcohols.  Thus,  derived  from  the  paraffin  propane  C,H8  we  may  have 
the  monatomic  alcohol  CsH7OH,  propyl  alcohol,  or  the  triatomic  alcohol  C3H5(OH)3, 
which  is  known  as  glycerin,  or  glycerol. 

Other  alcohols  of  physiological  importance  are  cholesterol  and  cety]  alcohol.  Cho- 
lesterol is  a  monatomic  alcohol  with  the  formula  027H15OH.  It  is  very  complex  in 
structure,  and  belongs  to  the  aromatic  scries.  Recent  work  points  to  an  affinity  of 
cholesterol  with  the  terpenes,  which  have  hitherto  been  found  only  as  the  product  of 
the  metabolism  of  plant  cells.  Cholesterol  is  a  constant  constituent  of  protoplasm. 
It  occurs  in  large  quantities  in  the  medullary  sheath  of  nerves;  it  is  a  normal  con- 
stituent of  bile  and  may  form  concretions  (biliary  calculi)  in  the  gall  bladder.  In 
combination  with  fatty  acids  it  is  an  important  constituent  of  sebum  and  of  wool'fat. 

CH3 

I 
Another  alcohol— cetyl  alcohol — C16HslO  —  (OH„)i4  occurs  in  the  feather  glands  of 

I 

CHjjOH 

the  duck  and  tonus  ,m  important  constituent  of  the  wax,  spermaceti,  obtained  from 
a  cavity  in  the  skull  of  the  sperm  whale. 

ALDEHYDES.  By  oxidation  of  any  of  the  alcohols  we  obtain  another  group  of 
compounds  the  aldehydes.  From  ethyl  alcohol,  for  instance,  by  warming  with  potas- 
sium bichromate  and  dilute  sulphuric  acid,  ethyl  aldehyde  is  produced  and  given  off.     In 

H 

H  I 

these  aldehydes  the  group  C— H    is  converted  into  the  group  C  =  O,  and  it  is  the 

I    "OH  | 

possession  of  this  group  which  determines  the  aldehyde  character  of  any  compound, 
as  well  as  the  reactions  which  are  typical  of  this  class  of  compounds. 

Some  of  the  typical  reactions  of  aldehydes  may  be  here  shortly  summarised  : 

(1)  They  act  as  reducing  agents,  the  CHO  group  being  converted  into  the  group 
COOH,  which  is  distinctive  of  an  acid.  We  may  therefore  say  that  on  oxidation 
aldehydes  are  converted   into  the  corresponding  fatty  acids  as  follows: 

i  +0=     | 

CHO  COOH 

(ethyl  aldehyde)       (acetic  acid) 

On  account  of  the  case  with  which  this  oxidation  takes  place,  aldehydes  act  as  strong 
reducing  agents.  Warmed  with  an  alkaline  solution  of  cupric  hydrate,  they  take  up 
oxygen,  reducing  the  cupric  to  a  red  precipitate  of  cuprous  hydrate.  If  warmed  with 
an  ammoniacal  solution  of  silver  (i.e.  silver  nitrate  solution  to  which  ammonia  has 
been  added  until  the  precipitate  first  formed  is  just  redissolved),  they  reduce  the  silver 
nitrate  with  the  formation  of  a  mirror  of  metallic  silver  on  the  surface  of  the  glass 
vessel  in  which  they  are  heated. 

(2)  On  warming  with  phenyl  hydrazine,  they  give  the  typical  compounds,  hydra- 
zones  and  osazones.  which  are  also  given  by  the  sugars  and  will  be  mentioned  in 
connection   with  these   bodies. 

(3)  They  also  form  addition  products.  With  ammonia,  they  yield  the  group  of 
compounds  known  as  aldehyde  ammonia.     Thus  : 

CH3  CH3 

I  +  NH3  =    |     NH2 

CHO  CfH 


48  PHYSIOLOGY 

With  sodium  hydrogen  sulphite  the  following  reaction  takes  place  : 
CH3  CH3 

|        +  NaHSO  =   |        X)H 
CHO  CH^ 

XS03Na 
These  compounds  of  aldehydes  with  sodium  sulphite  can  be  readily  obtained  in  a 
crystalline  form  and  furnish  a  convenient  means  of  separating  the  aldehydes  from  their 
solutions. 

(4)  All  the  aldehydes  possess  a  strong  tendency  towards  polymerisation.  Ethyl 
or  acetic  aldehyde  treated  with  strong  sulphuric  acid  gives  the  compound  paraldehyde. 
Thus  : 

3('2H40  C6H1203. 

(acetic  aldehyde)  (paraldehyde) 
If  warmed  with  strong  potash  the  polymerisation  occurs  to  a  still  further  extent  with 
the  formation  of  resinous  substances  of  unknown  composition,  but  at  any  rate  of  a 
very  high  molecular  weight,  the  so-called  '  aldehyde  resin.'  Formic  or  methyl  aldehyde, 
CHoO,  may  in  the  same  way  undergo  polymerisation  with  the  formation  of  a  mixture 
of  substances  belonging  to  the  group  of  sugars,  namely,  the  hexoses,  as  follows  : 

6CH20  =  C6H12O0. 
This  formation  of  sugar  from  formic  aldehyde  probably  plays  an  important  part  in  the 
assimilation  of  the  carbon  from  the  carbonic  acid  of  the  atmosphere  by  the  green  parts 
of  plants. 

ACIDS.     By  the  oxidation  of  the  group  CHO  of  the  aldehydes  we  obtain  the  group 
C'OOH,  which  is  characteristic  of  an  organic  acid.     Thus,  formic  aldehyde  on  oxidation 
gives  the  compound  HCOOH,  formic  acid.     Ethyl  or  acetic  aldehyde,  CH3CHO,  with 
an  atom  of  oxygen,  gives  the  compound  CH3COOH,  acetic  acid. 
CH3  CH3 

1+0=      | 
CHO  COOH. 

Since  these  acids  are  derived  from  the  paraffins  a  whole  series  of  them  exists  corre- 
sponding to  the  series  of  paraffins,  and  known  as  the  fatty  acids.  Examples  of  this 
group  are : 

Formic  acid         Acetic  acid  Propionic  acid  Butyric  acid 

HCOOH  CH3  CH3  CH3 

I  I  I 

COOH  CH2  CH2 

I  I 

COOH  <H„ 

I 

COOH. 
In  addition  to  these  fatty  acids,  there  are  also  unsaturated  acids,  derived  from 
the  unsaturated  hydrocarbons. 

DERIVATIVES   OF   THE   FATTY   ACIDS 
AMINO- ACIDS  are  derived  from  the  fatty  acids  by  the  replacement  of  one  atom 
of  hydrogen  by  the  group  NH2. 

Thus  from   propionic  acid  we  may  have : 

CH2NH2  CH3 

I  I 

CH2  or  CH.NH2 

I  I 

COOH  COOH. 

0  a 

The  second  form,  the  a-amino  acid,  is  the  only  one  which  occurs  in  the  body. 


PROXIMATE  CONSTITUENTS   OF  THE  ANIMAL  BODY      49 

OXYACIDS  are  formed  by  the  replacement  of  one  H  atom  by  the  group  OH. 
Thus: 

CH3 

I 
CHOH  is  oxypropionic  acid  or  lactic  acid. 

I 
COOH 

KETO- ACIDS.  Oxyacids  are  formed  by  the  oxidation  of  the  group  CH2  or  CH3 
If  at  the  same  time  the  H2  group  be  removed  by  oxidation  a  keto-acid  may  be  formed. 
This  is  probably  the  manner  in  which  such  acids  arise  in  the  body,  though  it  is  more 
usual  to  regard  a  keto-acid  as  the  result  of  oxidation  of  a  ketone.     Thus  : 

CH}  CII3  ^-Hg 

I  I  I 

CO  CO  CO 

I  I  I 

CH3  CH2.OH  COOH 

(acetone)  (pyruvic  acid — 

a  keto-acid) 

ACID  AMIDES  are  formed  from  a  fatty  acid  by  replacing  the  —  OH  of  the  —  COOH 
group  by  -  NH2>  e.g. : 

CHj  CH3 

from 
CO.NH2  COOH. 

(acetamide)  (acetic  acid) 

AMINES.  These  may  be  regarded  as  formed  from  ammonia  NH3  by  replacing 
one  or  more  of  the  H  atoms  by  an  organic  radical.     Thus  we  may  have  : 

GHg  <  '|  1  CH3 

N-H  N^CH3  N^CH3 

VH  "H  XCH3 

i  met  liy  Limine)  (dimethvlamine)  (trimethylamine) 

Under  the  action  of  living  organisms  primary  amines  may  be  formed  from  a-amino 
acids  by  a  process  of  decarboxylation.     Thus  : 

CH3  CH3 

I 

CH.NH,  -  CO.,  -  CH„.NH, 

I 
COOH 

(o-amino-propiouic  acid)         (ethylamine) 


AROMATIC   COMPOUNDS 

These  all  contain  a  nucleus,  made  up  of  six  carbon  atoms,  which  is  extremely  stable, 
so  that  processes  of  oxidation,  reduction,  &c,  can  be  carried  out  in  the  compound 
without  destruction  of  the  nucleus.  The  simplest  aromatic  compound  is  benzene 
C6H6.  It  behaves  as  a  saturated  compound.  It  is  represented  as  a  hexagon  with  a 
hydrogen  atom  at  each  angle. 

H 

h/\h 

H^H 


50  PHYSIOLOGY 

All  the  hydrogen  atoms  are  of  equal  value.  They  may  he  replaced  hy  other  groups, 
such  as  OH,  CI,  NH.>.  or  by  more  complex  groups  belonging  to  the  fatty  serieB,  e.g. 
CH3,  C2HS,  &c.     Monosubstitution  derivatives  exist  only  in  one  form  : 

C6H6.X 
Disubstitution  compounds  exist  in  three  forms,  according  to  the  relative  position  of  the 
substituted  H  atoms.     These  are  known  as  the  ortho,  meta,  and  para  compounds,  and 
have  the  formulse  : 


X 

X 

X 

„Ax 

Hf> 

HC 

H 

«UH 

„IJx 

< 

H 

H 

H 

X 

ortho- 

nieta- 

para- 

The  following  are  some  of  the  most  important  monosubstitution  derivatives  of 
benzene : 

Nitrobenzene  (.'6H6.N02. 

Aniline  <"'nH5.NH2. 
Benzene  sulphonic  acid    C6H5.S03H. 

Phenol  ( ',;H5.OH. 

Toluene  Cr,H5.CH3. 

Benzyl  alcohol  C6Hs.CH2OH. 

Benzylaldehyde  C6H5.GHO. 

Benzoic  acid  C6H5.COOH. 

Of  the  disubstitution  compounds,  we  need  mention  only  the  following  : 
The  di/u/dro.ri/benzenes : 

Pyrocatechin  or  catechol  Resorcinol               Hydroquinone 

OH  OH                               OH 
OH 


OH 

para- 


,OH 

.Salicylic  acid  (o-hydroxybenzoic  acid)  C6H4 

XCOOH. 


Tyrosin  (parahydroxyphenyl  alanine)  : 

OH 


CH2.CH(NH2)COOH. 

Examples  of  trisubstitution  derivatives  of  benzene  are  : 

OH 

.  <>H 

Pyrogallol 

TQH 


PROXIMATE  CONSTITUENTS   OF  THE   ANIMAL    BODY      51 
OH 


Homogentisic  acid 


Adrenaline 


CH.,.COOH 


OH 
OH 


OH 


CH.OH 

I 

(-H..XHM  H: 

OH 


Picric  acid 


NO, 


NO., 


OPTICAL   ACTIVITY 

Most  of  the  compounds  produced  by  the  agency  of  living  organisms  exhibit  optical 
activity,  i.e.  have  the  property  of  rotating  the  plane  of  polarised  light  either  to  the 
right  Or  to   the   left.  , 

In  an  ordinary  wave  of  light  the  vibrations  of  the  waves  take  place  in  all  planes 
perpendicular  to  the  direction  of  its  propagation.  When  such  a  ray  is  passed  through 
a  Nicol's  prism  (made  of  Iceland  spar)  it  emerges  as  a  plane  polarised  beam,  i.e.  waves 
in  one  plane  only  are  transmitted.  Another  Nicol's  prism  will  allow  such  a  ray  to  pass 
only  if  it  is  parallel  to  the  first  prism.  If  it  is  rotated  through  a  right  angle,  no  light 
will  pass.  A  Nicol's  prism  may  thus  be  used  to  determine  the  plane  of  polarisation 
of  any  beam  of  light. 

In  the  polarimeter  two  Nicol's  prisms  mounted  parallel  to  one  another  are  employed. 
One  of  them  (the  polariser)  is  fixed  ;    the  other  (the  analyser)  can  be  rotated  round 


s, 


^     |c    S, 


©c 

Flo.   16.     Diagram  of  polarimeter. 
B,  polariser  ;  D,  analyser  ;  O,  tube  containing  solution  under  examination. 

the  axis  of  the  beam  of  light  passing  through  the  first.  When  both  prisms  are  parallel 
light  passes  through  the  analyser.  On  interposing  a  solution  of  an  optically  active 
substance  between  the  two  prisme,  the  plane  of  polarisation  of  the  beam  is  rotated, 
so  that  the  light  passing  through  the  analyser  is  diminished.  The  light  may  be  brought 
to  its  original  intensity  by  rotating  the  analyser  either  to  the  right  (clockwise)  or  to  the 
left.  In  this  way  the  direction  and  degree  of  the  optical  activity  may  be  determined. 
Optical  activity  is  connected  with  the  molecular  arrangement  of  the  substance  exhibiting 
this  property,  and  depends  on  the  presence  of  one  or  more  '  asymmetric  carbon  atoms  ' 
in  the  molecule. 

CH3  (H; 

Thus  in  lactic  acid  H.COH,  or  in  alanine  HCXH...  the    middle    carbon    atom    is 

I  I 

COOH  COOH 

asymmetric,  i.e.  it  is  unequally  loaded  on  the  four  sides, 


52  PHYSIOLOGY 

We  can  imagine  such  a  carbon  atom  as  occupying  the  interior  of  a  tetrahedron. 

A  B 


Fig.   17 

In  this  tetrahedron,  if  we  represent  the  four  groups  combining  with  the  carbon  by 
Rj,  R2,  R3,  R4,  they  can  be  arranged  either  as  in  A  or  B.  It  is  evident  that  no  amount 
of  turning  about  will  convert  the  tetrahedron  A  into  tetrahedron  B,  but  that,  if  we 
hold  A  before  a  mirror,  its  image  in  the  mirror  will  be  represented  by  B.  One  arrange- 
ment is  therefore  the  mirror  image  of  the  other,  and  a  compound  containing  one  such 
carbon  atom  will  be  capable  of  existing  in  two  forms,  namely,  one  form  corresponding 
to  A,  the  other  form  corresponding  to  B.  It  is  found  that  the  unequal  loading  of  the 
carbon  atom,  which  is  present  in  such  an  asymmetric  arrangement,  causes  the  com- 
pound containing  the  asymmetric  carbon  to  have  an  action  on  polarised  light.  One 
of  the  varieties  will  rotate  polarised  light  to  the  right,  while  its  mirror  image  will  rotate 
polarised  light  to  the  left.  A  mixture  of  equal  parts  of  the  two  compounds  will  rotate 
equally  to  left  and  right,  i.e.  will  have  no  action  on  polarised  light. 

The  variety  rotating  to  the  right  is  dextrorotatory,  and  the  other  laevorotatory,* 
while  the  mixture  of  the  two  is  known  as  the  racemic  or  inactive  variety.  The  three 
forms  are- said  to  be  stereoisomeric,  and  are  distinguished  as  the  d,  I,  and  i  forms 
respectively.  If  two  asymmetric  carbon  atoms  are  present  in  a  compound,  we  may 
have  four  stereoisomers  ;  and  generally  if  there  are  n  asymmetric  atoms  in  a  molecule, 
there  will  be  2"  possible  stereoisomers.  These  will  not  all  be  necessarily  optically  active, 
since  the  dextrorotation  due  to  one  asymmetric  carbon  atom  may  be  exactly  neutralised 
by  the  l;evorotation  due  to  another,  so  that  '  internal  compensation  '  takes  place  and 
the  substance  is  optically  inactive.  Thus  in  tartaric  acid  four  forms  are  known,  namely, 
d,  I,  racemic  or  i,  and  mesotartaric,  also  inactive,  in  whicli  internal  compensation  occurs. 
These  four  varieties  may  be  represented  as  follows  : 

COOH  COOH 

HCOH  HOCH 

HOCH  HCOH 

COOH  COOH 

d-tartaric  acid  7-tartaric  acid 


COOH 
HCOH 
HCOH 

COOH 

mesotartaric  acid 


inactive  tartaric  acid 


Several  methods  may  be  employed  to  separate  the  racemic  form  into  its  two  optically 
active  components.  One  of  these  methods,  first  employed  by  Pasteur,  is  to  grow 
moulds  in  the  solution.  One  of  the  optical  isomers  is  destroyed,  leaving  the  other 
unchanged.  Another  method  is  the  fractional  crystallisation  of  the  salts  with  alkaloids, 
e.g.  strychnine  in  the  case  of  lactic  acid. 

*  The  specific  rotatory  power  of  a  substance  is  equal  to  the  number  of  degrees 
through  which  the  plane  of  polarisation  is  rotated  when  it  passes  through  a  100  per  cent, 
solution  of  the  substance  in  a  tube  1  decimetre  long.  Thus  polarised  light  passing 
through  such  a  tube  of  10  per  cent,  glucose  solution  would  show  a  rotation  of  5-25 
degrees,  i.e.  its  specific  rotatory  power  is  +  52-5. 


SECTION  III 

THE   FATS 

These  substances  are  widely  distributed  throughout  the  animal  and  vege- 
table kingdoms.  In  the  higher  animals  they  are  the  main  constituents  of 
the  fatty  or  adipose  tissue  lying  under  the  skin  and  between  the  muscles, 
and  often  forming  large  accumulations  around  the  viscera.  In  the  marrow 
of  bones  they  may  amount  to  96  per  cent.  They  also  occur  in  fine  particles 
distributed  through  the  protoplasm  of  cells  and  probably  also  in  combination 
with  the  other  constituents  which  make  up  protoplasm.  Large  amounts  are 
also  found  in  certain  members  of  the  vegetable  kingdom,  as,  for  instance, 
in  the  fatty  seeds  and  nuts,  e.g.  linseed,  olives,  Brazil  nuts. 

CHEMISTRY  OF  THE   FATS 

The  fats  are  esters  of  glycerol  and  the  fatty  acids.  Glycerol  is  a  trihydric 
or  triatomic  alcohol  and  can  therefore  form  esters  with  one,  two,  or  three 
of  its  hydroxyl  groups  ;  thus  with  acetic  acid  the  following  compounds  are 
known : 

(1)  (2) 

CHaOH  CH..OH 

I  I 

CHOH  CH— 0— OC.CH3 

I  I 

CH20— OC.CH3  CH2OH 

a  -monacetin  d-monaeetin 


nionoglycerides 

(3)  (4)  (5) 

CH2—  0— OC.CH,  CH2OH  OH,— 0— OC.CH3 

1  1  r 

CHOH  CH— 0— OC.CH3  CH— O— OC.CH3 

I'  I  I 

CH2— 0— OC.CH3  CH2— 0— OC.CH3     .       CH2— O— OC.CH3 

o,  a  diacetin  a,  §  diacetin  triacetin 


diglyceridea 


triglyceride 


In  these  compounds  the  phenomenon  of  isomerism  occurs  owing  to  the 
presence  of  primary  and  secondary  alcohol  groups  in  glycerol.     In  the  case 

53 


54  PHYSIOLOGY 

of  the  diglycerides  and  the  triglycerides  mixed  esters,  in  which  the  fatty  acid 
radical  varies,  are  possible  : 

(6)  (7) 

CH2— 0— OC.CH3  CH2OH 

I  I 

CHOH  '     CH— 0— OC.CH3 

I'  I 

CH2— 0— OC.CH2.CH3  CH2— 0— OC.CH2CH3 

(8) 
CH„— O— OC.CH3 

I 
( JH— 0— OC.CH2.CH3 

I 
CH  2 — O— OC.CH2.CH2.CH3 

The  glyceryl  esters  which  compose  the  fatty  material  of  living  matter — 
whether  animal  or  plant — are  mainly  triglycerides,  the  monoglycerides  and 
diglycerides  being  seldom  found  in  nature.  The  natural  fat  is  usually 
found  to  consist  of  a  mixture  of  triglycerides  ;  these  triglycerides,  instead 
of  being  mixed  esters  as  in  formula  (8),  are  generally  simple  esters  as  in 
formula  (5).  The  differences  in  the  composition  of  the  natural  fats  depend 
therefore  on  the  variety  of  the  fatty  acid  radical  combined  with  the  glycerol. 

The  fatty  acids  which  enter  into  the  composition  of  the  triglycerides 
belong  to  two  main  homologous  series  : 

A.  The  saturated  fatty  acids,  namely  : 

Formic  acid,  H.COOH 
Acetic  acid,  CH3.COOH 
Propionic  acid,  CH3.CH2.COOH 
Butyric  acid,  CH3.CH2.CH2.COOH 
Valerianic  acid,  CH3.(CH2)3.COOH 
Caproic  acid,  CH3.(CHs)4.COOH 
Caprylic  acid,  CH3.(CH2)6.COOH 
Capric  acid,  CH3(CH2)8.COOH 
Laurie  acid,  CH3(CH2)10.COOH 
Myristie  acid,  CH3(CH2)12.COOH 
Palmitic  acid,  GHs(CH2)14.COQH 
Stearic  acid,  CHs(CH2)16.COOH 
Arachidic  acid.  CH3(GH2)18.COOH 
Behenic  acid,  CH3(CH2)20.COOH 
Lignoceric  acid,  CH3(CH2)22.COOH 

B.  The  unsaturated  fatty  acids,  namely  : 

(1)  Acrylic  serie's,  e.g.  oleic  acid  (CnrLn.202) 

(2)  Linoleic  series,  e.g.  linoleic  acid  (CnH2n".402) 

(3)  Linolenic  series,  e.g.  linolenic  acid  (CnH,u_  n02) 

Of  the  long  list  of  fatty  acids  given  above  only  a  few  occur  to  any  extent 


THE  FATS  55 

in  the  animal  body.  In  milk,  although  the  greater  part  of  the  fat  consists 
of  the  triglycerides  of  oleic,  palmitic,  and  stearic  acids,  other  members  of  the 
series  given  above  are  present  in  small  amounts.  On  the  other  hand,  the 
adipose  tissue,  strictly  so  called,  consists  almost  exclusively  of  the  fats  de- 
rived from  the  fatty  acids,  palmitic,  stearic,  and  oleic,  i.e.  tripalmitin,  tri 
stearin,  and  triolein.  The  great  differences  in  the  appearance  of  the  fat  of 
different  animals  are  due  to  the  varying  amounts  in  the  relative  quantities  of 
these  three  fats  which  may  be  present.  While  triolein  is  liquid  at  0°  C,  tri- 
stearin  and  tripalmitin  are  solid  at  the  temperature  of  the  body.  According 
to  the  relative  amounts  of  these  three  substances  therefore,  we  may  have  a 
fat  which  like  mutton  suet  is  solid  at  the  body  temjDerature,  or  a  fat  con- 
taining much  olein  which  is  still  fluid  and  runs  away  when  the  body  is  opened 
after  death,  even  when  it  has  ahead)'  cooled. 

PROPERTIES  OF  THE  FATS.  The  fats  are  colourless  substances 
devoid  of  smell.  They  are  insoluble  in  water,  in  which  they  float.  They  are 
soluble  in  warm  absolute  alcohol,  but  separate  out  into  crystalline  form  on 
cm  ding.  They  are  easily  soluble  in  ether.  If  they  are  strongly  heated  with 
potassium  bisulphate  they  givevoff  pungent  vapours  of  acrolein  derived  from 
the  decomposition  of  the  glycerin  of  their  molecule. 

C3H5(OH)3      2HLO  =  C3H40 

11  they  are  heated  with  water  or  steam  or  submitted  to  the  action  of  certain 
leinieiits,  they  undergo  hydrolysis,  taking  up  three  molecules  of  water,  and 
are  split  into  three  molecules  of  fatty  acid  and  one  molecule  of  glycerin,  e.g., 

C3H5(C10H31O2)3  +  3H20  -3HC16H3102  +  C3H5(OH)3 

(neutral  fat — tripalmitin)  (palmitic  acid)  (glycerin) 

This  process  may  occur  spontaneously  when  fat  is  left  exposed  to  the  air. 
Fat  which  has  been  artificially  split  in  this  way  is  said  to  be  rancid.  Most 
natural  fats  generally  contain  a  small  amount  of  fatty  acid  which  gives  them 
an  acid  reaction. 

On  boibng  a  neutral  fat  for  a  long  time  with  an  aqueous  solution  of 
potassium  or  sodium  hydrate,  or  better  still  with  an  alcoholic  solution  of 
potassium  or  sodium  ethylate,  the  fat  undergoes  saponification,  giving  the 
alkaline  salt  of  a  fatty  acid  and  glycerin.  The  former  compound  is  spoken  of 
as  a  soap.  In  water  the  soaps  form  a  sort  of  pseudo-solution  on  heating  which 
sets  to  a  solid  jelly  on  cooling.  From  a  dilute  watery  solution  the  soap  can 
be  thrown  down  in  the  solid  form  by  the  addition  of  neutral  salts.  Fats  are 
insoluble  in  and  non-miscible  with  water.  If  shaken  up  with  water  the 
droplets  rapidly  run  together  and  rise  to  the  surface,  forming  a  continuous 
layer  of  the  oil  or  fat.  The  same  thing  happens  if  an  absolutely  neutral  fat 
be  shaken  up  with  a  dilute  solution  of  sodium  carbonate.  If  however  the 
fat  be  slightly  rancid,  i.e.  if  fatty  acid  be  present,  the  latter  combines  with 
the  alkali  with  the  expulsion  of  ('02  to  form  a  soap.  The  presence  of  soap 
in  colloidal  solution  in  the  water  at  once  diminishes  or  abolishes  the  surface 
tension  between  the  neutral  fat  and  the  water.     Like  many  other  colloidal 


56  PHYSIOLOGY 

solutions,  a  soap  solution  presents  the  phenomenon  of  surface  aggregation, 
i.e.  the  concentration  of  the  soap  at  the  surface  is  increased  to  such  an  extent 
as  to  form  practically  a  solid  pellicle  of  molecular  dimensions  on  the  surface  of 
the  fluid.  The  same  pellicle  formation  occurs  at  the  surface  of  every  oil 
globule,  so  that  on  shaking  up  rancid  oil  with  dilute  sodium  carbonate,  the 
whole  of  the  oil  is  broken  up  into  fine  droplets,  which  show  no  tendency  to 
run  together  again  and  remain  in  suspension  in  the  water.  The  suspension 
of  fine  oil  droplets,  which  has  the  appearance  of  milk,  is  spoken  of  as  an 
emulsion.  It  can  be  at  once  destroyed  by  adding  acid.  This  decomposes 
the  soap,  setting  free  the  fatty  acids,  which  are  insoluble  in  the  water.  The 
pellicle  around  each  globule  is  destroyed,  and  the  globules  run  together  as 
neutral  oil  would  in  pure  water. 

In  order  to  characterise  any  given  animal  fat  or  mixture  of  fats  the  following  reactions 

are  made  use  of : 

(1)  The  '  acid  number  '  of  the  fat,  i.e.  its  content,  in  free  fatty  acids,  is  determined 

N 
by  titrating   it   in   ethyl  alcohol   solution         with  alcoholic  solution  of  potash,  using 

phenolphthalein  as  an  indicator.  , 

(•2)  The  '  saponification  number.'  This  represents  the  number  of  milligrammes 
of  potassium  hydrate  necessary  to  saponify  completely  one  gramme  of  fat. 

(3)  The  percentage  of  volatile  fatty  acids  is  determined  by  saponifying  the  fat, 
then  treating  it  with  a  mineral  acid  to  set  free  the  fatty  acids  and  distilling  over  the 
volatile  acids  in  a  current  of  steam. 

(4)  The  iodine  number  is  the  amount  of  iodine  which  is  taken  up  by  a  given  weight 
of  fat.  It  is  a  measure  of  the  amount  of  unsaturated  fatty  acid  present,  i.e.  in  ordinary 
fat,  oleic  acid. 

Besides  the  glycerides,  a  certain  number  of  substances  occur  in  the  body 
derived,  not  from  a  combination  of  fatty  acids  with  glycerol,  but  from  a 
formation  of  esters  of  the  fatty  acids  and  other  alcohols,  e.g.  cholesterol  or 
cetyl  alcohol.  Thus,  spermaceti  is  a  mixture  of  cetyl  palmitate  with  small 
quantities  of  other  fats.  The  fatty  secretion  of  the  sebaceous  glands  in 
man  and  the  higher  animals,  which  furnishes  the  natural  oil  of  hair,  wool, 
and  feathers,  consists  of  cholesterol  esters  with  small  traces  of  glycerides. 
Lanoline,  which  is  purified  wool  fat,  consists  almost  entirely  of  cholesteryl 
stearate  and  palmitate.  These  cholesterol  fats  are  attacked  with  extreme 
difficulty  by  ferments  or  micro-organisms.  It  is  probably  on  this  account 
that  they  are  manufactured  in  the  body  for  protective  purposes.  So  far  as 
we  know,  when  once  formed,  they  are  incapable  of  further  transformation  in 
the  body.  They  are  not  appreciably  altered  by  the  digestive  ferments  of  the 
alimentary  canal,  and  the  cholesterol  is  said  to  pass  through  the  latter 
unaltered.*  Cholesterol  is  also  found  in  combination  with  fatty  acids  in 
every  living  cell.  Whenever  protoplasmic  structures  are  extracted  with 
boiling  ether,  a  certain  amount  of  cholesterol  is  present  with  the  fats  which 
are  so  extracted.  In  view  of  the  great  stability  of  this  substance  when 
exposed  to  the  ordinary  mechanisms  of  chemical  change  in  the  body,  it  seems 
probable  that  the  part  played  by  cholesterol  is  that  of  a  framework  or 

*  According  to  Gardner,  cholesterol  may  be  absorbed  from  the  intestine. 


THE   FATS  57 

skeleton,  in  the  interstices  of  which  the  more  labile  constituents  of  the 
protoplasm  can  undergo  the  constant  cycle  of  changes  which  make  up  the 
phenomena  of  life. 

PHOSPHOLIPINES   OR   PFOSPHATIDES 

The  fats  form  the  chief  constituent  of  the  deposited  and  reserve  fat 
throughout  the  animal  kingdom  and  are  also  contained  in  the  protoplasm  of 
the  living  cell.  The  chief  fatty  constituents  of  protoplasm  differ  from  the 
above  fats  in  the  following  particulars  :  they  contain  phosphoric  acid  and  an 
amine.  On  this  account  they  have  been  called  phosphorised  fats.  Thudi- 
chum,  who  isolated  various  compounds  of  this  nature  from  brain,  suggested 
the  term  phosphatides  as  a  general  name  for  them.  The  term  lipoid  has  also 
been  used,  but  it  includes  all  the  substances  composing  a  cell  which  are  soluble 
in  ether,  e.g.  cholesterol,  cetyl  alcohol,  and  the  fats.  Leathes  has  suggested 
the  term  phosphobpine  for  those  compounds,  for  it  denotes  that  the  com- 
pound is  partly  fat  (lip),  that  it  contains  phosphorus,  as  well  as  a  nitrogenous 
basic  radical  (ine).  The  phospholipines  comprise  the  substances  lecithin. 
cephalin,  cuorine,  sphingomyeline.  In  brain  and  other  tissues  similar  com- 
pounds, which  contain  no  phosphorus,  occur,  and  in  the  place  of  glycerol  w  e 
may  find  galactose.  Leathes  has  proposed  calling  these  compounds  lipines 
and  galactolipines. 

Lecithin,  the  chief  phospholipine,  is  an  ester  compounded  of  two  fatty 
acid  radicals,  phosphoric  acid,  glycerol,  and  the  amine,  choline.  The 
various  lecithins  may  be  distinguished,  according  as  they  contain  different 
fatty  acid  radicals,  as  oleyl-lecithin,  stearyl-lecithin.  The  following  formula 
represents  distearyl-lecithin : 

CHa— 0— OC.(CH2)18CH3 
| 

CH— O— OC.(CH2)leCH3 
I 

CH2-0  O 

W 
HCK        xO.CH2.CH2.N(CH3)3 


OH 

On  warming  with  baryta  water  lecithin  is  broken  down  into  fattv  acid, 
glycerophosphoric  acid,  and  choline.     The  latter  base,  which  is  trimethvl- 

|  C2H4OH 
oxethvl-ammoniuni   hvdrate,     N  •  (CH3)3         must  be   distinguished    from 

(oh 

|C2H3 

neurine.  N     (CH3)3   which    is   triniethvl-vinvl-aimnonium   hydrate,    and    is 
I  OH 

much  more  poisonous  than  choline.  Choline  forms  a  salt  with  hydrochloric 
acid  which,  with  platinum  chloride,  yields  a  double  salt  of  characteristic 
crystalline  form,  insoluble  in  absolute  alcohol.  The  universal  distribution  of 
lecithin  seems  to  indicate  that  it  plays  an  important  part  in  the  metabolic 


58  PHYSIOLOGY 

processes  of  the  cell.  There  is  no  doubt  that  it  may  serve,  inter  alia,  as  a 
source  of  the  phosphorus  required  for  building  up  the  conrplex  nucleo-proteins 
of  cell  nuclei.  It  seems  to  represent  an  intermediate  stage  in  the  utilisation 
of  neutral  fats  by  protoplasm,  and  its  occurrence  in  the  brain  as  a  constituent 
of  more  complex  molecules,  which  contain  also  a  carbohydrate  nucleus 
(galactosides,  such  as  cerebrin),  might  be  interpreted  as  indicating  some 
share  also  in  the  metabolism  of  carbohydrates. 

Lecithin  may  be  extracted  from  tissues  by  boiling  with  absolute  alcohol. 
On  cooling  the  alcoholic  extract  in  a  freezing  mixture,  the  lecithin  separates 
out  as  granules  or  semi-crystalline  masses.  When  dried  in  vacuo,  it  forms 
a  waxy  mass,  which  melts  at  40°  to  50°  C.  In  water  it  swells  up  to  form  a 
paste  which,  under  the  microscope,  is  seen  to  consist  of  oily  drops  or  threads, 
the  so-called  myelin  droplets.  In  a  large  excess  of  water  it  forms  an  emulsion 
or  a  colloidal  solution.  Its  power  of  taking  up  water  on  the  one  hand,  and 
i!  s  solubility  in  alcohol  and  similar  media  on  the  other,  give  it  an  intermediate 
position  between  the  water-soluble  crystalloids  and  the  insoluble  fats,  and 
enable  it  to  play  an  important  part  both  as  a  vehicle  of  nutritive  substances 
and  as  a  constituent  of  the  lipoid  membrane,  which  bounds  and  determines 
the  osmotic  relationships  of  all  living  cells. 

The  phospholipids  are  provisionally  classified  according  to  the  proportions  of 
N  and  P  in  their  molecule,  as  follows  : 

(a)  Mono-amino-monoi)hosphatides,N  :  P=  1  :  1  (includinglecithin  andcephalin). 

(b)  Diamino-mono-phosphatides,  N:P  =2:  1   [e.g.  sphingomyelin). 

(c)  Mono-amino-diphosphatides,  N  :  P  =  1  :  2  (e.g.  cuorin,  a  lipine  extracted  from 
"  heart  muscle  by  Erlandsen). 

(d)  Diamino-diphosphatides,  N  :  P  =2:2. 

(e)  Triamino-monophosphatides,  N  :  P  =  3  :  1  (an  example  has  been  reported  as 

occurring  in  egg  yolk). 
All  these  bodies  (except  cuorin)  are  obtained  by  the  extraction  of  the  brain  or  of  nerve 
fibres.  Many  also  occur  in  egg  yolk.  The  galacto-lipines  include  two  substances 
extracted  from  the  brain,  viz.  phrenosin  and  kerasin.  Both  these  on  decomposition 
yield  galactose,  a  nitrogenous  base  called  sphmgosine  and  a  fatty  acid.  We  know 
little  or  nothing  of  their  significance. 


SECTION  IV 
THE   CARBOHYDRATES 

The  carbohydrates  are  a  group  of  bodies  of  wide  distribution  and  great 
importance  in  both  the  vegetable  and  animal  kingdoms.  In  plants  the  first 
product  of  assimilation  of  carbon  is  a  carbohydrate,  and  in  animals  these 
substances  form  one  of  the  most  important  sources  of  energy.  They  consist 
of  the  elements  carbon,  hydrogen,  and  oxygen,  the  two  last-named  being 
almost  invariably  in  the  proportions  necessary  to  form  water.  It  is  on  this 
account  that  the  term  carbohydrate  has  been  given  to  the  group.  Their 
general  formula  might  be  expressed  CnH,nOn.  Certain  derivatives  of  the 
group,  obtained  by  the  substitution  of  methyl  and  other  radicals  for  a 
hydrogen  atom,  though  necessarily  classified  with  carbohydrates  on  account 
of  their  reactions,  do  not  conform  to  this  general  formula,  e.g.  rhamnose, 
Cr,Hi206.  All  the  carbohydrates  which  are  of  importance  in  the  animal 
economy  contain  six  carbon  atoms  or  a  multiple  of  this  number.  Analogous 
substances  however  can  be  prepared  containing  less  or  more  than  this 
number  of  carbon  atoms.  A  series  of  compounds  exist  which  contain  in  their' 
molecule  2,  3,  4,  5,  6,  7,  8,  9  carbon  atoms,  and  are  termed  dioses,  trioses, 
tetroses,  pentoses,  hexoses,  heptoses,  and  so  on  ;  the  termination  '  ose  '  with 
the  Greek  numeral  prefixed,  indicating  the  number  of  carbon  atoms,  gives 
them  a  distinct  designation.  These  are  all  oxidation  products  of  polyatomic 
alcohols,  being  either  ketones  or  aldehydes  of  these  alcohols.     Thus  from 

COH 

I 
glycerol     we    may     obtain     glyceryl     aldehyde    CHOH  and    dioxvacetone 

I 
CH2OH  OH  ..OH 

I 
CO.       Both  these  substances  behave  as  sugars  and  belong  to  the  group  of 

I 
CH2OH 

i  rinses.     They   are  generally  obtained  together  and  are  called  glycerose. 
CH.OH 
I 
From  the  hexatomic   alcohol   (OHOH),  we  may  obtain  either  the  aldehyde 


OH..OH 


;>4 


60  PHYSIOLOGY 

CH2OH 

I 
COM  CO 

I  I 

(CHOH)4  or  the  ketone    (CHOH)3.     These  two  oxidation  products  of    tl 

I  I 

CH2OH  CH2OH 

polyatomic  alcohols  are  known  as  aldoses  and  ketoses  respectively.  All  thet 
compounds  are  distinguished  by  the  termination  '  ose.'  It  is  convenien 
to  call  those  compounds  containing  six  carbon  atoms  the  sugars,  becausi 
it  is  to  this  group  that  the  natural  sugars  belong. 

Stereoisomerism  in  the  Sugars.     It  will  be  noticed  that  of  the  six  carbon 

CH2OH 
I 
atoms  contained  in  the  sugar  molecule,  e.g.  the  aldose    (CHOH)4,  four  are 

I 
COH 

asymmetric,  i.e.  their  four  combining  affinities  are  saturated  with  groups 
of  different  kinds,  viz.  several  carbon  atoms,  one  H  atom,  and  one  OH 
group  . 

C 

I 
H— O— OH 


They  must  therefore  present  many  stereoisomers  forms.  If  n  represent  the 
number  of  asymmetric  carbon  atoms  in  a  compound,  the  possible  number  of 
stereoisomers  is  2n.  Thus  an  aldehexose  with  four  asymmetric  carbon  atoms 
(CHOH)4  must  present  24  isomers,  i.e.  sixteen  isomeric  compounds,  so  that 
there  must  be  sixteen  sugars  all  possessing  the  formula  CH2OH(CHOH)4COH, 
in  addition  to  the  inactive  sugars  obtained  by  a  mixture  of  two  oppositely 
active  members  of  this  group.  Of  the  sixteen  possible  sugars  of  this  formula, 
as  many  as  fourteen  have  been  found  or  have  been  artificially  prepared. 
Only  a  small  number  are  however  of  any  physiological  importance.  These 
include  the  aldoses,  glucose,  mannose,  and  galactose,  and  the  ketose,  fructose 
or  levulose.  All  the  other  sugars  are  unassimilable  by  the  animal  cell  and 
are  not  manufactured  by  plants. 

Since  these  sugars  can  be  divided  into  the  optically  active  and  the  inactive 
varieties,  an  obvious  mode  of  designation  would  be  to  represent  them  as 
d-,  1-,  and  i-  varieties  respectively,  i.e.  dextro-rotatory,  lsevo-rotatory,  and 
inactive.  On  Fischer's  suggestion  however,  this  mode  of  nomenclature  has 
been  altered  in  favour  of  representing,  by  the  letter  prefixed,  not  the  optical 
qualities  of  the  substance  in  question,  but  its  relation  to  other  substances, 
especially  glucose.  Thus,  d-fructose  means  that  fructose  is  the  ketose  corre- 
sponding to  the  dextro-rotatory  glucose,  d-fructose  itself  being  lsevo-rotatory, 
though  its  active  asymmetric  C  atoms  are  identically  arranged  with  those  in 
glucose.     With  this  limitation  one  may  say  that  it  is  only  the  d-hexoses  of  a 


THE  CARBOHYDRATES  61 

articular  form  which  are  assimilable,  and  therefore  of  physiological  im- 
irtance.  The  small  differences  in  the  configuration  of  the  four  d-sugars 
n  be  readily  seen  if  their  graphic  formula?  be  compared  : 

CHO  CHO  f!H,OH  CHO 

I  I  I  I 

H.C.OH  HO.C.H  CO  H.C.OH 

I  I  I  I 

HO.C.H  HO.C.H  HO.C.H  HO.C.H 

I  I  I  I 

H.C.OH  H.C.OH  H.C.OH  HO.C.H 

I  I  I  I 

H.C.OH  H.C.OH  H.C.OH  H.C.OH 

I  ,1  I  I 

CH2OH  CH2OH  CH2OH  CH2OH 

d-glucose  d-mannose  d-fructose  d-galactose 

THE   PENTOSES.     C5H10O6 

These  bodies  occur  largely  in  plants  in  the  form  of  complex  polysaccharides,  the 
pentosanes,  which  give  pentoses  on  hydrolysis  with  acids.  Two  forms  of  pentose 
have  been  found  in  the  animal  body,  namely,  i-arabinose,  which  has  been  isolated 
from  the  urine  in  cases  of  pentosuria,  and  1-xylose  (or  d-ribose,  Levene),  which  occurs 
built  up  into  the  nucleic  acid  molecule  of  the  pancreas  and  perhaps  other  organs.  The 
pentoses  can  apparently  be  utilised  by  herbivora  as  food-stuffs.  We  know  nothing  as 
to  the  part  they  play  in  the  animal  body  or  as  to  the  causation  of  the  rare  condition  of 
pentosuria.  Since  however  they  are  reducing  substances  and  the  presence  of  pentose 
in  urine  might  therefore  lead  to  a  suspicion  of  diabetes,  it  is  necessary  to  mention  the 
tests  by  which  the  presence  of  pentoses  may  be  detected.  The  two  following  are  the 
chief  tests  for  pentoses : 

(1)  The  solution  supposed  to  eon  tain  a  pentose  is  mixed  with  an  equal  volume  of 
concentrated  hydrochloric  acid.  To  the  mixture  is  added  a  small  quantity  of  solid 
orein  and  the  whole  is  heated.  If  pentose  is  present  the  solution  becomes  at  first 
reddish-blue  and  later  bluish-green.  The  colour  can  be  extracted  on  shaking  the 
fluid  with  amyl  alcohol,  the  solution,  on  spectroscopic  examination,  showing  an  absorp- 
tion band  between  C  and  D. 

(2)  Instead  of  adding  orcin,  we  may  add  phloroglucin  to  the  mixture  of  hydrochloric 
acid  and  pentose.  The  solution  on  heating  becomes  first  cherry  red  and  then  cloudy. 
On  shaking  with  amyl  alcohol  a  red  solution  is  obtained  which  shows  a  band  between 
D  and  E. 

THE    HEXOSES   AND  THEIR   DERIVATIVES 

The  most  important  of  the  carbohydrates  belong  to  this  class  and  are 
either  hexoses  or  formed  by  a  combination  of  two  or  more  hexose  molecules. 
They  are  divided  into  three  main  groups  : 

(1)  Monosaccharides,  with  the  formula  C6H1206,  examples  of  which  pre 
glucose,  fructose,  &c. 

(2)  Disaccharides,  which  are  derived  from  two  molecules  of  a  monosac- 
charide with  the  elimination  of  a  molecule  of  water,  as  follows  : 

2C6H1206  -  H20  =  C12H22On. 

(Examples,  maltose  and  cane  sugar.) 


62  PHYSIOLOGY 

(3)  Polysaccharides,  composed  of  three  or  more  molecules  of  a  mono- 
saccharide. The  number  of  molecules  which  are  associated  in  the  com- 
pounds of  this  group  may  be  very  large.  We  can  regard  their  general 
formation  as  represented  by  the  following  equation  : 

nC,H1206  -nH30  =  (C.H1,0,)n- 

(Examples,  starch,  dextrin,  &c.) 

THE  MONOSACCHARIDES 
Only  four  hexoses  out  of  the  large  number  which  have  been  synthetised 
are  assimilable  by  the  animal  body.  These  are  mannose,  glucose,  galactose, 
and  fructose,  the  three  former  being  aldoses,  while  the  last  is  a  ketose.  All 
of  them  are  derivatives  of  d-glucose.  They  may  be  synthetised  in  several 
ways.  The  most  interesting,  because  it  probably  represents  the  mechanism 
of  synthesis  of  hexoses  in  plants,  is  the  formation  from  formaldehyde.  In 
alkaline  solutions  formaldehyde  polymerises  with  the  formation  of  a  mixture 
of  hexoses  known  as  acrose.  From  this  mixture  a-acrose  can  be  isolated  by 
the  formation  of  its  osazone  and  the  reconversion  of  this  osazone  into  sugar. 
It  is  found  to  be  identical  with  i-fructose.  If  a  solution  of  this  i-fructose  be 
treated  with  yeast,  d-fructose  is  fermented,  leaving  1-fructose  behind.  For 
the  preparation  of  d-fructose  it  is  necessary  to  convert  the  inactive  sugar  into 
the  corresponding  acid,  mannonic  acid.  This  with  strychnine  or  morphia 
forms  salts  which  can  be  separated  into  the  d-  and  1-  groups  by  fractional 
crystallisation.  From  the  d-  modification  d-mannose  can  be  obtained,  and 
this  by  conversion  into  the  osazone  and  reconversion  into  a  sugar  gives 
d-fructose. 

All  the  monosaccharides,  however  many  carbon  atoms  they  contain,  present  certain 
general  reactions  determined  by  their  chemical  composition. 

(a)  Like  ordinary  aldehydes  and  ketones,  the  sugars  act  as  strongly  reducing  sub- 
stances, and,  like  aldehydes,  reduce  ammoniacal  solution  of  silver  to  metallic  silver, 
and  many  of  the  higher  oxides  of  metals  to  lower  oxides.  On  this  behaviour  is  founded 
the  commonest  of  all  the  tests  for  the  presence  of  reducing  sugar — Trommel's  test. 

(6)  On  oxidising  a  monosaccharide  the  COH  group  becomes  converted  to  COOH. 
Thus  glucose  on   oxidation  gives  gluconic  acid  : 

COH(CHOH)4CH2OH  +  O  =  C'0()H(CHUH)4CH2OH. 

On  further  oxidation  the  end  group  CH2OH  also  is  affected,  and  we  obtain  a  dibasic 
acid.     Thus  glucose  gives  saccharic  acid. 

(c)  By  means  of  nascent  hydrogen  the  monosaccharides  can  be  reduced  to  the 
corresponding  polyatomic  alcohol.  Thus  the  three  hexoses,  glucose,  fructose,  and 
galactose  give  the  corresponding  three  alcohols,  sorbite,  mannite,  and  dulcite  C6H1406. 

(d)  Another  important  general  reaction  of  the  monosaccharides  depending  on  the 
COH  or  the  CO  group  is  the  reaction  with  phenyl  hydrazine.  On  warming  a  solu- 
tion of  sugar  with  a  solution  of  phenyl  hydrazine  in  acetic  acid,  the  following  reactions 
take  place.     The  first  reaction  results  in  the  production  of  a  hydrazone  : 

CH„OH(CHOH)3CHOHCHO  +  H,N.NH.C6H5  = 
CH2OH(CHOH)3CHOH.CH  :  N.NH.C6H5  +  H20. 

The  hydrazone  then  reacts  with  another  molecule  of  phenyl  hydrazine  with  the  pro- 
duction of  an  osazone : 


THE  CARBOHYDRATES  63 

CH.,(()H)(CHOH)3CHOH.CH:  N.NH.C6H5  +  H,N.NH('6H5  - 
CH„OH(CHOH)3C.CHN.NH.C0H5 
II 
N.NH.C6H6  +  H20  +  H2. 

The  hydrogen  formed  in  this  reaction  acts  upon  a  second  molecule  of  phenyl  hydrazine, 
splitting  it  into  aniline  and  ammonia.  On  this  account  it  is  always  necessary  to  have 
an  excess  of  phenyl  hydrazine  in  the  operation. 

The  osazones  form  well-defined  crystalline  products  which  are  generally  yellowish 
in  colour  and  differ  in  their  melting-point  and  in  their  crystalline  form.  They  are 
therefore  of  extreme  value  in  the  separation  and  identification  of  different  carbohy- 
drates. They  can  be  also  used  for  the  artificial  preparation  of  certain  sugars.  Under 
the  influence  of  acetic  acid  and  zinc  dust  they  form  osamines,  which  on  treatment  with 
nitrous  acid  are  reconverted  into  the  corresponding  sugar,  generally  a  ketose. 

GLUCOSE,  DEXTROSE  or  GRAPE  SUGAR,  is  the  chief  constituent  of  the 
sugar  of  fruits,  especially  of  grapes.  It  occurs  in  the  body  as  the  end- 
product  of  the  digestion  of  starch.  When  pmc  it  forms  white  crystals  which 
melt  at  100°  C,  and  lose  the  one  molecule  of  water  of  crystallisation  at 
1 10°  C.  It  is  easily  soluble  in  water,  and  the  solution  shows  bi-rotation. 
Its  final  specific  rotatory  power  at  20°  C.  is  52 '74. 

TESTS  FOR  GLUCOSE.  Trommer's  test  depends  on  the  power  possessed  in 
common  with  the  other  sugars  of  reducing  cupric  hydrate  to  cuprous  oxide.  The 
sugar  solution  is  made  alkaline  with  caustic  potash  or  soda,  and  a  few  drops  of  copper 
sulphate  solution  added.  On  heating  the  blue  solution  thus  obtained  to  boiling,  it 
turns  yellow,  and  a  yellowish-red  precipitate  of  cuprous  hydrate  is  produced.  This 
test  is  generally  performed  with  Fehling's  solution,  which  consists  of  an  alkaline  solution 
of  cupric  hydrate  in  Rocheile  salt.  The  proportions  in  making  the  solutions  are  so 
arranged  that  10  c.c.  of  Fehling's  solution  are  completely  reduced  by  -05  gramme  glucose. 
This  reaction  is  made  use  of  for  the  quantitative  determination  of  glucose  in  solution. 
The  determination  may  be  carried  out  either  volumetrically,  as  in  Fehling's  or  Pavy's 
method,  or  gravimetrically,  as  in  Allihn's  method. 

Moore's  Test.  A  solution  of  glucose  treated  with  a  little  strong  caustic  potash 
or  soda  and  warmed,  becomes  first  yellow  and  then  gradually  dark  brown,  and  gives 
off  a  smell  of  caramel. 

With  ordinary  yeast,  glucose  solutions  ferment  readily,  giving  off  C02,  and  form 
alcohol  with  small  traces  of  amyl  alcohol,  glycerin,  and  succinic  acid. 

With  phenyl  hydrazine  glucose  gives  well-marked  needles  of  glucosazone.  These 
are  precipitated  when  the  liquid  is  still  hot,  the  precipitate  being  increased  as  the 
liquid  cools.  The  crystals  form  bundles  of  fine  yellow  needles  which  are  almost  in- 
soluble in  water,  but  are  soluble  in  boiling  alcohol.  When  purified  by  recrystallisation 
they  melt  at  204-205°  C. 

On  treating  a  watery  solution  of  glucose  with  benzoyl  chloride  and  caustic  soda 
and  shaking  till  the  smell  of  benzoyl  chloride  has  disappeared,  an  insoluble  precipitate 
is  produced  of  the  benzoic  ester  of  glucose.  This  method  has  been  often  used  for 
isolating  glucose  from  fluids  in  which  it  occurs  in  minute  quantities. 

Molisch's  Test.  On  treating  0-5  c.c.  of  dilute  glucose  solution  with  one  drop  of  a 
10  per  cent,  alcoholic  solution  of  a-naphthol,  and  then  pouring  1  c.c.  of  concentrated 
sulphuric  acid  gradually  down  the  side  of  the  tube,  a  purple  ring  is  produced  at  the 
junction  of  the  two  fluids,  which  on  shaking  spreads  over  the  whole  fluid.  This  reaction 
depends  on  the  formation  of  furfurol  from  the  glucose. 

In  order  to  identify  glucose  in  a  normal  fluid,  the  following  tests  may  be  applied, 
after  removing  any  protein  which  may  be  present: 

(1)  Reduction  of  cupric  hydrate  or  Fehling's  solution. 


64  PHYSIOLOGY 

(2)  Estimation  of  reducing  power  of  solution. 

(3)  Estimation  of  rotatory  power  of  solution  on  polarised  light. 

(4)  Formation  of  osazone  crystals  with  phenyl  hydrazine.  These  crystals  must 
come  down  while  the  fluid  is  still  hot.  They  must  be  purified  and  their  melting-point 
taken.  A  determination  by  combustion  of  their  nitrogen  content  will  give  direct 
information  whether  the  sugar  is  a  monosaccharide  or  disaccharide.  < 

(5)  The  solution  is  made  acid  and  boiled  for  some  time.  It  is  then  made  up  to  its 
former  volume  and  its  reducing  power  and  effect  on  polarised  light  once  more  taken. 
In  the  case  of  a  disaccharide,  which  would  be  converted  into  monosaccharide  by  boiling 
in  acid  solution,  these  two  readings  would  be  altered,  whereas  neither  the  rotatory 
power  nor  the  reducing  power  of  glucose  would  undergo  any  change. 

(6)  Fermentation  with  ordinary  yeast. 

A  positive  result  would  exclude  glycuronic  acid. 

D-FRUCTOSE,  or  LiEVULOSE,  occurs  mixed  with  dextrose  in  honey 
and  in  fruit  sugar.  It  is  also,  with  glucose,  formed  by  the  digestion  or  inver- 
sion of  cane  sugar.  It  is  crystallisable  with  difficulty.  Its  watery  solution 
is  laevo-rotatory,  and  reduces  Fehling's  solution  somewhat  less  strongly  than 
glucose,  its  reducing  power  being  92,  if  we  take  that  of  glucose  as  100.  It 
ferments  readily  with  yeast ;  with  phenyl  hydrazine  it  gives  the  same  osazone 
as  is  formed  from  glucose. 

GALACTOSE  is  formed  by  the  digestion  or  hydrolysis  of  milk  sugar  or 
lactose.  It  is  also  obtained  on  hydrolysing  cerebrin,  a  constituent  of  the 
brain,  with  dilute  mineral  acids,  and  by  the  hydrolysis  of  certain  vegetable 
gums.  It  is  much  less  soluble  in  water  than  glucose.  It  is  dextro-rotatory 
and  shows  marked  bi-rotation.  With  ordinary  yeast  it  ferments  but  ex- 
tremely slowly.  One  species  of  yeast  is  known,  namely,  saccJiaromyces  apicu- 
latus  which,  while  fermenting  d-fructose  and  glucose,  has  no  effect  on  galac- 
tose. This  yeast  can  therefore  be  used  to  isolate  galactose  from  a  mixture  of 
the  monosaccharides.  It  reduces  Fehling's  solution,  its  reducing  power 
being  somewhat  less  than  that  of  glucose.  Yeasts  can  be  trained  to  ferment 
galactose. 

MANNOSE.  Mannose,  though  an  assimilable  sugar,  is  of  such  rare  occurrence  in 
our  food-stuffs  that  it  plays  practically  no  part  in  animal  physiology.  It  is  dextro- 
rotatory, reduces  Fehling's  solution,  ferments  easily  with  ordinary  yeast,  and  gives 
an  osazone  which  is  identical  with  that  derived  from  glucose. 


DERIVATIVES   OF   THE   HEXOSES 

Two  derivatives  of  glucose  are  of  considerable  physiological  importance,  namely, 
glucosamine  and  glycuronic  acid. 

Glucosamine,  C6H13N06,  has  the  structural  formula  : 

CH2OH 

I 
(CH.OH)3 

I 
CH.NH2 

I 
CHO 


THE  CARBOHYDRATES  65 

It  is  obtained  from  chitin,  which  forms  the  exoskeleton  of  large  numbers  of  the  inver- 
tebrata,  by  boiling  this  with  concentrated  hydrochloric  acid.  It  is  stated  to  have 
been  obtained  as  a  decomposition  product  of  certain  proteins  and  their  derivatives, 
such  as  the  mucins.  It  is  of  special  interest  as  affording  an  intermediate  product 
between  the  carbohydrates  and  the  oxy-ainino  acids  which  can  be  obtained  by  the 
disintegration  of  proteins.  In  solution  it  is  dextro-rotatory,  reduces  Fehling's  solu- 
tion, and  gives  an  osazone  resembling  that  derived  from  glucose. 

GLYCURONIC  ACID.  O6H10O,,  may  be  regarded  as  one  of  the  first  results  of 
oxidation  of  the  glucose  molecule.  The  group  which  has  undergone  oxidation  is  not  the 
readily  oxidisable  CHO  group,  but  the  CH2OH  group  at  the  other  end  of  the  molecule. 
The  formula  of  this  acid  is  therefore : 

COOH 

I 
(CH.OH)4 

I 
CHO. 

In  the  free  state  it  does  not  occur  in  the  animal  body.  It  is  constantly  found  in  the 
urine  after  administration  of  certain  drugs  such  as  phenol,  camphor,  or  chloral,  and 
then  occurs  as  a  conjugated  acid  with  these  substances.  These  conjugated  acids  are 
laevo-rotatory,  though  the  free  acid  is  dextro-rotatory.  In  the  free  state  it  reduces 
Fehling's  solution  and  gives  an  osazone  which  is  not  sufficiently  characteristic  to  dis- 
tinguish from  glucosazone.  It  does  not  undergo  fermentation  with  yeast.  This  test 
is  therefore  the  best  means  of  distinguishing  the  acid  in  urine  from  glucose. 


THE   FORMATION   OF    GLUCOSIDES 

The  graphic  formulae  given  on  p.  61  do  not  explain  all  the  possible  modes  of  arrange- 
ment of  the  groups  of  the  sugar  molecules.  Many  of  these  sugars,  when  dissolved  in 
water,  present  the  phenomenon  known  as  multi-rotation.  If  their  rotatory  power 
be  taken  immediately  after  solution,  it  is  found  to  be  greater  or  less  than  the  rotatory 
power  taken  some  hours  or  days  later.  Glucose,  for  instance,  immediately  after  solu- 
tion, has  a  high  specific  rotatory  power,  which  diminishes  rapidly  if  the  solution  be 
boiled,  and  more  slowly  if  it  be  allowed  to  stand.  Finally,  the  specific  rotatory  power 
becomes  constant  at  +  52-5°  D.  This  change  in  rotatory  power  seems  to  be  associated 
with  a  change  in  the  arrangement  of  the  groups,  the  aldose  for  example  assuming, 
by  the  shifting  of  a  mobile  oxygen  atom,  what  is  known  as  a  lactone  arrangement. 

Thus  glucose  COH(CHOH)2CHOH.CHOH.CH2OH  becomes 
CHOH.(CHOH)2.CH.CHOH.CH,OH 


This  change  in  the  arrangement  of  the  molecule  renders  a  further  stereoisomerism 
possible,  owing  to  the  fact  that  now  the  end  group  which  was  formerly  COH  becomes 

H 

I 

0— C— OH 

I 

c 

so  that  now  there  are  five  instead  of  four  asymmetric  carbon  atoms.     The  two  isomers 

5 


1,1, 


PHYSIOLOGY 


if  glucose,  which  are  thus  rendered  possible,  are  represented  by  (he  following  structural 


formulae  : 


OH— C— H 


BOCH 


In  these  molecules  the  OH  attached  to  the  end  group  can  be  replaced  by  other  radicals, 
including  other  sugar  molecules.  In  this  way  we  get  the  formation  of  glucosides.  Thus, 
if  glucose  be  dissolved  in  methyl  alcohol  and  be  treated  with  hydrochloric  acid,  we 
obtain  a  and  j'i  methyl  glucosides,  the  formula;  of  which  would  be  represented  as  follows  : 
H— C— OCH,  CH30— C— H 


HOCH 


HCOH  HCOH 

I  I 

CH..OH  0H,OH 

Instead  of  methyl  we  might  insert  other  groups,  and  even  other  hexose  groups,  such 

as  glucose  or  galactose,  obtaining  the  two  sugars  maltose  and  lactose,  which  may  thus 

be  regarded  as  glucosides — maltose  as  the  a-glucoside  of  glucose,  lactose  as  the  /3-galae- 

toside  of  glucose.     The  mode  of  combination  of  the  two  hexose  groups  to  form  these 

disaccharides  may  be  represented  as  follows  : 

H       H     OH        H        H 

CH2OH— C—  C  —  C—  C  —  C  glucose  rest 

OH  HOH 


0 


HO     H     HO     HO 

OHC —  C  —  C  — C  —  C  —  CH,  glucose  rest 
H     OH      H       H 
O 


maltose. 


CH,OH  - 


H         OH      H 
-  C  —  C—  C  —  C  - 
OH      H     H  OH 


•  C  galactose  rest  \ 


0 


lactose 


HO      H  HO    HO 
OHC  —  C  —  C  —  C  —  C—  CH2  glucose  rest 
H  OH      H      H 


THE  CARBOHYDRATES  67 

A  very  large  number  of  glucosides  occur  as  plant  products.     Among  these  we  may 
mention  amygdalin,  salicin,  phloridzin,  indican,  &c. 

THE   DISACCHARIDES 

The  disaccharides  are  formed  by  the  union  of  two  molecules  of  mono- 
saccharides with  the  elimination  of  one  molecule  of  water,  and  can  be  re- 
garded, according  to  the  manner  in  which  the  molecules  are  combined,  as 
glucosides,  galactosides,  &c.  On  hydrolysis,  e.g.  on  heating  with  acids,  they 
take  up  one  molecule  of  water  and  are  split  up  into  the  corresponding  mono- 
saccharides. Thus  cane  sugar  gives  equal  parts  of  glucose  and  fructose, 
maltose  gives  equal  parts  of  glucose  and  glucose,  while  milk  sugar  or  lactose 
gives  equal  parts  of  glucose  and  galactose. 

CANE  SUGAR,  sometimes  known  as  saccharose,  is  widely  distributed 
throughout  the  vegetable  kingdom,  and  forms  an  important  article  of  diet. 
It  has  no  reducing  power  on  Fehling's  solution.  It  is  strongly  dextro-rcta- 
tor)'  and  has  a  specific  rotatory  power  of  +  66  "5°.  On  hydrolysis  it  is 
converted  into  equal  molecules  of  glucose  and  fructose.  Owing  to  the  fact 
that  fructose  rotates  polarised  light  more  strongly  to  the  left  than  glucose 
does  to  the  right,  the  mixture  of  the  two  monosaccharides  so  obtained  is 
laevo-rotatory.  On  this  account  the  change  from  free  cane  sugar  to  the 
mixture  of  monosaccharides  is  known  as  inversion,  and  the  mixture  is  often 
spoken  of  as  '  invert  sugar.'  The  term  '  inversion '  has  since  been  loosely 
applied  to  the  process  of  hydrolysis  itself,  so  that  we  often  speak  of  the 
inversion  of  maltose  or  of  lactose,  meaning  thereby  the  hydrolysis  of  these 
sugars  with  the  production  of  their  constituent  monosaccharides.  With 
veast ,  cane  sugar  first  undergoes  inversion  by  a  special  ferment  present  in  the 
yeast  (invertase),  and  the  mixture  of  fructose  and  glucose  is  then  fermented. 

MALTOSE  is  formed  during  the  hydrolysis  of  starch  by  acids  or  by 
digestive  ferments,  and  is  also  the  chief  sugar  in  germinating  barley  or  malt. 
It  is  strongly  dextro-rotatory,  ferments  easily  with  yeast,  and  reduces 
Fehling's  solution ;  its  reducing  power  is  about  70  per  cent,  of  that  of 
glucose.  With  phenyl  hydrazine  it  gives  phenyl  maltosazone,  which  forms 
definite  yellow  crystals  with  a  melting-point  of  206°  C. 

MILK  SUGAR  or  LACTOSE  is  found  only  as  a  constituent  of  milk. 
It  forms  colourless  rod-like  crystals,  which  are  much  less  soluble  in  water 
than  are  the  two  other  disaccharides.  On  account  of  this  solubility  it  is  much 
less  sweet  than  either  cane  sugar  or  maltose.  It  is  dextro-rotatory  and 
shows  bi-rotation.  It  is  not  fermented  by  ordinary  yeast.  Before  fermen- 
tation can  occur  the  lactose  must  be  split  by  the  agency  of  acids  or  by  a 
ferment,  lactase,  which  occurs  in  the  animal  body  and  in  certain  moulds,  into 
the  monosaccharides  glucose  and  galactose.  Lactose  reduces  Fehling's 
solution  and  gives  with  phenyl  hydrazine  lactosazone,  which  is  easily  soluble 
in  hot  water  and  therefore  does  not  come  down  until  the  fluid  is  cold. 

THE   POLYSACCHARIDES 
These  play  an  important  part  throughout  the  whole  vegetable  kingdom, 
where  all  the  supporting  tissues  of  the  plants,  their  protective  substances, 


68  PHYSIOLOGY 

an<]  many  of  their  reserve  materials  consist  of  members  of  this  group.  In 
the  animal  body,  where  the  supporting  tissues  are  composed  chiefly  of  deriva- 
tives of  proteins,  the  sole  significance  of  polysaccharides  lies  in  their  value  as 
food-stuffs.  In  plants,  anhydrides  both  of  hexoses  and  pentoses  occur  in 
bewildering  variety.  Here  however  we  may  confine  our  attention  to  those 
members  of  the  group  of  polysaccharides  which  are  important  as  food-stuffs. 
STARCH  (CJIioOt)  is  present  in  large  quantities  in  nearly  all  vegetable 
foods,  and  is  an  important  constituent  of  the  cereals,  from  which  flour  and 
bread  are  derived,  as  well  as  of  tubers,  such  as  the  potato.  In  the  plant  cells 
it  occurs  as  concentrically  striated  grains  within  minute  protoplasmic 
structures— the  amyloplasts,  the  office  of  which  it  is  to  manufacture  starch 
from  the  glucose  present  in  the  cell  sap.  When  freed,  by  breaking  up  the 
cells  and  washing  with  water,  it  forms  a  white  powder  consisting  of  micro- 
scopic grains,  each  of  which  presents  the  characteristic  concentric  striation. 
It  is  insoluble  in  cold  water.  In  hot  water  the  grains  swell  up  and  burst. 
forming  a  thick  paste,  which  sets  to  a  jelly  on  cooling.  This  semi-solution, 
as  well  as  the  original  starch-grains,  gives  an  intense  blue  colour  on  the 
addition  of  iodine.  On  treating  starch  with  cold  alkalies  or  cold  dilute  acid, 
it  is  converted  into  a  soluble  modification,  the  so-called  soluble  starch  or 
amylodextrin,  which  also  gives  a  blue  colour  with  iodine.  This  modification 
is  also  produced  as  the  first  stage  of  the  action  of  diastatic  ferments  upon 
starch.  On  boiling  with  dilute  acids,  starch  is  converted  first  into  a  mixture 
of  dextrins,  then  into  maltose,  and  finally  into  glucose.  On  acting  upon 
starch  with  various  ferments,  such  as  the  diastase  which  may  be  extracted 
from  malt  or  germinating  barley,  or  with  the  amylase  occurring  in  saliva  or 
pancreatic  juice,  it  undergoes  hydrolysis,  the  final  result  of  the  action  being  a 
mixture  of  four  parts  of  maltose  to  one  part  of  dextrin.  As  to  the  inter- 
mediate stages  in  this  reaction  opinions  are  still  divided.  The  first  product 
is  soluble  starch,  amylodextrin,  giving  a  blue  colour  with  iodine.  This 
breaks  up  into  a  reducing  sugar,  and  another  dextrin,  erythrodextrin,  which 
gives  a  red  colour  with  iodine ;  and  this  dextrin,  on  further  hydrolysis, 
yields  reducing  sugar  and  achroodextrin,  which  is  not  coloured  by  the 
addition  of  iodine.  Thus  there  are  a  series  of  successive  hydrolytic  decom- 
positions of  the  molecule,  each  resulting  in  the  splitting  off  of  a  molecule 
of  sugar  and  the  production  of  a  lower  dextrin. 

The  DEXTRINS  are  ill-defined  bodies  which  are  difficidt  to  separate. 
They  are  amorphous  white  powders,  easily  soluble  in  water,  forming  solutions 
which,  when  concentrated,  are  thick  and  adhesive.  They  are  insoluble  in 
alcohol  and  ether.  With  cupric  hydrate  and  caustic  alkali  they  form  blue 
solutions,  which  reduce  slightly  on  boiling.  They  are  not  precipitated  by 
situration  with  ammonium  sulphate.  On  boiling  with  dilute  acids,  they  are 
converted  entirely  into  glucose. 

The  changes  undergone  by  starch  during  its  hydrolysis  by  means  of  diastase  have 
been  used  by  Brown  and  his  co-workers  as  a  method  of  arriving  at  some  idea  of  the 
size  and  structure  "of  the  starch  molecule.  Proceeding  from  the  discovery  that  the 
end-products  of  this  reaction  consisted  of  81  per  cent,  maltose  and  19  per  cent,  dextrin, 


THE  CARBOHYDRATES  69 

they  concluded  that  starch  must  consist  of  five  dextrin-like  groups,  four  of  which  are 
arranged  symmetrically  round  the  fifth.     At  each  stage  one  of  these  groups  is  split  off  and 

hydrolysed    to    form    malto-dextrin  :    { ,_,  *£  2J.   "  •    one    molecule  of   water    being 

'  J  UC12H2oOlo)2j 

taken  up.  The  malto-dextrin  group  is  then  changed  into  maltose  by  the  further 
assimilation  of  two  molecules  of  water.  The  central  dextrin-like  group  is  attacked 
with  great  difficulty  by  the  ferment,  and  therefore  remains  at  the  end  of  the  reaction  as 
achroodextrin.  The  malto-dextrin,  the  penultimate  stage  in  the  action  of  diastase, 
can  be  regarded  as  formed  by  the  condensation  of  three  molecules  of  maltose  attached 
by  the  oxygen  of  two  CHO  groups,  so  that  one  CHO  group  remains  free  and  determines 
the  reducing  power  of  the  malto-dextrin  molecule.  Its  formula  may  therefore  be 
represented  as  follows  : 

<C12H21O10 


< 


:^if>W-9n^-'a 


Ci2H21O10<' 

the  sign  (  being  used  to  denote  the  open  terminal  CHO  group. 
N 
They  further  found  that  the  stable  dextrin  remaining  at  the  end  of  the  diastatic 
hydrolysis  of  starch  probably  had  the  formula  of  •40C6H10O5H2O,  and  might  be  regarded 
as  a  condensation  of  forty  glucose  molecules  with  the  elimination  of  thirty-nine  mole- 
cules of  water.  The  starch  molecule  cannot  be  less  than  five  times  that  of  the  stable 
achroodextrin.  Since  the  latter  has  a  molecular  weight  of  6498,  the  molecular  weight  of 
starch  cannot  be  less  than  32,400,  and  its  empirical  formula  can  be  represented  by : 

100C12H20O10.  or  (80C12H20O10.40C6H10O5). 

INULIN.  Another  kind  of  starch,  known  as  inulin,  occurs  in  dahlia 
tubers.  Tt  is  easily  hydrolysed  by  weak  acids,  and  is  entirely  converted  into 
d-tiuctose,  or  lsevulose. 

GLYCOGEN,  or  animal  starch,  is  found  in  the  liver,  muscles,  and  other 
tissues  of  the  body,  and  occurs  in  large  quantities  in  all  foetal  tissues.  It  is 
a  white  powder,  soluble  in  water,  forming  an  opalescent  solution.  It  is 
precipitated  from  its  solution  on  the  addition  of  alcohol  to  60  per  cent.,  or  by 
saturation  with  solid  ammonium  sulphate.  On  boiling  with  acids,  it  is 
entirely  converted  into  glucose.  It  is  affected  by  the  ferments  diastase  and 
amylase,  in  the  same  way  as  vegetable  starch,  giving  first  dextrins  and  finally 
a  mixture  of  maltose  and  dextrin.  With  iodine  it  gives  a  mahogany-red 
colour  which,  like  the  blue  colour  produced  in  starch,  is  destroyed  by  boiling, 
to  return  again  on  coobng.  We  shall  have  occasion  to  consider  its  properties 
more  fully  when  we  are  dealing  with  the  functions  of  the  liver. 

THE  CELLULOSES.  Cellulose  (C6H1006)x  is  a  colourless,  insoluble 
material,  or  mixture  of  materials,  which  forms  the  cell  walls  of  the  younger 
parts  of  plants,  and  is  therefore  a  constituent  of  most  of  our  vegetable 
foods.  It  is  insoluble  in  water  or  dilute  acids  or  alkalies,  its  only  solvent 
being  an  ammomacal  cupric  oxide  solution.  On  boiling  with  strong  acids, 
it  gradually  undergoes  hydrolysis  and  yields  sugar,  the  nature  of  which 
varies  according  to  the  source  of  the  cellulose.  In  herbivorous  animals  cellu- 
lose undergoes  digestive  changes  and  forms  an  important  constituent  of  their 


70  PHYSIOLOGY 

food.  The  solution  of  the  cellulose  in  this  case  is  effected  by  the  agency,  not 
of  ferments  secreted  by  the  wall  of  the  gut,  but  of  micro-organisms  which 
swarm  in  the  paunch  of  ruminants  and  in  the  caecum  of  other  herbivora.  In 
some  cases  the  effective  agent  is  a  cytase  present  in  the  vegetable  cells 
themselves.  Since  this  ferment  is  destroyed  by  boiling,  cooked  hay  is  much 
less  digestible  than  hay  in  the  raw  condition.  In  certain  invertebrata  it  seems 
probable  that  a  true  cellulose-digesting  ferment,  or  cytase,  is  secreted  by  the 
walls  of  the  alimentary  canal.  In  man  cellulose  undergoes  practically  no 
change  in  digestion,  and  serves  merely  by  its  bulk  to  promote  peristalsis  and 
the  normal  evacuation  of  the  bowels.  A  further  consideration  of  its  chemical 
properties,  as  well  as  of  the  closely  allied  vegetable  materials,  gums,  pectins, 
mucilages,  derived  for  the  most  part  from  the  condensation  of  pentose 
molecules,  may  be  dispensed  with  here. 


SECTION  V 

THE    PROTEINS 

As  sources  of  energy  to  the  organism  all  three  classes  of  food-stufls  are 
valuable  in  proportion  to  their  heat  equivalents,  and  it  is  often  a  matter  of 
indifference  whether  the  main  bulk  of  the  energy  required  is  supplied  at 
the  expense  of  fat  or  at  the  expense  of  carbohydrate.  The  proteins  however 
form  the  most  important  constituent  of  living  protoplasm.  On  this  account 
protein  must  always  be  present  in  the  food  to  supply  the  material  necessary 
for  building  up  new  protoplasm  in  the  growing  animal  and  for  replacing 
the  waste  of  living  material  which  is  taking  place  in  the  discharge  of  its 
normal  functions.  Regarding  the  complexity  of  reaction  presented  by  living 
protoplasm  as  determined  in  the  first  instance  by  the  chemical  and  physical 
complexity  of  this  material  itself,  we  should  expect  to  find  that  the  proteins 
forming  its  main  constituents  would  themselves  partake  of  some  of  this 
quality.  The  carbohydrates  and  fats,  although  in  many  cases  made  up  of 
huge  molecules,  are  nevertheless  built  up  on  a  very  simple  type.  Starch, 
for  instance,  with  a  molecular  weight  of  over  30,000,  is  formed  simply  by  the 
polymerisation  of  glucose  molecules.  The  ordinary  fats,  stearin  and 
palmitin,  consist  of  fatty  acids  with  long  straight  chains  of  CH2  groups 
combined  with  the  glyceryl  radical.  Their  molecular  weight  is  very  large, 
but  their  molecules  are  simple  in  structure.  When  however  we  break  up  a 
protein  molecule  we  meet  with  a  great  number  of  subsidiary  groups,  the 
presence  of  which  is  essential  to  the  making  of  a  nutritive  protein. 

Owing  to  this  complexity  of  structure  it  is  not  easy  to  give  a  simple 
definition  in  chemical  terms  of  what  we  mean  by  the  term  '  protein.'  It  is 
necessary  rather  to  describe  certain  of  the  qualities  presented  by  this  group, 
the  possession  of  which  we  regard  as  essential  to  the  conception  of  a  protein. 

Elementary  Composition.  All  proteins  contain  oxygen,  hydrogen,  nitro- 
gen, carbon,  and  sulphur.  The  proportion  of  these  elements  in  the  various 
proteins  may  be  represented  as  follows  : 

C   50 "6-54 "5  per  cent. 
H    6-5-  7-3    „       „ 
N  150-176    „       „ 
S    0-3-   22    „       ,. 
O  21-5-23-5    „      „ 

Nearly  all  the  proteins  contain  a  small  trace  of  phosphorus  varying  from 
0'i  to  0'8  per  cent.  It  is  doubtful  however  how  far  this  phosphorus  forms 
an  integral  part  of  the  protein  molecule. 

71 


72  PHYSIOLOGY 

IJ/n/sical  Characters.  The  proteins  are  amorphous  indiffusible  substances 
belonging  to  the  class  of  bodies  known  as  colloids.  Most  of  them  are  soluble 
either  in  water,  weak  salt  solutions,  or  in  dilute  acids  or  alkalies.  They  are 
inert  bodies  and  tasteless.  Although  they  form  compounds  with  various 
metallic  salts,  acids,  or  alkalies,  these  compounds  are  but  ill  defined,  and  the 
relative  proportions  of  the  ingredients  vary  according  to  the  conditions  under 
which  the  compound  was  formed.  As  is  the  case  with  most  colloids  when 
in  solution  or  pseudo-solution,  they  can  be  brought  into  an  insoluble  form 
by  various  simple  agencies,  such  as  shaking,  change  of  temperature,  altera- 
tion of  reaction,  or  addition  of  neutral  salts.  Coagulation  by  heat  forms  a 
distinguishing  feature  of  a  number  of  members  of  this  class,  which  are  there- 
fore spoken  of  as  '  coagulable  proteins.'  For  instance,  white  of  egg  is  a 
solution  of  different  proteins.  On  diluting  it  with  weak  salt  solution  no 
precipitation  takes  place.  If  however  the  solution  be  heated  to  about  80°  C. 
a  precipitate  of  coagulated  protein  is  formed.  If  a  strong  solution  be  boiled 
the  whole  fluid  sets  to  a  solid  white  mass  (hydrogel).  This  change  is  irrever- 
sible, i.e.  it  is  not  possible  by  lowering  the  temperature  to  bring  the  white  of 
egg  again  into  solution,  and  many  properties  of  the  protein  have  been  changed 
in  the  act  of  coagulation.  With  certain  proteins  and  their  allies  the  coagula- 
tion on  change  of  temperature  is  a  reversible  process.  Thus  an  alkaline 
solution  of  caseinogen,  the  chief  protein  of  milk,  if  treated  with  a  little  cal- 
cium chloride  and  heated,  undergoes  coagulation  and  sets  into  a  jelly,  but  on 
cooling  the  mixture  the  coagulum  once  more  enters  into  solution.  Ordinary 
gelatin,  which  is  closely  allied  to  the  proteins,  with  water  forms  a  solid  jelly 
below  20°  C,  and  a  fluid  solution  above  this  temperature. 

If  a  protein  be  heated  in  a  current  of  air  or  oxygen  it  undergoes  com- 
bustion. In  all  cases  a  certain  amount  of  incombustible  material  is  left, 
consisting  of  inorganic  salts  which  were  closely  attached  to  the  protein 
molecule.  If  a  solution  of  protein  be  subjected  to  long-continued  dialysis, 
the  proportion  of  ash  may  be  diminished  very  largely,  but  in  no  case  has 
any  experimenter  succeeded  in  obtaining  a  preparation  of  protein  absolutely 
ash-free.  On  this  account  it  has  been  thought  that  the  salts  of  the  ash  must 
be  in  chemical  combination  with  the  protein  ;  but  having  regard  to  the 
physical  character  of  colloidal  solutions,  which  we  shall  study  in  the  next 
chapter,  and  the  power  of  adsorption  of  substances  possessed  by  such  solu- 
tions, there  is  no  need  to  regard  these  salts  as  essential  constituents  of  the 
protein. 

Crystallisation  of  Proteins.  Although  the  indiffusibility  of  protein  solutions  differen- 
tiates them  from  the  crystalloid  substances  such  as  sugar  or  sodium  chloride,  under 
certain  conditions  it  is  possible  to  obtain  crystals  consisting,  largely  at  any  rate,  of 
proteins.  Thus  in  the  seeds  of  certain  plants,  e.g.  hemp  seeds,  Brazil  nut,  pumpkin 
and  castor-oil  seeds,  the  so-called  aleurone  crystals  may  be  seen  under  the  microscope 
enclosed  in  the  protoplasm  of  the  cells.  These  crystals  consist  of  proteins  belonging  to 
the  class  of  globulins.  By  chemical  means  they  can  be  separated  from  the  surrounding 
tissues  and,  after  washing,  dissolved  in  a  solution  of  magnesia.  Drechsel  showed  that 
on  dialysing  such  a  solution  against  alcohol,  the  fluid  undergoes  gradual  concentration, 
and  crystalline  granules  of  the  magnesia  compound  of  the  protein  separate  out.     These 


THE   PROTEINS  73 

crystals  contain  1-4  p.c.  MgO.  A  better  method  of  obtaining  such  crystals  has  been 
devised  by  Osborne.  The  ground  seeds  are  extracted  with  10  per  cent,  sodium  chloride 
solution,  and  filtered.  The  filtrate  is  diluted  with  water  heated  to  50°  or  60°  C.  until  a 
slight  turbidity  forms.  After  warming  the  diluted  solution  until  this  turbidity  dis- 
appears, and  then  allowing  it  to  cool  slowly,  the  protein  separates  in  well-developed 
crystals.  It  is  possible  also  to  obtain  crystals  of  animal  proteins.  Haemoglobin,  the 
oxygen -carrying  protein  of  the  red  blood  corpuscles,  can  be  made  to  crystallise  with 
extreme  ease.  With  some  animals,  such  as  the  rat,  it  is  only  necessary  to  bring  the 
haemoglobin  into  solution,  by  the  addition  of  a  little  distilled  water  and  ether  to  the 
blood,  to  cause  the  crystallisation  of  the  liberated  haemoglobin. 

Egg  albumin  and  serum  albumin  may  also  be  crystallised  with  ease  by  a  method 
devised  by  Hofmeister  and  improved  by  Hopkins.  If,  for  instance,  we  wish  to  crystallise 
egg  albumin,  white  of  eggs  is  treated  with  an  equal  bulk  of  saturated  solution  of  ammo- 
nium sulphate  in  order  to  precipitate  the  globulin.  It  is  then  filtered,  and  the  filtrate 
is  treated  with  saturated  ammonium  solution  until  a  slight  permanent  precipitate 
is  produced.  This  precipitate  is  then  just  redissolved  by  the  cautious  addition  of  water, 
and  dilute  acetic  acid  (10  per  cent.)  is  added  drop  by  drop  until  a  slight  precipitate  is 
produced.  The  flask  is  now  corked  and  allowed  to  stand  for  twenty-four  hours,  when 
the  precipitate,  which  will  have  increased  in  quantity,  will  be  found  to  consist  entirely 
of  acicular  crystals.  A  similar  method  may  be  used  for  seruni  albumin.  In  each  case 
the  crystals  contain  a  considerable  proportion  of  ammonium  sulphate.  This  may  be 
replaced  by  sodium  chloride  by  washing  the  crystals  with  a  saturated  solution  of 
this  salt.  By  absolute  alcohol  the  crystals  may  be  coagulated  and  may  be  then  washed 
practically  free  from  salt,  but  it  is  not  possible  to  obtain  crystals  of  coagulable  protein 
free  from  the  presence  of  some  salt. 

Although  by  repeated  crystallisation  of  egg  albumin  a  product  may  be  obtained 
which  is  absolutely  constant  in  both  its  physical  and  chemical  characters,  we  cannot 
ascribe  to  crystallisation  the  same  importance  in  securing  purity  and  homogeneity  of 
the  substance  that  we  can  when  we  are  dealing  with  inorganic  salts.  This  is  due  to  the 
fact  that  these  crystals  take  up  other  colloids  with  great  ease.  When  haemoglobin,  for 
instance,  is  crystallised  from  blood,  the  first  crop  of  crystals,  although  thoroughly 
washed  from  their  mother  liquor,  always  contain  a  considerable  proportion  of  serum 
albumin.  Indeed,  the  presence  of  colloidal  material  seems  to  render  the  production 
of  the  so-called  mixed  crystals  much  more  easy.  Thus  Schultz  has  shown  that  in 
urine  mixed  inorganic  crystals  can  be  obtained.  Human  urine  is  allowed  to  stand 
twenty-four  to  forty-eight  hours  with  dicalcium  phosphate  and  then  filtered.  On 
allowing  the  filtrate  to  evaporate  slowly,  a  crystalline  precipitate  is  produced  consist- 
ing of  whetstone-shaped  crystals  which  are  doubly  refracting.  On  treating  these 
crystals  with  dilute  acetic  acid  this  acid  extracts  calcium  phosphate  from  the  crystals. 
The  original  shape  of  the  crystals  is  however  retained.  The  only  difference  under 
the  microscope  consists  in  the  fact  that  they  have  now  lost  their  doubly  refracting 
power  on  polarised  light.  They  consisted  of  a  mixture  of  calcium  sulphate  and  calcium 
phosphate  from  which,  on  treatment  with  acid,  only  the  calcium  phosphate  was  dis- 
solved out. 

The  Molecular  Weight  of  Proteins.  We  may  arrive  at  an  approximate  idea 
of  the  minimum  size  of  the  protein  molecule  in  various  ways,  though  in  all 
cases  our  calculations  are  apt  to  be  vitiated  by  the  difficulty  of  obtaining  a 
preparation  which  is  homogeneous,  i.e.  chemically  pure,  and  by  the  ease 
with  which  molecules  of  the  size  which  we  must  assume  for  proteins  form 
adsorption  combinations  in  varying  proportions  with  other  substances. 
If  we  assume  that  each  molecule  of  the  respective  protein  contains  only  one 
atom  of  sulphur,  we  can  calculate  its  molecular  weight.  It  is  evident  that 
the  protein  which  contains  1  per  cent,  of  sulphur  will  have  a  molecular  weight 


74  PHYSIOLOGY 

of  3200.     In  this  way  the  following  molecular  weights  have  been  arrived  at 
(Abderhalden)  : 

Sulphur  per  cent.  Molecular  weight. 

Edestin 0-87             . .  3680 

Oxyhemoglobin         .         .          .           0  43             . .  7440 

(horse) 

Serum  albumin           .          .         .            1-89             ..  1700 

(horse) 

Egg  albumin     .         .          .         .            1-30             . .  2460 

Globulin 1-38             ..  2320 

The  greater  part  at  any  rate  of  the  sulphur  in  the  protein  molecule  occurs 
as  a  constituent  of  a  substance,  cystine,  each  molecule  of  which  contains  two 
atoms  of  sulphur.  Each  molecule  of  protein  must  also  contain  two  atoms  of 
sulphur,  and  we  must  regard  double  the  molecular  weight  given  in  this  Table 
as  the  minimum  molecular  weights  of  these  various  proteins.  Some  idea  of 
the  molecular  complexity  represented  by  these  weights  may  be  gained  by 
writing  out  the  empirical  formula?  of  the  various  proteins,  e.g., 

Egg  albumin  .......     C204H322N52O66S2 

Protein  in  haemoglobin  (from  horse)  .         .     C680H10!(fiN210(),,1S  , 

Protein  in  haemoglobin  (from  dog)  .  .  .  C,25H117iNic,40214S„ 
Crystallised  globulin  (from  pumpkin  seeds)  .  C202H481N200S3S8 
With  some  proteins  we  may  make  use  of  other  elements  to  arrive  at  an 
idea  of  the  approximate  molecular  weight.  Thus  oxyhemoglobin  contains 
between  0'4  and  0'5  per  cent.  iron.  If  we  assume  that  each  molecule  of 
oxyhemoglobin  contains  one  atom  of  iron,  its  molecular  weight  must  be 
from  11,200  to  14,000. 

Attempts  have  been  made  to  solve  the  same  question  by  studying  the  compounds 
of  proteins  with  inorganic  salts  or  oxides.  Thus,  the  crystals  of  globulin  from  pumpkin 
seeds  prepared  with  magnesia  contain  1-4  per  cent.  MgO.  Assuming  that  one  mole- 
cule of  protein  has  combined  with  one  molecule  MgO,  the  molecular  weight  of  the 
protein  must  be  about  2800. 

(If  x  be  the  molecular  weight 

x  _  100  -  1-4 
40  hi 

. •  .  x  =  2817) 
Harnack  has  shown  that  many  proteins  are  precipitated  from  their  solutions  as 
copper  compounds  by  the  addition  of  copper  sulphate.  Harnack  found  that  this  pre- 
cipitate of  copper  contained  either  1-34  —  1-37  Cu.  or  2-48  —  2-73  per  cent.  Cu.  The 
smaller  percentage  would  correspond  to  a  molecular  weight  of  4700,  while  the  second 
number  might  be  accounted  for  on  the  hypothesis  that  each  molecule  of  protein  was 
combined  with  two  atoms  of  copper.  Similar  attempts  have  been  made  by  determining 
the  amount  of  acid  or  alkali  necessary  to  keep  certain  types  of  protein  in  solution. 
We  shall  see  later  on  however  that  the  amounts  vary  largely  with  the  physical  con- 
dition and  previous  history  of  the  colloidal  substance.  We  are  dealing  here  not  with 
compounds  in  the  strict  chemical  sense  of  the  term,  but  with  adsorption  compounds, 
where  the  quantities  taken  up  are  determined  not  only  by  the  chemical  nature  of  the 
protein  itself,  but  by  the  state  of  aggregation  of  its  molecules.  It  is  therefore  impossible 
to  lay  any  great  stress  on  the  determinations  of  the  molecular  weight  which  have  been 
effected  in  this  way. 


THE   PROTEINS  75 

Some  clue  to  the  size  of  the  protein  molecule  is  afforded  by  determinations 
of  the  osmotic  pressure  or  molecular  concentration  of  their  solutions  by 
physical  methods.  When  we  determine  the  freezing-point  or  boiling-point 
of  protein  solutions,  the  depression  of  freezing-point,  or  elevation  of  boiling- 
point  is  so  small  that  it  falls  within  the  limit  of  experimental  error  or  is 
no  greater  than  can  be  accounted  for  by  the  inorganic  salts  present  in  the 
solution.  Since  however  colloidal  membranes,  such  as  films  of  gelatin 
or  vegetable  parchment,  are  impervious  to  proteins,  we  can  directly  deter- 
mine the  osmotic  pressure  of  their  solutions.  In  many  cases  no  osmotic 
pressure  whatever  is  found.  In  other  cases,  e.g.  egg  albumin  or  serum,  the 
colloidal  constituents  of  these  solutions  are  found  to  give  an  osmotic  pressure 
of  such  a  height  that  1  per  cent,  protein  corresponds  to  about  4  mm.  Hg. 
pressure.  Such  an  osmotic  pressure  would  indicate  a  molecular  weight  for 
the  serum  proteins  of  about  30,C(  0.  A  determination  of  the  osmotic  pressure 
of  haemoglobin  by  Hiifner  gave  a  molecular  weight  about  16,000.  These 
results  however  must  be  received  with  caution,  since  we  are  not,  justified 
in  applying  to  these  gigantic  molecules  data  derived  from  a  study  of  smaller 
molecules  such  as  salt  or  sugar.  Even  if  we  accept  these  determinations  of 
osmotic  pressure  as  indicating  the  molecular  weights  I  have  just  quoted,  it  is 
evident  that  a  very  slight  degree  of  aggregation  of  the  molecules  into  larger 
complexes  will  bring  the  osmotic  pressure  below  the  point  at  which  it  is 
measurable,  and  would  transform  the  solution  into  a  suspension  of  particles 
in  which  one  could  not  expect  to  find  any  osmotic  pressure  whatsoever. 

THE  STRUCTURE  OF  THE  PROTEIN  MOLECULE. 

We  can  arrive  at  some  idea  of  the  manner  in  which  the  protein  molecule 
is  built  up  only  by  breaking  it  down  bit  by  bit,  employing  methods  which, 
while  resolving  the  large  molecule  into  its  proximate  constituents,  will  not 
act  too  forcibly  in  changing  the  whole  arrangements  of  these  constituents. 
The  relation  of  the  starches  or  polysaccharides  to  the  sugars  was  found  by 
studying  the  hydrolysis  of  the  former,  and  it  is  by  the  hydrolysis  of  the  pro- 
teins that  we  have  arrived  at  most  of  our  present  knowledge  of  their  con- 
stitution. Contributory  evidence  may  also  be  gained  by  the  use  of  oxidising 
agents  or  by  employing  the  refined  methods  of  analysis  possessed  by  certain 
liviug  organisms — bacteria,  by  which  means  we  can  effect  limited  oxidations 
or  reductions  or  can  replace  an  NH,  group  by  H,  or  a  COOH  group 
by  H. 

ACID  HYDROLYSIS  OF  PROTEINS.  For  this  purpose  rather  stronger 
acids  are  used  than  for  the  hydrolysis  of  starch.  The  protein  is  heated  for 
twenty-four  hours  in  a  flask  fitted  with  a  reflux  condenser  either  with  con- 
centrated hydrochloric  acid  or  with  a  25  per  cent,  sulphuric  acid.  Hydro- 
chloric acid  was  first  made  use  of  by  Hlasiwetz  and  Habermann,  who  added  a 
certain  amount  of  stannous  chloride  to  the  mixture  in  order  to  prevent  any 
oxidation  taking  place.  We  obtain  in  this  way  an  acid  fluid  containing  an 
extremely  complex  mixture  of  various  substances,  all  of  which  belong  to  the 


76  PHYSIOLOGY 

class  of  amino-acids,  and  must  be  regarded  as  the  proximate  constituents  of 
the  protein  molecule. 

A  similar  hydrolytic  change  may  be  effected  by  the  use  of  digestive 
ferments  obtained  either  from  the  alimentary  canal  of  higher  vertebrates  or 
from  certain  plants.  Thus  we  may  use  pepsin,  the  active  constituent  of  the 
gastric  juice,  trypsin,  the  proteolytic  ferment  secreted  by  the  pancreas, 
papain,  or  other  vegetable  ferments  obtained  from  papaya,  from  pineapple 
juice,  and  so  on.  These  ferments  are  all  milder  in  their  action  than  the 
strong  acids.  Pepsin  for  instance  effects  only  a  partial  decomposition  of  the 
protein  molecule.  Its  action  results  in  the  formation  of  substances  which 
still  present  all  the  protein  reactions  and  are  classified  as  hydra  ted  proteins 
or  as  proteoses  and  peptones.  Trypsin  carries  the  protein  a  stage  further 
and  gives  a  mixture  of  amino-acids.  Certain  groups  however  of  the  protein 
molecule  present  a  considerable  resistance  to  the  action  of  trypsin,  so  that 
when  its  action  is  complete  these  groups  are  still  found  not  yet  broken  down 
into  their  constituent  amino-acids. 

The  putrefactive  processes  determined  by  the  process  of  bacteria  in 
solutions  of  proteins  are  somewhat  too  complicated  in  their  results  to  throw 
much  illumination  on  the  structure  of  the  protein  molecule  itself.  This 
method  is  however  of  extreme  value  when  it  is  applied  to  isolated  con- 
stituents of  the  proteins.  Under  the  action  of  these  bacteria  we  may  have  a 
process  of  deamination  which  may  be  accompanied  by  simple  hydrolysis  or 
by  reduction.  In  the  former  case  an  ammo-acid  may  be  converted  into 
an  oxyacid,  in  the  latter  case  into  a  fatty  acid. 

Thus  tyrosine  under  the  action  of  bacteria  of  putrefaction  may  split  up 
into  ammonia  and  oxyphenyl  propionic  acid. 

OH.C6H4.CH2.CHNH2.COOH  +  H   = 
HO.C6H4.CH2.CH2.COOH  +  NH3 

Under  the  action  of  yeasts  an  amine  may  become  an  alcohol. 

C5Hn.NH2  +  H.,0  -  CsHu.OH  +  NH3 

(amylamine)  (amylalcohol) 

On  the  other  hand,  the  effect  of  the  bacteria  may  be  to  split  off  carbon 
dioxide   from  the  amino-acids.     Thus,  the  diamino-acid,  lysine, 

CHJSTH,  CHJSTH., 

I    "  I 

CH„  CHS 

I  I 

CH,  becomes  CH2  pentamethylene*  diamine. 

I       '  I 

CH2  CH2 

I  I 

CH.NH2  CH2NH2 

I 
COOH 

Tyrosine  becomes  p.    oxyphenylethylamine,   a  substance  having  marked 


THE  PROTEINS  77 

physiological  effects,  and  an  important  constituent  of  ergot.  Phenylalanine 
C,H«.CHt.CH.NH,.COOH,  becomes  phenylethylamine  C6H5.CH2.CH2.NH2. 
These  reactions  are  therefore  of  value  in  determining  the  exact  grouping  of  the 
atoms  in  the  more  complex  of  the  proximate  constituents  of  the  proteins. 

Since  all  the  known  disintegration  products  of  the  proteins  belong  to  the 
class  of  amino-acidSj  it  may  be  of  value  to  point  out  some  of  the  distinguishing 
features  of  this  class  of  bodies. 

PROPERTIES  OF  AMINO-ACIDS.  An  amino-acid  is  derived  from  an 
organic  acid  by  the  replacing  of  one  atom  of  hydrogen  by  the  amino  group 
NH2.     Thus  from  the  acids, 

acetic  acid  propionic  acirl 

CH3  CH3 

I  I 

COOH  CH2 

I 
COOH 

we  may  obtain  the  mono-ammo-acids, 

amino-acetic  acid         alanine  or  et-amino-propionic  acid 
CH2NH2  CH3 

I  I 

COOH  CH.NH2 

I 
COOH 

It  will  be  noticed  that  in  the  fatty  acids  with  more  than  two  atoms  of  carbon 
the  position  of  the  NH2  group  may  be  varied.  Thus,  instead  of  alanine 
we  may  have  another  amino-propionic  acid,  namely  : 

CH2NH2 

I 

CH2 

I 

COOH 

This  acid  would  be  spoken  of  as  ^-amino-propionic  acid,  alanine  being 
a-amino- propionic  acid.  This  nomenclature  is  always  used  to  distinguish 
the  position  of  the  NH2  group,  so  that  we  may  have  mono-amino-acids  a, 
/?,  y,  d,  e  .  .  .  and  so  on.  Practically  all  the  amino-acids  which  occur  as 
constituents  of  the  protoplasmic  molecule  belong  to  the  a  group. 

On  inspection  of  the  formula  of  glycine  it  is  evident  that  only  one  isomer 
of  this  body  is  possible.  In  alanine,  however,  the  carbon  atom  to  which 
NH2  is  attached,  is  asymmetric,  since  its  four  combining  affinities  are  each 
attached  to  different  groups.     Thus  : 

C 

I 
H— C— NH„ 


In  this  case,  therefore,  there  is  a  possibility  of  stereoisomerism,  and  alanine 
must  have  an  influence  on  polarised  light.     If  the  compound 


78  PHYSIOLOGY 

CH, 

I 
HCNH2 
] 
COOH 

is  dextro-rotatory,  then  its  stereoisomer 

CH3 
I 
HjNCB 
I 
COOH 

will  be  laevo-rotatory,  and  it  will  be  possible  to  obtain  ;i  racemic  modification 

without  any  influence  on  polarised  light  by  mixing  equal  molecules  of  these 

two  isomeric  forms.     Ail  the  amino-acids  derived  from  proteins  are  optically 

active,  whereas  those  obtained  by  synthesis  are  inactive,  and  special  means 

have  to  be  devised  in  order  to  obtain  from  the  artificially  formed  racemic 

amino-acid  either  the  d-  or  Z-amino-acid. 

If  more  than  one  hydrogen  atom  in  an  organic  acid  be  replaced  by  NH2 

we  obtain  diamine-  and  triamino-acids.      Thus  ornithine,  obtained  by  the 

splitting  up  of  arginine,  one  of  the  commonest  disintegration  products  of 

protein,  is  a-(5:diamino-valerianic  acid. 

CH,NH„ 

I 
CH, 


CH.NH2 

I 
(dull 

The  presence  in  the  amino-acids  of  the  basic  radical  NH2  and  of  the  acid  group 
COOH  lends  to  these  bodies  a  double  character.  In  themselves  devoid  of  strong 
chemical  qualities,  possessing  neither  acid  nor  alkaline  reaction,  they  are  able  in  the 
presence  of  strong  acids  or  bases  to  act  either  as  base  or  acid.  When  in  solution  by 
themselves  it  is  possible  that  there  is  an  actual  closing  of  the  ring  by  a  soluble  union 
between  the  NH2  group  and  the  COOH  group,  so  that  e.g.  the  formula  of  glycine 
may  be  : 

CH2— NH3 

I  I 

CO  — o 

When  such  a  neutral  compound  is  treated  with  acid  this  bond  is  loosed  and  we  have 
the  salt  of  the  amino-acid.  Thus,  with  hydrochloric  acid,  glycine  forms  glycine 
hydrochlorate  : 

CHijNH^Cl 

I 
COOH 

a  salt  which  still  possesses  an  acid  group  and  which  is  therefore  capable  of  combining 
with  ethyl  to  form  the  hydrochlorate  of  the  ester  of  the  amino-acid.     Thus  : 

CH2.NH,HC1 
I 

COOCoHs 


THE   PROTEINS  79 

With  liases  the  amino-acids  form  salt-like  compounds  such  as  potassium  amino-  acetate  : 

CH,NH, 

I 
COOK 

Amino-acids  also  combine  with  one  another.  This  power  of  combination  much  increases 
the  difficulty  of  separating  the  constituents  from  a  mixture  of  amino-acids.  Amino- 
acids,  which  singly  are  extremely  insoluble,  are  readily  soluble  when  in  the  presence 
of  other  amino-acids. 

On  account  of  the  dual  nature  of  the  ammo-acid  molecule,  these  substances  act 
as  feeble  conductors  of  the  electric  current,  i.e.  as  electrolytes.  The  charge  carried 
by  an  amino -acid  and  its  ionisation  depends  upon  the  conditions  in  which  it  is  placed. 
Since  it  may  act  either  as  the  cation  or  the  anion,  it  is  spoken  oii  as  an  ampJioterir, 
electrolyte. 

One  reaction  of  the  amino-acids  is  of  special  interest  in  connection  with  the  respira- 
tory functions  of  the  body,  namely,  the  formation  of  carbamino-acids.  If  a  stream  of 
carbon  dioxide  he  passed  into  a  mixture  of  an  amino-acid,  e.g.  glycine,  with  lime,  the 
carbon  dioxide  is  taken  up.  On  filtering  the  mixture  a  clear  liquid  passes  through  which 
gradually  in  course  of  time  deposits  a  precipitate  of  calcium  carbonate.  The  filtrate 
first  obtained  contains  a  compound  of  calcium,  calcium  glycine  carbonate.  The 
formula  is   as  follows  : 

CH..NH 


> 


;o.co 

COO  Ca 

METHODS  OF  SEPARATING  AMINO-ACIDS.  By  the  hydrolysis  of  protein 
!>\  means  of  acid  or  of  trypsin,  we  obtain  a  complex  mixture  of  amino-acids.  From 
this  mixture  certain  amino-acids  are  separated  with  ease.  Thus  tyrosine,  which  is  ex- 
tremely insoluble,  crystallises  out  on  concentrating  the  fluid,  and  further  concentration 
leads  to  the  separation  of  leucine.  The  other  acids,  which  keep  each  other  mutually 
in  solution,  are  however  very  difficult  to  isolate.  We  owe  to  Fischer  the  first  general 
method  for  their  separation.     We  may  take  one  experiment  as  an  example. 

Five  hundred  grammes  of  casein  are  heated  for  some  hours  under  a  reflux  con- 
denser with  li  litres  of  strong  hydrochloric  acid.  The  liquid  is  then  saturated  with 
gaseous  hydrochloric  acid  and  allowed  to  stand  for  three  days  in  the  ice-chest.  Crystals 
of  hydroehlorate  of  glutamic  acid  separate  out.  The  filtrate  from  these  crystals  is 
evaporated  at  405  (_'.  under  diminished  pressure  to  a  syrupy  consistence,  and  is  then 
dissolved  in  1J  litres  of  absolute  alcohol.  Hydrochloric  acid  is  then  passed  into  the 
solution  to  complete  saturation,  the  mixture  being  warmed  for  a  short  time  on  the 
water  bath,  and  the  mixture  is  once  more  evaporated  to  a  syrupy  consistence.  By  this 
treatment  all  the  amino-acids  have  been  converted  into  the  hydrochlorates  of  their 
esters,  e.g.  : 

(HoNHoHCl  C2H4NH,HC1 

I  I 

COOC,H5  COOC2H6    &c. 

From  the  hydrochlorates  the  esters  are  set  free'  by  the  addition  of  potassium  carbonate, 
the  mixture  being  cooled  in  a  freezing  mixture.  By  this  means  the  esters  of  aspartic 
and  glutamic  acids  are  separated  and  are  extracted  by  shaking  with  ether.  The 
remaining  esters  are  then  liberated  by  the  addition  of  33  per  cent,  caustic  soda  together 
with  potassium  carbonate,  and  are  again  extracted  by  ether.  The  combined  ethereal 
solutions  are  dried  by  standing  over  fused  sulphate  of  soda  and  then  evaporated,  when 
a  residue  containing  the  free  esters  is  obtained.  These  esters  are  then  separated  by 
fractional  distillation  under  a  very  low  pressure  obtained  by  means  of  the  Fleuss 
pump,  the  second  receiver  of  the  apparatus  being  cooled  in  liquid  air.  The  various 
fractions  of  aminoesters  obtained  in  this  way  are  hydrolysed — the  lower  fractions  by 


80  PHYSIOLOGY 

boiling  for  some  hours  with  water,  the  higher  fractions  by  boiling  with  baryta.  The 
acids  obtained  by  the  hydrolysis  can  then  be  further  purified  by  means  of  fractional 
crystallisation. 

THE  DISINTEGRATION  PRODUCTS  OF  THE  PROTEINS. 

By  the  methods  just  described  the  following  substances  have  been 
isolated  from  proteins : 

A.     FATTY  SERIES 

(1)  Mono-amino-acids  (Monobasic) 

GLYCINE  or  GLYCOCOLL  This,  the  simplest  member  of  the  group,  is 
amino-acetic  acid : 

CHjNHj 

I 
COOH 

It  occurs  in  considerable  quantities  among  the  disintegration  products  of 
gelatin  and  to  a  slight  extent  among  those  derived  from  certain  of  the  pro- 
teins.    Like  the  other  a-amino-acids,  it  has  a  sweetish  taste,  whence  its  name 
was  derived  (yXvxocr  =  sweet,  icoXkr)  ==  glue). 
ALANINE  is  a-amino- propionic  acid : 
CH3 

I 
CH.NH, 

I 
COOH 

It  is  optically  active,  the  alanine  derived  from  proteins  being  dextro- 
rotatory. 

Closely  allied  to  alanine  is  the  amino-acid  SERINE,  which  was  first 
obtained  by  the  hydrolysis  of  silk  and  has  since  been  found  as  a  constituent 
of  a  large  number  of  proteins.     Its  formula  is  : 

CH2OH 

I 
CH.NH2 

I 
COOH 

i.e.  it  is  amino-oxypropionic  acid.  Its  special  interest  lies  in  the  fact  that 
it  was  one  of  the  first  of  the  amino-oxyacids  to  be  isolated,  and  it  is  possible 
in  these  acids  that  we  must  seek  the  intermediate  stages  between  carbo- 
hydrates and  proteins. 

AMINO-VALERIANIC  ACID  has  the  formula 
CH3  CH3 

V 

CH 

I 

CH.NH2 
I 
COOH 
It  occurs  only  in  small  quantities  in  the  protein  molecule. 


THE  PROTEINS  81 

LEUCINE,  one  of  the  oldest  known  members  of  the  group  of  amino-acids, 
is  obtained  in  large  quantities  from  the  disintegration  of  nearly  all  the  animal 
proteins,  of  which  in  some  cases  it  may  form  as  much  as  20  per  cent.  It 
has  the  formula 

CH3  CH3 

\y 

CH 

I 
CH2 

I 
CH.NH2 

I 
COOH 

i.e.  it  is  amino-isobutyl  acetic  acid.  On  evaporating  a  tryptic  digest  of 
protein,  impure  leucine  crystallises  out  in  the  form  of  imperfect  crystals, 
the  so-called  '  leucine  cones.' 

Lately  another  isomer  of  leucine  has  been  discovered,  namely,  a-amino-methyl 
ethyl  propionic  acid.     This  is  called  isoleucine. 

(2)  Mono-amino  Derivatives  of  Dibasic  Acids 

Of  these  two  are  known,  namely,  aspartic  and  glutamic  acids. 

ASPARTIC  ACID  is  a-amino-succinic  acid  : 

COOH 

I 
CH.NH2 

I 
CH2! 

I 

COOH 

and  glutamic  acid  is  the  next  homologue,  namely,  a-amino-glutaric  acid  : 

COOH 

I 
CH.NH2 

I 
CH2 

I 

CH2 
I 
COOH 

Owing  to  the  possession  of  two  carboxyl  groups  these  amino-acids  have  a 
much  more  pronounced  acid  character  than  is  the  case  with  the  other 
members  of  the  group  which  we  have  been  studying. 

Aspartic  acid  was  first  found  in  the  shoots  of  asparagus  in  the  form  of  the  amide, 
asparagine : 

mull 

I 
CHNH2 

I 
CH2 

I 
CONH, 


82  PHYSIOLOGY 

This  substance  is  very  widely  distributed  throughout  the  vegetable  kingdom  and 
is  present  in  seedlings  in  very  large  quantities,  as  much  as  25  per  cent,  of  the  dried 
weight.  In  plants  it  apparently  serves  either  as  a  reserve  material  or  as  the  form 
in  which  the  greater  part  of  the  nitrogen  is  conveyed  from  the  reserve  organs  to  be 
Imilt   up  into  the  protoplasm  of  the  growing  parts  of  the  plant. 

(3)  Diamino-ccids 
Of  these  two  are  known,  namely,  lysine  and  ornithine.     Owing  to  the 
presence  of  two  NH2  groups  in  their  molecule,  they  possess  marked  basic 
characters,  and  are  precipitated  from  the  acid  solution  obtained  by  the 
hydrolysis  of  proteins  on  adding  phosphotungstic  acid.     Since  lysine,  argi- 
nine,  and  histidine  (another  amino-acid  which  will  be  described  later)  all 
contain  six  carbon  atoms  in  their  molecule,  these  three  bodies  were  classed 
together  by  Kossel  as  the  '  hexone  '  bases.     Apart  however  from  their  high 
content  in  nitrogen,  the  chemical  resemblance  between  these  bodies  is  no 
closer  than  between  them  and  the  other  members  of  the  amino-acid  series. 
Another  body  isolated  by  Fischer  in  small  quantities  is  supposed  to 
belong  to  this  class  and  to  have  the  composition  diamino-trioxydodecoic  acid. 
LYSINE  CgH14N202  is  a-£-diamino-caproic  acid  having  the  formula 
CH.,NH, 
I 

(CH2)3 
I 
CH.NH2 

I 
C'OOH 

ARGININE,  which  was  first  discovered  in  plants  (the  cotyledons  of 
lupins),  is  not  a  simple  amino-acid,  but  a  compound  of  an  amino-acid  with 
guanidin.  If  boiled  with  baryta  water  it  splits  up  into  urea  and  a  substance 
reacting  as  a  base  which  was  called  ornithine.* 

ORNITHINE,  diamino-valerianic  acid,  has  the  formula 
CH2NH2 
I 
(CH2)2 

C'H.NH, 
I 
C'OOH 

The  constitution  of  arginine  is  analogous  to  that  of  creatine,  one  of  the 
most  abundant  nitrogenous  extractives  of  muscle,  which  has  the  formula 
HN  =  C   — N(CH3)CH2COOH 
I 
H,N 

It  is  methyl  guanidine  acetic  acid.'  On  boiling  creatine  with  baryta  water 
it  takes  up  a  molecule  of  water  and  splits  in  the  situation  of  the  dotted  line 
in  the  formula,  giving 

*  Ornithine  had  been  previously  discovered  in  the  urine  of  fowls  after  the  admini- 
stration of  benzoic  acid,  in  the  form  of  an  acid  known  as  ornithuric  acid. 


THE   PROTEINS 


83 


H.,N 


Vo  (urea)  and  NH(CHs)CH2COOH  (methyl  glycine). 

H2isr 

This  latter  substance  is  known  as  sarcosine  and  is  derived  from  glycine  by 
the  replacement  of  one  atom  of  hydrogen  by  a  methyl  group  CH3. 

Arginine  has  a  similar  formula.  On  the  left-hand  side  of  the  dotted  line 
the  formula  would  be  identical  with  that  of  creatine.  On  the  right-hand 
side  the  sarcosine  group  is  replaced  by  a  diamino-acid  of  the  fatty  series, 
diainino-valerianic  acid  or  ornithine. 

DIAMINO-TRIOXYDODECOIC  acid  is,  as  its  name  implies,  a  derivative  of 
a  twelve  carbon  acid.     Its  constitutional  formula  has  not  yet  been  made  out. 

B.     AMINO-ACIDS  CONTAINING  AN  AROMATIC  NUCLEUS 

The  best  known  of  these  is  TYROSINE,  which  has  the  formula 
OH 
/\ 

',.11, 


I'lU'H.NHoCOOH 

It  is  paraoxyphenyl  a-alanine      It  is  one  of  the  first  of  the  amino-acids  to  be 

split  off  from  the  protein  molecule  under  the  influence  of  hydrolytic  agents. 

Owing  to    its     insolubility  it 

rapidly       separates     out     as 

bundles  of    fine  needle-shaped 

crystals     at    the     sides     and 

bottom  of  the  vessel. 

When  tyrosine  is  treated 
with  an  acid  solution  of 
mercuric  nitrate  containing  a 
little  nitrous  acid,  a  precipi- 
tate is  produced,  and  on 
boiling,  the  precipitate  and 
the  supernatant  fluid  assume 
a  deep  red  colour.  This  re- 
action is  given  by  all  benzene 
derivatives  in  which  one  atom 
of  hydrogen  in  the  ringis re- 
placed by  one  OH  group.  This 
is  known  as  Hoffmann's  test, 
hut  is  identical  with  Millon's  reaction,  which  is  given  by  all  proteins  con- 
taining tyrosine  in  their  molecules. 

Closely  allied  to  the  foregoing  compound  is  another  aromatic  amino-acid 
namelv.  PHENYL  ^-ALANINE  ; 


Fia.   18.     Tyrosine  crystals.     (Plim.mkh.) 


84  PHYSIOLOGY 


CH2CH.NH2COOH 
It  is  an  almost  constant  constituent  of  proteins. 

TRYPTOPHANE  was  known  long  before  it  had  been  isolated,  owing  to 
the  fact  that  with  bromine  water  it  gives  a  rose-red  colour.  It  had  long 
been  observed  that  this  substance  was  to  be  obtained  at  a  certain  stage  in  the 
digestion  of  proteins  by  pancreatic  juice,  but  nothing  was  known  about  its 
constitution  until  Hopkins  succeeded  in  isolating  it  by  precipitation  with 
mercuric  sulphate  dissolved  in  5  per  cent,  sulphuric  acid.  Cystine  is  also 
precipitated  by  this  reagent,  but  comes  down  with  a  less  concentration  of  the 
salt  than  tryptophane,  so  that  it  is  possible  to  separate  the  two  substances 
by  a  species  of  fractional  precipitation.  Tryptophane  can  be  isolated  by 
decomposing  the  mercury  salt  with  sulphuretted  hydrogen,  and  is  obtained 
in  a  crystallised  form.  On  distillation  it  gives  an  abundant  yield  of  indol  and 
skatol,  bodies  also  obtained  during  the  putrefaction  of  proteins.  Trypto- 
phane itself  is  indol  amino-propionic  acid  : 

iC.CH!!CHNHi!.COOH 


\/\/CH 
NH 

C.     AMINO-ACIDS  OF  HETEROCYCLIC  COMPOUNDS 

Three  of  the  disintegration  products  of  proteins  can  be  grouped  in  this 
class.     Two  of  them  contain  the  pyrrol  ring,  namely,  proline  and  oxyproline. 

PROLINE,  which  was  first  isolated  by  Fischer,  is  a-pyrrolidin  carboxylic 

acid  and  has  the  formula 

CH2 — CH2 

I  I 

CH2  CH.COOH 

V 

NH 
OXYPROLINE  is  the  oxy-derivative  of  this  body  and  has  the  formula 
C5H8N03,  the  exact  position  of  the  oxy-group  having  not  yet  been  deter- 
mined. Doubts  have  been  expressed  whether  the  pyrrol  group  is  present 
as  such  in  the  protein  molecule,  or  whether  proline,  for  example,  is  not 
formed  by  the  closing  of  an  open  chain  of  a  compound  belonging  to  the 
amino-acids  in  the  fatty  series.  Thus  from  an  oxy-amino-valerianic  acid 
CH2OH.CH2.CH2.CH.NH2.COOH  we  can  by  dehydration  make  the  com- 
pound CH2CH2.CH2.CH.COOH,  the  formula  of  which  will  be  seen  to  be 


NH 
identical  with  that  given  for  proline. 

The  third  member  of  this  group  contains  the  iminazol  ring 


THE   PROTEINS  85 

CH—  NH 

II  /CH 

CH W 

and  is  known  as  HISTIDINE.     Its  structural  formula  is  as  follows  : 
CH— NH  v 
II  )   CH 

.      I 

CH2.CH.NH2.COOH 

i.e.  it  is  iminazol  a-amino-propionic  acid  or  iminazol  alanine.     Since  it  occurs 

in  the  phosphotungstic  precipitate  from  the  products  of  acid  disintegration 

of  proteins  and  contains  six  carbon  atoms,  it  was  formerly  classified  with 

lysine  and  arginine  as  a  hexone  base. 

D.     SULPHUR-CONTAINING    AMINO-ACIDS 

Sulphur  forms  an  integral  part  of  the  molecule  of  all  classes  of  proteins 
except  protamines.  In  some  substances  allied  to  proteins,  such  as  keratin, 
it  may  occur  to  the  extent  of  3  per  cent.  On  boiling  proteins  with  caustic 
potash  or  soda,  a  portion  of  the  sulphur  is  split  off  to  form  a  sulphide,  which 
gives  a  black  precipitate  on  addition  of  copper  salts.  On  this  account  it  was 
formei'ty  thought  that  the  sulphur  must  be  present  in  two  forms,  the  oxidised 
and  the  unoxidised,  in  the  protein  molecule.  Recent  investigation  has 
showu  however  that  practically  the  whole  of  the  sulphur  is  present  in  the 
form  of  CYSTINE,  and  that  this  body  on  boiling  with  alkaline  solutions  gives 
up  only  a  little  more  than  half  its  content  in  sulphur. 

This  substance,  which  has  been  known  for  many  years  as  the  chief  con- 
stituent of  a  rare  form  of  urinary  calculus  and  as  occurring  in  the  urine  in 
certain  cases  of  disordered  metabolism,  is  again  a  derivative  of 'the  three- 
carbon  propionic  acid.  On  reduction  it  gives  a  body  known  as  cysteine, 
which  is  a-amino-thiopropionic  acid. 

CH,SH 

i 
CH.NH, 

I 
COOH 

Cystine  itself  is  compounded  of  two  cysteine  molecules  joined  together  by 

their  sulphur  atoms  and  has  the  formula 

CH2 — S — S — CH  * 

I  I   " 

CH.NH2         CH.NH2 

I  I 

COOH  COOH 

E.     OTHER  CONSTITUENTS   OF   THE   PROTEIN   MOLECULE 

When  we  add  together  the  total  amino-acids  obtainable  by  the  acid 
disintegration  of  any  given  protein,  a  considerable  proportion  of  the  original 
protein  remains  unaccounted  for.  This  remainder  must  have  a  greater 
content  in  hydrogen  and  oxygen  than  the  amino-acids  envmerated  above, 


86  PHYSIOLOGY 

and  it  has  been  suggested  that  among  the  missing  unascertained  con- 
stituents of  proteins  may  be  oxyamino-acids,  of  which  serine  would  form 
one  of  the  lowest  members.  The  isolation  of  such  substances  would  present 
considerable  interest,  in  that  it  would  supply  the  intermediate  stages  between 
the  constituent  groups  of  the  protein  molecule  and  the  carbohydrates,  the 
first  product  of  assimilation  by  living  organisms.  Only  one  such  intermediate 
body  has  so  far  been  isolated,  namely,  glucosamine,  an  amino-derivative  of 
glucose.  It  was  first  shown  by  Pavy  that  from  the  products  of  disintegration 
of  a  protein  such  as  egg-white  it  was  possible  to  obtain  a  reducing  substance 
and  to  isolate  an  osazone  resembling  in  its  characters  those  derived  from 
the  sugars.  Since  then  various  observers  have  shown  that  this  reducing 
substance  is  most  probably  glucosamine  : 

CH2OH 

I 
M'HOH)3 

I 

<'H.NH„ 


Although  this  substance  may  be  obtained  from  crystallised  egg  albumin  or 
crystallised  serum  albumin,  authorities  are  not  yet  convinced  that  it  forms 
an  integral  part  of  these  proteins.  Both  egg-white  and  serum  contain 
proteins  belonging  to  the  class  of  mucins,  ovomucoid  and  serum  mucoid,  each 
of  which  yields  on  acid  hydrolysis  from  16  to  30  per  cent,  glucosamine.  Since 
various  observers  have  obtained  results  varying  from  1  to  16  per  cent,  gluco- 
samine for  crystallised  egg  albumin,  it  seems  possible  that  in  every  case 
the  crystals  carried  down  with  them  some  of  the  carbohydrate-rich  mucoid, 
and  that  the  varying  results  were  due  to  the  different  amounts  of  mucoid 
present  in  the  crystals.  By  our  ordinary  methods  it  is  impossible  to  prepare 
a  specimen  of  either  egg  albumin  or  serum  albumin  which  is  entirely  free  from 
this  amino-derivative  of  carbohydrate. 

Connected  with  this  group  of  proteins  may  be  reckoned  the  diamino- 
trioxydodecoic  acid  already  mentioned  as  occurring  among  the  disintegration 
products  of  proteins. 

THE   BUILDING  UP  OF  THE  PROTEIN  MOLECULE 

By  simple  hydrolysis  the  protein  molecule  may  be  broken  down  into  a 
large  number  of  amino-acids.  Analyses  of  various  proteins  show  that  these 
amino-acids  are  present  in  different  proportions  in  the  individual  proteins, 
so  that  in  many  cases  a  large  number  of  identical  amino-acid  groups  must 
be  present  in  the  protein  molecule  with  smaller  numbers  of  other  groups. 
In  endeavouring  to  form  an  idea  of  the  manner  in  which  the  amino-acids  can 
be  linked  together  into  one  gigantic  molecule,  Hofmeister  first  put  forward 
the  idea  that  the  linkage  follows  the  general  formula  :• 

— CH2— NH— CO— 
or  — NH— CH„— CO— NH— 


THE  PROTEINS  87 

This  theory  of  the  constitution  of  proteins  was  based  on  the  fact  that  a 
similar  grouping  was  known  to  occur  in  leucinimide,  obtained  by  the  con- 
densation of  two  molecules  of  leucine, 

r4H9 

I 

/'" 

NH  CO 

I  I 

00  NH 


C4H9 

and  also  by  the.  fact  that  only  a  small  proportion  of  the  NH2  groups  present 
in  the  separated  amino-acids  exist  free  in  the  protein  molecule.  By  the 
action  of  nitrous  acid  the  terminal  NH2  groups  are  split  off  and  replaced  by 
OH.  When  proteins  are  treated  with  nitrous  acid  only  a  small  proportion  of 
the  total  nitrogen  is  split  off  in  this  way.  The  linking  of  the  amino  groups 
must  therefore  take  place  by  means  of  the  nitrogen,  i.e.  by  NH  groups. 
Synthetic  experiments  have  fully  confirmed  this  hypothesis.  In  1883 
Curtius  obtained  a  substance  giving  the  biuret  reaction,  the  so-called 
'  biuret  base,'  by  the  spontaneous  polymerisation  of  glycocoll  ester.  This 
base  has  been  shown  by  recent  researches  to  consist  of  four  glycine  molecules 
arranged  together  in  an  open  chain.  The  clue  to  the  structure  of  this  base 
was  given  by  Fischer,  who  has  devised  a  number  of  ingenious  methods  for 
combining  together  amino-acids  of  any  character  and  in  an}'  number.  Thus 
from  two  molecules  of  glycine  we  may  obtain  the  compound  glycyl  glycine, 
as  follows  : 

NH2.CH,.COOH  +  HNH.CH,.COOH  -  H20  = 
NH2.CH2.CO.NH.CH,.COOH 

This  may  be  prepared  in  various  ways.  In  one  method  glycine  is  converted  into 
its  ester  CH2.NH,.CO.OCH3.  In  a  watery  solution  this  undergoes  spontaneous  con- 
version into  glycine  anhydride  which  belongs  to  the  class  of  bodies  known  as  diketo- 
piperazins,  as  follows  : 

.OH,— CO 
2NH2.CH2CO.OCH3  =  2CH3OH  +  NH<(  \NH 

methyl  alcohol  \  CO— CH„ 

On  treating  this  with  dilute  alkali  it  takes  up  water,  splitting  in  the  situation  of  the 
dotted  line  and  forming  glycyl  glycine,  NH2CH2CO.NH.CH2COOH. 

More  general  methods  have  been  devised  by  Fischer  for  the  same  purpose,  depending 
on  the  use  of  the  halogen  acyl  chlorides. 

Thus   chloraeetylchloride   and   alanine   yield   chloracetalanine  : 

C1.CH2.C0C1  +  NH,.CH(CH3).COOH  = 
C1.CH2.C0  -  NH.CH(CH3)COOH  +  HC1. 

By  the  subsequent  action  of  ammonia,  the  halogen  group  is  replaced  by  the  amino 
group,  and  a  dipeptide  results  : 


88  PHYSIOLOGY 

Cl.CH2.CO  -  NH.CH(CH3)COOH  +  2NH3  = 
NH2.CH2.CO  -  NH.CH(CH3)COOH  +  NH4C1. 
Different  halogen  acyl  chlorides    are  used    for  introducing    the  various    amino-acid 
radicals,  e.g.  chloracetylchloride  for  glycyl,  a-brornopropionylchloride  for  alanyl,  &c. 

By  various  such  methods  Fischer  has  succeeded  in  combining  compounds 
containing  as  many  as  eighteen  amino-acids,  e.g.  alanyl  leucine,  glycyl 
tyrosine,  dialanyl  cystine,  dileucyl  cystine,  leucyl  pentaglycyl  glycine,  and 
so  on.  The  last  named  would  be  built  up  out  of  one  molecule  of  leucine  and 
six  molecules  of  glycine.  These  compounds  have  been  designated  by 
Fischer  as  poly  peptides,  to  signify  their  close  connection  with  the  peptones 
produced  by  the  agency  of  digestive  ferments  on  the  proteins.  He  dis- 
tinguishes di-,  tri-,  tetra-,  &c,  peptides  according  to  the  number  of  individual 
amino-acids  taking  part  in  the  formation  of  the  compound.  The  poly- 
peptides resemble  in  all  respects  the  peptones.  Most  of  them,  even  if 
derived  from  relatively  insoluble  amino-acids,  are  soluble  in  water,  insoluble 
in  absolute  alcohol.  They  dissolve  in  mineral  acids  and  in  alkalies  with  the 
formation  of  salts,  thus  resembling  in  their  behaviour  the  amino-acids. 
They  have  a  bitter  taste,  although  the  amino-acids  from  which  they  are 
formed  have  a  slightly  sweet  taste,  in  this  way  again  resembling  the  natural 
peptones.  The  higher  members  of  the  series  give  certain  reactions,  such  as 
the  biuret  reaction,  which  are  regarded  as  characteristic  of  peptones,  and  like 
the  latter  are  precipitated  by  phosphotungstic  acid.  Their  behaviour  with 
trypsin  depends  on  the  optical  behaviour  of  the  amino-acids  from  which  they 
are  formed.  If  synthetised  from  the  amino-acids  identical  with  those 
occurring  in  the  disintegration  of  natural  proteins,  they  resemble  the  pep- 
tones in  undergoing  hydrolysis  and  disintegration  into  their  constituent 
amino-acids.  Trypsin  however  has  no  influence  on  polypeptides  com- 
pounded of  the  inactive  amino-acids,  or  of  the  amino-acids  which  are  the 
optical  opposites  of  those  which  form  the  constituents  of  normal  proteins. 
Though  most  of  the  amino-acids  which  occur  naturally  are  laevo-rotatory, 
the  polypeptides  formed  from  them  are  generally  strongly  dextro-rotatory. 

Thus  in  the  building  up  of  the  protein  molecule  there  is  an  almost  indefi- 
nite coupling  up  of  numerous  amino-acid  groups,  the  connecting  element  in 
each  case  being  the  nitrogen.  Of  the  two  or  more  optical  isomers  possible  of 
each  amino-acid  containing  more  than  two  carbon  atoms,  only  one  is  made 
use  of  for  this  purpose.  A  still  further  flexibility  in  its  reactions  to  its 
environment  is  conferred  on  the  protein  molecule  by  changes  occurring  with 
great  readiness  in  the  intra-molecular  grouping  of  its  constituent  atoms. 
Thus,  if  we  take  the  simplest  member  of  the  class  of  polypeptides,  glycyl 
glycine,  four  structural  formulae  are  possible,  namely : 

(1)  NH2CH2CO  -  NH.CH2.COOH 

(2)  NH.CHo.CO 

I  >o 

CO.CH2.NH3 

(3)  NH2.CH2.C(OH)  =  N.CH2.COOH 


THE   PROTEINS 


89 


W 


N.CH.CO 


C(OH)CH,.NH3 


> 


(2)  and  (4)  being  the  intramolecular  form  of  the  formulae  (1)  and  (3).  (3)  and 
(4)  are  sometimes  spoken  of  as  the  enolic  form.  If  we  consider  that  perhaps 
some  hundred  of  the  amino-acid  groups  may  go  to  making  up  a  single 
protein  molecule,  it  is  possible  to  form  some  conception  of  the  enormous 
variability  in  reaction  possible  to  such  a  compound. 


THE  CONSTITUTION  OF  DIFFERENT  PROTEINS 

All  the  proximate  constituents  of  proteins,  so  far  as  we  know,  are  amino- 
acids.  Of  these  the  following  have  been  isolated,  namely,  glycine,  alanine, 
amino-valerianic  acid,  leucine,  isoleucine,  proline,  oxyproline,  serine,  phenyl 


a 

5  3 

«« 

•3 
3 

2 

3 

a 

| 

s 

B 

S  3  c 

Glycine 

0 

0 

3-S 

0-9 

0 

0 

0 



16-5 

4-7 

Alanine      . 

2-7 

8-1 

3-6 

2-7 

1-5 

4-2 

— 

— 

0-8 

1-5 

Serine 

0-6 

— 

0-33 

0-12 

0-5 

0-6 

7-8 

— 

0-4 

0-6 

Amino- valeri- 

anic acid 

— 

— 

present 

0-3 

7-2 

— 

4-3 

— 

10 

0-9 

Leucine     . 

20-0 

71 

20-9 

6-0 

9-35 

290 

0 

— 

21 

7-1 

Proline 

10 

2-25 

1-7 

2-4 

6-70 

2-3 

110 

— 

5-2 

3-4 

Oxyproline 

— 

— 

20 

— 

0-23 

1-0 

— 

— 

3  0 

— 

Glutamic  acid    . 

7-7 

8-0 

6-3 

36-5 

15-55 

1-7 

— 

— 

0-88 

3-7 

Aspartic  acid     . 

3-1 

1-5 

4-5 

1-3 

(l-39 

4-4 

— 

— 

0-56 

0-3 

Phenylalanine    . 

31 

4-4 

2-4 

2-6 

:3-2_ 

4-2 

— 

— 

0-4 

0 

Tyrosine   . 

21 

11 

21 

2-4 

4-5 

1-5 

— 

—  • 

0 

3-2 

Tryptophane 

present 

present 

present 

10 

1-50 

present 

— 

— 

0 

— 

Cystine 

2-3 

0-2 

0-25 

0-45 

? 

,0-3 

— 

— 

— 

10+ 

Lysine 

— 

2-15 

10 

0 

5-95 

4-3 

0 

12-0 

2-75 

11 

Arginine   . 

214 

11-7 

3-4 

3-81 

5-4 

87-4 

58-2 

7-62 

4-5 

Histidine  . 

11 

1-7 

2-5 

110 

0 

12-9 

0-4 

0-6 

alanine,  glutamic  acid,  aspartic  acid,  tyrosine,  tryptophane,  cystine,  lysine 
histidine,  arginine,  and  '  di-amino-trioxydodecoic  '  acid. 

The  question  now  arises  whether  all  the  different  varieties  of  protein  owe 
their  peculiarities  to  the  presence  of  different  amino-acids  or  whether  the 
greater  number  of  the  amino-acids  above  mentioned  are  present  in  all  pro- 
teins, the  differences  between  the  latter  being  determined  by  differences  in  the 
arrangement  and  relative  amounts  of  their  proximate  constituents.  .  A  large 
number  of  analyses  of  different  proteins  have  been  made  by  Abderhalden, 
Osborne,  and  others,  utilising  the  methods  for  the  isolation  of  amino-acids 
devised  by  Fischer.  The  constitution  of  some  representative  proteins  as 
determined  in  this  way  is  given  in  the  Table  above. 


90  PHYSIOLOGY 

These  results  show  that  all  tin-  proteins  contain  a  very  considerable 
proportion  of  the  total  number  of  amino-acids  which  have  as  yet  been 
isolated  from  acid  digests  of  proteins.  The  differences  in  various  proteins 
cannot  therefore  be  determined  by  qualitative  differences  in  their  constituent 
molecules,  but  must  depend  on  the  relative  amounts  of  the  amino-aeids 
which  are  present  and  on  their  arrangement  in  the  whole  molecule.  As  regards 
relative  amounts  of  amino-acids  we  find  very  striking  differences,  i  Thus 
glutamic  acid,  which  forms  8  per  cent,  of  egg  albumin  and  only  f  '7  per  cent, 
of  globin  (derived  from  haemoglobin),  amounts  to  36"5  per  cent,  in  gliadin, 
the  protein  extracted  from  wheat  flour.  Striking  differences  are  also  notice- 
able in  the  relative  proportions  of  the  cUamino-acids  and  bases,  the  so-called 
hexone  bases.  Whereas  in  casein  they  form  about  12  per  cent,  of  the  total 
molecule,  in  globin  they  form  about  20  per  cent. ;  and  in  the  protamine's, 
salmine  and  sturine,  about  85  per  cent,  of  the  total  molecule  consists  of  t  bese 
bodies.  On  this  account  the  two  last-named  bodies  have  a  strongly  basic 
character.  From  these  figures  it  is  evident  also  that  certain  of  the  amino- 
acids  must  occur  many  times  over  in  the  protein  molecule.  Thus  in  globin. 
if  we  assume  the  presence  of  one  tyrosine  molecule,  then'  must  be  at.  least 
thirty-two  leucine  and  ten  histidine  molecules.  On  these  data  the  molecular 
weight  of  haemoglobin  would  come  out  at  about  14,000,  a  figure  which  agrees 
with  that  derived  from  a  study  of  the  amounts  of  sulphur  and  iron  respec- 
tively in  its  molecule. 

THE    DISTRIBUTION    OF   NITROGEN   IN   THE   PROTEIN 
MOLECULE 

Attempts  have  been  made  to  differentiate  among  the  proteins  by  a 
method  which,  while  less  laborious  than  the  isolation  and  recognition  of  the 
individual  amino-acids,  may  yet  throw  some  light  on  the  manner  in  which 
the  nitrogen  is  combined  within  the  molecule,  and  on  the  relative  amounts  of 
the  different  classes  of  nitrogen  groups  which  may  b?  present.  One  method, 
which  was  devised  by  Hausmann.  is  carried  out  as  follows.  One  gramme  of 
the  protein  is  dissociated  by  boiling  with  strong  hydrochloric  acid.  The 
nitrogen,  which  has  been  split  off  as  ammonia  and  is  present  in  the  solution 
as  ammonium  chloride,  is  then  distilled  off  with  magnesia  and  received 
into  decinormal  acid,  where  its  amount  can  be  determined  by  titration.  This 
nitrogen  is  variously  designated  as  amide  nitrogen,  ammonia  nitrogen,  or 
easily  displaceable  nitrogen.  The  remaining  fluid,  freed  from  ammonia,  is 
precipitated  with  phosphotungstic  acid.  By  this  means  all  the  diamino-acids 
and  bases  are  thrown  down.  The  nitrogen  in  the  precipitate  is  determined 
by  Kjeklahl's  method  and  is  called  diamino-  or  basic  nitrogen.  In  the 
remaining  fluid,  which  contains  mono-amino-acids,  the  total  nitrogen,  the 
mono-amino-nitrogen,  is  determined  by  Kjeldahl's  method.  Table  I.,  p.  91. 
gives  some'  of  I  he  results  obtained  in  this  manner,  and  shows  that  there  are 
considerable  differences  in  the  distribution  of  the  different  kinds  of  nitrogen 
among  the  various  classes  of  proteins.  The  method  is  however  only  a 
rough  one  as  compared  with  the  separation  of  the  individual  maino-acids. 


THE   PROTEINS 
Table  I. 


91 


Amide      Amino 


Protamines 


Salmi 


Salmon-roe 
Sturgeon-roi 


Sturine 

Histones  Histone  Thymus 

Albumins 
and  [Ovalbumin      Egg-white 

phospho-      l  Caaeinogen      Milk 
proteins 


Globulins 

Alcohol  - 
soluble 
proteins 


Globulin 
I  Edestin 

I  Zein 

i  Gliadin 

,  Prot- 

I     albumose 

■  Hetero- 

'      albumose 


Wheat 
Hemp  seed 

Maize 

Wheal  and  rye 


Witte's 

peptone 
Witte's 

peptone 


- 

0 

3-3 

15-51 

8-64 

15-62 

10-36 

18-39 

7-72 

18-64 

1008 

1613 

18-40 

17-66 

23-78 

— 

714 

6-45 

87-8 
83-7 


■AS- 


6813 

21-27 

6600 

22-34 

53-40 

37-10 

57-83 

31-70 

77-56 

3  03 

7(1-27 

5-54 

68-17 

25-42 

57-4 

38-93 

1-87 
1-34 


1-52 
0-64 


0-99 
0-79 


Table  II. — Distribution  of  the  Nitrogen  in  Various  Proteins 

(Van  Slyke) 


Gliadin 

Edestin 

Hair 

(dog) 

Gelatin 

Fibrin 

ll;t' - 

cyanin 

Ox  haemo- 
globin 

Ammonia  N    . 

25-52 

9-99 

10-05 

2-25 

8-32 

5-95 

5-24 

Melanine  N     . 

0-86 

1-98 

7-42 

0-07 

317 

1-65 

3-60 

Cystine  N 

1-25 

1  49 

6-60 

0 

0-99 

0-80 

0  ? 

Arginine  N 

5-71 

27-05 

15-33 

14-70 

13-86 

15-73 

7-70 

Histidine  N 

5-20 

5-75 

3-48 

4-48 

4-83 

13-23 

12-70 

Lysine  N 

0-75 

3-86 

5-37 

632 

11-51 

8-49 

10-90 

Amino   N   of   the 

nitrate 

51-98 

47-55 

17-50 

56-30 

54-30 

51-30 

57-00 

Non-amino  \  oi  the 

filtrate      (proline, 

oxyproline,          !, 

tryptophane) 

8-50 

1-7(1 

310 

14-90 

2-70 

3-80 

2-90 

99-77 

99-37 

99-85 

99-02 

99-58 

100-95 

10000 

An  improved  means  of  determining  the  distribution  of  nitrogen  in  the 
protein  molecule  bas  been  devised  by  Van  Slyke.  Some  of  his  results  art- 
given  in  Table  II.,  above. 

*  When  a  protein  is  boiled  for  a  long  time  with  strong  aeid,  a  black  precipitate  maj 
occur  which  contains  nitrogen.     This  is  known  as  humin  nitrogen. 


92  PHYSIOLOGY 

TESTS   FOR   PROTEIN 
A.    COLOUR    REACTIONS    OF    THE   PROTEINS 

These  are  of  importance  since  in  many  cases  they  are  an  indication  of  the  nature 
of  the  groups  present  in  the  protein  molecule. 

(1)  THE  BIURET  REACTION.  When  a  solution  of  a  protein  is  made  strongly 
alkaline  with  caustic  potash  or  soda,  and  dilute  copper  sulphate  added  drop  by  drop, 
a  colour  varying  from  pink  to  violet  is  produced.  In  the  case  of  the  proteoses  and 
peptones  (the  hydrated  proteins)  the  colour  is  pink  ;  in  the  case  of  the  coagulable 
proteins,  violet.  According  to  Schiff  this  colour  is  given  by  all  compounds  containing 
the  following  groups  : 

XO.NHj, 
NH<( 

XCO.NH2 
CO.NH2 
CH2< 

CO.NH2 
CO— NH2 

I 
CO— NH, 


and  the  group 


(NH2)C— CO— NH— C 


We  have  already  seen  that  this  grouping  is  typical  of  the  protein  molecule. 

(2)  THE  XANTHOPROTEIC  REACTION.  On  adding  strong  nitric  acid  to 
a  solution  of  protein  and  boiling,  a  yellow  colour  is  produced  which  turns  to  a  deep 
orange  when  excess  of  caustic  alkali  or  ammonia  is  added.  The  production  of  this 
reaction  points  to  the  existence  of  benzene  derivatives  in  the  protein  molecule,  and 
it  is  therefore  a  general  test  for  the  presence  of  aromatic  groups. 

(3)  MILLON'S  REACTION.  Millon's  reagent  is  a  solution  of  mercuric  nitrate 
in  water  containing  free  nitrous  acid.  On  adding  a  few  drops  of  this  to  a  protein  solu- 
tion a  white  precipitate  is  produced  which  turns  a  brick-red  colour  on  boiling.  It 
depends  on  the  presence  in  the  protein  of  a  hydroxy-derivative  of  benzene,  and  is 
determined  hi  the  protein  by  the  tyrosine,  which  is  oxyphenylalanine. 

(4)  SULPHUR  REACTION.  On  warming  a  solution  of  protein  with  caustic 
soda  in  the  presence  of  lead  acetate,  a  black  colour  is  produced  owing  to  the  precipi- 
tation of  lead  sulphide.  The  depth  of  coloration  gives  a  rough  indication  of  the  amount 
of  sulphur  in  the  protein  under  investigation. 

(5)  THE  HOPKINS  AD AMKIEWICZ  REACTION.  It  was  stated  by  Adam- 
kiewicz  that  on  the  addition  of  acetic  acid  and  concentrated  sulphuric  acid  to  protein, 
a  violet  colour  was  produced.  Hopkins  and  Cole  showed  that  the  success  of  this  reaction 
depended  on  the  presence  of  glyoxylic  acid  CHO.COOH  as  an  impurity  in  the  acetic 
acid  used.     The  test  is  therefore  performed  now  as  follows  : 

Glyoxylic  acid  is  prepared  by  the  action  of  sodium  amalgam  on  a  solution  of  oxalic 
acid.  A  few  drops  of  this  solution  are  added  to  the  solution  of  protein,  and  strong 
sulphuric  acid  poured  down  the  side  of  the  tube.  A  bluish  violet  colour  is  produced 
at  the  junction  of  the  two  fluids.  This  reaction  is  due  to  the  presence  in  the  protein 
of  tryptophane. 

The  so-called  Liebermann's  reaction  has  been  shown  by  Cole  to  be  essentially  a 
modification  of  the  above,  and  is  due  also  to  the  presence  of  tryptophane.  In  this 
test  the  protein  is  precipitated  by  alcohol,  washed  with  ether,  and  heated  with  con- 
centrated hydrochloric  acid,  when  a  blue  colour  is  produced,  glyoxylic  acid  being 
derived  from  the  alcohol  and  ether. 


THE  PKOTEINS  93 

(6)  REACTIONS    INDICATING   THE   PRESENCE   OF   CARBOHYDRATES. 

Molisch's  test  is  applied  as  follows.  A  few  drops  of  alcoholic  solution  of  a-naphthol 
and  then  strong  sulphuric  acid  are  added  to  a  protein  solution.  A  violet  colour  is 
produced,  which  on  addition  of  alcohol,  ether,  or  potash  turns  yellow.  The  reaction 
is  determined  by  the  presence,  either  as  an  impurity  or  a  constituent  part  of  the  mole- 
cule, of  a  carbohydrate  radical  which,  under  the  influence  of  strong  sulphuric  acid,  is 
converted  into  furfurol.  The  furfurol  gives  the  colour  reaction  with  the  a-naphthol. 
Another  test  for  the  carbohydrate  radical  is  the  orcin  reaction.  A  small  quantity 
of  the  dried  albumin  is  added  to  5  c.c.  of  fuming  hydrochloric  acid,  and  the  mixture  is 
then  warmed.  When  the  albumin  is  nearly  all  dissolved,  a  little  solid  orcin  is  added 
on  the  point  of  a  knife,  and  then  a  drop  of  ferric  chloride  solution.  After  warming 
this  mixture  for  some  minutes,  a  green  colour  is  produced  which  is  soluble  in  arnyl 
alcohol  and  gives  a  definite  absorption  spectrum. 

B.    METALLIC  SALTS 

The  following  metallic  salts  form  double  insoluble  compounds  with  proteins,  and 
therefore  cause  a  double  precipitation  when  added  to  solutions  of  these  bodies  :  ferric 
chloride,  copper  sulphate,  mercuric  chloride,  lead  acetate,  zinc  acetate. 

C.     ALKALOIDAL  REACTIONS 

Proteins,  like  the  polypeptides  and  the  amino-acids  of  which  they  are  composed, 
may  function  either  as  weak  acids  or  as  weak  bases,  according  as  they  are  treated  with 
bases    or    acid  radicals     respectively.      In   the  presence  of    strong  acids   therefore, 
proteins  act  like  organic  bases,  and  are  thrown  down  in  an  insoluble  form  by  the  various 
alkaloidal  precipitants.     With  certain  proteins,  such  as  the  protamines,  where  there 
is  a  preponderance  of  basic  groups,  it  is  not.  necessary  to  add  mineral  acid  in  order 
to  ensure  the  precipitation.     The  following  are  the  principal  alkaloidal  precipitants 
which  may  be  employed  : 
(a)  Phosphotungstic  acid. 
(6)  Phosphomolybdic  acid, 
(c)  Tannic  acid. 
{d)  Potassium  mercuric  iodide, 
(e)  Acetic  acid  and  potassium  ferrocyanide. 

(/)  Trichloracetic  acid.     (In  order  to  precipitate  all  the  coagulable  proteins  from 
a  solution,  it  is  treated  with  an  equal  volume  of  10  per  cent,  trichloracetic  acid, 
well  shaken  and  filtered.) 
(g)  Metaphosphoric  acid. 
(h)  Salicyl-sulphonic  acid. 

These  two  latter  are  generally  employed  in  a  5  per  cent,  solution. 
(i)  Picric  acid. 

A  mixture  of  picric  and  citric  acids  is  largely  employed,  under  the  name  of 
Esbach's  reagent,  as  a  precipitant  for  coagulable  proteins  in  the  urine. 

D.     TESTS  DEPENDING  ON  THE  COLLOIDAL  CHARACTER  OF  THE 
PROTEIN 

(1)  HEAT  COAGULATION.  On  boiling  proteins  in  a  very  slightly  acid  solution 
some  are  coagulated  and  form  an  insoluble  white  precipitate.  This  test  is  applicable 
to  albumins,  globulins,  and  under  certain  conditions  to  the  derived  albumins.  In 
order  that  the  separation  of  protein  in  this  way  may  be  complete,  it  is  necessary  to 
provide  for  the  presence  of  neutral  salts  and  also  for  the  maintenance  of  a  slight  acidity. 
The  best  method  of  carrying  out  this  test  therefore  is  to  boil  the  protein  in  slightly 
alkaline  or  neutral  solution  after  the  addition  of  2-5  per  cent,  of  sodium  chloride  or 
sodium  sulphate.  While  the  solution  is  in  active  ebullition,  1  per  cent,  acetic  acid  i« 
added  drop  by  drop  until  the  reaction  is  just  acid  to  litmus.  By  this  means  a  nearly 
perfect  separation  of  all  the  coagulable  proteins  may  be  effected. 


'.H  PHYSIOLOGY 

(2)  HELLER'S  TEST.  On  pouring  a  solution  of  protein  carefully  down  the  Bide 
of  a  test-tube  containing  strong  nitric  acid  so  as  to  form  a  layer  on  the  top,  a  white 
layer  of  coagulated  protein  is  produced  at  the  junction  of  the  two  tluids.  A  similar 
coagulative  effect  is  given  by  other  strong  mineral  acids. 

(3)  PRECIPITATION  BY  NEUTRAL  SALTS.  On  addition  of  a  neutral  salt  in 
excess  to  a  colloidal  solution,  the  relation  between  the  solvent  and  the  particles  which 
are  in  suspension  or  pseudo-solution  is  altered.  II  is  therefore  possible  in  many 
cases  by  the  addition  of  neutral  salts  to  separate  out  the  dissolved  colloid  without 
otherwise  altering  its  characters  in  any  way,  so  that,  on  collecting  the  precipitate 
and  separating  the  salt  carried  down  with  it,  it  can  be  dissolved  again  by  adding  water. 
Some  classes  of  proteins  can  be  salted  out  very  readily,  while  others  require  a  much  higher 
concentration  of  salt  before  they  are  precipitated. 

The  salts  which  are  generally  employed  for  salting  out  proteins  have  been  divided 
by  Schryver  into  three  classes  : 

Class  I.  Class  II.  Class-III. 

Sodium  chloride.  Potassium  acetate.  Ammonium  sulphate. 

Sodium  sulphate.  Calcium  chloride.  Zinc  sulphate. 

Sodium  acetate.  Calcium  nitrate. 
Sodium  nitrate. 
Magnesium  sulphate. 

The  two  calcium  salts  are  however  rarely  employed,  as  they  tend  to  render  the 
precipitated  protein  insoluble. 

The  salts  of  the  first  class  require  much  higher  concentration  for  the  precipitation 
of  the  proteins  than  those  of  the  second,  and  these  than  those  of  the  third.  Since  the 
degree  of  concentration  of  any  salt  necessary  for  the  precipitation  of  any  particular 
protein  is  characteristic  for  this  body,  it  is  possible  to  employ  a  fractional  process  of 
salt  precipitation  in  order  to  separate  mixtures  of  proteins  into  their  components. 
Owing  however  to  the  tenacity  with  which  different  colloids  adhere  to  one  another, 
it  is  difficult,  even  after  many  repetitions  of  the  process  of  fractional  salting  out,  to 
obtain  products  which  can  be  regarded  as  free  from  admixture.  For  the  purpose  of 
fractional  precipitation  the  salts  most  frequently  employed  are  those  of  the  third  class, 
namely,  ammonium  sulphate  and  zinc  sulphate.  We  shall  have  to  deal  with  results 
obtained  by  this  method  when  treating  of  the  separation  of  albumoses  and  peptones. 
The  precipitability  of  different  proteins  with  neutral  salts  serves  also  as  the  basis  of 
the  ordinary  classification  of  these  bodies. 

THE  CLASSIFICATION  OF  PROTEINS 

It  is  possible  that  in  the  future,  when  we  know  all  the  disintegration 
products  of  the  various  proteins  and  the  manner  in  which  they  are  arranged 
in  the  molecule,  the  classification  of  these  bodies  will  be  based  on  their  con- 
stitution. At  the  present  time  it  is  obviously  impossible  to  make  any  classi- 
fication on  such  a  basis,  since  the  necessary  knowledge  is  wanting,  and 
we  have  therefore  to  use  a  purely  artificial  classification,  such  as  that  adopted 
by  the  Chemical  and  Physiological  Societies  in  1907,  based  chiefly  on  the 
solubilities  of  the  various  proteins  in  water  and  salt  solutions.  We  shall 
here  only  indicate  the  characters  of  the  main  groups  into  which  proteins 
are  conventionally  divided,  and  leave  the  closer  study  of  the  individual 
proteins  to  be  dealt  with  in  connection  with  the  organs  or  tissues  in  which 
they  are  found. 

(1)  THE  PROTAMINES.  These  occur  in  the  body  only  in  combination 
with  other  groups.     They  are  obtained  from  the  ripe  spermatozoa  of  certain 


THE    PROTEINS  95 

fishes,  where  they  are  in  combination  with  nucleic  acid.  They  are  charac- 
terised by  the  very  large  amount  of  bases  contained  in  their  molecule, 
amounting  to  85  per  cent,  of  the  total  substance.  It  was  formerly  thought 
by  Kossel  that  the  protamines  contained  only  diamino-acids  and  bases,  but 
it  has  been  shown  later  that  a  small  proportion  of  mono-amino-acids  may 
also  be  obtained  from  their  disintegration  (v.  Table,  p.  98).  On  account  of 
their  constitution  they  possess  strongly  basic  characters  and  form  well- 
marked  salts,  e.g.  sulphates  and  chlorides,  as  well  as  double  salts  with 
platinum  chloride.  They  contain  no  sulphur  and  do  not  coagulate  on 
heating. 

(2)  HISTONES.  This  class  of  proteins,  like  the  protamines,  only  occurs  in 
combination  with  other  groups,  such  for  instance  as  nuclein  and  haematin. 
They  may  be  obtained  from  red  blood-corpuscles,  where  they  form  the 
globin  part  of  the  haemoglobin  molecule,  or  from  the  leucocytes  of  the  thymus 
gland,  or  from  the  spermatozoa  of  fishes.  The  histones  are  precipitated 
from  their  watery  solutions  by  addition  of  ammonia,  but  are  soluble  in 
excess  of  this  reagent.  In  the  presence  of  salts  they  are  coagulated  on  boiling. 
With  cold  nitric  acid  they  give  a  precipitate  which  dissolves  on  warming,  but 
is  thrown  down  again  on  cooling.  The  most  characteristic  feature  of  this 
class  of  bodies  is  however  the  high  proportion  of  diamino-acids  and  bases 
contained  in  their  molecule. 

(3)  ALBUMINS.  These  are  soluble  in  pure  water  and  are  precipitated 
by  complete  saturation  with  ammonium  sulphate,  zinc  sulphate,  or  sodio- 
magnesium  sulphate. 

Egg  Albumen  forms  the  greater  part  of  the  white  of  egg.  It  gives 
the  ordinary  protein  tests,  coagulates  on  heating  at  about  75°  C,  and 
is  precipitated  from  its  solutions  if  shaken  with  a  drop  of  dilute  acetic 
acid  in  excess  of  ether.  It  is  lsevo-rotatory,  its  specific  rotatory  power 
being— 35'5°. 

Serum  Albumen  occurs  in  large  quantities  in  the  blood  plasma,  serum, 
lymph,  and  tissue  fluids  of  the  body.  It  coagulates  at  75°  C,  and  is  dis- 
tinguished from  egg  albumen  by  its  greater  specific  rotatory  power,  —56°, 
and  by  the  fact  that  it  is  not  precipitated  by  ether  and  sulphuric  acid.  Some 
vegetable  proteins  belong  to  this  class,  e.g.  the  leucosin  of  wheat. 

(4)  GLOBULINS.  These  bodies  are  insoluble  in  pure  water  and  require 
the  presence  of  a  certain  amount  of  neutral  salt  to  dissolve  them.  They  are 
precipitated  from  their  solutions  by  complete  saturation  with  magnesium 
sulphate  or  by  half-saturation  with  ammonium  sulphate.  The  chief  members 
of  this  class  are  : 

Crystallix.  obtained  from  the  crystalline  lens  by  passing  a  stream  of 
carbon  dioxide  through  an  aqueous  extract  of  this  body. 

Serum  Globulin  or  Paraglobulin,  a  constituent  of  blood  plasma  and 
blood  serum. 

Fibrinogen,  which  occurs  in  blood  plasma  and  is  converted  into  fibrin 
when  the  blood  clots. 

Paramyosinogen,  a  norma]  constituent  of  muscle. 


96  PHYSIOLOGY 

Midway  between  these  two  groups  may  be  placed  the  muscle  protein, 
myosin  (or  myosinogen),  which,  though  soluble  in  pure  water,  resembles 
the  class  of  globulins  in  the  ease  with  which  it  is  precipitated  by  the  addition 
of  neutral  salts. 

In  addition  to  the  members  of  the  globulins  named  above  and  derived 
from  the  animal  body,  proteins  allied  to  this  class  form  an  important  con- 
stituent of  plants,  and  are  found  in  large  quantities  in  many  seeds  used  as 
articles  of  food.  These  are  vegetable  globulins.  Prominent  members  of  the 
group  are  the  edestins,  which  may  be  obtained  from  hemp  seeds,  cotton  seeds, 
and  sunflower  seeds,  zein  from  maize,  legumin  from  beans. 

(5)  GLIADINS,  contained  in  cereals,  and  soluble  in  alcohol. 

(6)  GLUTELINS,  proteins  also  obtained  from  cereals  and  soluble  in  weak 
alkalies. 

(7)  DERIVATIVES  OF  PROTEINS.  A.  METAPROTEINS.  These  may 
be  regarded  as  compounds  of  the  protein  molecule  or  of  part  of  the  molecule 
with  acid  or  basic  radicals. 

Acid  Albumin,  or  acid  metaprotein,  is  formed  by  the  action  of  warm  dilute 
acids  or  of  strong  acids  in  the  cold  on  any  of  the  preceding  bodies.  If  a  weak 
alkali  be  added  so  as  nearly  to  neutralise  the  solution  of  acid  metaprotein, 
this  latter  is  precipitated.  If  the  precipitate  be  suspended  in  water  and 
heated,  it  is  coagulated  and  becomes  insoluble  in  dilute  acids  or  alkalies. 

Alkali  Albumin,  or  alkaline  metaprotein,  is  formed  by  the  action  of 
strong  caustic  potash  on  white  of  egg  or  on  any  other  protein,  or  by  adding 
alkali  in  excess  to  a  solution  of  acid  metaprotein.  It  is  precipitated  on 
nsutralisation  of  its  solution. 

In  close  association  with  this  group  may  be  included  the  proteins  as  they  occur 
in  combination  with  the  metallic  salts,  such  as  copper  sulphate.  On  splitting  off  the 
copper  moiety  from  these  compounds,  the  protein  left  is  practically  free  from  ash,  and 
behaves  in  many  respects  like  an  albuminate,  being  insoluble  in  absolutely  pure  water, 
but  easily  dissolved  by  the  addition  of  a  trace  of  free  acid  or  alkali. 

A  group  of  protein  derivatives  described  by  Hopkins  is  produced  by  the  action 
of  the  free  halogens  on  protein  solutions.  We  get  in  this  way  two  definite  classes  of 
compounds.  One  class,  which  contains  the  largest  percentage  of  halogen,  is  obtained 
by  treating  a  protein  solution  with  chlorine,  bromine,  or  iodine,  dissolving  up  the 
resultant  precipitate  in  alcohol  and  pouring  the  alcoholic  solution  into  ether,  when  the 
halogen  compound  is  thrown  down  as  a  fine  white  precipitate.  By  dissolving  this 
precipitate  in  weak  soda  and  precipitating  with  acid,  we  obtain  a  series  of  compounds 
containing  only  about  one-third  as  much  of  the  halogen  as  is  contained  in  the  first 
precipitate,  suggesting  that  the  halogen  forms  both  substitution  and  additive  com- 
pounds with  the  protein  molecule. 

Albumins,  globulins,  and  metaproteins  are  often  associated  together  as 
the  coagulable  proteins,  since  they  may  be  thrown  down  entirely  from  their 
solution  on  boiling  in  slightly  acid  medium  in  the  presence  of  neutral  salts. 

B.  HYDRATED  PROTEINS.  When  proteins  are  subjected  to  the 
action  of  superheated  w-ater  or  steam,  or  heated  with  acids,  or  acted  on  at 
the  body  temperature  by  certain  ferments,  e.g.  pepsin,  trypsin,  or  papain, 
they  undergo  a  change  which  is  attended  by  the  addition  of  a  number  of 


THE  PROTEINS  97 

molecules  of  water  to  the  protein  molecule  (hydrolysis).  This  action,  when 
carried  to  its  end,  results  in  the  production  of  the  amino-acids  which  we  have 
already  dealt  with. 

These  hydrolytic  changes  proceed  by  a  series  of  stages,  so  that  the 
intermediate  products  still  present  many  of  the  protein  reactions.  The 
hydrated  proteins  are  divided  into  two  groups,  proteoses  and  peptones. 
The  formation  of  these  intermediate  products  is  especially  marked  with  the 
proteolytic  ferments.  Pepsin  with  hydrochloric  acid,  the  ferment  of  the 
gastric  juice,  for  example,  only  breaks  down  the  protein  molecule  as  far  as  the 
proteoses  and  peptones.  Trypsin  also  gives  rise  to  both  proteoses  and  pep- 
tones as  intermediate  products.  The  action  of  these  ferments  on  proteins  is 
in  fact  closely  analogous  to  the  action  of  diastase  on  the  great  polysaccharide 
molecule  of  starch.  In  this  case,  as  intermediate  products  we  have  first 
dextrins  of  various  complexity,  secondly  maltose,  and  finally,  if  the  ferment 
maltase  be  also  present,  dextrose.  The  monotony  of  the  starch  molecule 
determines  a  great  similarity  of  composition  between  its  various  disintegra- 
tion products.  It  may  be  regarded  as  an  anhydride  of  many  (100  or  more) 
molecules  of  a  hexose,  and  the  intermediate  stages  in  this  hydrolysis  are  also 
hexoses  and  their  anhydrides.  The  protein  molecule  is  distinguished  by  the 
variety  of  the  groups  which  enter  into  its  formation,  and  this  heterogeneous 
character  of  the  molecule  renders  possible  a  much  greater  variety  of  inter, 
mediate  products  than  we  find  in  the  starches.  Thus  a  protein  molecule  may 
consist  of  the  groups,  A,  B,  C,  D,  E,  F,  G,  H,  &c.  When  hydrolysis  occurs 
it  may  result  in  the  immediate  splitting  off,  say,  of  part  of  group  A,  while 
the  residue  breaks  up  into  a  series  of  proteoses  whose  composition  may  be 
represented  as  ABF,  ABC,  DFG,  BDEF,  &c.  With  further  hydrolysis  these 
groups  are  broken  into  still  smaller  ones,  and  the  penultimate  stages  of  the 
hydrolysis  will  be  polypeptides  similar  to  those  which  have  been  synthetised 
by  Fischer  from  the  ultimate  products  of  protein  hydrolysis.  No  sharp 
dividing  line  can  be  drawn  between  the  proteoses,  peptones,  and  poly- 
peptides. Of  the  last  group  we  have  already  seen  that  the  higher  members 
give  the  biuret  reaction  as  well  as  the  other  protein  reactions,  if  the  necessary 
groups,  e.g.  tyrosine,  tryptophane,  are  present  in  the  molecule.  The  prote- 
oses and  peptones  are  however  ill-defined  bodies.  We  have  at  present  no 
satisfactory  means  of  isolating  the  different  members  of  these  groups  and 
obtaining  them  in  a  state  of  chemical  purity.  Their  classification  is  there- 
fore, like  that  of  the  proteins  generally,  a  conventional  one,  depending  on 
their  solubilities  and  their  precipitability  by  neutral  salts,  especially  ammo- 
nium sulphate.  Both  proteoses  and  peptones  give  the  xanthoproteic  and 
Millon's  reactions  common  to  all  proteins,  and,  like  these,  are  precipitated 
by  such  reagents  as  mercuric  chloride,  potassio-mercuric  iodide,  or  phospho- 
tungstic  acid.  On  adding  excess  of  caustic  potash  and  a  drop  of  dilute 
copper  sulphate  to  solutions  of  either  of  these  classes  of  bodies,  a  pink  colour 
is  produced  which  deepens  to  a  violet  on  addition  of  more  copper  (the  biuret 
reaction).  Their  solutions  can  be  boiled  without  undergoing  coagulation. 
Many  of  them  may  be  thrown  down  from  then  solutions  by  absolute  alcohol, 

7 


98  PHYSIOLOGY 

but  are  not  rendered  insoluble  even  by  prolonged  standing  under  the  alcohol. 
The  characters  of  the  different  members  of  these  groups  will  be  considered 
at  greater  length  when  dealing  with  the  changes  undergone  by  the  proteins 
during  the  process  of  digestion.  At  present  we  may  merely  summarise  the 
distinguishing  features  of  these  two  classes. 

(a)  Proteoses,  e.g.  albumose  from  albumin,  caseose  from  casein,  elastose 
from  elastin.  All  of  these  are  precipitated  from  their  solutions  on  saturation 
with  ammonium  sulphate.  In  the  presence  of  a  neutral  salt  they  give  a 
precipitate  on  the  addition  of  nitric  acid.  This  precipitate  is  dissolved 
on  heating  the  solution,  but  reappears  on  cooling.  All,  with  the  exception  of 
heteroalbumose,  are  soluble  in  pure  water,  and  all  are  soluble  in  weak 
salt  solutions  or  dilute  acids  or  alkalies.  They  are  slightly  diffusible  through 
animal  membranes. 

(b)  Peptones,  e.g.  fibrin  peptone,  gluten  peptone.  These  are  all  soluble 
in  pure  water,  diffuse  fairly  readily  through  animal  membranes,  but  other- 
wise give  the  same  reactions  as  albumoses.  From  the  latter  class  peptones 
are  distinguished  by  the  fact  that  they  are  not  precipitated  on  saturation  of 
their  solutions  either  in  acid  or  alkaline  reaction  with  ammonium  sulphate 
or  any  other  neutral  salt.     Many  of  them  are  soluble  in  alcohol. 

(8)  THE  PHOSPHOPROTEINS.  In  this  class  may  be  grouped  a  number 
of  substances  of  very  diverse  properties,  which  however  resemble  one 
another  in  containing  phosphorus  as  an  integral  part  of  their  molecule. 
When  subjected  to  digestion  with  pepsin  and  hydrochloric  acid  they  are 
dissolved,  but  a  small  quantity  of  a  phosphorus-containing  complex  may 
remain  behind  undissolved.  This  residue  has  been  called  paranuclein  or 
pseudonuclein.  It  is  in  reality  derived  from  nucleoprotein,  which  is  present 
in  the  phosj^hoprotein  as  impurity  and  should  be  called  simply  nuclein.  The 
phosphoproteins  have  markedly  acid  characters.  They  are  insoluble  in  pure 
water,  easily  soluble  in  alkalies  and  ammonia  from  which  the  original  body 
is  thrown  down' again  on  addition  of  acid.  Their  solutions  in  alkali  are  not 
coagulated  by  heating.  To  this  class  belong  caseinogen,  the  chief  protein  of 
milk,  vitellin,  the.  main  protein  in  the  yolk  of  egg,  and  the  vitellins  in  the  eggs 
of  fishes  and  frogs.  The  vitellins  are  generally  associated  with  a  large  amount 
of  lecithin.  The  phosphoproteins  differ  from  the  nucleoproteins,  which  also 
contain  phosphorus,  in  the  facts  that  they  are  readily  decomposed  by  caustic 
alkali  with  the  liberation  of  phosphoric  acid,  and  do  not  contain  purine 
bases.  The  phosphorus  of  the  nucleoproteins  is  not  split  off  by  alkali 
(1  per  cent.),  and  on  hydrolysis  the  nucleic  acid  constituent  gives  rise  to 
purine  bases. 

(9)  CONJUGATED  PROTEINS.  Various  complex  bodies  which  play  an 
important  part  in  building  up  cells  and  in  the  various  processes  of  the  body 
make  up  this  group  of  compounds.  They  resemble  one  another  only  in  the 
fact  that  in  each  of  them  a  protein  radical  is  combined  with  some  other  body, 
often  spoken  of  as  the  prosthetic  group.* 

*  By  the  Germans  the  term  '  proteid  '  is  often  applied  to  this  group.  In  English 
however  the  term   '  proteid  '  has  been  generally  used  for  the  simple  protein  known 


THE  PROTEINS  99 

(a)  Chromoproteins.  Of  this  class,  consisting  of  a  colouring-matter 
combined  with  a  protein,  the  most  important  is  haemoglobin.  This  substance, 
which  is  the  red  colouring-matter  of  the  red  corpuscles  of  the  blocd  and  plays 
an  important  part  in  the  processes  of  respiration,  acting  as  an  oxygen  carrier 
from  the  lungs  to  the  tissues,  is  composed  of  the  protein,  globin,  united  with 
an  iron-containing  body,  hsematin.  Oxyhaemoglobin  contains  from  4-5  per 
cent,  haematin  (C32H32N404Fe).  It  is  easily  crystallisable,  and  its  physical 
and  chemical  characters  have  therefore  been  more  precisely  determined  than 
is  the  case  with  most  other  members  of  the  group  of  conjugated  proteins.  We 
shall  have  to  deal  more  fully  with  its  properties  in  the  chapters  on  Blood  and 
Respiration. 

(h)  The  Nucleoproteins.  These  are  formed  by  the  combination  of  a 
phosphorised  organic  acid,  nucleic  acid,  with  a  protein  which  may  belong  to 
any  of  the  classes  we  have  enumerated  above.  Some  of  the  best-marked 
members  of  this  group  consist  of  compounds  of  nucleic  acid  with  basic  histones 
or  protamines.  The  combination  between  protein  and  the  prosthetic  group 
seems  to  take  place  in  two  stages.  If  a  nucleoprotein  be  subjected  to  gastric 
digestion  a  large  amount  of  the  protein  goes  into  solution  as  proteose  or 
peptone,  leaving  an  insoluble  remainder.  This  precipitate  is  not  however 
nucleic  acid,  but  still  contains  a  protein  group,  the  compound  being  spoken 
of  as  nuclein.  From  the  latter  nucleic  acid  can  be  split  off  by  heating  with 
strong  acids  or  other  means.  The  nucleoproteins  are  soluble  in  water  and 
salt  solutions,  and  are  easily  soluble  in  dilute  alkalies.  They  have  acid 
characters  and  are  precipitated  by  the  addition  of  acids.  The  nucleins,  on 
the  other  hand,  are  insoluble  in  water  and  salt  solutions,  but  are  easily 
dissolved  by  dilute  alkalies.  The  nucleins  and  nucleoproteins  form  the  chief 
and  invariable  constituent  of  cell  nuclei.  They  may  be  therefore  prepared 
from  the  most  diverse  organs.  The  heads  of  the  spermatozoa  of  the  salmon 
consist  entirely  of  nuclein.  Miescher  and  Schmiedeberg  found  that  the 
nuclein  obtained  from  this  source  contained  60 -5  per  cent,  nucleic  acid  and 
35*56  protamine,  and  was  in  fact  a  nucleate  of  protamine.  The  nuclein 
derived  from  the  spermatozoa  of  echinoderms  has  been  found  to  be  a  com- 
pound of  nucleic  acid  and  histone.  From  organs  rich  in  cells,  such  as  the 
thymus  and  the  pancreas,  and  from  nucleated  red  blood-corpuscles,  nucleo- 
proteins may  be  obtained  which  can  be  broken  down  into  nuclein  and  protein, 
the  nuclein  again  being  composed  of  a  protein  residue  with  nucleic  acid. 

As  first  extracted  from  the  animal  cell  the  nucleoproteins  are  associated  with  a 
considerable  proportion  of  lecithin,  and  in  this  labile  compound  form  the  '  tissue 
fibrinogen  '  of  Wooldridge.  To  prepare  this  substance  an  organ  rich  in  cells,  such  as 
the  thymus,  is  minced  and  extracted  with  water  or  normal  salt  solution.  After  separa- 
ting the  cells  by  means  of  the  centrifuge,  the  clear  fluid  is  decanted  off  and  acidified 
with  acetic  acid.  A  precipitate  is  produced  consisting  of  '  tissue  fibrinogen.'  This 
substance  is  soluble  in  excess  of  acid  and  is  easily  soluble  in  alkalies.     All  the  tissue 

to  the  Germans  as  '  Eiweisskorper.'  On  account  of  the  confusion  which  has  risen 
from  this  double  use  of  the  term  '  proteid,'  I  have  attempted  to  avoid  it  altogether  in 
this  volume. 


100  PHYSIOLOGY 

fibrinogens  arc  highly  unstable  bodies  and  undergo  changes  in  the  mere  act  of  pre- 
cipitation and  re  Bolution.  When  injected  into  the  blood  they  cause  intravascular 
clotting.  On  digestion  with  gastric  juice  they  yield  a  precipitate  of  nuclein,  and  this 
precipitate  contains  a  large  proportion  of  the  lecithin  present  in  the  original  substance. 
In  the  nucleoproteins  nucleic  acid  is  combined  with  proteins  in  two  degrees,  a  large 
portion  of  the  protein  being  separable  by  gastric  digestion,  while  the  remainder  needs 
stronger  reagents  for  its  dissociation.  The  relation  of  the  two  portions  of  the  nucleo- 
protein  may  be  represented  therefore  by  the  following  schema  : 

Nucleo-protein 

Protein  Nuclein 

Protein  Nucleic  acid 

(generally  histone 
or  protamine) 

By  various  means,  all  .of  which  involve  hydrolysis,  the  nucleic  acid  may 
be  broken  up  into  its  proximate  constituents.  These  differ  according  to 
the  source  of  the  nucleic  acid.  Whatever  the  source,  the  disintegration 
products  belong  to  closely  allied  groups  of  substances.  These  may  be 
grouped  as  follows  : 

(1)  Phosphoric  Acid.  The  proportion  of  phosphorus  varies  within  but 
narrow  limits  in  the  different  nucleic  acids,  the  average  being  about  10  per 
cent.  It  is  probable  that  the  phosphoric  acid  represents,  so  to  speak,  the 
combining  medium  for  the  groups  contained  in  the  nucleic  acid  molecule,  as 
is  the  case  with  the  various  groups  wThich  make  up  the  lecithin  molecule. 

(2)  The  Purine  Bases.  Among  the  products  of  disintegration  of  nucleic 
acid  we  find  constantly  one  of  the  bases  adenine,  C5H5N5,  and  guanine 
(C5H5N50).  These  substances,  with  the  products  of  their  oxidation,  xan- 
thine. C5H4N402,  hypoxanthine,  C6H4N,0,  have  long  been  known  to  be 
closely  allied  to  uric  acid,  C5H4N403,  but  their  true  relationships  have  only 
been  thoroughly  known  since  the  researches  of  Fischer  on  this  group. 
According  to  Fischer  they  can  be  all  regarded  as  derivatives  of  the  body 
purine, 

!N=6CH 

I  I 

2HC    5C— NH7 

II  I!  >H8 
3N— K'— N9  '' 

Each  grouj)  in  this  purine  ring  is  generally  designated  with  a  number  indicated 
in  the  structural  formula,  in  order  that  it  may  be  possible  to  represent  the 
position  of  any  substituted  groups  in  its  derivatives.  Uric  acid  itself  is 
2-6-8- trioxyp urine  with  the  following  formula  : 

HN— CO 

I       I 
OC     C— NH 

I     II         >co 
HN— C— NH 


THE   PROTEINS    ■  101 

It  can  be  synthetised  by  fusing  together  in  a  sealed  tube  trichlorolactamide 
and  urea.     Thus : 

NH,    CONH2  NH— CO 

r    i  ii 

CO    +  CHOH  +  NH„  =     CO      C—  NH  +  NH4C1.  +  2HC1 

I  I  >CO  I         ||  >CO 

NH2     CC13  NH./  NH— C—  NHX 

The  relation  of  xanthine,  hypoxanthine,  guanine,  and  adenine  to  uric  acid 
is  shown  by  the  following  formulae  : 


NH— CO  HN CO 

II  II 

CO      C— NH  CO— C— NH 

I       II         >co  Vh 

NH— C— NH  HN C— N  '' 

Uric  acid  Xanthine 

2-6-8-trioxypurine  2-6-dioxy  purine 


HN— CO 

i       i 

N 
i 

-  C.NH2 
i 

NH— CO 

1       1 
HC     C— NH 

1 
HC 

1 
C— NH 

1           1 
NH2C        C— NH 

II       II            V'H 
N— C  — N  * 

II 
N- 

II        )c» 

-    C— N     ^ 

II          II          JCH 

N—     C— N  # 

Hypoxanthine 

Adenine 

Guanine 

6-oxypurine 

6-amino-purine 

2 -amino  6-oxypurine 

Closely  allied  to  this  gronp  of  bodies  are  the  chief  constituents  of  tea, 
coffee,  and  cocoa,  namely  caffeine,  which  is  trimethyl  dioxypurine,  and 
theobromine,  which  is  dimethyl  dioxypurine.  From  the  structural  formulae 
given  it  will  be  seen  that  the  purine  radical  contains  two  nuclei.  The 
nucleus 

N—  C 

I  I 

c    c 

I   I 

N— C 
is  spoken  of  as  the  pyrhnidine  nucleus,  pyrimidine  havmg  the  formula 

1N=6CH 

I       I 
2HC    5CH 
I       II 
3N— 4CH 

The  other  is  the  radical  which  we  have  met  with  already  in  histidine,  a 
disintegration  product  of  proteins,  namely  imuiazol : 

HC— NH 

II  )CH 
HC— N    '' 

Besides  the  purine  bases  proper,  we  find  among  the  disintegration  products 
of  nucleic  acid  a  series  of  bases  derived  from  the  pyrimidine  ring.     These 
are  uracil,  thymine,  and  cytosine. 
Uracil  is  2-6-dioxvpvrimidine, 


102 


PHYSIOLOGY 

NH-  •( II ) 

I  I 

CO—  CH 


Thymine  is  5- methyl  uracil, 


NH— CH 


NH— 'CO 
I  I 

CO     Ci'H., 

I        II 
NH— CH 


while  oytosine  is  G-amino-2-oxvpvrimidine, 

N     =C.NH, 

I  I 

CO      CH 

I  II 

NH-  CH 

Besides  these  two  groups  of  nitrogenous  compounds  derived  from  the 
purine  and  pyrimidine  rings,  many  nucleic  acids  yield  on  hydrolysis  a  carbo- 
hydrate. Thus  Hammarsten  has  isolated  a  pentose  from  the  nucleo- 
proteins  of  the  pancreas.  It  is  supposed  that  the  nucleic  acid  of  the  thymus 
gland  contains  a  hexose,  since  it  is  possible  to  split  off  from  it  lsevulinic  acid, 
which  is  one  of  the  first  products  of  the  decomposition  of  a  hexose.  The 
complex  constitution  of  the  nucleic  acids  and  nucleoproteins  may  be 
rendered  clearer  from  the  following  schema  : 


on  digestion  yields 


Nucleo-protein 


nuclein         proteoses  and  peptones 


dissolved  in  alkali  and  precipitated  with  hydrochloric  acid 
yields 


nucleic  acid  acid  derivatives  of  protein,  histories  or  protamines 

hydrolysed  yields 


phosphoric  acid 


reducing  sugar 
pentose  or 
hexose 


purine  bases 
adenine 
guanine 


pyrimidine 
uracil 
thymine 
cytosine 


It  must  not  be  imagined,  however,  that  all  these  disintegration  products 
are  present  in  all  nucleic  acids.  Thus  the  nucleic  acid  derived  from  the 
pancreas,  the  so-called  guanylic  acid,  yields  of  the  purine  bases  only  guanine, 
and  of  the  pyrimidine  bases  only  thymine  and  uracil,  and  every  variety  is 
met  with  as  we  analyse  the  nucleic  acids  of  different  origin.  The  fact  that 
nucleic  acid  is  a  characteristic  and  necessary  constituent  of  all  nuclei  adds 
interest  to  the  divergence  of  its  constituent  radicals  from  those  which  dis- 
tinguish the  proteins  of  the  cell  protoplasm.     Further  importance  is  lent  to 


THE  PROTEINS  103 

this  section  of  the  chemistry  of  the  body  by  the  close  relationship  which  we 
shall  have  to  study  later  between  the  nuclein  metabolism  of  the  body  and 
the  production  and  excretion  of  uric  acid. 

The  researches  ofLevenehave  thrown  light  on  the  manner  in  which  these  different 
groups  are  bound  together  to  form  nucleic  acid.  In  the  acid  obtained  from  the  thymus 
the  carbohydrate  group  Hexose  is  joined  to  a  nitrogenous  ring  compound,  forming 
what  is  termed  a  'nucleoside.'  Four  of  these  nucleosides,  in  thymic  acid,  join 
with  four  molecules  of  phosphoric  acid  to  form  a  '  tetra-nucleotide.'  The  formula 
provisionally  assigned  to  thymic  acid  is  therefore  as  follows  : 

HO 

O  =  PO-C6H10O4 C6H4N50 

guanine  group 
HO  O 

I 


0  =  PO C„HaO, C,,H,N.,0 


HO 
HO 


thymine  group 


O 


0     PO      -    C6H80, e^N-jO 

eytosine  group 
HO 


0=PO CsH10O4-C?H4NB 

adenine  group 
HO 

Other  nucleic  acids  are  simpler  in  constitution  and  may  be  composed  of  only  one 
or  two  nucleotide  groups.  Thus  the  inosinie  acid  of  muscle  is  a  mono-nucleotide,  con- 
sisting of  phosphoric  arid  linked  by  a  pentose  group  with  hypoxanthine.  The  defi- 
nition of  a  nucleotide  would  thus  be  a  compound  in  which  a  carbohydrate  group  links 
a  phosphoric  acid  group  witli  a  purine  or  a  pyrimidine  group.  Nucleic  acids  are  simple 
or  compound  nucleotides.  The  pentose  in  inosinie  acid  is  d-Ribose.  The  same 
pentose  occurs  in  yeast  nucleic  acid.  The  nucleic  acid  of  the  pancreas,  also  called 
Guanylic  acid,  ((insists  of  phosphoric  acid  linked  with  guanine  by  a  molecule  of  d-Ribose. 

(c)  The  Glycoproteins.  In  the  glycoproteins  the  prosthetic  group  is 
represented  by.  a  carbohydrate  radical,  generally  containing  nitrogen,  such 
as  glucosamine  or  galactosamine.  They  are  split  into  their  two  constituents, 
protein  and  carbohydrate  radical,  on  prolonged  boiling  with  dilute  mineral 
acids  or  by  the  action  of  alkalies.  They  may  be  divided  into  the  two  main 
groups  of  mucins  and  mucoids. 

The  mucins  play  a  large  jjart  in  the  animal  kingdom  as  protective  agents. 
They  form  the  slimy  secretion  which  covers  the  inner  surface  of  the  mucous 
membranes  and  the  outer  surface  of  many  marine  animals,  and  is  secreted 
either  by  the  goblet  cells  of  the  epithelium  or  by  special  groups  of  cells 
collected  together  to  form  a  mucous  gland.'.;  They  may  be  precipitated  from 
their  solutions  or  semi-solutions  by  the  addition  of  acids,  and  after  precipita- 
tion need  the  addition  of  alkalies  for  their  re-solution.     They  are  not  coagu- 


104  PHYSIOLOGY 

lable  by  heat.  The  presence  of  their  protein  moiety  causes  them  to  give 
the  various  typical  protein  tests,  such  as  the  xanthoproteic,  Millon's,  the 
biuret  reactiou,  ami  so  on,  Prolonged  boiling  with  acids  splits  the  molecule, 
with  the  production  of  acid  metaprotein  and  albumoses  and  glucosamine. 
From  the  mucin  of  frogs'  eggs  a  similar  treatment  results  in  the  production 
of  galactosamine. 

With  the  mucins  may  be  classified  certain  bodies  which  have  been  derived  from 
ovarian  cysts,  namely,  pseudomucin  and  paramucin.  Pseudomucin  occurs  as  a  con- 
stituent of  the  colloid  material  from  ovarian  tumours.  It  forms  slimy  solutions  which 
do  not  coagulate  by  heat  and  are  not  precipitated  by  acetic  acid.  It  is  precipitated 
by  alcohol,  the  precipitate  being  soluble  in  water  even  after  standing  a  long  time  under 
the  alcohol.  On  boiling  with  ,acid  it  gives  a  reducing  substance.  Paramucin  differs 
from  the  above  in  reducing  Fehling's  solution  before  boiling  with  acids.  Otherwise 
it  resembles  pseudomucin.  Leathes,  in  investigating  this  body,  isolated  from  it  a 
reducing  substance  which  apparently  was  an  ammo-derivative  of  a  disaccharide, 
perhaps  in  combination  with  glycuronic  acid. 

The  mucoids  include  a  number  of  substances  which  may  be  extracted 
from,  various  tissues  by  the  action  of  weak  alkalies,  e.g.  from  tendons,  bone, 
and  cartilage.  The  best  studied  example  of  this  group  is  the  chondromueoid 
which,  wTith  collagen,  forms  the  ground  substance  of  cartilage.  Chondro- 
mueoid is  especially  rich  in  sulphur  and  gives  protein  by  long  treatment  with 
weak  alkali.  On  boiling  for  a  short  time  with  acid  it  is  decomposed  into 
sulphuric  acid  and  chondroitin,  and  this  latter,  on  further  action  of  the  acid, 
is  converted  into  a  substance  chondrosin,  which  is  certainly  an  amino- 
derivative  of  a  polysaccharide  containing  the  elements  of  glycuronic  acid 
and  an  amino-disaccharide.  Chondroitin-sulphuric  acid  occurs  not  only  in 
cartilage  but  also  in  bone,  yellow  elastic  tissue,  white  fibrous  tissue,  and  as  a 
constant  constituent  of  the  lardacein  or  amyloid  substance  which  occurs  as  a 
deposit  in  the  middle  coat  of  the  blood-vessels  as  the  result  of  syphilis  or 
long-continued  suppuration,  and  gives  rise  to  the  condition  known  as  '  lar- 
daceous  disease.'  Another  example  of  this  class  of  mucoids  is  ovomucoid, 
which  is  a  constituent  of  egg-white.  In  order  to  prepare  ovomucoid  the 
globulin  and  albumin  are  precipitated  by  boiling  diluted  egg-white.  From 
the  filtrate  ovomucoid  can  then  be  thrown  down  by  alcohol.  A  similar  body 
has  been  prepared  from  blood  serum.  Both  these  mucoids  yield  a  large 
amount  of  reducing  substance  on  hydrolysis.  Thus  from  100  grm.  of  ovo- 
mucoid it  is  possible  to  prepare  30  grm.  of  glucosamine. 

(10)  THE  ALBUMINOIDS  OR  SCLERO-PROTEINS.  Under  this  heading 
are  grouped  a  number  of  diverse  substances  which  play  an  important  part 
in  building  up  the  framework  of  the  body.  Their  value  as  skeletal  tissue 
seems  to  be  determined  by  their  insoluble  character.  On  this  account  it  is 
practically  impossible  to  speak  of  purifying  them.  In  every  case  wre  can 
simply  take  the  residue  of  a  skeletal  tissue  which  is  left  after  extraction  of 
the  soluble  constituents.  When  broken  down  by  the  action  of  strong  acids, 
they  yield  a  series  of  disintegration  products  which  are  included  among  those 
we  have  already  studied  as  the  disintegration  products  of  proteins.  Their 
difference  from  the  proteins  w?hich  are  employed  in  metabolism  for  their 


THE  PROTEINS  105 

nut  ritive  value  is  caused  either  by  the  absence  of  certain  groups  common  to 
all  the  nutritive  proteins,  by  the  presence  of  an  excess  of  one  or  two  groups, 
or  by  the  presence  of  certain  polypeptides  which  present  considerable  resist- 
ance to  the  action  of  digestive  ferments.  This  class  plays  the  part  in  the 
animal  economy  which  in  the  vegetable  kingdom  is  rilled  by  the  anhydrides 
of  the  hexoses  and  pentoses,  e.g.  the  celluloses,  lignin,  the  pentosanes,  &c. 
Collagen  forms  the  main,  constituent  of  white  fibrous  tissue  and  the  ground 
substance  of  bone  and  cartilage.  It  is  insoluble  in  water,  hot  or  cold,  and  in 
trypsin.  Under  the  action  of  acids  or  when  subjected  to  prolonged  boiling 
with  water,  especially  under  pressure,  it  is  converted  into  gelatin,  which  is 
soluble  in  hot  water,  forming  a  colloidal  solution  liquid  at  high  temperatures, 
but  setting  to  a  jelly  when  cold.  When  subjected  to  acid  hydrolysis  it  gives 
a  series  of  amino-acids  from  which  tyrosine  and  tryptophane  are  wanting. 
On  this  account  gelatin  does  not  give  any  reaction  either  with  Millon's 
reagent  or  with  glyoxylic  acid.  On  the  other  hand,  there  is  a  preponderance 
of  such  groups  as  glycine  and  phenylalanine,  and  it  is  probable  that  glycine, 
phenylalanine,  and  leucine  are  joined  together,  perhaps  with  other  amino- 
acids,  to  form  a  polypeptide  which  is  not  attacked  by  digestive  ferments,  and 
therefore  determines  the  resistance  of  the  original  collagen  molecule  to  solu- 
tion. Gelatin  is  precipitated  by  tannic  acid,  but  not  by  acetic  acid.  It  is 
dissolved  with  hydrolysis  by  gastric  juice  or  by  pancreatic  juice,  whereas 
collagen,  its  anhydride,  is  unaffected  by  the  latter.  On  prolonged  boiling  in 
water  it  is  converted  into  a  modification  which  does  not  form  a  jelly  on 
cooling.  Under  the  action  of  formaldehyde  it  is  converted  into  an  insoluble 
modification  which  does  not  melt  on  warming. 

Beticulin.  This  name  has  been  applied  to  the  tissue  which  forms  the  supporting 
network  of  adenoid  tissue,  and  has  also  been  described  in  the  spleen,  the  mucous  mem- 
brane of  the  intestine,  liver,  and  kidneys.  It  differs  from  collagen  in  resisting  digestion 
by  gastric  juice,  and  also  in  containing  phosphorus  in  organic  combination.  According 
to  Halliburton  there  is  no  essential  difference  between  reticulin  and  collagen. 

The  keratins  are  produced  by  the  modification  of  epithelial  cells  and 
form  the  horny  layer  of  the  skin  as  well  as  the  main  substance  of  hairs, 
wool,  nails,  hoofs,  horns,  and  feathers.  They  are  distinguished  by  their 
insolubility  in  water,  dilute  acids  or  alkalies,  and  in  the  higher  animals 
pass  through  the  alimentary  canal  unchanged.  Although  differing  in  their 
elementary  composition,  according  to  the  tissue  from  which  they  are  pre- 
pared, they  are  all  distinguished  by  the  very  large  amount  of  sulphur  present 
in  their  molecule.  The  greater  part  of  this  sulphur  is  in  the  form  of  cystine, 
i  if  which  as  much  as  10  per  cent,  can  be  extracted  from  keratin.  They  also 
yield,  on  acid  hydrolysis,  tyrosine  in  larger  quantities  than  is  the  case  with 
the  ordinary  proteins. 

Neurokeratin,  which  forms  the  basis  of  the  neuroglial  framework  of  the 
central  nervous  system,  must  be  grouped  by  its  general  behaviour  as  well  as 
by  its  origin  with  the  keratins.  It  resembles  the  other  members  of  this  class 
in  its  insolubility  and  in  its  high  content  in  sulphur.  It  is  extracted  from 
nervous  tissues  by  boiling  these  with  alcohol  and  ether  and  then  submitting 


io<> 


PHYSIOLOGY 


tin-  tissue  to  prolonged  tryptic  digestion,  which  leaves  the  neurokeratin 
unaffected. 

Elastin  is  a  constant  constituent  of  the  connective  tissues,  where  it  forms 
the  elastic  fibres.     In  some  localities,  as  in  the  ligamentum  nuchse,  practically 


Fibroin 

Keratin 

Keratin 

Keratin 

of 

Elastin 

from 

from 

from 

Gelatin 

silk 

horn 

horsehair 

feathers 

Glycine   .... 

3(50 

25-75 

0-45 

4-7 

2-6 

16-5 

Alanine   . 

2111 

6-6 

1-6 

1-5 

1-8 

0-8 

Amino-valerianic  acid 

on 

Ml 

4-5 

0-9 

0-5 

10 

Proline    . 

present 

1,7 

5-2 

Leucine  . 

1-5 

21  4 

15-3 

71 

8-0 

21 

Phenylalanine 

1-5 

3-9 

1-9 

0-0 

lid 

0-4 

Glutamic  acid 

0-0 

0-8 

17-2 

3-7 

2-3 

0-88 

Aspartic  acid 

present 

prewut 

2-5 

0-3 

11 

0-56 

Cystine   . 

— 



7-5 

— 

— 

Serine 

1-6 

— 

11 

0-6 

0-4 

0-4 

Tyrosine . 

10-5 

0-34 

3-6 

3-2 

30 

0'C 

Tryptophane 

— 

— 

— 

— 

— 

00 

Lysine     . 

traces 

— 

0-2 

11 

— 

2-75 

Arginine. 

10 

0-3 

2-7 

4-5 

— 

7-62 

Histidine 

small 

— 

— 

0-6 

-~ 

o-4 

Oxypniliiic 

— 

— 

— 

— 

— 

30 

the  whole  tissue  is  made  up  of  these  fibres.  Elastin  is  insoluble  in  water, 
alcohol,  or  ether,  or  in  dilute  acids  and  alkalies.  It  is  slowly  dissolved  on 
'prolonged  treatment  with  gastric  juice,  but  is  practically  unaffected  in  the 
alimentary  canal.     It  gives  the  xanthoproteic  and  Millon's  tests. 

Other  members  of  this  group  are  fibroin,  which  forms  the  main  substance  of  silk, 
spongin,  the  horny  framework  of  sponges,  conchioiin,  the  ground  substance  of  shells, 
and  perhaps  the  amyloid  substance  or  lardacein  which  we  have  already  mentioned  in 
connection  with  the  mucoids.  All  these  sclero -proteins  present  considerable  differ- 
ences in  their  qualitative  and  quantitative  composition  in  amino-acids.  Their  proxi- 
mate composition  is  shown  in  the  Table  given  above  (Abderhalden). 

We  have  finally  to  mention  a  miscellaneous' collection  of  bodies  which  are  allied 
to  the  proteins  and  are  distinguished  by  their  extreme  insolubility.  They  are  often 
designated  as  albumoids.  Of  their  composition  we  know  practically  nothing.  Under 
this  name  are  grouped  such  substances  as  those  forming  the  membrana  propria  of 
glands,  the  sarcolemma  of  striated  muscle,  the  albumoid  of  the  crystalline  lens,  the 
ground  substance  of  the  chorda  dorsalis,  the  organic  basis  of  fish  scales,  and  many 
similar  substances.  In  every  case  the  substance  is  characterised  necessarily  according 
to  its  place  of  origin,  little  or  nothing  being  known  as  to  its  chemical  composition. 


SECTION  VI 

THE    MECHANISM   OF   ORGANIC   SYNTHESIS 

THE  ASSIMILATION  OF  CARBON 

The  building  up  of  protoplasm  from  the  material  which  is  available  at  the 
earth's  surface  must  be  an  endothermic  process.  The  food  presented  to  the 
plant  contains  the  necessary  elements,  but  as  a  rule  in  a  state  of  complete 
oxidation.  The  energy  of  the  living  plant,  as  of  animals,  is  derived  almost 
entirely  from  the  oxidation  of  its  constituents.  The  building  up  of  un- 
organised into  organised  material  must  therefore  be  effected  at  the  expense 
of  energy  supplied  from  without.  The  source  of  this  energy  is  the  sun's  rays. 
The  machine  for  the  conversion  of  solar  radiant  energy  into  the  chemical 
potential  energy  of  protoplasm  is  the  green  leaf.  Here  a  deoxidation  of  the 
carbon  dioxide  of  the  atmosphere  takes  place,  with  the  production  of  carbo- 
hydrates, generallv  in  the  form  of  starch.  The  formation  of  starch  must  be 
regarded  as  the  first  act  in  the  life-cycle,  since  this  substance  serves  as  a 
source  of  energy  to  the  already  formed  protoplasm  in  its  work  of  building  up 
all  the  other  constituents  of  the  living  cell.  It  is  the  solar  energy  captured 
by  the  green  leaf  which  is  utilised  by  all  plants  devoid  of  chlorophyll,  as  well 
as  by  the  whole  animal  kingdom. 

There  are  one  or  two  exceptions  to  this  statement.  Thus  the  bacterium  nitro- 
somonas,  described  by  Winogradsky,  grows  on  a  medium  devoid  of  all  organic  con- 
stituents, and  derives  the  energy  for  its  constructional  activity  from  that  set  free  in 
the  conversion  of  ammonia  into  nitrites.  The  sulphur  bacteria  apparently  derive 
their  energy  from  the  decomposition  of  hydrogen  sulphide  and  the  liberation  of  sulphur. 

The  fundamental  importance  of  this  process  of  assimilation  for  the  whole 
of  physiology  justifies  some  account  of  the  researches  which  have  been 
directed  to  the  elucidation  of  its  mechanism.  The  production  of  oxygen  by 
the  green  plant  wras  discovered  by  Priestley  in  1772,  and  a  few  years 
later  Ingenhaus  showed  that  this  production  occurred  only  in  the  light  and 
was  effected  only  by  green  plants.  '  De  Saussure  (1804)  pointed  out  that  the 
essential  process  concerned  was  a  setting  free  of  the  oxygen  from  the  carbon 
dioxide  of  the  atmosphere,  and  recognised  that  the  co-operation  of  water 
was  also  necessary.  Mohlin  1851  observed  the  formation  of  starch  grains 
in  the  chlorophyll  corpuscles,  and  regarded  these  as  the  first  products  of 
assimilation.  The  organs  of  carbon  dioxide  assimilation  are  the  chloroplasts. 
These,  which  are  responsible  for  the  green  colour  of  plants,  are  generally 
small  oval  bodies  embedded  in  the  cytoplasm,  but  sometimes,  as  in  spirogyra, 
ma)7  have  the  form  of  spiral  bands.  In  a  plant  which  has  been  kept  for  some 
time  in  the  dark,  or  in  an  atmosphere  free  from  carbon  dioxide,  they  present 

107 


108  PHYSIOLOGY 

no  enclosed  grannies.  Within  three  to  five  minutes  after  exposure  to  light 
in  the  presence  of  carbon  dioxide,  starch  granules  make  their  appearance 
within  them,  and  grow  rapidly,  assuming  the  typical  laminated  structure. 
Bngelmann  has  pointed  out  a  means  by  which  it  can  be  proved  that  the 
chloroplasts  carry  out  this  process  without  the  co-operation  of  the  rest  of  the 
cytoplasm.  Certain  bacteria  have  a  great  avidity  for  oxygen  and  present 
movements  only  in  the  presence  of  this  gas.  If  a  filament  of  spirogyra  be 
placed  in  a  suspension  of  these  bacteria  and  be  examined  under  a  microscope, 
the  bacteria  will  be  seen  to  congregate  in  the  immediate  neighbourhood  of  the 
chlorophyll  bands.  The  same  phenomenon  is  observed  in  the  case  of 
chlorophyll  corpuscles  isolated  by  breaking  up  the  cells  in  which  they  were 
contained.  These  corpuscles  therefore  take  up  carbon  dioxide  and  water, 
and  form  carbohydrate  and  oxygen,  as  follows : 

n(6C02  +  5H20)  =  (C,H10O6)n  +  n(602) 

The  whole  structure  of  the  green  leaf  is  directed  to  the  furthering  of  this 
process.  Its  cells  contain  chlorophyll  corpuscles,  which  change  their  position 
according  to  the  intensity  of  the  illumination.  A  free  supply  of  air  to  all 
the  cells  is  provided  by  means  of  the  stomata  on  the  under  surface  of  the 
leaf.  Horace  Brown  has  shown  that  the  rate  at  which  carbon  dioxide  diffuses 
through  such  fine  openings  is  as  great  as  if  the  whole  leaf  were  an  absorbing 
surface.  We  get  therefore  optimum  absorption  of(  carbon  dioxide  by  the 
leaf,  with  the  maximum  protection  of  the  absorbing  tissue  and  the  necessary 
limitation  of  loss  of  water  by  transpiration. 

In  view  of  the  very  small  amount  of  carbon  dioxide  in  the  atmosphere, 
the  extent  of  the  assimilatory  process  is  remarkable.  One  square  metre  of 
leaf  of  the  catalpa  can  lay  on  1  grm.  of  solid  per  hour,  using  up  for  this  pur- 
pose 784  ccm.  carbon  dioxide.  The  rapidity  of  assimilation  is  increased 
within  limits  by  increasing  the  intensity  of  the  light  falling  on  the  plant, 
though  an  over-stimulation  of  the  process  is  prevented  by  the  movements  of  - 
the  chloroplasts  just  mentioned.  It  is  also  increased  by  raising  the  per- 
centage of  carbon  dioxide  in  the  atmosphere  supplied  to  the  leaf.  Ihe 
optimum  percentage  of  carbon  dioxide  will  of  course  vary  with  the  other 
conditions  of  the  leaf.  In  certain  experiments  Kreusler  found  the  optimum 
to  be  about  1  per  cent.  Taking  the  amount  of  assimilation  in  normal  air  with 
•03  per  cent,  carbon  dioxide  at  100,  the  assimilation  in  an  atmosphere  con- 
taining 1  per  cent,  was  237,  and  was  not  increased  by  raising  the  percentage 
of  carbon  dioxide  to  7  per  cent.  Owing  to  the  decomposition  of  the  organic 
matter  of  the  soil,  the  percentage  of  carbon  dioxide  near  the  ground  is  always 
greater  than  in  the  higher  strata  of  the  atmosphere — a  fact  which  is  taken 
advantage  of  by  the  low-growing  plants  and  herbage.  Other  necessary  con- 
ditions of  assimilation  are  the  presence  of  water  and  the  maintenance  of  a 
certain  external  temperature.  The  absorption  of  the  sun's  rays  by  the  leaf 
raises  the  temperature  of  the  latter  above  that  of  the  surrounding  medium, 
and  so  quickens  the  process  of  assimilation. 

The  assimilation  of  carbon  dioxide,  the  formation  of  starch,  and  the 


THE  MECHANISM  OF  OKGANIC  SYNTHESIS  109 

evolution  of  oxygen  will  go  on  in  the  isolated  chloroplast.  In  the  absence 
of  chlorophyll,  as  in  an  etiolated  leaf,  the  formation  of  starch  will  take  place 
if  the  plant  be  supplied  with  a  sugar  such  as  glucose,  and  this  conversion 
represents  the  main  function  of  the  hucoplasfs  present  in  all  the  cells  of  the 
reserve  organs  of  plants.  In  the  absence  of  chlorophyll  no  decomposition  of 
carbon  dioxide  takes  place,  so  that  this  pigment  is  evidently  essential  for 
the  utilisation  of  the  sun's  energy.  Chlorophyll  may  be  extracted  from 
leaves  by  means  of  absolute  alcohol.  A  solution  is  thus  obtained  which  is 
green  by  transmitted  and  red  by  reflected  light,  i.e.  chlorophyll  is  a  fluorescent 
substance.  It  presents  four  absorption  bands,  the  chief  being  an  intense 
black  band  between  Fraunhofer's  lines  B  and  C.  If  the  chlorophyll  is  the 
means  of  conversion  of  the  solar  into  chemical  energy,  the  conversion  must 
take  place  at  the  expense  of  the  light  which  is  absorbed  by  the  pigment. 
One  would  expect  therefore  the  process  of  assimilation  to  be  most'  pro- 
nounced in  those  parts  of  the  spectrum  corresponding  to  the  absorption 
bands — an  expectation  which  has  been  realised  by  experiment. 

As  to  the  exact  chemical  changes  effected  by  these  absorbed  rays  physio- 
logists are  still  undecided.  There  can  be  no  doubt  that  an  early  product  of 
the  process  is  a  hexose,  which  is  rapidly  converted  into  cane  sugar  or  into 
starch.  It  was  suggested  by  Baeyer  in  1870  that  carbon  dioxide  was 
reduced  to  formaldehyde,  which  later  by  condensation  yielded  sugar.  We 
know  that  formaldehyde  easily  polymerises  to  form  a  mixture  of  hexoses, 
but  until  recently  no  evidence  had  been  brought  forward  of  its  presence  as 
an  intermediate  product  in  the  assimilatory  process.  For  most  plants, 
indeed,  formaldehyde  is  extremely  poisonous,  though  certain  algse,  as  well 
as  the  water-plant,  Ebdea,  can  stand  a  solution  containing  -001  per  cent, 
formaldehyde.  Bokorny  stated  that  spirogyra  could  form  starch  out  of  such 
derivatives  of  formaldehyde  as  sodium  oxymethyl-sulphonate,  or  from 
methylal.  The  difficulty  in  these  cases  is  that  possibly  a  spontaneous 
formation  of  sugar  from  the  formaldehyde  had  taken  place  in  the  solution  and 
that  the  plants  were  using  up  the  sugar  rather  than  the  formaldehyde  as  the 
source  of  their  starch. 

One  must  assume,  with  Timiriazeff ,  that  the  function  of  chlorophyll  in 
the  process  of  assimilation  is  that  of  a  sensitiser.  Just  as  the  addition  of 
eosin  to  the  emulsion  used  for  coating  photographic  plates  will  render  these 
sensitive  to  the  red  and  green  parts  of  the  spectrum,  i.e.  will  excite  change  in 
the  silver  salt  when  light  from  these  parts  of  the  spectrum  falls  upon  it,  so 
the  chlorophyll  serves  as  a  means  by  which  the  absorbed  solar  energy  can  b'e 
utilised  for  the  production  of  chemical  change  in  the  chloroplast.  Attempts 
have  been  made  to  imitate  this  process  outside  the  plant.  Thus  Bach  passed 
a  stream  of  carbon  dioxide  through  a  1-5  per  cent,  solution  of  a  fluorescent 
substance,  uranium  acetate,  in  sunlight.  As  a  result  there  was  a  precipitate 
of  uranium  oxide  and  peroxide,  with  the  formation  of  traces  of  formaldehyde. 
Usher  and  Priestley,  on  treating  a  solution  of  carbon  dioxide  with  1-5  per 
cent,  uranium  acetate  or  sulphate  in  bright  sunlight,  obtained  uranium 
peroxide  and  formic  acid,  but  no  formaldehyde.     The  formation  of  peroxides 


110  PHYSIOLOGY 

in  these  conditions  suggests  that  the  first  change  in  the  chloroplast  may  be 
as  follows  : 

C02  +  3H20  =  2H202  +  CH20 

Such  a  reaction  must  be  regarded  as  reversible  since  the  hydrogen  per- 
oxide first  formed  would  tend  to  oxidise  the  formaldehyde  again.  Moreover 
it  would  have  a  destructive  influence  on  the  chlorophyll  itself,  which  is  easily 
oxidised.  In  order  therefore  that  the  reaction  should  go  on  in  one  direction 
only,  i.e.  that  of  assimilation,  means  must  be  present  in  the  chlorophyll  cor- 
puscles for  the  removal  of  both  hydrogen  peroxide  and  formaldehyde  as  soon 
as  they  are  formed.  The  removal  of  the  hydrogen  peroxide  can  be  effected 
by  a  catalase,  which  is  fairly  widely  distributed  in  plants  and  has  been  shown 
by  the  last-named  authors  to  be  present  in  the  chloroplasts.  In  order  to 
demonstrate  the  production  of  the  first  result  of  assimilation,  i.e.  formalde- 
hyde, the  further  stages  in  its  conversion  must  be  stopped  by  killing  the  plant 
and  the  catalase  it  contains.  They  therefore  placed  leaves,  which  had  been 
boiled,  in  water  saturated  with  carbon  dioxide  and  exposed  them  to  bright 
sunlight.  The  leaves  were  bleached  by  the  oxidation  of  the  chlorophyll,  and 
some  substance  of  an  aldehydic  nature  was  produced,  as  shown  by  the 
red  colour  obtained  on  placing  them  in  rosaniline,  previously  decolorised 
with  sulphurous  acid. 

Two  proofs  were  brought  forward  that  this  substance  was  formaldehyde  : 

(o)  Some  of  the  bleached  leaves  were  soaked  for  twelve  hours  in  aniline  water.     The 

chloroplasts  under  the  microscope  were  seen  to  contain  crystals  resembling   methylene 

aniline. 

(b)  The  leaves  were  distilled  in  a  current  of  steam.     The  distillate  was  shown  to 

contain  formaldehyde  by  the  formation  of  methylene  aniline  crystals  on  treatment 

with  aniline,  and  by  the  preparation  from  it  of  the  characteristic  tetrabrome  derivative 

of  hexamethylenetetramine. 

Usher  and  Priestley  conclude  that  the  first  products  of  the  photolysis 
of  carbonic  acid  are  hydrogen  peroxide  and  formaldehyde.  Both  these 
substances  are  rapidly  removed  from  the  reaction.  The  hydrogen  peroxide 
is  broken  up  by  the  catalase  into  water  and  oxygen  which  is  turned  out  by  the 
plant.  The  formaldehyde  is  at  once  polymerised  in  the  protoplasm  of  the 
chloroplast  with  the  formation  first  of  a  hexose  and  then  of  starch.  The 
formaldehyde,  if  not  removed  in  this  way,  destroys  the  catalase.  The 
hydrogen  peroxide,  if  not  broken  up  by  the  catalase,  destroys  the 
chlorophyll. 

The  relations  between  the  various  factors  in  this  process  may  be  dia- 
grammatically  expressed  thus  : 


THE  MECHANISM  OF  ORGANIC  SYNTHESIS  111 

Carbon  dioxide  +  Water 


I    f 
(//  not  removed,  destroys)^.     Chlorophyll 

r 


Hydrogen  peroxide  +  Formaldehyde 

,  (//  not  removed,  poisons)   * 
Enzyme  Living  protoplasm 

i  4 

Oxygen  ( 'arbohydrates 

In  thus  reducing  certain  of  the  stages  in  the  assimilation  of  carbon 
to  phenomena  which  can  be  imitated  outside  the  living  organism,  we  have 
made  considerable  strides  in  the  '  understanding  '  of  the  process.  The  stage 
for  which  the  vitality  of  the  chloroplast  is  absolutely  essential  is  the  formation 
of  starch  from  formaldehyde.  Outside  the  body,  our  polymerisation  of 
formaldehyde  results  in  the  formation  of  a  mixture  of  sugars  which  are  optic- 
ally inactive.  The  same  process,  in  the  living  cell,  leads  to  the  production 
of  optically  active  sugars  which  are  connected  stereochemically  and  mutually 
convertible  one  into  the  other,  e.g.  fructose  and  glucose.  The  derivatives  of 
protoplasm,  containing  asymmetric  carbon  atoms,  are  in  the  same  way 
optically  active,  and  it  seems  that  the  asymmetry  of  the  protoplasmic 
molecule  conditions  a  corresponding  asymmetry  in  the  substance  which  it 
builds  on  to  itself.  The  protoplasm  furnishes,  so  to  speak,  a  mould  in  which 
polymerisation  of  formaldehyde  can  result  only  in  the  production  of  sugars 
of  certain  definite  stereochemical  configurations. 

Few,  if  any,  chemical  reactions  are  pure.  Nearly  all  are  attended  with 
by-reactions,  so  that  the  yield  of  end  product  never  attains  100  per  cent,  of 
the  theoretical  yield.  Even  if  the  above  mechanism  be  regarded  as  the 
chief  one,  it  is  probable  that  side  reactions  take  place  at  the  same  time,  so  that 
we  may  have  the  formation  of  substances  such  as  glyoxylic  acid  and  other 
derivatives  of  the  fatty  acid  series.  Such  by-products  might  play  an  im- 
portant part  in  the  other  synthetic  activities  of  the  cell,  and  especially  in  the 
formation  of  fats  and  proteins. 

THE  FORMATION  OF  PROTEINS 
Our  knowledge  of  the  mechanism  by  which  proteins  are  synthetised  in 

plants  is  still  more  incomplete  than  that  of  the  synthesis  of  carbohydrates, 
and  we  are  reduced  in  most  cases  to  a  discussion  of  the  possible  ways  in 
which,  from  our  knowledge  of  the  chemical  behaviour  of  the  constituents  of 
the  protein  molecule,  we  might  conceive  of  its  formation.  We  can  at  any 
rate  state  the  problems  which  have  to  be  solved  and  study  the  conditions 
under  which  the  synthesis  of  protein  is  possible  in  plants  and  in  animals. 

We  know  that  plants  are  independent  of  any  organic  food  for  building 
up  their  various  constituents,  whether  carbohydrate,  protein,  or  fat,  pro- 
vided only  that  they  possess  chlorophyll  corpuscles  and  so  are  able  to  utilise 


112  PHYSIOLOGY 

the  energy  of  the  sun's  rays.  Most  plants  will  grow  in  the  dark  if  supplied 
with  sugar  and  with  combined  nitrogen  either  in  the  form  of  ammonia  or  of 
nitrates.  The  higher  plants  are  especially  dependent  on  the  presence  of 
nitrogen  in  the  latter  form,  and  it  is  on  this  account  that  the  nitrifying  bac- 
teria of  the  soil  acquire  so  great  an  importance  for  agriculture.  From  the 
carbon  dioxide  of  the  atmosphere  or  from  the  hexose  formed  by  the  assimila- 
tion of  carbon,  and  from  nitrogen,  in  the  form  either  of  ammonia  or  nitrates, 
together  with  inorganic  sulphates,  the  plant  cell  is  able  to  build  up  all  the 
various  types  of  protein  which  are  distributed  throughout  the  vegetable 
kingdom.  Our  study  of  the  disintegration  products  of  proteins  has  shown 
that  this  class  of  bodies  contains  a  large  number  of  the  most  diverse  groups, 
having  as  a  common  character  the  possession  of  nitrogen  in  their  molecule, 
generally  as  an  NIL  or  NH  group.  These  disintegration  products  can  be 
classified  as  follows : 

(a)  Open  chain  amino-acids. 

(b)  Heterocyclic  compounds,  including  : 

(1)  Pyrrol  derivatives. 

(2)  Pyrimidine  derivatives. 

(3)  Iminazol  derivatives. 

These  two  last  groups  co-exist  in  all  the  purine  compounds. 

(c)  Benzene  derivatives. 

(d)  Indol  derivatives. 

The  first  step  in  the  synthesis  of  proteins  is  probably  the  formation  of  these 
constituent  groups.  Just  as  in  digestion  the  protein  molecule  is  taken  to 
pieces  with  the  formation  of  the  different  amino-acids,  so  in  the  synthetic 
action  of  protoplasm  the  reverse  process  of  dehydration  occurs,  resulting 
in  a  coupling  up  of  the  different  groups,  as  has  been  effected  by  Fischer  in  the 
case  of  the  polypeptides.  Wherever  transport  of  protein  from  one  part  of  the 
organism  to  another  is  necessary  the  protein  is  carried,  not  in  its  original 
form,  but  in  the  hydrolysed  condition  of  amino-acids.  Thus  the  germination 
of  seeds  which  contain  rich  stores  of  protein  is  accompanied  by  a  liberation 
of  proteolytic  ferments  within  the  cells  of  the  seeds,  and  the  breakdown 
of  the  reserve  protein  into  its  constituent  amino-acids.  As  amino-acids  it 
is  transported  into  the  growing  tip  and  leaves  of  the  seedling,  analysis  of  the 
latter  showing  a  very  large  percentage  of  nitrogen  in  the  form  of  amino-acids. 
This  is  especially  the  case  if  the  synthetic  functions  of  the  growing  tip  are 
hindered  by  interference  with  assimilation,  as,  e.g.  by  keeping  the  plant  in  the 
dark.  Under  these  circumstances,  asparagine  may  form  as  much  as  25 
per  cent,  of  the  total  dried  weight  of  the  seedling.  In  animals  the  greater 
part  of  the  protein  of  the  food  is  broken  down  into  its  constituent  amino- 
acids  in  the  intestine.  These  are  absorbed  and  probably  carried  to  the 
different  organs  of  the  body,  where  they  are  resynthetised,  generally  in 
different  proportions  from  those  of  the  original  protein,  into  the  protein 
specific  for  the  organ  or  tissue.  The  same  process  of  hydrolysis  and 
subsequent  synthesis  occurs  whenever  the  transport  of  protein  is  neces- 
sary from  one  organ  to  another.     We  shall  later  on  have  to  discuss  the 


THE  MECHANISM  OF  ORGANIC  SYNTHESIS 


113 


possibility  of  synthesis  of  the  different  amino-acids  in  animals.  We  need 
therefore  at  present  deal  only  with  the  possible  methods  by  which,  from  the 
glucose  or  substances  produced  in  the  assimilation  of  carbon  and 
from  the  ammonia  or  nitrates  derived  from  the  soil,  the  plant  is  able 
to  make  the  different  groups  which  go  to  the  building  up  of  the  protein 
molecule. 

All  the  amino-acids  contain  the  NH,  group  in  the  a  position.  We  can 
therefore  consider  them  as  formed  by  the  interaction  of  an  a-oxyacid  and 
ammonia.     Thus : 


CH3 
I 
CH.OH  +  NHS 

I 
COOH 

lactic  acid 


r'H3 

I 

CH.NH,  +  H20 

I 
COOH 

alanine 


This  particular  example,  namely,  the  formation  of  alanine,  may  occur 
at  the  expense  of  the  glucose  produced  as  the  first  product  of  assimilation 
of  carbon  dioxide.  If  a  solution  of  glucose  together  with  lime  be  exposed  to 
sunlight  for  a  considerable  time  it  undergoes  decomposition  with  the  forma- 
tion of  lactic  acid.     Thus  : 

C6H120,;  2C3H603 

glucose  lactic  acid 

This  change  of  glucose  to  lactic  acid  under  the  catalytic  influence  of  the 

alkaline  calcium  hydrate  probably  occurs  by  means  of  a  shifting  of  the 

elements  of  the  water,  a  process  which  in  many  long  chains  seems  to  occur 

with  considerable  facility,  and  is  dependent  on  the  spatial  configuration  of 

the  molecule  involved.     Thus  the  change  of  sugar  to  lactic  acid  is  readily 

effected  by  means  of  many  micro-organisms  in  the  case  of  glucose,  fructose, 

and  mannose,  but  with  considerable  difficulty  in  the  case  of  galactose.     In 

the  three  former  sugars  the  atoms  round  the  two  middle  carbon  atoms  of  the 

chain  are  disposed  thus  : 

I  I 

OH.C.H  H.C.OH 


H.C.OH 


OH.C.H 


When  either  of  these  arrangements  reacts  with  water,  thus 


CH..OH 

I 
CHOH 

I 
OH.C.H 


HCOH 

I 
CHOH 

I 
COH 


OH 


<'H,OH 

I 
CHOH 

COH  +  H20 

CH.OH 

I 
CHOH 

I 
COH 


114  PHYSIOLOGY 

we  obtain  two  molecules  of  glyceric  aldehyde,  which  then  by  a  further 
shifting  of  the  OH  and  H  groups  becomes 

CH8 
I 

CH.OB 
I 

GOOH 
lactic  acid 

Lactic  acid  with  ammonia  and  some  dehydrating  agent  will  give  amino- 
propionic  acid  or  alanine.  The  formation  of  the  higher  amino-acids  in- 
volves a  process  of  reduction  of  the  sugar  first  formed  in  the  chlorophyll 
granules.  It  is  possible  however  that  the  starting-point  for  the  amino-acid 
synthesis  may  be,  not  a  hexose  itself,  but  some  other  substances,  formed, 
so  to  speak,  as  by-products  in  the  assimilation  of  sugar  from  carbon  dioxide. 
We  have  seen  reason  to  believe  that  the  first  result  of  the  action  of  the  sun's 
rays  within  the  chlorophyll  corpuscle  is  formaldehyde.  This  substance  in 
the  presence  of  calcium  carbonate  when  exposed  to  the  light  gives  a  mixture 
of  glyceryl  aldehyde  and  dihydroxyacetone.  If  we  can  assume  that  acetone 
is  formed  from  the  latter  by  a  process  of  reduction,  we  might  possibly  derive 
leucine  from  an  interaction  of  this  substance  with  lactic  acid  and  ammonia. 
Thus  : 

CH3        CH3 
CH3     OH3  OH   / 

I  I  I 

CO  +  CH.OH  +  NH3  +  H,     =    CH2         +2H,0 

•     I  I  I 

CH3      COOH  CH.NH2 

I 
COOH 

As  an  intermediate  product  in  the  synthesis  of  starch,  glvoxylic  acid 
CHO 

has  been  described  as  occurring  in  the  green  parts  of  plants.     This 
COOH 

substance  with  ammonia  gives  formyl  glycine,  and  by  the  splitting  off  of 
formic  acid,  glycine  or  amino-acetic  acid.  Why  nitrates  are  necessary  for 
certain  forms  of  plants  is  not  at  present  understood.  In  the  proteins  nitrogen 
always  occurs  in  an  unoxidised  form  as  NH  or  NH2,  and  the  nitrates  taken 
up  from  the  soil  must  therefore  undergo  reduction  before  they  can  be  built 
into  the  protein  molecule.  It  is  supposed  that  they  may  pass  through  a  series 
of  reductions,  namely  : 

HN03  HNO,  HNO  H2N— OH 

nitric  acid  nitrous  acid  hypoiiitrous  acid  hydroxylamine 

and  that  the  latter  substance  then  reacts  with  formaldehyde  or  other  sub- 
stance derived  from  the  carbon  dioxide  assimilation  to  form  amino-com- 
pounds.  -  In  general  we  may  say  that  the  probable  mechanism  of  formation 
of  amino-acids  is  the  production  of  a-oxyacids,  which  then  react  with 
ammonia  to  form  the  amino-acids  of  the  protein  molecule ;    but  of  the 


THE  MECHANISM  OF  ORGANIC  SYNTHESIS  115 

exact  steps  in  this  process  we  are  at  present  ignorant.  Knoop's  work  would 
point  to  the  ketonic  acids  as  forming  one  step,  and  as  interacting  with 
ammonia,  with  simultaneous  reduction,  to  form  amino-acids. 

The  pyrrol  ring  which  occurs  in  proline  and  in  oxyproline  may  possibly 
be  derived  from  an  open  chain  amino-acid,  and  it  has  in  fact  been  suggested 
that  the  proline  found  in  the  products  of  the  acid  digestion  of  proteins  is 
derived  from  ornithine  by  a  process  of  condensation  with  the  loss  of  ammonia. 
Thus  : 

CH.NH2.CH2.CH3.CH.NH2COOH  becomes 
CH2.CH2.CH2.CH.COOH 

NH 

or,  as  it  is  generally  written  : 

CH„— CH2 

I  I 

CH„    CH.COOH 

NH 

Its  pre-existence  in  the  protein  molecule  is  however  practically  assured,  and 
it  plays  an  important  part  in  the  building  up  both  of  chlorophyll  and  of 
hsematin,  the  prosthetic  group  of  haemoglobin. 

CH— NH 
Iminazol  ||  JCH 

CH— N    " 

occurs  in  histidine  (which  is  iminazol  alanine),  and  can  be  formed  fairly 

readily  by  the  action  of  certain  catalytic  agents  on  a  mixture  of  glucose  and 

ammonia.     Thus,  if  a  solution  of  glucose  with  ammonia  and  zinc  oxide  be 

exposed  to  light,  methyl  iminazol  is  formed  in  large  quantities.     Windaus 

and  Knoop  imagined  that  in  this  process  glyceric  aldehyde  and  formaldehyde 

are  first  formed,  and  that  these  then  interact  with  ammonia  to  form  methyl 

iminazol. 

CH3 

I 
C    —  NH 

II  >CH 
CH— N 

It  is  interesting  to  note  that,  if  we  attach  to  this  compound  carbamide 
or  urea,  we  obtain  a  body  belonging  to  the  class  of  purines.  Xanthine, 
for  instance,  would  have  a  formula 

NH— CO 
I  I 

CO      C—  NH 

I  II  >'H 

NH— CH— N  " 

Thus  by  the  action  of  simple  catalytic  agencies  on  sugar  and  ammonia 
we  can  obtain  the  iminazol  nucleus,  and  by  easy  transitions  pass  through 


116  PHYSIOLOGY 

this  to  the  purine  nucleus  with  its  contained  ring,  the  pyrimidine  nucleus, 
found  in  the  bases  cytosine,  uracil,  &c,  which  occur  in  the  nucleins. 

With  regard  to  the  formation  of  the  aromatic  constituents  of  the  protein 
molecule,  i.e.  those  containing  the  benzene  and  indol  rings,  we  have  at 
present  very  little  indication  even  of  the  lines  along  which  it  might  be 
1 1.  isai ble  to  prosecute  our  researches.  It  has  been  suggested  that  inosite  may 
represent  some  stage  in  the  formation  of  the  benzene  ring  from  the  open  chain 
found  in  the  carbohydrates.  Inosite  has  the  same  formula  as  glucose, 
namely,  C6H1206,  but  is  a   saturated  ring  compound  : 

CHOH 
CHOH  fN  CHOH 


CHOH  \y  CHOH 
CHOH 

and  may  be  expected  to  be  formed  as  a  result  of  polymerisation  of  formalde- 
hyde. We  have  no  evidence  however  of  the  possibility  of  such  a  formation, 
and  the  relations  of  this  substance  with  the  benzene  compounds  are  by  no 
means  intimate.  It  is  of  such  universal  occurrence,  both  in  plants  and 
animals,  that  it  is  difficult  to  refrain  from  the  suspicion  that  it  may  play  some 
part  as  an  intermediate  stage  between  the  fatty  and  the  aromatic  series. 
Since  plants  are  able  to  manufacture  all  these  varied  substances  out  of 
the  products  of  assimilation  of  carbon  and  ammonia  or  nitrates,  they  must 
also  find  no  difficulty  in  transforming  one  amino-acid  into  another,  and  we 
know  that  most  plants  can  procure  their  nitrogen  from  a  solution  of  a  single 
amino-acid  as  well  as  from  a  nutrient  fluid  containing  the  nitrogen  in  the  form 
of  ammonia.  In  animals  the  power  of  transforming  one  amino-acid  into 
another,  of  one  group  into  another,  is  probably  strictly  limited.  So  far  as 
we  know,  nearly  all  the  amino-acids  utilised  in  the  building  up  of  the  animal 
proteins  are  derived  directly  from  those  contained  in  the  food.  On  the 
other  hand,  we  have  evidence  in  the  animal  body  of  synthesis  of  the  purine 
bodies,  and  therefore  of  the  pyrimidine  and  iminazol  rings.  The  hen's  egg 
at  the  beginning  of  incubation  contains  very  little  nuclein,  nearly  the  while 
of  its  phosphorus  being  present  in  the  form  of  phosphoproteins  and  lecithin. 
As  incubation  proceeds  these  substances  disappear,  their  place  being  taken 
by  the  nucleins  which  form  the  chief  constituent  of  the  nuclei  of  the  developing 
chick.  In  the  same  way  the  ovaries  and  testes  of  the  salmon  are  formed 
during  their  sojourn  in  fresh  water  at  the  expense  of  the  skeletal  muscles, 
especially  those  of  the  back.  Here  again  there  is  a  transformation  of  a  tissue 
poor  in  purine  bases  into  a  tissue  which  consists  almost  exclusively  of  nucleins 
and  protamines.  Whether  in  this  case  there  is  a  direct  conversion  of  the 
monc-amino-acids  of  the  muscle  proteins  into  the  diamino-acids  and  bases 
typical  of  protamines,  we  do  not  know.  It  is  more  probable  that  only 
diamino-acids  and  bases  previously  existing  in  the  muscle  are  utilised  for  the 


THE  MECHANISM  OF  ORGANIC  SYNTHESIS  117 

formation  of  the  generative  glands,  the  other  amino-acids  being  oxidised 
and  utilised  for  the  ordinary  energy  requirements  of  the  animaL 

THE  SYNTHESIS  OF  FATS 

In  some  plants  fat  globules  have  been  stated  to  appear  as  the  first  products 
of  the  assimilation  of  carbon  dioxide  under  the  influence  of  sunlight,  but 
there  is  no  doubt  that  as  a  rule  the  formation  of  fats  as  reserve  material  in 
seeds  or  fruits  occurs  at  the  expense  of  carbohydrates.  In  the  higher  animals 
too,  although  a  certain  amount  of  the  fat  of  the  body  is  derived  from  the  fat 
taken  up  with  the  food,  the  organism  can  also  manufacture  neutral  fat  out 
of  the  carbohydrates  presented  to  it  in  its  food.  The  problem  therefore 
of  the  synthesis  of  the  fats  is  the  problem  of  the  conversion  of  a  sugar  such 
as  glucose  into  glycerin  and  the  fatty  acids.  Although  this  conversion 
is  armarently  so  easily  effected  by  the  living  organism,  it  is  one  which  from  the 
chemical  standpoint  involves  considerable  difficulties.  On  account  of  the 
fact  that  the  higher  fatty  acids  consist  largely  of  oleic  and  stearic  acids,  i.e. 
acids  containing  eighteen  carbon  atoms  in  their  chain,  it  has  been  thought 
that  the  synthesis  might  be  brought  about  by  the  linking  together  of  three 
molecules  of  a  hexose.  Such  a  change  would  involve  a  series  of  difficult 
chemical  transformations.  For  instance,  no  less  than  sixteen  out  of  the 
eighteen  oxygen  atoms  present  in  the  three  glucose  molecules  woidd  have 
to  be  dislodged  in  order  to  convert  the  chain  into  stearic  acid.  Moreover, 
although  these  two  acids  contain  a  multiple  of  six  carbon  atoms,  a  whole 
array  of  fats  are  found  both  in  plants  and  animals  which  could  not  be  derived 
by  a  simple  aggregation  of  glucose  molecules ;  and  it  is  worthy  of  note  that,  of 
all  the  fatty  acids  which  occur  in  nature,  all  those  with  more  than  five  carbon 
atoms  contain  an  even  number  of  carbon  atoms.  Thus  in  milk,  -in  addition 
to  the  three  common  fats,  tristearin,  tripalmitin,  and  triolein,  we  find  the 
glycerides  of  caproic,  caprylic,  capric,  lauric,  and  myristic  acids,  i.e.  acids 
with  6,  8,  10,  12,  and  14  carbon  atoms.  In  all  cases  these  acids  are  the 
normal  acids  with  straight  unbranched  chains.  It  seems  probable  that  in 
the  transformation  of  carbohydrate  into  fatty  acid  the  latter  is  built  up,  not 
by  six  carbon  atoms,  but  by  two  carbon  atoms  at  a  time.  It  has  been 
suggested  by  Magnus  Levy  and  by  Leathes  that  the  transformation  may 
occur  by  way  of  lactic  acid.  We  have  seen  already  that  glucose  and  the 
sugars  of  analogous  composition  may  be  converted  under  the  influence  either 
of  sunlight  or  of  micro-organisms  into  lactic  acid.  Lactic  acid  breaks  down 
with  readiness  into  aldehyde  and  formic  acid. 

CH3       CH3 

I  I 

CHOH   =   CHO  +  H 

I  I 

COOH  COOH 

Aldehyde  undergoes  condensation  to  form  aldol. 


118 


PHYSIOLOGY 


CHO 


CH, 

I 

i   Hull 


CH, 

I 
CHO 

aldehyde  aldol 

Aldol  reacts  with  water  and  undergoes  a  shifting  of  its  OH  and  H  groups, 

in  a  manner  with  which  we  are  already  familiar  as  occurring  in  the  conversion 

of  glucose  into  lactic  acid,  forming  butyric  acid.     We  may  represent  the 

reaction  in  the  following  way,  placing  the  water  molecules  opposite  those 

groups  of  the  aldol  molecule  with  which  they  react : 

OH, 

I 
H         HO     CH  H 


OH 


gives 


CH, 


O  C     H       OH 


CH, 


CH, 

|     "        +  2H20 
CH, 

I 
COOH 

It  will  be  seen  that  although  water  must  enter  into  the  reaction  there  is 
no  addition  of  water  to  the  aldol  in  order  to  form  the  butyric  acid. 

It  has  been  suggested  that  similar  reactions  might  account  for  the  forma- 
tion of  the  higher  fatty  acids,  in  which  case  one  molecule  of  acetic  aldehyde 
would  be  added  to  the  fatty  acid  in  order  to  build  up  the  acid  which  is  next 
highest  in  the  series.  Although  certain  of  the  higher  acids  have  been  pre- 
pared in  this  way,  proof  is  still  wanting  that  a  continuous  series  of  syn- 
theses may  be  effected  by  the  continuous  addition  of  aldehyde.  Such  a 
hypothesis  is  however  more  probable  than  the  direct  conversion  of  three 
molecules  of  sugar  into  one  molecule  of  stearic  acid.  The  latter  change 
would  be  associated  with  a  very  great  absorption  of  energy,  whereas  a  con- 
tinuous building  up  of  fatty  acids,  by  the  addition  of  aldehyde  obtained 
through  lactic  acid  from  the  disintegration  of  hexose  molecules,  requires  only 
a  small  expenditure  of  energy,  which  could  be  obtained  by  the  combustion 
of  the  formic  acid  formed  as  a  by-product  in  the  process.  If  we  suppose  that 
the  synthesis  of  the  higher  fatty  acids  from  sugar  is  carried  out  in  this  way, 
the  energy  equations  would  be  as  follows  (Leatb.es  )  : 

1  g.  rnol.  glucose     ) |2  g.  mols.  aldehyde  +  2  g.  mols.  formic  acid. 

677-2  cals.  j  ~ "*"  (  2  +  275-5  +  2  X  61-7 

=  674-4  cals. 


THE  MECHANISM   OF  OEGANIC  SYNTHESIS  119 

2  g.  mols.  aldehyde  )  (1  g.  mol.  aldol     | |1  g.  mol.  butyric  acid. 

551  cals.  j     "*"{         546-8  cals.     j      *\         517-8  cals. 

Or,  tracing  the  same  change  on  as  far  as  palmitic  acid : 

4  g.  mols.  glucose  ) (1  g.  mol.  palmitic  acid  +  8  g.  mols.  formic  acid. 

2708  cals.  j         {         2362  cals.  +  494  cals. 

=  2856  cals. 

In  the  first  stage  of  the  synthesis,  the  reaction  leading  to  butyric  acid,  the 
net  result  would  be,  supposing  the  formic  acid  to  be  oxidised,  that  some  160 
calories  or  nearly  25  per  cent,  of  the  whole  energy,  would  be  rendered  avail- 
able for  other  purposes.  In  the  latter  stages  leading  to  palmitic  acid  some 
of  the  energy  derived  from  the  oxidation  of  the  formic  acid  would  be  required 
for  effecting  the  synthesis,  and  only  about  12-5  per  cent,  of  the  original 
amount  contained  in  the  sugar  would  be  set  free.  It  is  worth  noting  that 
in  the  butyric  fermentation  of  sugar  by  micro-organisms  there  is  a  production 
first  of  lactic  acid,  and  this  substance  then  disappears  to  give  place  to  butyric 
acid.  At  the  same  time  carbonic  acid  and  hydrogen  are  evolved,  both  gases 
being  derived  from  the  decomposition  of  the  formic  acid.  In  the  process  a 
certain  amount  of  caproic  acid  is  always  produced,  and  the  crude  butyric 
acid  of  fermentation  is  used  as  the  source  from  which  commercial  caproic 
acid  is  derived. 

Attempts  to  produce  the  higher  fatty  acids  by  the  condensation  of  successive 
molecules  of  aldehyde  have  so  far  resulted  only  in  the  production  of  branched  chains 
of  carbon  atoms,  whereas  the  normal  fatty  acids  of  the  body  are  straight  chains  ; 
though  Raper  has  shown  that  the  normal  caproic  acid  may  be  formed  by  the  condensa- 
tion of  aldol  with  itself.  Miss  Smedley  has  suggested  that  a  more  probable  line  of 
synthesis. lies  through  pyruvic  acid.  Pyruvic  acid,  which  may  be  produced  in  the  body 
from  lactic  acid,  and  so  from  carbohydrate,  is  fermented  by  yeast  with  the  production  of 
acetaldehyde  and  carbon  dioxide,  by  means  of  a  ferment  carboxylase.  If  we  assume 
the  existence  of  a  similar  ferment  in  the  cells  of  the  body,  it  would  split  this  acid  into 
aldehyde  and  C02.  Aldehyde  however  combines  with  a  molecule  of  pyruvic  acid  to 
form  a  higher  keto  =acid,  which  might  either  be  oxidised  to  the  fatty  acid  containing  one 
carbon  atom  less,  or  might  be  again  transformed  by  enzymes  into  an  aldehyde  capable 
of  reacting  with  another  molecule  of  pyruvic  acid.  These  changes  are  represented  in  the 
following  equations: 

CH3CO.<JOOH  =  OH3<JHO  +  CO., 
CH3CHO  +  CH3CO.COOH  =  CH3CHOH.CH2.CO.COOH 
CH3CHOH.CH2.CO.COOH  +  O    =  CH3CHOH.CH2COOH  +  C02 
/3-oxyacids  would  thus  be  a  normal  stage  in  the  building  up  as  well  as  in  the  breaking 
down  of  fatty  acids. 

The  glycerin  which  enters  into  the  formation  of  the  ordinary  neutral 
fats  can  be  synthetised  by  both  plants  and  animals,  and  there  is  every 
ground  for  believing  that  it,  like  the  fatty  acids,  may  be  derived  from 
carbohydrates.  We  have  alread}r  seen  that  in  the  conversion  of  glucose 
into  lactic  acid  the  first  step  is  the  formation  of  glyceric  aldehyde, 


120  PHYSIOLOGY 

CH„OH  CH2OH 

I  I 

CHOH  CHOH 

I  I 

CHOH  CHO 


cm  Ml  CH2OH 

I  I 

CHOH  ilKill 

I  I 

CHO  CHO 

and  it  is  easy  to  understand  how  by  a  process  of  reduction  the  aldehyde 
is  converted  into  the  corresponding  alcohol,  namely,  glycerin.  The  synthesis 
of  the,  neutral  fat  from  glycerin  and  fatty  acid  is  a  change  which  can  be 
accomplished  by  many  ferments.  It  is  one  involving  practically  no  absorp- 
tion or  expenditure  of  energy.  The  change  is  a  reversible  one,  and  we  find 
both  in  plants  and  animals  that  a  hydrolysis  of  neutral  fat  into  fatty  acid 
and  glycerin  always  occurs  when  a  transport  of  the  fat  is  required,  while 
the  laying  down  of  fat  as  a  store  of  energy  is  always  preceded  by  a.  resynthesis 
of  the  neutral  fat.  We  shall  have  occasion  to  deal  in  greater  detail  with  these 
questions  when  we  have  to  discuss  the  formation  and  fate  of  the  fat  in  the 
animal  body. 


CHAPTER  IV 
THE   ENERGETIC   BASIS   OF   THE    BODY 

SECTION  I 
THE    ENERGY   OF   MOLECULES   IN  SOLUTION 

Every  vital  act  involves  at  the  same  time  a  transformation  of  the  material 
basis  of  the  living  cell  and  a  transformation  of  energy.  The  ultimate 
source  of  the  energies  displayed  by  the  animal  organism  is  the  chemical 
energy  of  the  substances  taken  in  as  food.  In  all  the  changes  undergone  by 
either  matter  or  energy  in  the  body  there  is  neither  destruction  nor 
creation.  The  living  organism  may  therefore  be  regarded  in  one  sense  as  a 
machine,  that  is  to  say,  a  system  for  the  conversion  of  one  form  of  energy 
into  another.  Thus  the  steam-engine  converts  the  potential  energy  of  over- 
heated steam  into  mechanical  work  ;  a  gas-engine  the  chemical  energy  of  an 
explosive  mixture  of  gases  into  heat  and  mechanical  energy  ;  in  a  battery 
there  is  a  transformation  of  chemical  into  electrical  energy  ;  in  a  dynamo,  of 
mechanical  into  electrical  energy,  and  so  on.  In  the  living  cell  the  chemical 
energy  of  the  food  may  undergo  conversion  into  any  of  the  other  forms 
mentioned  above,  i.e.  heat,  work,  electrical  difference  of  potential,  or  it  may 
be  used  for  the  production  of  other  chemical  substances  possessing  peihaps 
as  much  potential  energy  as  or  more  than  the  food-stuffs  themselves. 

Protoplasm,  which  is  the  seat  of  all  these  changes  in  both  plants  and 
animals,  is  active  only  within  fairly  narrow  limits  of  temperature,  approxi- 
mately between  5°  and  40°  C.  In  consistence  it  is  slimy  and  wet,  water 
forming  from  70  to  95  per  cent,  of  its  bulk.  No  substance  introduced  into 
the  protoplasm  has  any  influence  on  it,  unless  it  be  soluble,  and  the  first 
stage  in  the  preparation  of  food-stuffs  for  assimilation  always  consists  in  a 
process  of  solution.  The  sole  source  of  energy  to  the  body  being  that  con- 
veyed with  the  food,  it  follows  that  all  the  energy  with  which  we  have  to 
deal  is  the  energy  of  molecules  in  watery  solution,  the  playground  of  whose 
activities  is  a  jelly-like  mass  of  colloidal  material,  heterogeneous  yet  struc- 
turally continuous.  It  is  important  therefore  at  the  outset  to  inquire  into 
the  nature  of  this  energy  and  the  methods  by  which  it  may  be  measured. 

OSMOTIC  PRESSURE.  If  we  place  two  gas  jars  together,  mouth  to 
mouth,  as  in  Fig.  19,  the  upper  jar  containing  hydrogen  and  the  lower  jar 
some  heavier  gas,  such  as  oxvgen  or  carbon  dioxide,  within  a  very  short  time 

121 


122 


PHYSIOLOGY 


the  gases  will  have  become  intimately  mixed,  and  each  jar  will  contain  an 
equal  amount  of  both  gases.  We  say  that  each  gas  has  diffused  into  the  other, 
and  ascribe  the  diffusion  to  the  movement  of  the  gaseous  molecules.  In 
closed  vessels  the  rapidly  moving  molecules  are  continually  impinging  on 
the  walls  of  the  vessels  and  rebounding,  and  it  is  this  bombardment  by  the 
gaseous  molecules  which  is  responsible  for  the  pressure 
exerted  by  a  gas  on  its  containing  walls.  If  we  double  the 
amount  of  gas  in  a  given  space,  we  double  the  amount  of 
molecules  which  strike  a  unit  area  of  the  wall  in  unit  time, 
and  therefore  double  the  pressure  exerted  by  the  gas  on  the 
vessel  wall.  In  this  way  we  may  explain  the  law  of  Boyle 
that  the  pressure  of  a  gas  is  inversely  proportional  to  its 
volume,  or  the  product  of  pressure  and  volume  at  a  given 
temperature  is  a  constant,  PV=C,  or  since  the  energy  of 
the  molecules  is  proportionate  to  the  absolute  temperature, 
(C^I    "~II<*      PV  =  RT,  the  familiar  gas  equation. 

The  molecules  of  substances  in  solution  behave,  within 
the  limits  of  the  solution,  in  a  manner  precisely  similar  to  the 
free  molecules  of  a  gas.  Thus,  if  a  vessel  be  half  filled  with 
a  10  per  cent,  solution  of  sugar  and  be  then  filled  up  by 
carefully  pouring  distilled  water,  so  as  to  form  a  distinct 
layer  on  the  heavier  sugar  solution,  the  sugar  at  once  begins 
to  move  upwards  into  the  distilled  water.  In  consequence 
of  the  resistance  offered  to  the  movement  of  the  sugar 
molecules  through  the  water,  this  process  of  diffusion  is  slow, 
but  if  the  vessel  be  left  undisturbed  and  free  from  any 
agitation  for  two  or  three  months,  the  sugar  will  be  found 
to  spread  gradually  throughout  the  liquid,  so  that  at  the  end  of  this 
time  all  parts  of  the  fluid  oontain  a    uniform  amount  of  sugar. 

This  process  of  diffusion,  like  that  of  gases,  must  be  ascribed  to  a  con- 
tinuous translatory  movement  of  the  dissolved  molecules.  Since  the  mole- 
cules possess  mass  and  are  endowed  with  a  velocity,  it  is  evident  that  they 
can  exercise  a  pressure  on  any  membrane  or  dividing  surface  which  tends  to 
hinder  their  free  passage  within  the  limits  of  the  solvent.  Thus  if  we  take 
a  pig's  bladder  containing  a  20  per  cent,  solution  of  dextrose  and  immerse 
it  in  distilled  water,  water  will  pass  in  and  distend  the  bladder  to  such  an 
extent  that  it  may  burst  from  the  rise  of  pressure  in  its  interior.  This 
swelling  of  the  bladder  is  due  to  the  fact  that  the  molecules  of  sugar  pass 
through  it  only  with  difficulty,  and  therefore  in  their  passage  outwards 
towards  the  confines  of  the  water  exert  a  pressure  on  the  walls,  driving  them 
apart  and  so  causing  a  distension  of  the  bladder.  It  is  impossible  however 
by  this  means  to  obtain  the  full  osmotic  pressure  due  to  the  pressure  exerted 
by  the  sugar  molecules,  since  the  bladder  wall  itself  is  not  absolutely  im- 
permeable to  sugar.  If  we  imagine  the  sugar  solution  confined  in  a  cylinder 
and  covered  with  a  layer  of  distilled  water,  the  movement  of  the  sugar 
molecules  will  cause  them  to  wander  from  the  lower  to  the  upper  part,  and 


Fig. 


THE  ENERGY   OF  MOLECULES  IN  SOLUTION  123 

this  process  of  diffusion  will  cease  only  when  the  concentration  has  become 

the  same  in  all  parts  of  the  solution.      Supposing  however  the  two  fluids  are 

separated  by  a  piston,  p  (Fig.  20),  which  is  '  semi-permeable,'  i.e.  allows  free 

passage  to  water,  but  not  to  the  dissolved  sugar,  the  molecules  of  sugar  will 

now  exert  a  pressure  on  the  piston  similar  to  that  exerted  on  the  walls  of  the 

containing  vessel,  and  will  tend  to  drive  it  upwards.     The  force  which  it  is 

necessary  to  apply  to  the  piston  to  prevent  its  upward  movement  will  be  the 

measure  of  the  osmotic  pressure  of  the  sugar  in  the  solution.     If  the  piston 

be  pressed  down  with  a  greater  force,  the  sugar  molecules  alone  are  pressed 

together,  since  water  can  pass  freely  through  the  surface  of  the  piston,  and 

the  sugar  solution  is  therefore  rendered  more  concentrated.     Since  force 

must  be  applied  to  the  piston  in  order  to  press  it  down,  work 

is  done  in  the  process,  so  that  the  concentration  of  any  solution 

involves  the  performance  of  an  amount  of  work  determined  by 

the  initial  and  final  osmotic  pressures  of  the  solution.     If,  on 

the  other  hand,   a  weight  be  applied  to  the  piston  which  is 

less  than  the  osmotic  pressure  exerted  by  the  sugar  solution, 

the  piston  with  its  weight  will  be   moved  upwards,  and  the 

solution  will  undergo  dilution  until  its  osmotic  pressure  exactly 

balances  the  weight  on  the  piston.     We  see  that  the  osmotic 

pressure  of  a  solution  represents  a  certain  amount  of  potential  Fig.  20. 

energy,  which  can  be  utilised  in  an  osmotic  machine,  such  as 

that  represented  in  the  diagram,  for  the  performance  of  work. 

THE  MEASUREMENT  OF  OSMOTIC  PRESSURE.  By  a  method 
differing  but  little  from  the  one  just  sketched  out,  Pfeffer  succeeded  directly 
in  measuring  the  osmotic  pressure  of  certain  solutions.  For  this  purpose 
Pfeffer  took  advantage  of  the  fact,  discovered  by  Traube,  that  various  pre- 
cipitates, if  deposited  in  the  form  of  membranes,  were  impermeable  to  the 
substances  producing  them  as  well  as  to  some  other  dissolved  substances, 
though  allowing  a  free  passage  of  water.  Thus,  if  a  drop  of  a  concentrated 
solution  of  potassium  ferrocyanide  suspended  to  a  glass  rod  be  introduced 
carefully  into  a  more  dilute  solution  of  copper  sulphate,  it  will  be  observed 
that  at  the  junction  of  the  drop  and  the  surrounding  fluid  there  is  a  brown 
membranous  precipitate  of  copper  ferrocyanide.  In  consequence  of  the 
greater  concentration  of  the  fluid  in  the  drop,  a  constant  passage  of  water 
takes  place  from  without  inwards  through  the  membrane,  and  the  drop 
therefore  grows  continually  in  size,  sometimes  sending  out  branches  as  a  result 
of  slight  currents  in  the  fluid  set  up  by  accidental  vibrations.  Sugar  intro- 
duced into  such  a  drop,  although  quickening  its  rate  of  growth,  does  not  pass 
out  into  the  surrounding  copper  sulphate  solution,  nor  is  there  any  passage 
of  copper  sulphate  inwards  or  potassium  ferrocyanide  outwards.  Pfeffer  con- 
ceived the  idea  of  depositing  such  a  semi-permeable  membrane  within  the 
interstices  of  a  clay  cell.  Strengthened  in  this  way,  it  is  able  to  afford  a 
resistance  to  pressure,  and  therefore  to  permit  of  the  contained  fluid  reaching 
its  full  osmotic  pressure.  For  this  purpose  a  porous  jar  carefully  cleansed 
and  containing  a  solution  of  sugar  mixed  with  a  little  copper  sulphate  is 


124 


PHYSIOLOGY 


dipped  into  a  weak  solution  of  potassium  ferrocyanide.  A  semi-permeable 
membrane  of  copper  ferrocyanide  is  thus  produced  in  the  pores  of  the  filter, 
and  this,  while  allowing  the  passing  of  water,  is  impermeable  to  the  sugar. 
The  tube  is  then  fitted  with  a  cork  provided  with  a  closed  mercurial  mano- 
meter and  is  immersed  in  distilled  water,  when  it  is  found  that  water  passes 
into  the  cell  until  the  pressure  within  the  latter  is  equal  to  the  osmotic 
pressure  of  the  dissolved  substances.  By  this  means  PfefEer  obtained  the 
following  results  with  a  1  per  cent,  solution  of  cane  sugar  at  different  tem- 
peratures : 


Temp.   °C 

Pressure  In  atmospheres 

Calculated 

Atm. 

Atm. 

6-8 

0-664 

0-665 

13-7 

0-691 

0-681 

22-0 

0-721 

0-701 

32-0 

0-716 

0-725 

36-0 

0-746 

0-735 

It  is  always  possible  to  calculate  the  pressure  of  a  gas  when  its  nature, 
its  mass,  and  its  volume  are  known.  By  Avogadro's  hypothesis,  equal 
volumes  of  gases  at  the  same  pressure  contain  equal  numbers  of  molecules. 
On  this  account  the  molecular  weight  of  any  gas  can  be  reckoned  directly 
from  its  density.  The  figures  obtained  by  PfefEer  show  that  the  same  laws 
apply  to  the  osmotic  pressure  of  substances  in  solution  as  to  the  pressure 
of  gases  in  their  free  state.  It  is  therefore  possible  to  reckon  the  osmotic 
pressure  which  would  be  exerted  by  1  per  cent,  sugar  in  solution  at  a  given 
temperature. 

This  calculation  is  carried  out  as  follows  :  A  gramme  molecule  of  any  gas  at  0°  C.  and 
760  mm.  Hg  has  a  volume  of  22-4  litres,  therefore  342  grammes  of  cane  sugar  (the 
molecular  weight  of  C12H22On  =  342),  if  it  could  be  converted  into  a  gas  at  0°  C.  and 
760  mm.  Hg,  would  have  a  volume  of  22-4  litres.     One  gramme  of  sugar  therefore  at 

22-4 
the  same  temperature  and  pressure  would  have  a  volume  of  ——■  litres  =65-5  c.c.     In 

Pfeffer's  experiment  the  gramme  of  sugar  was  dissolved  in  100  grammes  of  water, 

making  a  total  volume  at  0°  C.  of  106-6  c.c.     The  gaseous  pressure  of  the  sugar  molecules 

65-5 
in  this  solution  will  therefore  amount  to  =  0-651  atmosphere.     At  a  temperature 

100-6  * 

of  6-8  the  pressure  would  be  0.667  atmosphere,  as  against  the  observed  0-664  atmosphere. 

Pfeffer's  method  is  difficult  to  carry  out  and  is  not  applicable  to  all 
dissolved  substances,  since  the  cupric  ferrocyanide  membrane  is  permeable 
for  many  substances,  such  as  potassium  nitrate  or  hydrochloric  acid.  Other 
indirect  methods  have  therefore  been  applied  to  the  comparison  of  the 
osmotic  pressures  of  different  solutions. 


THE  ENERGY  OF  MOLECULES  IN  SOLUTION 


125 


DETERMINATION    OF    OSMOTIC    PRESSURE    BY   PLASMOLYSIS. 

Solutions  which  have  the  same  osmotic  pressure  are  spoken  of  as  isosmotic  or  isotonic. 
The  method  of  plasmolysis,  which  we  owe  to  the  botanist  De  Vries,  consists  essentially 
in  the  comparison  of  the  osmotic  pressure  of  solutions  with  that  of  the  cell  sap  of  certain 
plant  cells,  and  depends  on  the  fact  that  the  '  primordial  utricle,'  the  layer  of  protoplasm 
enclosing  the  cell  sap,  while  freely  permeable  to  water,  is  impermeable  to  a  large  number 
of  salts  Tind  other  crystalloids,  such  as  sugar.  It  is  therefore,  so  far  as  concerns  these 
substances,  '  semi-permeable.'  The  cells  which  have  been  most  used  for  this  purpose 
are  the  cuticular  cells  on  the  mid-rib  of  the  lower  surface  of  the  leaves  of  tradescanlia 
discolor.  If  some  of  these  cells  are  brought  into  a  concentrated  salt  solution,  which  is 
'  hypertonic  '  as  compared  with  the  cell  sap,  water  passes  out  of  the  cell  into  the  salt 
solution,  until  the  contents  of  the  cell  attain  a  molecular  concentration  equal  to  that 
of  the  surrounding  medium.  The  protoplasmic  layer  therefore  shrinks,  leaving  a  space 
between  it  and  the  cell  wall  (Fig.  7,  p.  23).  If  the  outer  solution  has  a  smaller  molecular 
concentration  than  the  cell  sap,  water  passes  into  the  cell  and  causes  here  a  rise  of 
pressure  which  simply  presses  the  protoplasm  still  more  closely  against  the  cell  wall.  If 
we  determine  the  concentration  of  the  salt  solution  at  which  the  shrinkage  of  the  proto- 
plasm, the  plasmolysis,  just  occurs,  and  another  smaller  concentration  at  which  plas- 
molysis is  absent,  we  know  that  the  concentration  of  the  cell  sap  lies  between  those 
of  the  two  salt  solutions.  Thus,  if  plasmolysis  occurs  in  a  solution  containing  0-6 
per  cent,  sodium  chloride  and  is  absent  in  a  solution  containing  059  per  cent,  of  the 
same  salt,  the  concentration  of  the  cell  sap  must  be  about  equivalent  to  a  O59o  per  cent. 
NaCl  solution.  Solutions  of  different  salts,  in  which  plasmolysis  just  occurs,  must  also 
be  isotonic  with  one  another.  Thus  a  1-01  per  cent,  solution  of  KN03  is  found  to  be 
isotpnic  with  a  0'58  per  cent.  NaCl  solution. 

DETERMINATION  BY  HAMBURGER'S  BLOOD-CORPUSCLE  METHOD. 
The  limiting  external  layer  of  red  blood  corpuscles  resembles  the  primordial  utricle  of 
plant  cells  in  being  impermeable  to  a  number  of  dissolved  substances.  If  therefore 
it  be  placed  in  a  solution  of  smaller  concentration  than  the  corpuscle  contents,  it  will 
swell  up  and,  since  it  has  no  supporting  cell  wall,  the  increase  in  size  will  go  on  until 
the  corpuscle  bursts,  and  its  contained  red  colouring-matter,  haemoglobin,  passes  into 
solution  in  the  surrounding  fluid.  If  the  corpuscles  be  then  allowed  to  settle  or  be 
centrifuged,  the  fact  that  haemolysis  has  occurred  is  shown  by  the  red  colour  of  the 
clear  supernatant  fluid.  With  a  given  sample  of  blood,  the  concentration  of  a  potassium 
nitrate  solution  is  found  at  which  the  first  traces  of  haemolysis  occur.  In  order  to 
determine  the  osmotic  pressure  of  a  solution,  say,  of  sugar  or  of  sodium  chloride,  these 
are  also  added  in  various  dilutions  to  blood  corpuscles  until  we  get  solutions  in  which 
haemolysis  just  occurs.  These  solutions  will  then  be  isotonic  with  the  first  determined 
potassium  nitrate  solutions.  As  an  example  of  this  method  may  be  adduced  the 
following   results  : 


Concentration 

Concentration 

of  the  solution 

of  the  solution 

in  which  the 

in  which  the 

Mean 

blood  corpascles 

blood  corpuscles 

concentration 

do  not  lose 

begin  to  lose 

hemoglobin 

hemoglobin 

Per  cent. 

Per  cent. 

Per  cent, 

Potassium  nitrate        .     '     . 

104 

0-96 

1-00 

Sodium  chloride 

0-60 

0-56 

0-585 

Cane  sugar 

6-29 

5-63 

5-96 

Potassium  iodide 

1-71 

1-57 

1-64 

Sodium  iodide   . 

1-54 

1-47 

1-505 

Potassium  bromide     . 

1-22 

113 

1-17 

126  PHYSIOLOGY 

OSMOTIC  PRESSURE  OF  ELECTROLYTES.  It  will  be  noticed  in  the 
last  Table  that  the  isotonic  solutions  of  different  salts  contain  these  salts 
in  the  proportion  of  their  molecular  weights,  i.e.  each  solution  contains  the 
same  number  of  molecules  of  dissolved  salt.  For  the  term  isotonic  we 
might  therefore  employ  equimolecular.  -When  however  these  salts  are 
compared  with  solutions  of  sugar,  it  is  found  that  the  osmotic  pressures  of 
the  salt  solutions  are  double  or  nearly  double  those  of  equimolecular  solu- 
tions of  sugar.  The  osmotic  pressure  of  a  sugar  solution  is  equal  to  the 
pressure  which  its  molecules  would  exert  if  they  occupied  the  same  space, 
in  a  gaseous  form.  A  dilute  salt  solution  therefore  acts  as  if  every  one  of  its 
molecules  were  doubled.  This  deviation  of  salt  solutions  from  solutions  of 
su^ar  is  bound  up  with  the  power  of  the  former  to  conduct  an  electric  current. 
A  sugar  solution  conducts  electricity  little  better  than  pure  water.     On  the 


ii  i  -i  i    '  i   «    ir 


i^-'i— :-^_—zrr:,.^,.v.,.,,i^:v:  ',  7~z^::::::::..~zz 


Fig.  21.  Diagram  to  illustrate  Barger's  method  of  determining  osmotic 
pressure.  The  upper  figure  shows  the  capillary  tube  with  nine  alter- 
nate drops  of  cane  sugar  and  the  substance  imder  investigation. 

other  hand,  the  smallest  trace  of  salt  added  to  distilled  water  enormously 
increases  its  conducting  power.  As  Arrhenius  has  shown,  this  increase  of  the 
osmotic  pressure  of  a  salt  solution  is  determined  by  the  dissociation  which  all 
these  salts  undergo  in  watery  solution.  A  dilute  solution  of  sodium  chloride 
contains,  not  the  molecule  NaCl,  but  an  equal  number  of  the  ions  Na  and  CI, 
Na  carrying  a  positive  charge  while  the  CI  ions  carry  a  negative  charge.  As 
regards  osmotic  pressure  and  various  other  properties,  each  of  these  charged 
ions  acts  as  a  whole  molecule.  It  is  the  existence  of  these  ions  which  confers 
on  the  salt  solution  the  power  of  conducting  electricity- — a  power  the  exercise 
of  which  is  attended  with  a  dissociation  (an  electrolysis)  of  the  salt  into  its 
constituent  ions,  the  electro-positive  ion  being  deposited  at  the  negative 
pole  while  the  electro-negative  ion  is  deposited  at  the  positive  pole.  The 
molecular  weight  of  NaCl  is  58'5.  The  molecular  weight  of  glucose  is  1£0. 
If  there  were  no  dissociation,  a  0-58  per  cent,  solution  of  NaCl  would  be 
isotonic  or  isosmotic  with  a  1"8  per  cent,  solution  of  glucose.  On  account  of 
the  ionic  dissociation  or  ionisation,  it  is  actually  isosmotic  with  a  glucose 
solution  of  about  3  5  per  cent. 


THE    ENERGY  OF  MOLECULE*    IN    SOLUTION 


127 


INDIRECT  METHODS  OF  MEASURING  OSMOTIC  PRESSURE.  Equi- 
molecular  solutions  have  the  same  osmotic  pressures.  Since  the  osmotic 
pressure  of  a.  solution  is  therefore  directly  dependent  on  the  number  of 
molecules  it  contains  in  unit  space,  any  method  which  will  give  us  informa- 
tion as  to  the  number  of  molecules  present  will  also  enable  us  to  determine 
the  osmotic  pressure.  Other  properties  of  solutions  which,  like  the  osmotic 
pressure,  are  functions  of  the  number  of  molecules 
present,  are  vapour -tension,  boiling-point,  freezing- 
point.  The  presence  of  a  substance  in  solution  in 
water  diminishes  its  vapour-tension  at  any  given 
temperature,  raises  its  boiling-point,  and  depresses 
its  freezing-point,  and  the  extent  of  the  deviation 
from  distilled  water  is  proportional  to  the  number 
of  dissolved  molecules  present.  The  determination 
of  the  rise  of  boiling-point,  though  much  employed 
by  chemists,  is  of  very  little  value  in  physiology, 
owing  to  the  fact  that  nearly  all  the  fluids  of  the  body 
are  seriously  modified  in  character  by  a  rise  of  tem- 
perature to  100°  C.  On  the  other  hand,  Barger  has 
suggested  an  ingenious  method  in  which  the  altera- 
t  ion  of  vapour-tension  is  made  the  basis  of  a  method 
for  determining  the  osmotic  pressure  of  small  quan- 
tities of  fluids  at  ordinary  temperatures.  And  this 
method  may  find  important  applications  in  phy- 
siology. 

BARGER' S  METHOD.  Drops  of  the  fluid,  the  vapour- 
tension  of  which  it  is  desired  to  ascertain,  are  drawn  up 
into  a  tube  (1-5  mm.  in  diameter),  so  as  to  alternate  with 
small  drops  of  cane  sugar  solution  of  known  content  (Fig.  21 ). 
Water  in  a  state  of  vapour  will  pass  from  the  solution  of 
which  the  vapour-tension  is  the  higher.  By  observing  the 
edge  of  a  drop  under  a  magnification  of  65  diams.,  it  can 
be  easily  seen  whether  it  has  grown  or  diminished  in  size. 
If  the  edge  of  the  drop  remains  stationary,  it  shows  that  the 
vapour-tension  and  the  osmotic  pressure  of  the  two  fluids 
are  equal.  A  series  of  triaLs  is  made  with  different  strengths 
of  salt  solution  until  this  equality  is  established.  In 
this  method  only  minimal  quantities  of  material  are  re- 
quired, and  the  determination  of  the  aqueous  tension  is 
made  at  ordinary  temperatures. 

The  method  however,  which  is  of  greatest  value 
in  physiology,  is  the  measurement  of  the  depression  of  freezing-point. 
The  depression  of  freezing-point  can  be  converted  directly  into  osmotic 
pressure  by  multiplying  the  depression  of  freezing-point  observed  by  the 
factor  122 '7.  Thus  a  1  per  cent,  solution  of  sodium  chloride  with  A  =  0'61 
will  have  an  osmotic  pressure  of  0"61  X  122  7  =  74*847  metres  of  water. 

The  determination  is  carried  out  in  a  Beckmann's  apparatus  with  a  thermometer 
leading  to  ,  ,', ,, ''  ( '.  (Fig.  22).    A  solution  freezes  at  a  lower  temperature  than  pure  water, 


Fie.  22.  Beckmann's 
apparatus  for  determi- 
nation of  freezing-point. 


128  PHYSIOLOGY 

and  the  depression  of  freezing-point  is  proportional  to  the  number  of  molecules  present. 
Thus  the  freezing-point  of  a  1  per  cent,  solution  of  NaCl  is  — 0-61°  C.  The  depression 
of  freezing-point  is  generally  represented  by  the  Greek  letter  A.  This  method  has 
the  advantage  that  the  fluids  are  in  most  cases  in  no  wise  altered  by  the  process  of  freez- 
ing, and  it  can  be  applied  to  solutions  containing  coagulable  proteins  which  would  be 
irretrievably  altered  by  any  considerable  rise  of  temperature. 

Every  substance  in  solution  possesses  therefore  a  certain  amount  of 
potential  energy  in  the  form  of  osmotic  pressure.  This  pressure  is  inde- 
pendent of  the  nature  of  the  substance  dissolved  and  is  determined  merely 
by  its  molecular  concentration.  It  can  be  used  as  a  driving  force  for  the 
movement  by  diffusion  of  the  molecules  themselves,  or,  by  the  use  of 
appropriate  mechanisms  or  '  machines,'  for  the  performance  of  mechanical 
work,  or,  as  will  be  seen  later,  for  the  production  of  electrical  differences 
of  potential. 

In  addition  to  this  osmotic  or  volume  energy  every  molecule  in  solution 
can  be  regarded  as  endowed  with  a  chemical  energy,  which  is  dependent 
not  only  on  the  number  of  molecules  present,  but  also  on  the  nature  of 
the  molecules.  In  the  case  of  electrolytes  and  of  substances  which  are 
susceptible  of  ionisation,  the  potential  or  intensity  of  the  chemical  energy 
of  each  molecule  is  capable  of  measurement.  On  the  other  hand,  the 
chemical  energy  of  a  substance  such  as  glucose  cannot  be  definitely  expressed 
apart  from  consideration  of  the  conditions  under  which  it  is  present.  If 
we  take  the  whole  course  of  transformations  undergone  by  glucose  in  the 
body,  we  may  speak  of  it  as  having  a  potential  energy,  which  is  measured 
by  the  total  heat  energy  given  out  by  this  substance  on  its  complete  com- 
bustion with  oxygen  to  carbon  dioxide  and  water.  In  the  intermediate 
changes  which  it  undergoes  during  its  metabolism  in  the  cells  of  the  body, 
this  energy  is  probably  set  free  by  degrees,  but  its  chemical  energy  in  any 
given  phase  cannot  be  measured  unless  the  conditions  and  the  end  results 
of  the  chemical  changes  which  it  is  undergoing  are  known.  This  chemical 
energy  may  be  utilised  for  the  production  of  heat,  for  the  performance 
of  chemical  work  in  the  building  up  of  other  substances,  or  by  the  multiplica- 
tion of  the  number  of  molecules  in  a  solution,  for  the  production  of  increased 
osmotic  pressure,  which  in  its  turn  may  be  converted  into  the  energy  of 
movement  either  of  masses  or  of  molecules. 


SECTION  II 

THE    PASSAGE    OF   WATER   AND    DISSOLVED 
SUBSTANCES    ACROSS   MEMBRANES 

We  have  already  semi  that  if,  in  a  solution,  the  concentration  of  the  dis- 
solve.! substance  or  solute  is  not  uniform,  there  is  a  movement  of  the  sub- 
stance  from  the  place  of  higher  to  the  place  of  lower  concentration,  and 
i  Ins  movement  proceeds  until  the  concentration  is  equal  throughout  the 
fluid.  This  movement  of  dissolved  substances  through  a  fluid  is  spoken  of  as 
diffusion,  and  is  analogous  in  all  respects  with  the  process  by  which  the  inter- 
mixture of  gases  is  attained.  The  movement  in  the  case  of  dissolved  sub- 
stances, as  of  gases,  takes  place  from  the  region  of  higher  to  the  region  of  lower 
(osmotic)  pressure.  It  can  therefore  be  ascribed  to  differences  of  pressure, 
or  rather  to  the  factor  which  we  regarded  as  responsible  for  the  production  of 
the  pressure,  viz.  the  movement  of  the  molecules  themselves.  The  rate  of 
diffusion  is  not  the  same  for  all  substances.  In  gases  the  rate  varies  inversely 
as  the  square  root  of  the  density  of  the  gas.  Thus  hydrogen  (density  =  1) 
diffuses  four  times  as  rapidly  as  oxygen  (density  =  16).  We  find  similar 
differences  between  the  rates  of  diffusion  of  dissolved  substances — differ- 
ence which  also  are  determined  in  all  probability  by  the  weight  and 
size  of  the  individual  molecules,  although  the  relation  between  molecular 
weight  and  rate  of  diffusion  is  not  so  simple  as  the  ratio  between  these  two 
quantil  ies  in  gases.  The  diffusibility  of  a  substance  is  given  by  its  diffusion 
coefficient.  The  amount  of  dissolved  substance,  which  diffuses  in  a  unit 
of  time  across  a  given  area  of  fluid,  is  proportional  to  the  difference  between 
the  osmotic  pressures  at  two  cross-sections  of  the  column  of  fluid  at  an  in- 
finitesimally  small  distance  apart.  If  we  take  a  cylindrical  mass  of  solution 
which  is  one  centimetre  long  and  has  a  sectional  area  of  one  square  centimetre 
(Fig.  23),  and    maintain  a  constant 


A 


difference  of  concentration  between 
A  and  B  =1,  the  diffusion  coefficient 
is  the  amount  of  substance  which 
diffuses  in  a  unit  of  time  from  A  to 
B.      Thus  the  statement   that  the 

diffusion  coefficient  of  urea  is   0-810    "  Tcm . 

at  7-5°  C.  denotes  that  if  A  be  con-  Flo  23 

tinually   filled  with    a    1  per   cent. 

solution  of  urea,    while   in   B   a  constant    current   of   distilled    water  is 
kept  up  so  as  to  maintain  the   concentration  at   zero,  in  the  course  of  a 

129  9 


130  PHYSIOLOGY 

day  0-810  gramme  of  urea  will  pass  from  A  to  B  through  the  cylinder  of  one 
centimetre  in  length  and  one  square  centimetre  in  cross-section.  The  deter- 
mination of  these  diffusion  coefficients  presents  many  difficulties.  The  task 
is  however  rendered  easier  by  the  fact,  first  ascertained  by  Graham,  that 
diffusion  of  salts  occurs  as  rapidly  through  a  solid  jelly  of  gelatin  or  agar-agar 
as  through  water.  It  is  therefore  possible  to  make  the  plug  in  the  diagram 
solid  by  the  admixture  of  one  of  these  two  substances,  and  to  maintain  a  con- 
stant concentration  on  the  two  sides  of  it  by  the  circulation  of  fluid  without 
affecting  the  rate  of  diffusion  through  the  cylinder  by  setting  up  accidental 
currents. 

More  important  from  the  physiological  point  of  view  than  diffusion 
through  fluids  is  the  exchange  of  fluids  (water  and  dissolved  substances), 
which  may  take  place  across  membranes.  Such  processes  are  of  constant 
occurrence  in  all  parts  of  the  body  and  are  concerned  in  such  functions  as 
the  formation  and  absorption  of  lymph,  the  absorption  from  and  secretion 
into  the  intestines,  absorption  from  serous  cavities,  and  so  on.  In  many 
of  these  functions  we  shall  have  to  consider  later  whether  the  transference 
across  the  membrane  is  determined  solely  by  the  nature  and  concentration 
of  the  fluids  on  the  two  sides  of  it  or  is  effected  by  the  active  intervention, 
involving  the  expenditure  of  energy,  on  the  part  of  living  cells  forming 
constituent  elements  of  the  membrane  itself.  It  is  worth  our  while  there- 
fore to  consider  at  some  greater  length  the  purely  physical  factors  which  may 
be  concerned  in  the  passage  of  water  and  dissolved  substances  across 
membranes. 

In  the  case  of  fluids  containing  only  one  substance  in  solution,  the 
exchange  across  the  membrane  will  be  determined  entirely  by  the  osmotic 
pressures.  Thus,  if  two  watery  solutions,  with  the  same  osmotic  pressure, 
are  separated  by  a  membrane  through  which  diffusion  can  take  place,  no 
change  in  volume  occurs  on  either  side  of  the  membrane.  If  the  solutions 
on  either  side  of  the  membrane  are  of  unequal  osmotic  pressure,  water  passes 
from  the  side  where  the  pressure  is  lower  to  the  side  where  it  is  higher,  and 
there  is  a  simultaneous  passage  of  the  solute  from  the  side  of  greater  to  the 
side  of  less  concentration. 

If  however  the  solutions  on  the  two  sides  contain  dissimilar  substances, 
with  different  diffusion  coefficients,  the  conditions  are  more  complicated, 
and  may  tend  even  to  produce  a  movement  of  fluid  in  apparent  opposition  to 
the  difference  of  osmotic  pressure.  Under  these  circumstances  the  nature 
of  the  membrane  itself  is  all-important.  We  may  therefore  shortly  consider 
the  various  modes  in  which  interchanges  may  take  place  across  membranes 
of  varying  permeability.  We  shall  see  that  the  close  analogy  which  exists 
between  substances  in  solution  and  gases,  when  dealing  with  '  semi- 
permeable '  membranes,  is  also  borne  out  by  experiment  when  used  to  predict 
the  behaviour  of  solutions  separated  by  such  permeable  membranes  as 
occur  in  the  body. 

The  simplest  case  is  that  in  which  two  fluids  are  separated  by  a  perfect 
S3mi-permeable  membrane  that  permits  the  passage  of  water  but  is  absolutely 


PASSAGE  OF  WATER  AND  DISSOLVED   SUBSTANCES     131 

impermeable  to  dissolved  substances.  In  this  case  the  transference  of  water 
from  one  side  to  the  other  depends  entirely  on  the  difference  of  osmotic 
pressure  between  the  two  sides. 

If  we  suppose  two  vessels,  A  and  B  (Fig.  24),  separated  by  such  a  mem- 
brane, A  containing  a  solution  of  a  and  B  a  solution  of  (S  water  will  pass 
from  A  to  B  so  long  as  the  osmetic  pressure  of  /?  is  greater  than  the  osmotic 
pressure  of  the  solution  of  a.  If  B  be  subjected  to  a  hydrostatic  pressure 
greater  than  the  osmotic  difference  between  the  two  fluids,  water  will  pass 
from  B  to  A  until  the  force  causing  filtration  or  transudation  (the  hydrostatic 
pressure)  is  equal  to  the  force  causing 
absorption  into  B  (the  difference  of 
osmotic  pressures).  Under  no  circum- 
stances will  there  be  any  transference 
of  salt  or  dissolved  substance  between 
the  two   sides.     Such  semi-permeable 

membranes  as    this,   however,    rarelv  „ 

Jig.  24. 
occur  m  the  body  over  any  extent  of 

surface.     The  external   layer  of  the   cell   protoplasm  may  resemble   the 

protoplasmic  pellicle  of  plant  cells  in  possessing  this  '  semi-permeability  '  ; 

but  in  nearly  all  cases  where  we  have  a  membrane  made  up  of  a  number 

of  cells,  it  can  be  shown  to  permit  the  free  passage  of  at  any  rate  a  large 

number  of  dissolved  substances. 

Let  us  now  consider  what  will  occur  when  the  two  solutions  A  and  B 
are  separated  by  a  membrane  which  permits  the  free  passage  of  salts  and 
water.  If  the  osmotic  pressure  of  B  be  higher  than  A  at  the  commencement 
of  the  experiment,  the  force  tending  to  move  water  from  A  to  B  will  be  equal 
to  this  osmotic  difference.  But  there  is  at  the  same  time  set  up  a  diffusion 
of  the  dissolved  substances  from  B  to  A  and  from  A  to  B.  The  result  of  this 
diffusion  must  be  that  there  is  no  longer  a  sudden  drop  of  osmotic  pressure 
from  B  to  A.  and  the  result  of  the  primary  osmotic  difference  on  the  move- 
ment of  water  will  be  minimised  in  proportion  to  the  freedom  of  diffusion 
which  takes  place  through  the  membrane.  Now  let  us  take  a  case  in  which 
A  and  B  represent  equimolecular  and  isotonic  solutions  of  a  and  /?.  It  is 
evident  that  the  movement  of  water  into  A  will  vary  as  Ap  —Up  *  =  0.  But 
diffusion  also  occurs  of  a  into  B  and  of  /?  into  A.  Now  the  amount  of  sub- 
stance diffusing  from  a  solution  is  proportional  to  the  concentration,  and 
therefore  to  its  osmotic  pressure,  as  well  as  to  its  diffusion  coefficient. 

Hence  the  amount  of  a  diffusing  into  B  will  vary  as  A  p.  ale  (when  k  is 
the  diffusion  coefficient). 

In  the  same  way  the  amount  of  /S  diffusing  into  A  will  vary  as  Bp.  /9k  . 

Hence,  if  ak  is  greater  than  /3k',  i.e.  if  a  is  more  diffusible  than  ft,  the 
initial  result  must  be  that  a  greater  number  of  molecules  of  a  will  pass  into  B 
than  of  /?  into  A.  The  solutions  on  the  two  sides  of  the  membrane  will  thus 
be  no  longer  equimolecular,  but  the  total  number  of  molecules  of  a  +  /?  in 
B  will  be  greater  than  the  number  of  inolecules  of  a  +  fi  in  A,  and  this  differ- 
*  Ap  =  osmotic  pressure  df  A,  &c. 


132  PHYSIOLOGY 

ence  will  be  most  marked  in  the  layers  of  fluid  nearest  the  membrane.  The 
result  therefore  of  the  unequal  diffusion  of  the  two  substances  is  to  upset  the 
previous  equality  of  osmotic  pressures.  The  layer  of  fluid  on  the  B  side  of 
the  membrane  will  have  an  osmotic  pressure  greater  than  the  layer  of  fluid 
in  immediate  contact  with  the  A  side  of  the  membrane,  and  there  will  thus  be 
a  movement  of  water  from  A  to  B.  Hence  if  we  have  two  equimolecular  and 
isotonic  solutions  of  different  substances  separated  by  a  membrane  permeable, 
to  the  solutes,  there  will  be  an  initial  movement  of  fluid  towards  the  side  of 
the  less  diffusible  substance. 

We  have  an  exact  parallel  to  this  in  Graham's  familiar  experiment,  in 
which  a  porous  pot  filled  with  hydrogen  is  connected  by  a  vertical  tube  with 
a  vessel  of  mercury.  In  consequence  of  the  more  rapid  diffusion  outwards  of 
the  hydrogen  than  of  atmospheric  air  inwards,  the  pressure  within  the  pot 
sinks  below  that  of  the  surrounding  atmosphere  and  the  mercury  rises  several 
inches  in  the  tube. 

We  must  therefore  conclude  that,  even  when  the  two  solutions  on  either 
side  of  the  membrane  are  isotonic,  there  may  be  a  movement  of  fluid  from 
one  side  to  the  other  with  a  performance  of  work  in  the  process.  In  fact, 
osmosis  may  occur  from  a  fluid  having  a  higher  towards  a  fluid  having  a 
lower  osmotic  pressure.  If,  for  example,  equimolecular  solutions  of  sodium 
chloride  and  glucose  be  separated  by  a  peritoneal  membrane,  the  osmotic 
flow  will  take  place  from  the  fluid  having  the  higher  osmotic  pressure — 
.  sodium  chloride.*  We  might  compare  with  this  experiment  the  results  of 
separating  hydrogen  at  one  atmosphere's  pressure  from  oxygen  at  two 
atmospheres'  pressure  by  means  of  a  plate  of  graphite.  In  this  case  the 
initial  result  will  be  a  still  further  increase  of  pressure  on  the  oxygen  side 
of  the  diaphragm — a  movement  of  gas  against  pressure  taking  place  in 
consequence  of  the  greater  diffusion  velocity  of  hydrogen. 

So  far  we  have  considered  only  the  behaviour  of  solutions  when  separated 
by  a  membrane,  the  permeability  of  which  to  salts  is  comparable  to  that  of 
water  ;  so  that  the  passage  of  salts  through  the  membrane  depends  merely  on 
the  diffusion  rates  of  the  salts.  There  can  be  no  doubt  however  that  we 
might  get  analogous  movements  of  fluid  against  total  osmotic  pressure 
determined,  not  by  the  diffusibility  of  the  salts,  but  by  the  permeability  of 
the  membrane  for  the  salts — -a  permeability  which  may  depend  on  a  state 
of  solution  or  attraction  existing  between  membrane  and  salts.  We 
have  an  analogue  to  such  a  condition  of  things  in  the  passage  of  gases 
through  an  india-rubber  sheet.  If  two  bottles,  one  containing  carbonic  acid, 
the  other  hydrogen,  be  separated  by  a  sheet  of  india-rubber,  carbon  dioxide 
passes  into  the  hydrogen  bottle  more  quickly  than  hydrogen  can  pass  out 
into  the  carbon  dioxide  bottle,  so  that  a  difference  of  presstire  is  created,  and 
the  rubber  bulges  into  the  carbon  dioxide  bottle.  We  might,  in  the  same 
way,  conceive  of  a  membrane  which  permitted  the  passage  of  dextrose  more 

*  In  consequence  of  ionic  dissociation  of  the  sodium  chloride,  a  decinormal  solution 
of  this  salt  will  have  an  osmotic  pressure  nearly  twice  as  great  as  that  of  a  similar 
solution  of  the  non-ionised  glucose. 


8 


PASSAGE   OF  WATER  AND  DISSOLVED  SUBSTANCES     133 

easily  than  that  of  urea.  The  importance  of  the  membrane  in  determining 
the  direction  of  the  osmotic  passage  of  fluid  is  wel]  illustrated  by  Raoult's 
experiments.  When  alcohol  and  ether  were  separated  by  an  animal  mem- 
brane, alcohol  passed  into  the  ether,  whereas  if  vulcanite  were  employed  for 
the  diaphragm,  the  osmotic  flow  was  in  the  reverse  direction,  and  an  enormous 
pressure  wras  set  up  on  the  alcohol  side  of  the  diaphragm.* 

The  next  point  to  be  considered  is  the  passage  of  a  dissolved  substance 
across  membranes,  in  consequence  of  differences  in  the  partial  pressure  of 
the  substance  in  question  on  the  two  sides  of  the  membrane.  Stress  has  been 
laid  by  Heidenhain  and  others  on  the  fact  that  in  the  peritoneal  cavity,  as 
well  as  from  the  intestine,  salt  may  be  taken  up  from  fluids  containing  a 
smaller  percentage  of  this  substance 
than  does  the  blood  plasma,  and 
they  regard  this  absorption  as  points 
ing  indubitably  to  an  active  inter- 
vention of  living  cells  in  the  process. 
This  argument  requires  examination. 
Let  us  suppose  the  two  vessels  A  and 
B  (Fig.  25)  to  be  separated  by  a  mem- 
brane which  offers  free  passage  to  water 
and  a  difficult  passage  to    salts.     Let 

A  contain  0-5  per  cent,  salt  solution  and  B  a  solution  isotonic  with  a  1  per 
cent.  NaCl,  but  containing  only  0-65  per  cent,  of  this  salt,  the  rest  of  its 
osmotic  tension  being  due  to  other  dissolved  substances.  If  the  membrane 
were  absolutely  '  semi-permeable,'  water  would  pass  from  A  to  B  until  the 
two  fluids  were  isotonic,  i.e.  until  A  contained  1  per  cent.  NaCl  (we  may 
regard  volume  B  as  infinitely  great  to  simplify  the  argument).  If  however 
the  membrane  permitted  passage  of  the  dissolved  substances,  the  course  of 
events  might  be  as  follows  :  At  first  water  would  pass  out  of  A,  and  salt  would 
diffuse  in  until  the  percentage  of  NaCl  in  A  was  equal  to  that  in  B.  There 
would  now  be  an  equal  partial  pressure  of  NaCl  on  the  two  sides  of  the 
membrane,  but  the  total  osmotic  pressure  of  B  would  still  be  higher  than  A. 
Water  would  therefore  still  continue  to  pass  from  A  to  B  more  rapidly  than 
the  other  ingredients  of  B  could  pass  into  A.  As  soon  however  as  more 
water  passed  out  from  A,  the  percentage  of  NaCl  in  A  would  be  raised  above 
that  in  B.  The  extent  to  which  this  occurs  will  depend  on  the  impermeability 
of  the  membrane.  As  the  NaCl  in  A  reaches  a  certain  concentration  it  will 
pass  over  into  B,  and  this  will  go  on  until  equilibrium  is  established  between 
A  and  B.  Extending  this  argument  to  the  conditions  obtaining  in  the 
living  body,  we  may  conclude  that  neither  the  raising  of  the  percentage  of  a 

*  Here  we  have  a  possible  clue  to  the  explanation  of  some  phenomena  of  cell  activity, 
to  which  the  term  '  vital '  is  often  assigned.  In  the  swimming-bladder  of  fishes,  for 
instance,  we  find  a  gas  which  is  extremely  rich  in  oxygen,  and  the  oxygen  is  said  to 
have  been  secreted  by  the  cells  lining  the  bladder.  It  is,  however,  possible  that  the 
processes  here  may  be  analogous  to  Graham's  atmolysis,  and  that  the  bladder  may 
represent  a  perfected  form  of  Graham's  india-rubber  bag. 


134  PHYSIOLOGY 

salt  in  any  fluid  above  that  of  the  same  salt  in  the  plasma,  nor  the  passage 
of  a  salt  from  a  hypotonic  fluid  into  the  blood  plasma,  can  afford  in  itself 
any  proof  of  an  active  intervention  of  cells  in  the  process. 

In  the  case  of  the  pleura,  for  example,  we  seem  to  have  a  membrane  which  is  very 
imperfectly  semi-ppi-rmiable.  It  is  permeable  to  salts,  but  presents  rather  more  resist- 
ance to  their  passage  onan  to  the  passage  of  water.  Hence  on  injecting  0-5  per  cent. 
NaCl  solution  into  the  pleural  cavity,  water  passes  from  the  pleural  fluid  into  the 
blood,  until  the  percentage  of  sodium  chloride  in  the  fluid  is  raised  perceptibly  above 
that  in  the  blood  plasma.  The  limit  of  the  resistance  of  the  pleural  membrane  to 
the  passage  of  salt  is  however  soon  reached,  and  then  salt  passes  from  pleural  fluid 
into  blood  ;  but  in  every  case  this  passage  is  from  a  region  of  higher  to  a  region  of 
lower  partial  pressure.  Hence  at  a  certain  stage  of  the  experiment  we  find  a  higher 
percentage  of  salt  in  the  pleura  than  in  the  blood-vessels,  although  the  total  amount 
of  salt  in  the  pleural  fluid  is  less  than  that  originally  put  in,  or,  in  other  words,  salt 
has  been  absorbed. 

We  have  already  seen  that  the  effective  osmotic  pressure  of  a  substance, 
i.e.  its  power  of  attracting  water  across  a  membrane,  varies  inversely  as  its 
diffusibility,  or  as  the  permeability  of  the  membrane  to  it.  What  then  will 
be  the  effect  if  on  one  side  of  the  membrane  we  place  some  substance  in 
solution  to  which  the  membrane  is  impermeable  ? 

We  will  suppose  that  A  and  B  both  contain  1  per  cent.  NaCl,  but  that 
B  contains  in  addition  some  substance  x  to  which  the  membrane  is  im- 
permeable. Since  the  osmotic  pressure  of  B  is  higher,  by  the  partial  pressure 
of  x,  than  that  of  A,  fluid  will  pass  from  A  to  B  by  osmosis.  But  the  conse- 
quence of  this  passage  of  water  will  be  to  concentrate  the  NaCl  in  A,  so  that 
the  partial  pressure  of  this  salt  in  A  is  greater  than  in  B.  NaCl  will  therefore 
diffuse  from  A  to  B,  with  the  result  that  the  former  difference  of  total 
osmotic  pressure  will  be  re-established.  Hence  there  will  be  a  continual 
passage  of  both  water  and  salt  from  A  to  B,  until  B  has  absorbed  the  whole 
of  A.  This  result  will  be  only  delayed  if  the  osmotic  pressure  of  A  is  at  first 
higher  than  B,  in  consequence  of  a  greater  concentration  of  NaCl  in  A. 
There  may  be  at  first  a  flow  of  fluid  from  B  to  A,  but  as  soon  as  the  NaCl 
concentration  on  the  two  sides  has  become  the  same  by  diffusion,  the  power 
of  x  to  attract  water  from  the  other  side  will  make  itself  felt,  and  this  attrac- 
tion will  be  proportional  to  the  osmotic  pressure  of  x.  We  shall  have 
occasion  to  discuss  a  specific  instance  of  this  case  when  dealing  with  the 
mechanism  of  absorption  of  fluid  by  the  blood-vessels  from  the  connective 
tissue  spaces. 

A  more  familiar  example  is  afforded  by  the  process  known  as  dialysis. 
Many  animal  membranes,  all  of  which  are  colloidal  in  character,  and  others 
such  as  vegetable  parchment,  while  freely  permeable  to  salts,  are  impermeable 
to  dissolved  colloids.  If  therefore  a  fluid  containing  both  colloids  and 
crystalloids  in  solution,  e.g.  blood-serum,  be  enclosed  in  a  tube  of  vegetable 
j>archment,  which  is  hung  up  in  a  large  bulk  of  distilled  water  (Fig.  2G),  all 
the  salts  diffuse  out,  and  if  this  be  frequently  changed,  we  obtain  finally  a 
fluid  within  the  dialyser  free  from  salts  and  other  crystalloid  substances,  but 
containing  the  whole  of  the  colloidal  proteins  originally  present. 


PASSAGE  OF  WATEE  AND  DISSOLVED  SUBSTANCES    135 

Thus  the  transference  of  fluids  and  dissolved  substances  across  membranes 
is  determined  not  only  by  the  osmotic  pressure  of  the  solutions,  but  also  by 
the  diffusion  coefficient  of  the  solutes  and  the  permeability  of  the  membrane. 
This  permeability  may  be  of  the  same  character  as  the  permeability  of  water, 
in  which  case  the  rates  of  passage  of  the  dissolved  substances  across  the 


Fig.  26.  Dialyser,  consisting  of  a  tube  of  parchment  paper  immersed  in  a  vessel 
through  which  a  constant  stream  of  sterile  distilled  water  can  be  passed. 
(Wroblesui.) 

membrane  vary  as, their  diffusibilities,  and  are  therefore  probably  some  func- 
tion of  their  molecular  weights.  On  the  other  hand,  the  membrane  may 
exhibit  a  certain  attraction  for,  or  power  of  dissolving,  some  of  the  solutes  to 
the  exclusion  of  others,  in  which  case  there  will  be  no  relation  between  the 
diffusibilities  and  the  rates  of  passage  of  the  dissolved  substances. 

Bayliss  has  drawn  attention  to  certain  other  factors  which  may  determine  permanent 
inequality  of  distribution  of  a  salt  on  the  two  sides  of  a  membrane  permeable  to  the  salt. 
If  Congo  red,  which  is  a  compound  of  an  indiffusible  colloid  acid  with  sodium,  be  placed 
in  an  osmometer  which  is  immersed  in  water,  a  certain  osmotic  pressure  is  developed. 
On  adding  sodium  chloride  either  to  the  inner  or  outer  fluid,  there  is  a  fall  in  the  osmotic 
pressure  if  time  be  allowed  for  equilibrium  to  be  established.  At  this  point  it  is  found 
that  the  outer  fluid,  which  is  free  from  dye,  contains  a  larger  percentage  of  sodium 
chloride  than  the  inner  solution  of  dye.  This  difference  is  permanent  and  is  more 
marked  the  greater  the  concentration  of  the  dye  salt.  In  the  following  Table  is  given 
the  concentrations  of  the  two  fluids  with  different  percentages  of  salt.  The  numbers 
indicate  the  litres  to  which  each  gramme  molecule  of  the  salt  is  diluted.     Apparently 


136 


PHYSIOLOGY 


Dye 

Chlorine 

Inside 

mil    i,i, 

30 

52 

30 

30 

465 

73-6 

30 

<5500 

180 

100 

32-9 

29-5 

the  difference  depends  on  the  fact  that  the  non-dissociated  salt  must  be  equal  on  the  I  w< . 
sides  of  the  membrane  and  that  the  dissociation  is  much  impeded  on  the  inner  side  on 
account  of  the  presence  there  of  another  salt  of  sodium.  A  sodium  salt  of  any 
other  indiffusible  substance,  e.g.  of,  a  protein  such  as  caseinogen,  would  behave  in  a 
precisely  similar  fashion. 


SECTION  III 

THE   PROPERTIES   OF  COLLOIDS 

Although  the  chemical  changes  involved  in  the  various  vital  phenomena 
occur  between  substances  in  watery  solution,  the  solution  in  every  casj  is 
bound  up  within  the  meshes  or  adsorbed  by  the  surfaces  of  a  heterogeneous 
mass  of  colloids.  The  complex  chemical  molecules  which  make  up 
protoplasm  itself  are  all  colloidal  in  character.  The  participation  of 
colloids  in  chemical  reactions  introduces  conditions  and  modes  of  reaction 
differing  widely  from  those  which  have  been  studied  in  watery  solutions. 
Our  knowledge  of  these  conditions  is  still  very  imperfect,  but  the  important 
part  played  by  colloids  in  the  processes  of  life  renders  it  necessary  to  discuss 
in  some  detail  their  properties  and  modes  of  interaction. 

The  term  colloid,  from  xoWy,  glue,  was  first  introduced  by  Thomas 
Graham,  Professor  of  Chemistry  at  University  College  from  1836  to  1855. 
Graham  divided  all  substances  into  twTo  classes,  viz.  crystalloids,  including 
such  substances  as  salt,  sugar,  urea,  which  could  be  crystallised  with  ease, 
diffused  rapidly  through  water,  and  were  cajiable  of  diffusing  through  animal 
membranes  ;  and  colloids,  which  included  substances  such  as  gelatin  or 
glue,  gum,  egg-albumin,  starch  and  dextrin,  were  non-crystallisable,  formed 
gummy  masses  when  their  solutions  were  evaporated  to  dryness,  diffused 
with  extreme  slowness  through  water,  and  would  not  pass  through  animal 
membranes.  The  process  of  dialysis  was  therefore  introduced  by  Graham 
for  the  separation  of  crystalloids  from  colloids.  Although  the  broad  dis- 
tinction drawn  by  Graham  between  colloids  and  crystalloids  still  holds  good, 
some  of  the  criteria  by  wdiich  he  distinguished  the  two  classes  are  no  longer 
strictly  applicable.  For  instance,  it  has  been  shown  that  many  typical 
colloidal  substances,  such  as  haemoglobin,  can  be  obtained  in  a  crystalline 
form.  On  the  other  hand,  all  gradations  exist  between  substances,  such  as 
egg-albumin,  which  are  practically  indiffusible,  and  those,  such  as  common 
salt,  which  are  very  diffusible.  Graham  pointed  out  that  colloids  exist  under 
two  conditions  : 

(1)  In  a  state  of  solution  or  pseudo-solution,  in  which  they  form  sols,  and 
are  distinguished  as  hydrosols,  when  the  solvent  is  water ;    and 

(2)  In  a  solid  state,  in  which  a  relatively  small  amount  of  the  colloid 
sets  with  a  large  amount  of  a  fluid,  such  as  water,  to  form  a  jelly.  This 
solid  form  is  known  as  a  gel.  The  most  familiar  instance  is  the  jelly  which 
is  obtained  on  dissolving  a  little  gelatin  in  hot  water  and  allowing  the  mixture 

137 


138  PHYSIOLOGY 

to  cool.  Such  a  jelly  is  known  as  a  hydrogel.  In  many  of  these  gels  the 
water  can  be  replaced  by  other  fluids,  such  as  alcohol,  without  any  alteration 
in  the  appearance  of  the  solid,  which  is  then  known  as  an  alcogel.  An 
example  of  an  alcogel  is  the  jelly  which  can  be  made  by  dissolving  soap  in 
warm  alcohol  and  allowing  the  mixture  to  cool. 

A  number  of  these  colloidal  substances  can  be  shown  on  purely  chemical 
grounds  to  consist  of  monstrous  molecules.  Thus  the  molecular  weight 
of  haemoglobin  is  at  least  16,000,  and  one  must  ascribe  similar  high  molecular 
weights  to  such  substances  as  egg-albumin  and  globulin.  Still  greater  must 
be  the  molecular  size  of  such  substances  as  the  cell  proteins,  which  may 
be  made  up  of  more  than  one  type  of  protein  built  up  with  various 
nucleins,  with  lecithin  and  cholesterin,  to  form  a  gigantic  complex,  to 
which  it  would  probably  not  be  an  exaggeration  to  ascribe  a  molecular 
weight  of  over  100,000.  This  chemical  complexity  is  not  however  a 
necessary  condition  of  the  colloidal  state,  as  is  shown  by  the  existence 
of  colloidal  silica,  of  colloidal  ferric  hydrate  and  alumina,  and  even  of 
colloidal  metals. 

On  neutralising  a  weak  solution  of  sodium  silicate  or  water-glass  by  means  of  HC1, 
we  obtain  a  solution  which  contains  sodium  chloride  and  silicic  acid.  On  dialysing  this 
mixture  for  some  days  against  distilled  water,  the  whole  of  the  NaC'l  passes  out,  and  a 
solution  of  silicic  acid  or  colloidal  silica  is  left  in  the  dialyser.  This  solution  can  be 
concentrated  over  sulphuric  acid.  When  concentrated  to  a  syrupy  consistence  it 
becomes  extremely  unstable.  The  addition  of  a  minute  trace  of  sodium  chloride 
or  other  electrolyte  to  the  solution  causes  it  to  set  at  once  to  a  solid  jelly  (gelatinous 
silica),  the  change  being  accompanied  by  an  appreciable  rise  of  temperature.  The 
change  is  irreversible,  in  that  it  is  not  possible  to  bring  the  silicic  acid  into  solution 
again  by  removal  of  the  electrolyte  by  means  of  dialysis.  If  however  it  be  allowed 
to  stand  with  weak  alkali  for  some  time,  it  gradually  passes  into  solution.  Analogous 
methods  are  employed  for  the  preparation  of  colloidal  Fe203  and  A1,03. 

Of  special  interest  are  the  colloidal  solutions  of  the  metals.  Faraday 
long  ago  pointed  out  that,  on  treating  a  weak  solution  of  gold  chloride  with 
phosphorus,  it  underwent  reduction  with  the  formation  of  metallic  gold. 
The  gold  was  not  precipitated,  but  remained  in  suspension  or  pseudo- 
solution,  giving  a  deep  red  *  or  a  blue  liquid,  according  to  the  con- 
ditions under  which  the  reaction  was  effected.  This  solution  was  homo- 
geneous in  that  it  could  be  filtered  without  change,  and  could  be  kept  for 
months  without  deposition  of  the  gold.  The  latter  was  however  thrown 
down  on  addition  of  mere  traces  of  impurity,  though  greater  stability  could 
be  conferred  on  the  solution  by  adding  to  it  a  little  '  jelly,'  i.e.  a  weak  solution 
of  gelatin.  In  1899  Bredig  showed  how  similar  hydrosols  might  be  prepared 
from  a  number  of  different  metals,  viz.  by  the  passage  of  a  small  arc  or 
electric  sparks  between  metallic  terminals  submerged  in  distilled  water. 
If,  for  example,  the  terminals  be  of  platinum,  the  passage  of  the  current 
is  seen  to  be  accompanied  by  the  giving  off  of  brown  clouds,  which  spread 
into  the  surrounding  fluid.     These  clouds  consist  of  particles  of  platinum 

*  Ruby  glass  is  a  colloidal  '  solid '  solution  of  gold  in  a  mixture  of  silicates. 


THE  PROPERTIES  OF  COLLOIDS  139 

of  all  sizes.  The  larger  settle  at  the  bottom  of  the  vessel,  the  smaller — ■ 
which  are  ultra-microsccpic  in  size,  i.e.  from  5  ^  to  40^* — remain  in  sus- 
pension, and  we  obtain  a  brown  fluid  which  can  be  filtered  through  paper 
or  even  through  a  Berkefeld  filter  without  losing  its  colour.  It  may  be 
kept  for  months  without  any  deposit  taking  place.  The  addition  of  minute 
traces  of  electrolytes  precipitates  the  platinum  particles,  leaving  a  colourless 
fluid.  We  shall  have  to  return  later  on  to  the  consideration  of  the  behaviour 
of  these  metallic  sols. 

Colloidal  solutions  or  sols  may  be  divided  into  two  classes,  emidsoids 
and  suspensoids,  accord'ng  as  they  may  be  regarded  as  suspensions  of  liquid 
in  liquid  or  as  suspensions  of  solid  particles. 

Most  protein  solutions  are  emulsoids,  while  the  metallic  sols  belong  to 
the  class  of  suspensoids.  Dilute  egg-white  is  an  emulsoid,  but  if  it  be  boiled, 
although  no  visible  precipitation  is  produced,  the  fine  particles  are  coagulated 
and  it  behaves  as  a  suspensoid. 

PROPERTIES  OF  GELS.  A  typical  hydrogel  is  the  firm  mass  in  which 
a  solution  of  gelatin  sets  on  cooling.  It  is  clear,  hyaline,  apparently  structure- 
less, and  possesses  considerable  elasticity,  i.e.  resistance  to  deforming  force. 
It  may  be  regarded  as  formed  by  the  separation  of  the  warm  pseudo-solution 
of  gelatin  into  two  phases  :  first  a  solid  phase,  rich  in  gelatin  and  forming 
a  tissue  or  meshwork,  in  the  interstices  of  which  is  embedded  the  second 
phase,  consisting  of  a  very  weak  solution  of  gelatin. 

If  the  process  be  observed  under  the  microscope,  according  to  Hardy  minute  drops 
first  appear  which,  as  they  en  Urge,  touch  one  another  and  form  networks.  In  stronger 
solutions  the  first  structures  to  make  their  appearance  consist,  not  of  the  more  con- 
centrated phase,  but  of  droplets  of  the  dilute  solution  of  gelatin  ;  the  stronger  solution 
collects  round  these  drops  and  solidifies  to  a  honeycomb  structure. 

In  many  cases  the  more  fluid  part  of  the  gel  is  practically  pure  water. 
In  such  a  case  immersion  in  alcohol  causes  a  diffusion  outwards  of  the  water, 
which  is  replaced  by  alcohol  with  the  formation  of  an  alcogel.  In  a  dry 
atmosphere  the  gel  loses  water  and  becomes  shrivelled  and  dry,  but  in 
some  cases,  e.g.  gelatin,  it  can  resume  its  former  size  and  characters  on 
immersion  in  water.  Other  gels,  such  as  silicic  acid  or  ferric  hydrate,  lose 
the  power  of  swelling  up  after  drying.  The  change  in  them  is  therefore 
irreversible.  A  gel  adheres  tothe  last  traces  of  water  with  extreme  tenacity. 
In  consequence  of  its  structure,  it  presents  an  enormous  extent  of  surface 
on  which  adsorption  can  take  place.  At  this  surface  the  vapour-tension  of 
fluids  is  diminished,  as  well  as  the  osmotic  pressure  of  dissolved  substances. 
On  this  account  gelatin  must  be  heated  for  many  hours  at  a  temperature 
of  120°  C.  in  order  to  be  thoroughly  dried.  When  dry,  it,  as  well  as  other 
solid  colloids,  can  exert  a  considerable  amount  of  energy  when  caused  to 
swell  up  by  moistening.  This  energy  was  made  use  of  by  the  ancient 
Egyptians  in  the  quarrying  of  their  stone  blocks  by  the  insertion  of  wedges 

*  One  fj.  is  one-thousandth  of  a  millimetre  ;  one  yu./x  is  one-thousandth  p,  i.e.  one- 
millionth  of  a  millimetre. 


140  PHYSIOLOGY 

of  wood  ;    water  was  poured  on  the  wood,  and  the  swelling  of  the  wedges 
split  the  rock  in  the  desired  direction.* 

On  account  of  the  extent  of  surface  it  is  practically  impossible  to  wash 
out  the  inorganic  constituents  from  a  gel.  The  diminution  of  the  osmotic 
pressure  of  many  dissolved  substances  at  surfaces  causes  the  concentration 
at  the  surface  of  the  solid  phase  to  be  greater  than  that  in  the  surrounding 
medium.  Thus  if  dry  gelatin  be  immersed  in  a  salt  solution  it  will  swell 
up,  but  the  solution  which  it  absorbs  will  be  more  concentrated  than  the 
solution  in  which  it  is  immersed,  so  that  the  proportion  of  salt  in  the  latter 
will  be  diminished.  When  however  equilibrium  is  established  between  a 
gel  and  the  surrounding  fluid,  it  is  found  to  present  no  appreciable  resistance 
to  the  passage  of  dissolved  crystalloids.  Thus  salt  or  sugar  diffuses  through 
a  column  of  solid  gelatin  as  if  the  latter  were  pure  water.  On  the  other 
hand,  gels  are  practically  impermeable  to  other  colloids  in  solution.  This 
impermeability  is  made  use  of  in  the  separation  of  crystalloids  from  colloids 
by  dialysis,  membranes  used  in  this  process  being  generally  irreversible 
and  heterogeneous  gels  (i.e.  vegetable  parchment,  animal  membranes). 
Other  gels,  such  as  tannate  of  gelatin  or  copper  ferrocyanide,  are  not  only 
impermeable  to  colloids,  but  also  to  many  crystalloid  substances.  These 
membranes  therefore  were  used  by  Pfeffer  for  the  determination  of  the 
osmotic  pressure  of  such  crystalloids  as  cane  sugar. 

PROPERTIES  OF  HYDROSOLS.  Substances  such  as  dextrin  or  egg- 
albumin  may  be  dissolved  in  water  in  almost  any  concentration.  If  a 
solution  of  egg-albumin  be  concentrated  at  a  low  temperature,  it  becomes 
more  and  more  viscous  and  finally  solid.  But  there  is  no  distinct  point 
at  which  the  fluid  passes  into  the  solid  condition.  Such  solutions  are  known 
as  hydrosols.  Much  discussion  has  arisen  whether  they  are  to  be  regarded 
as  true  solutions  or  as  pseudo-solutions  or  suspensions.  The  chief  criterion 
of  a  true  solution  is  its  homogeneity.  In  a  solution  the  molecules  of  the 
solute  are  equally  diffused  throughout  the  molecules  of  the  solvent,  and 
it  is  impossible,  without  the  application  of  energy,  to  separate  one  from 
the  other.  Thus  filtration,  gravitation  leave  the  composition  of  the  solution 
unchanged.  It  is  true  that,  by  the  employment  of  certain  kinds  of  mem- 
branes, e.g.  the  semi-permeable  copper  ferrocyanide  membrane,  it  is  possible 
to  separate  solute  from  solvent,  but  in  this  case  the  force  required  to  effect 
the  filtration  is  enormous  and  grows  with  every  increase  in  the  strength 
of  the  solution.  The  measure  of  the  force  required  is  the  osmotic  pressure 
of  the  solution,  and  it  becomes  natural  therefore  to  regard  the  possession 
of  an  osmotic  pressure  as  a  distinguishing  criterion  of  a  true  solution. 
Is  there  any  evidence  that  colloidal  solutions  also  display  an  osmotic 
pressure  ? 

I  have  shown  that  it  is  possible  to  determine  the  osmotic  pressure  of 
colloidal  solutions  directly,  taking  advantage  of  the  fact  that  colloidal  mem* 

*  According  to  Rodewald,  the  maximal  pressure  with  which  dry  starch  attracts 
water  amounts  to  2073  kilo,  per  sq.  cm. 


THE  PROPERTIES   OF  COLLOIDS 


141 


branes,  while  permitting  the  passage  of  water  and  salts,  are  impermeable 
to  colloids  in  solution. 

The  method  originally  adopted  was  as  follows  :  In  order  to  determine  the  osmotic 
pressure  of  the  colloidal  constituents  of  blood-serum,  150  c.c.  of  clear  filtered  serum  are 
filtered  under  a  pressure  of  30-40  atmospheres  through  a  porous  cell  which  has  been 
previously  soaked  with  gelatin.  The  first  10-20  c.c.  of  filtrate,  which  contain  the 
water  squeezed  out  of  the  meshes  of  the  gelatin  and  have  also  lost  salt  in  consequence 
of  absorption  by  the  gelatin,  are  rejected.  The  filtration  is  allowed  to  go  on  for  another 
twenty-four  hours,  when  about  75  c.c.  of  a  clear  colourless  filtrate  are  obtained,  per- 
fectly free  from  all  traces  of  protein,  but  possessing  practically  the  same  freezing-point 
as  the  original  serum.  (Although  the  colloids,  if  they  possess  an  osmotic  pressure,  must 
also  cause  a  depression  of  the  freezing-point,  any  such  depression  would  be  within 
the  errors  of  observation,  since  a  pressure  of  45  mm.  Hg  would  correspond  only  to 
0*005°  C.)  The  concentrated  serum  left  behind  in  the  filter  is  then  put  into  the  osmo- 
meter, the  filtrate  being  used  as  the  inner  fluid.  The  construction  of  the  osmometer 
is  shown  in  the  diagram  (Fig.  27). 

The  tube  BB  is  made  of  silver  gauze,  connected  at  each  end  to  a  tube  of  solid  silver. 
Round  the  gauze  is  wrapped  a  piece  of  peritoneal  membrane,  as  in  making  a  cigirette. 
This  is  painted  ail  over  with  a  solution  of  gelatin  (10  per  cent.)  and  then  a  second  layer 
of  membrane  applied.     Fine  thread  is  now  twisted  many  times  round  the  tube  to 


prevent  any  disturbance  of  the  membranes,  and  the  whole  tube  is  soaked  for  half  an 
hour  in  a  warm  solution  of  gelatin.  In  this  way  one  obtains  an  even  layer  of  gelatin 
between  two  layers  of  peritoneal  membrane  and  supported  by  the  wire  gauze.  The 
tube  so  prepared  is  placed  within  a  wide  tube,  AA,  which  is  provided  with  two  tubules 
at  the  top.  One  of  these,  O,  is  for  filling  the  outer  tube  ;  the  other  is  fitted  with  a 
mercurial  manometer,  M.  Two  small  reservoirs,  CC,  are  connected  with  the  outer 
ends  of  BB,  by  means  of  rubber  tubes.  The  whole  apparatus  is  placed  in  a  wooden 
cradle,  DD,  pivoted  at  X,  and  provided  with  a  cover  so  that  it  may  be  filled  with  fluids 
at  different  temperatures  if  necessary.  The  colloid  solution  is  placed  in  AA,  and  the 
reservoirs,  CC,  and  inner  tube,  BB,  are  filled  with  the  filtrate,  i.e.  with  a  salt  solution 
approximately  or  absolutely  isotonic  with  the  colloid  solution.  The  apparatus  is  then 
made  to  rock  continuously  for  days  or  weeks  by  means  of  a  motor.  In  this  way  the 
fluid  on  the  two  sides  of  the  membrane  is  continually  renewed,  and  the  attainment 
of  an  osmotic  equilibrium  facilitated.  With  this  apparatus  I  found  that  the  colloids 
in  blood-serum,  containing  from  7  to  8  per  cent,  proteins,  had  an  osmotic  pressure  of 
25  to  30  mm,  Hg,  which  would  correspond  to  a  molecular  weight  of  about  30,000. 


142  PHYSIOLOGY 

A  more  convenient  form  of  osmometer  has  been  devised  by  B.  Moore, 
using  parchment  paper  as  the  membrane.  With  this  osmometer,  the 
existence  of  an  osmotic  pressure  in  colloidal  solutions  has  been  definitely 
established  both  by  Moore  in  the  case  of  haemoglobin,  proteins,  and  soaps, 
and  by  Bayliss  in  the  case  of  colloidal  dyes,  such  as  Congo  red.  The  osmotic 
pressure  of  haemoglobin  was  found  I  y  Hiifner  to  correspond  to  a  molecular 
weight  of  about  10,000,  i.e.  a  molecular  weight  already  deduced  from  its 
composition  and  its  combining  powers  with  oxygen.  Often  however  the 
osmotic  pressure  is  very  much  smaller  than  would  be  expected  from  the 
molecular  weight  of  the  substance,  owing  to  the  fact  that  colloids  in  solution 
may  be  in  many  different  conditions  of  aggregation.  Thus  the  molecule 
of  colloidal  silica  must  be  many,  probably  thousands  of  times  larger 
than  the  molecule  as  represented  by  H,Si03.  The  osmotic  pressure 
being  proportional  to  the  number  of  molecules  in  a  given  volume  of  solution, 
the  larger  the  aggregate  the  smaller  would  be  the  total  number  of  molecules, 
and  the  smaller  therefore  the  osmotic  pressure  of  the  solution. 

It  is  in  consequence  of  the  huge  size  of  the  molecular  aggregates  that 
colloidal  solutions,  such  as  starch  or  glycogen,  and  probably  globulin,  display 
no  appreciable  osmotic  pressure.  We  cannot  divide  colloidal  solutions  into 
two  classes,  viz.  those  which  form  true  solutions  and  present  a  feeble  osmotic 
pressure,  and  those  which  form  only  suspensions  and  therefore  exert  no 
osmotic  pressure.  In  inorganic  colloids,  such  as  arsenious  sulphide,  Picton 
and  Linder  have  shown  that  all  grades  exist  between  true  solutions  and 
suspensions.  With  increasing  aggregation  of  the  molecules,  the  suspension 
becomes  coarser  and  coarser  until  finally  the  sulphide  separates  in  the  form 
of  a  precipitate. 

The  measurement  of  the  osmotic  pressure  of  the  colloids  of  serum  points 
to  their  having  a  molecular  weight  of  about  ?)0,CC0.  Chemical  evidence 
shows  that  haemoglobin  has  a  molecular  weight  of  about  16,0(0,  and  we 
have  every  reason  to  believe  that  the  much  more  complex  molecules  forming 
the  cell  proteins  may  have  molecular  weights  of  many  times  this  amount. 
When  however  we  arrive  at  molecular  weights  of  these  dimensions,  the 
disproportion  between  the  size  of  the  molecules  and  those  of  the  solvent, 
water,  becomes  so  great  that  a  homogeneous  distribution  of  the  two  sub- 
stances, solute  and  solvent,  is  no  longer  possible.  The  size  of  a  molecule 
of  water  has  been  reckoned  to  be  -7  x  10  — 8  mm.  A  molecule  10,((0 
times  as  large  would  have  a  diameter  of  -7  x  10  — 4  mm.  =  -07^,  a  size 
just  within  the  limits  of  microscopic  vision.  Long  before  molecules  attained 
such  a  size  they  would  no  longer  react  according  to  the  laws  which  have 
been  derived  from  the  study  of  the  behaviour  of  the  almost  perfect  gases, 
but  would  possess  the  properties  of  matter  in  mass.  They  have  a  surface 
of  measurable  extent,  and  their  relations  to  the  molecules  of  water  or  solvent 
will  be  determined  by  the  laws  of  adsorption  at  surfaces  rather  than  by 
the  laws  of  interaction  of  imleeules.  As  a  matter  of  fact  we  find  that  such 
solutions  present  an  amazing  mixture  of  properties,  some  of  which  betray 
them  as  mechanical  suspensions,  while  others  partake  of  the  nature  of  the 


THE   PROPERTIES   OF  COLLOIDS  143 

chemical  reactions  such  as  those  studied  in  the  simpler  compounds  usually 
dealt  with  by  the  chemist. 

OPTICAL  BEHAVIOUR  OF  HYDROSOLS.  Nearly  all  colloidal  solu- 
tions present  what  is  known  as  the  Faraday- Tyndall  phenomenon.  When 
a  beam  of  light  is  passed  through  an  optically  homogeneous  fluid,  the  course 
of  the  beam  is  invisible.  A  beam  of  sunlight  falling  into  a  dark  room  is 
rendered  visible  by  impinging  on  and  illuminating  the  dust  particles  in  its 
course.  Each  of  these  particles,  being  illuminated,  acts  as  a  centre  of  dis- 
persion of  the  light,  so  that  the  course  of  the  beam  is  apparent  to  a  person 
standing  on  one  side  of  it.  Tyndall  showed  that,  if  the  particles  were 
sufficiently  minute,  the  fight  dispersed  by  them  at  right  angles  to  the  beam 
was  polarised.  This  can  be  easily  tested  by  looking  at  the  beam  through 
a  Nicol's  prism.  If  the  prism  be  slowly  rotated,  it  will  be  found  that, 
while  at  one  position  the  light  is  bright,  in  the  position  at  right  angles  to  this 
it  becomes  dim  or  is  extinguished.  The  production  of  the  Tyndall  pheno- 
menon may  therefore  be  regarded  as  a  test  for  the  presence  of  ultra-micro- 
scopic particles,  varying  in  size  from  5  to  50  /iu.  The  phenomenon  is  perhaps 
too  sensitive  to  be  taken  as  a  proof  that  a  fluid  presenting  it  is  a  suspension 
rather  than  a  solution.  It  is  shown,  for  instance,  by  solutions  of  many 
bodies  of  high  molecular  weight,  such  as  raffinose  (a  tri-saccharide)  or  the 
alkaloid  brucine  (Bayliss). 

A  particle  having  a  diameter  less  than  half  the  wave-length  of  light, 
i.e.  about  300  /  or  -3  //,,  cannot  be  clearly  distinguished  under  any  power  of 
the  microscope.  The  fact  that  an  ultra-microscopic  particle  may  serve 
as  a  centre  for  dispersal  of  light  may  be  used  for  rendering  such  particles 
visible  under  the  microscope.  For  this  purpose  a  strong  beam  of  light  is 
passed  in  the  plane  of  the  stage  of  the  microscope  through  a  cell  containing 
the  hydrosol,  which  is  then  examined  under  a  high  power.  On  examining 
with  this  apparatus  a  dilute  gold  sol,  we  see  a  swarm  of  dancing  ]  oints 
of  light.  '  like  gnats  in  the  sunlight,"  which  move  rapidly  in  all  directions, 
rendering  it  almost  impossible  to  count  their  number  in  the  field.  The  coarser 
particles  present  slight  oscillations  similar  to  those  long  known  as  the  Brown- 
ian  movements.  The  smallest  particles  which  can  be  seen  show  a  combined 
movement,  consisting  of  a  translatory  movement,  in  which  the  particle 
passes  rapidly  across  the  field  in  one-sixth  to  one-eighth  of  a  second,  and  a 
movement  of  oscillation  of  much  shorter  period.  The  representation  of  the 
course  of  such  a  particle  is  given  in  Fig.  28. 

The  size  of  the  smallest  particles  seen  in  this  way  may  amount  to  -f  05  //. 
Not  all  colloidal  solutions  show  these  particles  in  the  ultra-microscope. 
In  some  cases  this  is  due  simply  to  the  small  size  of  the  particles,  and 
the  addition  of  any  substance,  which  causes  aggregation  and  therefore 
increase  in  the  size  of  the  particles,  will  bring  them  into  view.  In  others 
the  absence  of  optical  inhomogeneity  may  be  due  to  the  coincidence  of 
the  refractive  indices  of  the  two  phases  of  the  hydrosol,  or  to  the  ab  ence 
of  any  surface  tension  and  therefore  dividing  surfaces  between  the  two 
phases. 


144 


PHYSIOLOGY 


ELECTRICAL    PROPERTIES    OF    COLLOIDS 

In  the  case  of  many  hydrosols  the  ultra-microscopic  particles  of  which 
they  are  composed  carry  an  electric  charge  which,  according  to  the  nature 
of  the  solution,  may  be  either  positive  or  negative.  On  this  account,  the 
particles  move  if  placed  in  an  electric  field,  and  the  direction  of  their  move- 
ment reveals  the  nature  of  their  change.  Thus  colloidal  ferric  hydrate  is 
electro-positive  and  travels  from  anode  to  cathode.  Silicic  acid,  in  the 
presence  of' a  trace  of  alkali,  is  electro-negative,  and  the  same  is  true  of  a 
hydrosol  of  gold.  When  a  current  is  passed  through  these  hydrosols,  the 
colloidal  particles  travel  to.  the  anode,  where  they  are  precipitated.  In 
certain  colloids  the  charge  varies  according  to  the  conditions  under  which 
they  are  brought  into  solution.  If  for  instance,  egg-white  be  diluted  ten 
times  with  distilled  water,  filtered  and  boiled,  no  precipitate  occurs,  but 


Fig.  28.     Movements  of  two  particles  of  india-rubber  latex  in  colloidal  solution,  recorded  by 
cinematograph  and  ultra-mi  roBcope.     (Hentu.) 

we  obtain  a  colloidal  suspension  of  albumin.  When  thoroughly  dialysed, 
this  protein  is  insoluble  in  pure  water,  but  is  soluble  in  traces  of  either  acid 
or  alkali.  In  acid  solution  the  protein  particles  carry  a  positive  charge, 
whereas  in  alkaline  solution  their  charge  is  negative.  The  charged  condi- 
tion of  these  particles  must  play  a  considerable  part  in  keeping  them  asunder 
and  therefore  in  preventing  their  aggregation  and  precipitation.  This  is 
shown  by  the  fact  that  any  agency  which  will  tend  to  discharge  them  will 
cause  precipitation  and  coagulation.  Among  such  agencies  is  the  passage 
of  a  constant  current,  just  mentioned.  To  the  same  action  is  due  the 
coagulative  or  precipitating  effects  of  neutral  salts.  Thus  any  of  the 
colloids  we  have  mentioned,  ferric  hydrate,  silica,  gold,  or  boiled  albumen, 
are  thrown  down  by  the  addition  of  traces  of  neutral  salts,  and  it  is  found 
that  in  this  process  they  carry  with  them  some  of  the  ion  with  the  opposite 
charge  to  that  of  the  colloidal  particle.     Thus,  in  the  precipitation  of  the 


THE  PROPERTIES  OF  COLLOIDS  •         145 

electro-positive  ferric  hydrate  the  acid  ion  of  the  salt  is  the  determining 
factor,  the  coagulative  power  increasing  rapidly  with  the  valency  of  the  acid. 
On  the  other  hand,  in  the  precipitation  of  a  gold  sol  the  electro-positive  ion 
is  the  effective  agent,  and  here  again  the  coagulative  effect  is  enormously 
increased  by  a  rise  in  valency.  This  is  shown  in  the  following  Tables, 
where  it  will  be  seen  that  in  the  coagulation  of  gold,  barium  chloride  with 
the  divalent  Ba",  is  seven  times  as  powerful  as  K2S04  containing  the 
univalent  K'.  On  the  other  hand,  in  the  precipitation  of  the  electro- positive 
ferric  hydrate.  K,S04  with  a  divalent  S04",  is  400  times  as  effective  as 
BaCL. 

Amount  of  Salt  necessary  to  Precipitate  Colloidal  Solutions 
To  coagulate  Gold  To  coagulate  Fe203 


K2S04  1  g.  mol.  in  4,000,000  c.c. 
MgS04    „     „      „    4,000,000    „ 
BaCls      „     „      „         10,000    „ 
Nad       ..     .,     „        30,000    .. 


BaCl2  1  g.  mol.  in  500,000  c.c. 
NaCl       „    „      „    72,000    „ 
K,S04    „    „      „    75,000    „ 


The  presence  of  a  charge  is  not  however  a  necessary  condition  for  the 
stability  of  a  colloidal  solution.  Thus  the  proteins  of  serum,  globulin  in  a 
weak  saline  solution,  or  gelatin,  present  no  drift  when  exposed  to  a  strong 
electric  field.  In  such  cases  one  must  assume  the  stability  of  the  solution 
to  be  determined  by  the  absence  of  any  surface  tension  between  the  two 
phases  in  the  solution,  or  between  the  particles  of  solute  and  solvent. 
Thus  no  force  is  present  tending  to  cause  aggregation  of  the  particles. 

The  charged  condition  of  a  colloidal  particle  makes  it  behave  in  an 
electric  field  in  much  the  same  way  as  a  charged  ion  of  an  electrolyte,  and 
this  similarity  extends  also  to  its  chemical  behaviour,  so  that  we  have  a 
class  of  compounds  formed  resembling  in  many  respects  chemical  com- 
binations, but  differing  from  these  in  the  absence  of  definite  quantitative 
relations  between  the  reacting  substances.  This  class  of  continuously 
varying  chemical  compounds  has  been  designated  by  Van  Bemmelen  absorp- 
tion compounds.  Since,  however  the  interaction  must  take  place  at  the 
surface  layer  bounding  the  charged  particles,  it  will  be  perhaps  better,  as 
Bayliss  has  done,  to  use  the  term  adsorption.  The  huge  molecules  or  aggre- 
gates of  molecules  which  distinguish  the  colloidal  state  form  a  system  with 
a  considerable  inertia,  so  that  we  have  a  tendency  to  the  establishment 
of  conditions  of  false  equilibrium.  Once  a  configuration  is  established,  it 
is  necessary,  in  consequence  of  the  inertia,  to  overstep  widely  the  conditions 
of  its  formation  in  order  to  destroy  it.  Thus  a  10  percent,  gelatin  solution 
sets  at  21°C,  but  does  not  melt  until  warmed  to  2y-ti°C.  Solutions  of  agar 
in  water  set  at  about  35°C,  but  do  not  melt  under  90°C.  A  gel  of 
gelatin  takes  twenty-four  hours  after  setting  to  attain  a  constant  melting- 
point. 

The  factors  involved  in  the  formation  of  adsorption  or  absorption  com- 
binations are  therefore  : 

(1)  Extent  of  surface.  In  a  colloidal  solution  this  must  be  enormous 
in  proportion  to  the  mass  of  substance  in  solution.     Thus  a  10  c.c.  sphere 

10 


146 


PHYSIOLOGY 


with  a  surface  of  22  sq.  cm.,  if  reduced  to  a  fine  powder  consisting  of  spherules 
of  -C0000025  cm.  in  diameter,  will  have  a  surface  of  20,CC0,CC0  sq.  cm., 
i.e.  nearly  half  an  acre.  At  the  whole  of  this  surface  adsorption  may 
take  place,  involving  the  concentration  of  dissolved  electrolytes,  ions,  or 


(2)  Chemical  nature  of  particle. 

(3)  Electric  charge  on  the  surface.  The  sign  of  this  may  be  determined 
by  the  chemical  nature  of  the  colloid  and  its  relation  to  the  electrolytes  in 
the  surrounding  medium. 

Another  factor  which  may  determine  the  character  of  the  charge  on  the  particles 
has  been  pointed  out  by  Coelin.  This  observer  finds  that,  when  various  non-con- 
ducting bodies  are  immersed  in  fluids  of  different  dielectric  constants,  they  assume  a 
positive  or  negative  charge  according  as  their  own  dielectric  constants  are  higher  or 
lower  than  the  fluid  with  which  they  are  in  contact.  For  instance,  glass  (5  to  6)  is 
negative  in  water  (80)  or  alcohol  (26),  whereas  in  turpentine  (2-2)  it  is  positive.  In 
water,  as  Quincke  has  found,  nearly  all  non-conducting  bodies  take  on  a  negative  charge. 
Among  these  are  cotton-wool  and  silk.  Particles  of  these  in  water,  exposed  to  an 
electric  field,  move  towards  the  anode.     The  same  is  true,  as  Bayliss  has  shown,  of  paper. 

The  conditions  which  determine  the  formation  of  these  adsorption  com- 
pounds can  be  studied  in  their  simplest  form  on  the  adsorption  of  dyestuffs 
by  substances  such  as  paper.  If  we  take  a  series  of  solutions  of  a  dye, 
such  as  Congo-red,  in  progressively  diminishing  concentration,  and  place 
in  each  solution  the  same  amount  of  filter-paper,  we  find  that  a  part  of  the 
dye  is  taken  up  by  the  paper,  and  the  proportion  taken  up  is  larger  the  more 
dilute  the  solution.  This  relation  has  been  spoken  of  by  Bayliss  as  the  law 
of  adsorption.  This  is  illustrated  by  the  following  Table  of  results  of  such 
an  experiment : 


Concentration  of 
solution 

Proportion  of  dye 
in  solution 

Proportion  of  dye- 
in  paper 

Initial                         Final 

0-014                00056 

Per  cent. 
40 

Per  eent. 
60 

0-012                0-0024 
0010                00009 

20 
9-3 

80 
90-7 

0-008                00003 

4 

96 

0-006                0-00008 

0-004 

0-002 

13 
trace 
trace 

98-7 
practically  all 
practically  all 

If  put  into  the  form  of  a  curve,  where  the  ordinates  represent  the  per- 
centage of  dye  left  in  solution,  and  the  abscissae  the  original  concentration 
of  the  solution,  the  curve  only  approaches  the  ax,is  (i.e.  zero  concentration) 
asymptotically.  In  other  words,  however  dilute  the  original  solution  may 
be,  there  will  always  be  a  certain  amount  of  the  dye  left  unabsorbed  by 
the  paper.  Similar  relations  are  found  to  exist  between  proteins  and  electro- 
lytes.    By  continuously  washing  a  protein  or  gelatin  with  distilled  water, 


THE  PROPERTIES   OF  COLLOIDS  147 

the  removal  of  electrolytes  becomes  slower  and  slower,  but  it  is  practically 
impossible  within  finite  time  to  get  rid  in  this  way  of  the  last  traces  of  ash. 
Although  the  chemical  behaviour  of  colloids  is  largely  determined  by 
surface  phenomena,  it  presents  at  the  same  time  analogies  with  more  strictly 
chemical  reactions,  since  it  is  conditioned  by  the  chemical  structure,  of  the 
colloid  molecule  as  well  as  by  the  charge  carried  by  the  latter.  A  good 
example  of  these  adsorption  combinations  is  presented  by  globulin,  the 
behaviour  of  which  has  been  studied  by  Hardy.  This  may  be  obtained 
from  diluted  blood-serum  by  precipitation  with  acetic  acid.  Four  states 
can  be  recognised  in  both  the  solid  condition  and  in  solution,  viz.  globulin 
itself,  compounds  with  acid  or  with  alkali,  and  compounds  with  neutral 
salt.  The  amount  of  acid  and  alkali  combining  with  the  globulin  is  in- 
determinate, the  effect  of  adding  either  acid  or  alkali  to  the  neutral  globulin 
being  to  cause  a  gradual  conversion  of  an  opaque,  milky  suspension  into  a 
limpid,  transparent  solution.  On  drying  HC1  globulin,  the  dried  solid  is 
found  to  contain  all  the  chlorine  used  to  dissolve  it.  The  acid  may  therefore 
be  regarded  as  being  in  true  combination.  Both  acid  and  alkali  globulins 
act  as  electrolytes,  the  globulin  being  electrically  charged  and  taking  part 
in  the  transport  of  electricity.  In  order  to  produce  the  same  extent  of 
solution,  the  concentration  of  the  alkali  added  must  be  double  that  of  the 
acid.  The  relation  of  globulin  to  acids  and  alkalies  is  similar  to  that  of  the 
so-called  amphoteric  substances,  such  as  the  amino-acids.  An  amino-acid, 
such  as  glycine,  can  react  as  a  basic  anhydride  with  other  acids,  thus  : 

NH3  NH2HC1 

CH,/  +  HC1  =  CH  / 

NCO,H  C02H 

or  as  an  acid  anhydride  with  bases : 

CH2.NH2  CH2.NH2 

+  NaHO  =  |  +HaO 

COOH  COONa 

Like  these  too,  globulin  forms  soluble  compounds  with  neutral  salts.  An 
amphoteric  electrolyte  thus  acts  as  a  base  in  the  presence  of  a  strong  acid, 
and  as  an  acid  in  the  presence  of  a  strong  base. 

From  true  electrolytes,  colloidal  solutions  differ  in  the  fact  that  their 
particles  are  of  varying  size  according  to  the  conditions  in  which  they  exist 
and  carry  varying  charges  of  electricity,  whereas  an  ion  such  as  Na  or  CI 
has  a  mass  which  is  constant  for  the  ion  in  question,  and  always  carries 
the  same  electric  charge.  The  charged  particles  of  an  acid-  or  alkali-globulin 
may  be  distinguished  therefore  as  pseudo-ions. 

In  these  adsorption  combinations,  although  the  chemical  nature  of  the 
colloidal  molecules  is  concerned,  there  is  an  absence  of  definite  equilibrium 
points,  such  as  we  are  accustomed  to  in  most  chemical  reactions.  The  inertia 
of  the  system  and  the  large  size  of  the  molecules  determine  the  occurrence 
of  false  equilibria  and  of  delayed  reaction,  so  that  the  condition  and  behaviour 
of  a  colloidal  system  at  any  moment  are  determined,  not  entirely  by  the 


148  PHYSIOLOCxY 

quantitative  relations  of  its  components,  but  also  by  the  past  history  of  the 
system. 

COMBINATIONS    BETWEEN    COLLOIDS 

Besides  the  compounds  between  colloids  and  electrolytes,  combination, 
or  at  least  interaction,  takes  place  between  different  colloids.  Many  colloids 
are  precipitated  by  other  colloidal  solutions.  This  effect  is  always  found  to 
occur  when  the  colloidal  solutions  carry  different  charges.  Thus  ferric 
hydrate  in  colloidal  solution  is  precipitated  by  colloidal  silica  or  colloidal 
gold,  both  colloids  being  thrown  out  of  solution.  On  the  other  hand,  certain 
colloids  may  exercise  a  protective  influence  on  other  colloidal  solutions. 
Thus,  as  Faraday  first  showed,  colloidal  gold  is  much  more  stable  in  the 
presence  of  a  little  gelatin.  The  colloids  of  serum  can  dissolve  a  considerable 
amount  of  purified  globulin.  Although  the  latter  in  solution  shows  a  drift 
in  the  electric  field,  the  resulting  solution  is  quite  unaffected  by  the  passage 
of  a  current  through  it.  In  these  cases  the  protective  colloids  carry  no 
charge,  but  the  same  protective  effect  may  be  observed  if  a  large  excess 
of.  e.g.  an  electro-positive  colloid  be  added  to  an  electro-negative  colloid. 
This  interaction  between  different  colloids  probably  plays  an  important 
part  in  many  physiological  phenomena.  We  have  reason  to  believe  that 
the  reactions  between  toxin  and  antitoxin,  and  between  ferment  and  sub- 
strate, which  we  shall  study  later,  are  of  this  character,  and  that  the 
compounds  formed  belong  to  the  class  of  adsorption  combinations. 

THE  COAGULATION   OF  COLLOIDS 

Most  colloidal  solutions  are  unstable,  and  the  relations  between  the 
suspended  particle  or  molecule  and  the  surrounding  fluid  may  be  upset  by 
slight  changes  of  reaction  or  the  presence  of  minute  traces  of  salts.  As  a 
result  the  hydrosol  is  destroyed,  the  suspended  particles  aggregating  to 
form  larger  complexes.  These  aggregations  may  settle  to  the  bottom  of 
the  fluid  as  a  precipitate,  or  may  form  a  species  of  network,  the  result 
varying  according  to  the  nature  of  the  colloid  and  its  concentration.  Thus 
gelatin  changes  from  the  condition  of  hydrosol  to  hydrogel  with  fall  of 
temperature.  The  same  is  true  of  agar.  On  the  other  hand,  by  adding 
calcium  chloride  to  an  alkaline  solution  of  casein,  we  obtain  a  mixture  which 
sets  to  a  jelly  on  warming,  but  becomes  fluid  again  on  cooling.  Other  agen- 
cies may  lead  to  the  production  of  changes  which  are  irreversible.  Thus 
a  strong  solution  of  colloidal  silica  sets  to  a  solid  jelly  on  the  addition  of 
a  trace  of  neutral  salt,  and  it  is  not  possible  to  reform  the  hydrosol,  however ' 
long  the  jelly  is  submitted  to  dialysis. 

Two  methods  of  bringing  about  coagulation  of  hydrosols  deserve  special 
mention.  The  first  of  these  is  heat- coagulation.  If  a  solution  of  egg- 
albumin  or  globulin  be  heated  in  neutral  or  slightly  acid  medium  and  in  the 
presence  of  neutral  salt,  the  whole  of  it  is  thrown  down  in  an  insoluble  form. 
This  coagulated  protein  is  insoluble  in  dilute  acids  or  alkalies.  The  same 
coagulative  effect  of  heating  is  observed  in  the  metallic  sols.     With  con- 


THE  PROPERTIES  OF  COLLOIDS  149 

centrated  solutions  of  protein,  heat  coagulation  results  in  the  formation  of  a 
gel,  i.e.  a  network  of  insoluble  protein,  containing  water  or  a  very  dilute 
solution  of  protein  in  its  meshes.  In  dilute  solutions  the  result  is  the 
production  of  a  flocculent  precipitate. 

Another  method  is  the  so-called  mechanical  coagulation.  If  a  solution 
of  globulin  or  albumin  be  introduced  into  a  bottle,  which  is  then  violently 
shaken,  a  shreddy  precipitate  makes  its  appearance  in  the  solution,  and  this 
precipitate  increases,  so  that  by  prolonged  shaking  it  is  possible  to  throw 
down  80  or  90  per  cent,  of  the  dissolved  protein  in  the  coagulated  form. 
Ramsden  has  shown  that  this  mechanical  coagulation  is  a  surface  pheno- 
menon. It  depends  on  the  fact  that  a  large  number  of  substances  in  solution 
(viz.  any  which  lower  the  surface  tension  of  their  solutions)  undergo  concen- 
tration at  the  free  surface  of  the  fluid.  Such  substances  are  proteins,  bile- 
salts,  quinine,  saponin,  &c.  In  the  case  of  proteins  the  concentration  reaches 
such  an  extent,  and  the  molecules  at  the  surface  are  so  closely  packed 
together,  that  they  form  an  actual  solid  pellicle,  which  hinders  the  movement 
of  any  object,  such  as  a  compass  needle,  suspended  in  the  surface.  When  the 
solution  is  violently  shaken,  new  surfaces  are  constantly  being  formed,  and 
as  the  older  surfaces  are  withdrawn  into  the  fluid,  the  solid  pellicle,  on  them 
is  rolled  up  into  a  fine  shred  of  coagulated  protein,  and  this  process  will 
continue  until  there  is  no  protein  left  to  form  a  pellicle. 

We  must  conclude  that  colloidal  solutions,  although  differing  so  widely 
from  true  solutions  in  many  of  their  properties,  are  connected  with  these  by 
all  possible  grades.  In  a  solution  of  an  ordinary  crystalloid  or  electrolyte 
the  molecules  of  the  dissolved  substance  are  distributed  equally  and  homo- 
geneously among  the  molecules  of  the  solvent.  In  the  various  grades  of 
solution  a  colloid  solution  or  hydrosol  may  be  assumed  to  begin  when  the 
size  of  the  molecule  is  increased  out  of  all  proportion  to  that  of  the  molecules 
of  the  solvent.  The  '  dissolved '  ^olecules  now  have  the  properties  of 
matter  in  mass  and  to  present  surfaces  with  all  their  attendant  attributes. 
The  same  sort  of  solution  may  be  formed  with  smaller  molecules,  such  as 
Si02,  when  these  are  aggregated  together  with  adsorbed  water  into  huge 
molecular  complexes  or,  as  in  metallic  sols,  by  the  division  of  the  solid  metal 
into  ultra-microscopic  particles.  The  distinguishing  features  of  a  colloidal 
solution  are  due  to  this  lack  of  homogeneity,  and  to  the  fact  that  in  every 
solution  there  are  two  phases-— a  fluid  phase,  and  a  second  phase  which  is 
either  solid  or  a  concentrated  or  supersaturated  solution  of  the  colloid.  The 
huge  size  of  the  molecules  and  the  development  of  surface  not  only  determine 
the  formation  of  adsorption  combinations  but,  on  account  of  the  inertia  of 
the  system,  cause  a  delay  in  changes  of  state,  and  tend  to  the  formation  of 
false  equilibria  dependent  on  the  past  history  of  the  system. 

IMBIBITION 

All  colloids,  even  those  such  as  starch  or  gelatin,  which  are  insoluble 
in  cold  water,  exhibit  a  phenomenon,  viz.  '  Quellung  '  or  imbibition,  which 
in  many  cases  it  is  impossible  to  distinguish  from  the  process  of  solution. 


150  PHYSIOLOGY 

This  phenomenon,  which  was  long  ago  studied  by  Chevreul  and  has  been 
the  subject  of  a  series  of  careful  experiments  by  Overton,  is  exhibited  by 
all  animal  tissues  and  all  colloids.  Thus  elastic  tissue  dried  in  vacuo  absorbs 
from  a  saturated  solution  of  common  salt  36-8  per  cent,  of  water  and  salt.  If 
dried  colloids  be  suspended  in  a  closed  vessel  over  various  solutions,  they 
will  take  up  water  in  the  form  of  vapour  from  the  solution,  and  the  osmotic 
pressure  of  the  solution  in  question  will  inform  us  as  to  the  amount  of  work 
which  would  be  necessary  in  order  to  separate  the  water  again  from  the 
colloids. 

Thus  it  has  been  reckoned  that  to  press  out  water  from  gelatin  containing 
284  parts  of  water  to  100  parts  of  dried  gelatin  would  require  a  pressure  of 
over  two  hundred  atmospheres.  The  imbibition  pressure  of  colloids  in- 
creases rapidly  with  the  concentration  of  the  colloid  and  at  a  greater  rate  than 
the  latter.  In  this  respect  however  imbibition  pressure  resembles  osmotic, 
or  indeed  gaseous,  pressure.  At  extreme  pressures  the  pressure  of  hydrogen 
rises  more  rapidly  than  its  volume  diminishes.  In  solutions  this  effect  is 
more  marked  the  larger  the  size  of  the  molecule.  Thus  a  6-7  per  cent, 
solution  of  cane  sugar  has  the  same  vapour- tension,  and  therefore  the  same 
osmotic  pressure,  as  a  -67  per  cent.  NaCl  solution.  A  67  per  cent,  cane-sugar 
solution  has  however  the  same  osmotic  pressure  as  an  18-J  per  cent,  solution 
of  common  salt.  It  is  impossible  to  draw  any  hard  line  of  distinction  between 
imbibition  pressure  and  osmotic  pressure,  or  to  say  where  a  fluid  ceases  to  be 
a  solution  and  becomes  a  suspension.  All  grades  are  to  be  found  between  a 
solution  such  as  that  of  common  salt  with  a  high  osmotic  pressure  and  optical 
homogeneity,  and  a  solution  such  as  that  of  starch,  which  scatters  incident 
light  and  is  therefore  opalescent,  and  has  no  measurable  osmotic  pressure. 

The  close  connection  between  the  processes  of  imbibition  and  of  solution 
is  shown  also  by  the  fact  that  the  latter  occurs  only  in  certain  media,  the 
nature  of  the  media  being  dependent  on  the  chemical  character  of  the  sub- 
stances in  question.  Thus  all  the  crystalline  carbohydrates — such  as  grape 
sugar  and  cane  sugar — are  easily  soluble  in  water,  only  slightly  soluble  in 
alcohol,  and  practically  insoluble  in  ether  and  benzol.  The  amorphous 
carbohydrates  which  must  be  regarded  as  derived  by  a  process  of  condensa- 
tion from  the  crystalline  carbohydrates — e.g.  starch,  cellulose,  gum  arabic, 
&c. — have  a  strong  power  of  imbibition  for  water.  This  power  may  be 
limited,  as  in  the  case  of  cellulose,  or  may  be  unlimited,  as  in  the  case  of 
gum  arabic,  so  that  a  so-called  solution  results.  On  the  other  hand,  they 
swell  up  but  slightly  in  alcohol,  and  are  unaffected  by  ether  and  benzol. 
In  the  same  way  proteins  all  take  up  water  and  in  man}'  cases  form  a  so-called 
solution,  but  are  unaffected  by  ether  and  benzol — a  behaviour  which  is 
repeated  in  the  case  of  the  amino-acids,  out  of  which  the  proteins  are  built 
up,  and  which  are  easily  soluble  in  water  but  are  practically  insoluble  in  ether 
and  benzol.  On  the  other  hand,  india-rubber  and  the  various  resins  take  up 
ether,  benzol,  and  turpentine  often  to  an  indefinite  extent,  while  they  are  un- 
touched by  water.  With  this  behaviour  we  may  compare  the  easy  solubility 
of  the  hydrocarbons,  the  aromatic  acids,  and  esters  in  ether  and  benzol,  and 


THE  PROPERTIES  OF  COLLOIDS  151 

their  insolubility  in  water.  As  Overton  has  pointed  out,  the  power  of 
amorphous  carbohydrates  to  take  up  fluids  is  modified  by  alteration  of  their 
chemical  structure  in  the  same  direction  as  the  solubility  of  the  corresponding 
crystalline  carbohydrates.  Thus,  if  the  hydroxyl  groups  in  the  sugars  be 
replaced  by  nitro,  acetyl,  or  benzoyl  groups,  they  become  less  soluble  in 
water,  while  their  solubility  in  alcohol,  acetone,  &c,  is  increased.  In  the 
same  way  the  replacement  of  the  hydroxyl  groups  in  cellulose  by  N02  groups 
diminishes  the  power  possessed  by  this  substance  of  taking  up  water,  but 
renders  it  capable  of  swelling  up  or  dissolving  in  alcohol  and  acetone. 


SECTION  IV 

THE   MECHANISM   OF  CHEMICAL  CHANGES   IN 
LIVING   MATTER.     FERMENTS 

All  the  events  which  make  up  the  life  of  plants  and  animals  are  accompanied 
and  conditioned  by  chemical  changes  of  the  most  varied  character.  In  a 
previous  chapter  we  have  endeavoured  to  form  an  idea  of  the  ways  in  which 
some  of  the  synthetic  processes  that  occur  in  the  living  body  may  be  effected. 
We  saw  that,  although  it  was  possible  to  imitate  in  many  respects  the  vital 
syntheses  by  ordinary  laboratory  methods,  the  imitation  fell  far  short  of  the 
process  as  it  actually  occurs  in  the  living  cell,  both  in  completeness  of  the 
reaction  and  in  the  ease  with  which  it  could  be  effected.  We  can,  for 
instance,  by  passing  carbon  dioxide  over  red-hot  charcoal,  convert  it  into 
carbon  monoxide,  and  this  gas,  acting  on  dry  potassium  hydrate,  forms 
potassium  formate.  Formate  of  linie,  on  dry  distillation,  gives  a  small 
proportion  of  formaldehyde  which,  under  the  influence  of  dilute  alkalies, 
will  condense  to  the  mixture  of  sugars  known  as  acrose.  The  green  leaf 
in  sunlight  absorbs  the  minimal  quantities  of  carbon  dioxide  present  in  the 
atmosphere  and  converts  it  almost  quantitatively  into  starch  within  a  few 
minutes,  and  this  change  is  effected  in  the  absence  of  any  concentrated 
reagents  and  at  the  ordinary  temperature  of  the  atmosphere.  Many  of  the 
chemical  transformations  effected  by  living  cells  we  have  so  far  been  quite 
unable  to  imitate.  The  problem  of  the  synthesis  of  camphor,  of  the  terpenes, 
of  starch,  of  cellulose,  is  still  unsolved ;  and  even  in  the  case  of  those  sub- 
stances which  we  can  manufacture  outside  the  living  cell  our  methods  involve 
the  use  of  powerful  reagents  and  of  high  temperatures,  and  result  in  most 
cases  in  the  production  of  many  side  reactions,  besides  that  reaction  which 
it  is  our  special  object  to  imitate.  The  distinguishing  characteristics  of  the 
chemical  changes  wrought  by  the  living  cell  are  : 

(i)  The  rapidity  with  which  they  are  effected  at  ordinary  tempera- 
tures. 

,(2)  The  specific  direction  of  the  process,  which  is  therefore  almost 
complete,  with  a  surprising  absence  of  the  side  reactions  which  interfere 
to  such  an  extent  with  the  yield  of  the  methods  employed  in  a  chemical 
laboratory. 

This  second  characteristic  may  however  be  regarded  as  a  consequence 
of  the  first,  since  an  increase  in  the  velocity  of  any  given  reaction  will  deter- 

152 


CHEMICAL  CHANGES  IN  LIVING  MATTER.    FERMENTS    153 

mine  a  preponderance  of  this  reaction  over  all  other  possible  ones.  A  funda- 
mental question  therefore  in  physiology  must  relate  to  the  manner  in  which 
the  cell  is  able  to  influence  the  velocity  of  some  specific  reaction. 

In  spite  of  the  enormous  diversity  of  chemical  reactions  occurring  in  the 
body,  they  may  be  divided  into  a  relatively  small  number  of  types.  Nearly 
all  the  reactions  are  reversible.  The  chief  types  of  chemical  change  are  as 
follows  : 

(1)  HYDROLYSIS.  In  most  cases  this  involves  the  taking  up  of  water 
and  a  decomposition  into  smaller  molecules.  Thus  the  proteins  are  broken 
down  in  the  intestine  into  their  constituent  amino-acids.  The  disaccharid.es, 
such  as  maltose  or  lactose,  take  up  one  molecule  of  water  and  give  rise  to 
two  molecules  of  monosaccharide.  The  fats  take  up  three  molecules  of 
water  with  the  formation  of  fatty  acid  and  glycerin.  Hippuric  acid  is  broken 
down  into  benzoic  acid  and  glycine.  The  reverse  change,  that  of  dehydra- 
tion, is  also  effected  apparently  with  equal  facility  by  the  living  cell,  the 
hexoses  losing  water  and  being  converted  into  a  complex  starch  or  glycogen 
molecule,  while  the  amino-acids  are  built  up  first  into  polypeptides,  and 
these  again  into  the  complex  proteins  of  the  cell.  Besides  the  reactions  in 
which  there  is  a  difference  in  the  amount  of  free  water  on  the  two  sidts  of 
the  equation,  it  seems  probable  that  hydrolysis  and  simultaneous  dehydrolysis 
at  different  parts  of  the  molecule  determine  a  number  of  chemical  transforma- 
tions, which  at  first  sight  seem  to  involve  a  simple  splitting  of  the  molecule. 
An  example  of  such  a  process  is  afforded  by  the  conversion  of  glucose  into 
lactic  acid  described  on  p.  113. 

(2)  DEAMINATION.  This  process  involves  the  splitting  off  of  an  NH2 
group  from  an  amino-acid  as  ammonia,  and  its  replacement  by  H  or  OH. 
Many  tissues  of  the  body  appear  to  have  this  power.  In  most  cases  the 
nature  of  the  change  in  the  remaining  fatty  moiety  of  the  molecule  has  not 
yet  been  ascertained.  If,  for  instance,  to  a  mass  of  liver  cells  some  amino- 
acid,  such  as  glycine,  alanine,  or  leucine,  be  added,  ammonia  is  set  free  in 
proportion  to  the  amount  of  amino-acid  which  was  added.  This  ammonia  is 
therefore  assumed  to  be  derived  from  the  amino-acid,  and  it  has  been  sug- 
gested that  here  also  the  process  of  splitting  off  ammonia  is  a  hydrolytic  one 
and  that  the  NH2  group  is  replaced  by  OH.     Thus — 

CH3  CH3 

I  I 

CH.NH2  +  H20  =  CH.OH  +  NH3 

I  I 

COOH  COOH 

(alanine) 

Recent  work  by  Neubaue'r  tends  to  show  that  deamination  is  accompanied 
in  the  first  place  by  oxidation,  so  that  the  first  intermediate  product  formed 
is  not  an  a  oxy-acid,  but  an  a  ketonic  acid.  A  second  atom  of  oxygen  is 
then  taken  up,  and  carbon  dioxide  is  split  off,  with  the  production  of  the 
next  lower  acid  of  the  series. 


154  PHYSIOLOGY 

We  might  represent  these  changes  as  follows  : 

(1)  CH3  CHa 

I  I 

CHNH2  +  0  =  CO        +  NH3 

I  I 

COOH  COOH 

(2)  CH„ 

I  CH3 

CO  +0=|  +  co„ 

I  COOH 

I'UUII 

Is  the  reverse  change  ever  effected  in  the  animal  body  ?  If  it  were 
possible  to  replace  the  OH  group  in  an  oxy-fatty  acid  by  NH2  or  the  0  in  an 
a  ketonic  acid  by  HNH2,  it  ought  also  to  be  possible  to  nourish  an  animal 
from  a  mixture  of  carbohydrates  and  ammonia,  or  at  any  rate  by  supplying 
him  with  a  mixture  of  the  appropriate  oxy-acids  or  ketonic  acids  and  am- 
monia. Until  recently  there  was  no  evidence  that  the  animal  body  is  able  to 
utilise  nitrogen,  except  in  organic  combination  as  amino-acids  or  the  complex 
aggregate  of  amino-acids  known  as  proteins.  In  the  plant  the  process 
of  synthesis  of  protein  from  ammonia  and  a  carbohydrate  such  as  hexose  is 
continuously  going  on,  and  it  is  probable  that  the  formation  of  amino-acid 
occurs  by  a  process  the  reverse  of  that  which  we  have  just  been  studying. 
Knoop  has  shown  that  the  same  reversed  change  may  occur  even  in  a 
mammal,  and  that  here  again  the  intermediate  substance  is  an  a  ketonic 
acid.  On  administering  benzylpyruvic  acid  (C6H5.CH2.CH2.CO.COOH) 
to  a  dog,  a  certain  amount  of  benzylalanine  (C'6H5.CH2CH2CHNH2.COOH) 
appeared  in  the  urine.  The  first  phase  of  the  oxidative  deamination  of 
amino-acids  is  thus  a  reversible  one  and  may  be  represented : 

R                                           R  R 

I  I     OH  || 

CHNH2  +  0        1 ->         C<  <        >    CO  +  NH3 

I  |    NU2  | 

COOH  COOH  COOH 

(3)  DECARBOXYLATION.  Many  amino-acids  when  subjected  to  the 
agency  of  bacteria  lose  a  molecule  of  carbon  dioxide  and  are  converted  into 
a  corresponding  amine. 

For  instance,  lysine,  which  is  diamino-caproic  acid,  is  converted  into 

pentamethylene  diamine  or  cadaverine.     Thus  : 

CH2.NH2  CH2.NH2 

I  I 

CH2  CH2 

I  I 

CH2  becomes  CH2 

I  I 

CH2  CH2 

I  I 

CH.NH2  CH2.NH2 

I 
COOH 


CHEMICAL  CHANGES  IN  LIVING  MATTEE.    FERMENTS    155 

In  the  same  way  ornithine  derived  from  the  breakdown  of  arginine  is  con- 
verted by  putrefactive  bacteria  into  tetra-methylene  diamine  or  putrescine. 
Other  examples  of  this  process  of  decarboxylation  are  : 

Isoamylamine  from  leucine,  (CH3)2.CH.CH,.CH2.NH2. 

(5  phenylethylamine  from  phenylalanine,  C6H5.CH2,CH2.NH2. 

Para-oxyphenylethylamine  from  tyrosine,  OH.C6H4.CH2.CH2.NH2. 

A  similar  process  has  been  supposed  to  take  place  as  a  step  in  the  suc- 
cessive oxidation  of  the  carbon  atoms  in  the  long  chain  fatty  acids  or  carbo- 
hydrates, but  a  thorough  study  of  this  process  as  it  occurs  in  the  higher 
animals  is  still  wanting,  and  its  very  existence  is  indeed  still  hypothetical. 
In  the  case  of  the  fats  the  oxidation  takes  place  chiefly  or  entirely  in  the 
/S  position.  On  the  other  hand,  decarboxylation  certainly  takes  place  in 
substances  such  as  the  a  amino-acids,  where  the  first  oxidation  change  occurs 
in  the  a  group,  and  probably  closely  follows  this  oxidation  change.  The 
reverse  reaction,  namely,  the  insertion  of  the  group  CO.O  at  the  end  of  the 
long  carbon  chain,  is  not  known  to  take  place,  but  would  furnish  a  means 
by  which  the  organism  with  apparent  simplicity  could  build  up  long  carbon 
chains  and  so  imitate  the  process  which  in  the  laboratory  is  generally  effected 
bv  attaching  a  CN  group  to  the  end  of  the  molecule.  In  the  case  of  the 
fats  the  building  up,  like  the  oxidative  breakdown,  appears  to  occur  by 
two  carbon  atoms  at  a  time  ;  hence  all  the  fatty  acids  met  with  in  the  body 
have  an  even  number  of  carbon  atoms  in  their  chain. 

It  is  worthy  of  note  that  all  the  changes  which  we  have  been  considering 
— changes  which  not  only  account  for  the  greater  part  of  the  chemical  re- 
actions of  the  living  body,  but  may  lead  to  the  production  of  the  most 
complex  substances  known — are  performed  with  little  expenditure  or  evolu- 
tion of  energy.  This  is  evident  if  we  examine  the  heat  evolved  by  the 
total  combustion  of  one  gramme  molecule  of  the  initial  and  final  substances 
in  a  number  of  typical  reactions.  In  the  following  Table  these  are  given 
for  the  substances  involved  in  typical  instances  of  the  three  classes  of 
chemical  change  that  we  have  just  been  considering : 


(1)  Hydrolysis 

Initial 
substance 

Maltose 

Heat  of  com- 
bustion per 
gram  molecule 
.     1350 

Final 
substance 
2  Glucose 

Heat 

of 
combustion 

1354 

Glucose 

.       677 

2  Lactic  acid 

659 

Hippuric  acid 

.     1013 

( Glycine 

^  Benzoic  acid 

£}  '»8 

(2)  Deaj 

IINATION 

Initial 
substance 
Alanine 

Heat  of 
combustion 

.    389-2 

Final 
substance 
Lactic  acid  . 

Heat  of 
combustion 

329-5 

Leucine 
Aspartie  acid 

.    855 
.    386 

Caproic  acid 
Succinic  acid 

837 
354 

156  PHYSIOLOGY 

(3)  Decarboxylation 


liiitnil  Seal  oi 

nil  i  i im  i  combustion 

Alanine  ....     389 

Leucine  ....      855 


Final  Heat  ol 

substance  combustlc 

Ethylamine    .  .  .         409 

Isoamylamine  .  .         867 


(4)  OXIDATION  AND  REDUCTION.  The  fourth  class  of  chemical 
reactions  differs  from  those  just  described  in  being  attended  with  a  very 
considerable  energy  change.  This  class  involves  the  processes  of  oxidation 
and  reduction.  In  almost  every  living  cell,  by  far  the  largest  amount  of 
the  energy  available  for  the  discharge  of  the  functions  of  the  cell  is  derived 
from  the  oxidation  of  the  food-stuffs,  and  even  in  the  plant  the  energy, is 
obtained  from  the  oxidation  of  the  food-stuffs,  built  up  in  the  first  instance 
at  the  cost  of  the  energy  of  the  sun's  rays.  If  we  take  the  final  changes 
in  the  food-stuffs,  the  very  large  evolution  of  energy  attending  their  oxida- 
tion is  at  once  apparent.  Thus  in  the  conversion  of  glucose  into  C02  and 
water  there  is  an  evolution  for  each  gramme  molecule  of  077  calories.  In 
the  combustion  of  glycerin  397  calories  are  evolved.  In  the  oxidation  of  a 
fat  such  as  trimyristin  there  are  6650  calories  evolved.  The  change  does 
not  in  the  living  cell  occur  all  at  once,  but  the  molecule  is  oxidised  step  by 
step.  In  each  step  the  heat  change  will  however  be  probably  greater  than 
the  heat  changes  in  the  other  types  of  chemical  change  which  we  have  been 
considering. 

Since  the  mechanism  of  oxidation  in  the  animal  body  will  have  to  be 
discussed  at  length  in  a  subsequent  part  of  this  work,  we  may  at  present 
confine  our  attention  to  the  other  types  of  chemical  change.  Of  these, 
all  which  involve  a  splitting  of  a  large  molecule  into  smaller  ones  with  the 
taking  up  of  one  or  more  molecules  of  water,  as  well  as,  in  all  probability, 
those  in  which  the  reverse  change  of  dehydration  and  synthesis  occur,  are 
effected  in  the  body  by  means  of  ferments.  To  the  same  agency  are  also 
.  ascribed  the  process  of  deamination  which  takes  place  in  many  organs  of 
the  body  and,  though  with  less  certainty,  the  processes  which  involve 
decarboxylation. 

FERMENTS 

Under  the  name  ferments  we  include  a  number  of  substances  of  indefinite 
composition  whose  existence  is  chiefly  known  to  us  by  their  action  on  other 
substances.  A  ferment  has  been  defined  as  a  body  which  .on  addition  to  a 
chemical  system  is  able  to  effect  changes  in  this  system  without  supplying 
any  energy  to  the  reaction,  without  being  used  up,  and  without  taking 
any  part  in  the  formation  of  the  end  products.  It  differs  therefore  from 
the  reacting  substances  in  the  absence  of  any  strict  quantitative  relation- 
ships between  it  and  the  substances  included  in  the  system  in  which  its 
effects  are  produced.  Minimal  quantities  of  ferment  can  induce  chemical 
changes  involving  almost  indefinite  quantities  of  other  substances,  the  only 
result  of  increasing  the  quantity  of  ferment  being  to  quicken  the  rate  of 
the  change.  Since  they  are  effective  in  minimal  doses  they  occur  in  living 
tissues  in  minute  quantities,  and  it  is  partly  due  to  this  fact  that  it  has 


CHEMICAL  CHANGES  IN  LIVING  MATTEE.     FERMENTS    157 

hitherto  proved  impossible  to  obtain  any  preparation  of  a  ferment  which 
could  be  regarded  as  a  pure  substance.  The  difficulty  in  their  isolation 
is  increased  by  the  fact  that  all  of  them  are  colloidal  or  semi-colloidal  in 
character,  and  present  therefore  the  tendency  common  to  all  colloids  of 
adhering  to  other  colloidal  matter  as  well  as  to  surfaces  such  as  those  pre- 
sented by  a  precipitate.  A  common  method  of  isolating,  or  rather  obtaining 
a  concentrated  preparation  of  a  ferment,  is  to  produce  in  its  solution  an  inert 
precipitate  such  as  cholesterin  or  calcium  phosphate.  The  ferment  is 
carried  down  on  the  precipitate  and  may  be  obtained  in  solution  on  washing 
the  precipitate  with  water.  A  further  difficulty  in  their  preparation  lies 
in  the  unstable  character  of  many  members  of  the  group.  Although  they 
are  not  coagulated  by  alcohol,  they  are  nevertheless  gradually  changed,  so 
that  every  act  of  precipitation  of  a  ferment  tends  to  rob  it  of  some  of  its 
powers,  i.e.  of  the  only  characteristic  by  which  we  can  establish  its  identity. 
Of  these  ferments  a  large  number  have  already  been  described  as  taking 
part  in  the  ordinary  chemical  processes  of  life.  So  wide  is  their  dominion 
in  cell  chemistry  that  many  physiologists  have  thought  that  the  whole  of 
life  is  really  a  continual  series  of  ferment  actions.  The  following  list  repre- 
sents some  of  the  ferments  whose  existence  has  been  definitely  established 
in  the  animal  body.  The  greater  part  of  them  are  involved  in  the  processes 
of  digestion  in  the  alimentary  canal.  The  preponderance  however  of 
digestive  ferments  in  the  list  is  due  to  the  fact  that  we  know  more  about 
digestion  than  about  the  other  chemical  processes  taking  place  within  the 
cells  of  the  body. 

List  of  Fekments. 


Ferment 

Converting 

Into 

Amylase     (of     saliva,     pancreatic 

Starch 

Maltose  and  dextrin 

juice,  liver,  blood  serum,  &o.)     . 

Pepsin        ..... 

Proteins  . 

Proteoses  and  pep- 
tones 

Trypsin       ..... 

Proteins  . 

Peptones  and  amino- 
acids 

Enterokinase        .          . 

Trypsinogen 

Trypsin 

Erepsin       ..... 

Proteoses 

Amino-acids 

Lipase  ■  (of  pancreatic  juice,  liver. 

Neutral  fats 

Fatty    acid    and 

&c.) 

glycerin 

Maltaae       ..... 

.Maltose    . 

Glucose  . 

La  itase       ..... 

Milk  sugar 

Glucose  and  galactose 

Invertase  or   sucrase   . 

Cane  sugar 

Glucose  and  kevulose 

Arginase      ..... 

Arginin     . 

Urea  and  ornithine 

Urease         ...... 

Urea 

Ammonium  carbonate 

Lactic  acid  ferment 

Glucose    . 

Lactic  acid 

Zymase  (?  present  in  the  body) 

Glucose    . 

Alcohol  and  C02 

Deaminating  ferment  (?),  v.  p.  153 

Amino-acids 

Oxy -acids  (?) 

158  PHYSIOLOGY 

Many  other  ferments  will  probably  be  distinguished  with  increase  in 
our  knowledge  of  cellular  metabolism.  The  long  list  which  is  here  given 
suffices  to  show  how  great  a  part  these  bodies  must  play  in  the  normal 
processes  of  life.  A  study  of  the  conditions  of  ferment  actions  is  therefore 
essential  if  we  would  form  a  conception  of  the  chemical  mechanisms  of  the 
living  cell. 

It  is  important  to  note  that  all  the  changes  wrought  by  ferments  can 
be  effected  by  ordinary  chemical  means.  Thus  the  disaccharides  can  be 
made  to  take  up  a  molecule  of  water  and  undergo  conversion  into  mono- 
saccharides. If  a  solution  of  maltose  be  taken  and  bacteria  be  excluded 
from  the  solution,  it  undergoes  at  ordinary  temperatures  practically  no 
change.  If  the  solution  be  warmed,  a  slow  process  of  hydration  takes  place 
which  is  quickened  by  rise  of  temperature,  so  that  if  the  solution  be  heated 
under  pressure  to,  say,  110°  C,  hydrolysis  occurs  with  considerable  rapidity. 
If  however  a  little  maltase  be  added  to  the  solution,  the  change  of  maltose 
into  glucose  takes  place  rapidly  at  a  temperature  of  30°  C.  In  the  same 
way  a  solution  of  protein  may  be  kept  almost  indefinitely  without  undergoing 
hydrolysis,  which  however  can  be  induced  by  heating  the  solution  under 
pressure.  The  action  of  the  ferments  in  these  two  cases  is  to  quicken  a 
process  of  hydrolysis  which  without  their  presence  would  take  an  infinity 
of  time  for  its  accomplishment. 

In  this  respect  their  action  is  similar  to  that  of  acids,  and  indeed  of  a 
whole  class  of  bodies  wrhich  are  spoken  of  as  catalysers  or  catalysts.  A 
catalyser  is  a  substance  which  will  increase  (or  diminish)  the  velocity  of  a 
reaction  without  adding  in  any  way  to  the  energy  changes  involved  in  the 
reaction,  or  taking  any  part  in  the  formation  of  the  end-products.  Since 
the  catalyser  is  unchanged  in  the  process,  a  very  small  quantity  is  able  to 
influence  reactions  involving  large  quantities  of  other  substances.  By 
adding  acids  to  a  watery  solution  of  the  food-stuffs,  the  process  of  hydrolysis 
is  quickened  in  proportion  to  the  strength  and  concentration  of  the  acid. 
The  effective  catalytic  agents  in  this  process  appear  to  be  the  hydrogen  ions 
of  the  free  acid.  There  are  many  other  bodies,  besides  the  free  acids,  which 
may  act  as  catalysers,  and  a  study  of  the  conditions  under  which  catalysis 
takes  place  may  throw  some  light  on  the  essential  nature  of  the  action  of 
ferments. 

The  velocity  of  almost  any  reaction  in  chemistry  can  be  altered  by  the 
addition  of  some  catalytic  agent,  and  there  are  few  of  the  ordinary  reactions 
in  which  catalysis  does  not  play  some  part.  Among  such  processes  we  may 
instance  the  action  of  spongy  platinum  on  hydrogen  peroxide.  Hydrogen 
peroxide  undergoes  slow  spontaneous  decomposition  into  water  and  oxygen. 
If  a  little  spongy  platinum  be  added  to  it,  it  is  at  once  seen  to  decompose 
rapidly  with  the  evolution  of  bubbles  of  oxygen,  and  the  action  does  not 
cease  until  the  whole  of  the  hydrogen  peroxide  has  been  destroyed.  Spongy 
platinum  is  able  in  the  same  way  to  quicken  a  very  large  number  of  chemical 
reactions.  Thus  sulphur  dioxide  and  oxygen  when  heated  together  will 
combine  very  slowly  ;   the  combination  becomes  rapid  if  a  mixture  of  the 


CHEMICAL  CHANGES  IN  LIVING  MATTER.     FERMENTS    159 

two  gases  be  passed  over  heated  platinum.  The  same  reaction,  namely, 
the  combination  of  sulphur  dioxide  with  oxygen,  may  be  quickened  by  the 
addition  of  a  small  trace  of  nitric  oxide,  and  this  fact  is  made  use  of  in  the 
manufacture  of  sulphuric  acid  on  a  commercial  scale  by  the  ordinary  lead- 
chamber  process.  Hydrogen  peroxide  and  hydriodic  acid  slowly  interact 
with  the  formation  of  water  and  iodine.  This  reaction  may  be  quickened 
by  the  addition  of  many  substances,  among  which  we  may  mention  molybdic 
acid. 

There  is  moreover  a  specificity  in  the  action  of  catalysers,  though  not 
so  well  marked  as  with  ferments.  Whereas  all  the  disaccharides  are  con- 
verted by  acids  into  the  corresponding  monosaccharides,  a  ferment  such  as 
invertase  acts  only  on  cane  sugar,  and  has  no  action  on  maltose  or  lactose, 
each  of  which  requires  a  specific  ferment  (maltase,  lactase)  to  effect  their 
'  inversion.'  But  we  find  many  examples  of  a  restricted  action  even  among 
inorganic  catalysers.  Thus  potassium  bichromate  will  act  as  the  catalyser 
for  the  oxidation  of  hydriodic  acid  by  bromic  acid,  but  not  for  the  oxidation 
of  the  same  substance  by  iodic  acid.  Iron  and  copper  salts  in  minute  traces 
will  quicken  the  oxidation  of  potassium  iodide  by  potassium  persulphate, 
but  have  no  influence  on  the  course  of  the  oxidation  of  sulphur  dioxide 
by  potassium  persulphate.  Tungstic  acid  increases  the  velocity  of  oxida- 
tion of  hydriodic  acid  by  hydrogen  peroxide,  but  has  no  effect  on  the  velocity 
of  oxidation  of  hydriodic  acid  by  bromic  acid,  and  these  examples  may  be 
multiplied  to  any  extent.  One  cannot  'therefore  regard  the  limitation  of 
action  of  the  ferments  as  justifying  any  fundamental  distinction  being 
drawn  between  the  action  of  this  class  of  substances  and  catalysts. 

Whereas  the  influence  of  most  catalysers  on  the  velocity  of  a  reaction 
increases  rapidly  with  rise  of  temperature,  in  the  case  of  ferments  this  in- 
crease occurs  only  up  to  a  certain  point.  This  point  is  spoken  of  as  the 
optimum  temperature  of  the  ferment  action.  If  the  mixture  be  heated  above 
this  point  the  action  of  the  ferment  rapidly  slows  off  and  then  ceases.  This 
contrast  again  is  only  apparent.  The  ferments  are  unstable  bodies  easily 
altered  by  change  in  their  physical  conditions,  and  destroyed  in  all  cases 
at  a  temperature  considerably  below  that  of  boiling  water.  Thus  ferment 
actions,  like  catalytic  actions,  are  quickened  by  rise  of  temperature,  but 
the  effect  of  temperature  is  finally  put  a  stop  to  by  the  destruction  of  the 
ferment.  The  same  applies  to  those  inorganic  catalysers  whose  physical 
state  is  susceptible,  like  that  of  the  ferments,  to  the  action  of  heat.  Thus 
the  colloidal  platinum  '  sol '  exerts  marked  catalytic  effects  on  various 
reactions,  e.g.  on  the  decomposition  of  hydrogen  peroxide  and  on  the 
combination  of  hydrogen  and  oxygen.  The  reaction  presents  an  optimum 
temperature,  owing  to  the  fact  that  the  colloidal  platinum  is  altered,  coagu- 
lated, and  thrown  out  of  solution  when  this  is  heated  to  near  boiling-point. 
We  may  therefore  employ  either  class  of  reactions  in  trying  to  form  some 
conception  of  the  processes  which  are  actually  involved. 

Very  many  theories  have  been  put  forward  to  account  for  this  action 
of  catalysers  or  of  ferments.    Many  of  them  are  merely  transcriptions  in 


160  PHYSIOLOGY 

words  of  the  processes  which  actually  occur,  and  fail  to  throw  any  light 
on  their  real  nature.  The  essential  phenomena  involved  fall  directly  into 
two  classes.  In  the  first  class  we  must  place  those  which  are  determined 
by  the  influence  of  surface.  In  many  cases  the  combination  of  gases  can 
be  hastened  by  increasing  the  surface  to  which  they  are  exposed,  as  by 
passing  them  over  broken  porcelain  or  over  powdered  charcoal.  This  cata- 
lytic effect  is  certainly  connected  with  the  power  of  a  solid  to  condense 
gases  at  its  surface,  and  is  therefore  proportional  to  the  extent  of  surface 
exposed.  Thus  the  efficacy  of  platinum  in  hastening  the  combination  of 
hydrogen  and  oxygen  is  in  direct  proportion  to  its  fineness  of  subdivision, 
and  is  best  marked  when  the  metal  is  reduced  to  ultra-microscopic  dimen- 
sions, as  in  the  colloidal  solution  of  platinum.  Every  colloidal  solution 
must  be  regarded  as  presenting  an  enormous  surface  in  proportion  to  the 
mass  of  substance  in  solution.  There  is  therefore  a  direct  proportionality 
between  the  power  of  a  substance  to  condense  a  gas  on  its  surface  and  its 
power  to  quicken  the  velocity  of  chemical  changes  in  which  the  gas  is  in- 
volved. The  same  process  of  condensation  may  occur  with  dissolved  sub- 
stances. In  all  cases  where  the  presence  of  a  substance  in  solution  diminishes 
the  surface  tension  of  the.  solvent,  there  is  a  diffusion  of  dissolved  substances 
into  the  surface,  i.e.  a  concentration  of  dissolved  substances  at  the  surface 
of  contact.  It  was  suggested  by  Faraday  that  the  catalytic  property  of 
surfaces  was  due  to  this  condensation  of  molecules,  and  the  consequent 
bringing  of  the  two  sets  of  molecules  within  each  other's  sphere  of  influence. 
Whether  this  is  the  sole  factor  involved  is  doubtful,  since  mere  compression 
of  gases  or  increased  concentration  of  solutions  does  not  in  the  majority 
of  cases  result  in  such  a  quickening  of  the  velocity  of  reaction  as  is  brought 
about  by  the  effect  of  the  surface. 

It  is  possible  that  this  condensation  effect  or  adsorption  may  be  in  every 
case  combined  with  the  second  factor  which  we  must  now  consider,  namely, 
the  formation  of  intermediate  products.  If  we  boil  an  alkaline  solution 
of  indigo  with  some  glucose,  the  indigo  is  reduced  with  oxidation  of  the 
glucose.  The  mixture  therefore  becomes  colourless.  On  shaking  up  with 
air,  the  c  :>lourless  reduction  product  of  the  indigo  absorbs  oxygen  from  the 
atmosphere,  and  is  re-transformed  into  indigo.  These  two  processes  can 
be  repeated  until  the  whole  of  the  glucose  is  oxidised,  and  the  process  can 
be  made  continuous  if  air  or  oxygen  be  bubbled  through  a  heated  solution 
of  glucose  containing  a  small  trace  of  indigo.  In  this  case  the  indigo  does 
not  add  to  the  energy  of  the  reaction.  It  appears  unchanged  among  the 
final  products  and  a  small  amount  may  be  used  to  effect  the  change  of  an 
infinite  quantity  of  glucose.  It  therefore  may  be  said  to  act  as  a  ferment 
or  catalytic  agent.  Instead  of  an  alkaline  solution  of  indigo,  we  may  use 
an  ammoniacal  solution  of  cupric  oxide  for  the  purpose  of  carrying  oxygen 
from  the  atmosphere  to  the  glucose.  This  is  reduced  to  cuprous  hydrate 
on  heating  with  the  sugar,  but  cupric  hydrate  can  be  at  once  re-formed 
by  shaking  up  the  cuprous  solution  with  air.  It  has  been  thought  that  many 
or  all  of  the  catalytic  reactions  occur  in  the  same  way  by  two  stages,  i.e. 


CHEMICAL  CHANGES  IN  LIVING  MATTER.     FERMENTS    161 

by  the  formation  of  an  intermediate  product.  Thus,  in  the  old  lead  chamber 
process  for  the  manufacture  of  sulphuric  acid,  the  Ditric  oxide  may  be  sup- 
posed to  combine  with  the  oxygen  of  the  air  to  form  nitrogen  peroxide. 
This  interacts  with  sulphur  dioxide,  giving  sulphur  trioxide  and  nitric  oxide 
once  more.  The  nitric  oxide,  which  we  alluded  to  before  as  the  catalyser, 
may  in  this  way  be  regarded  as  the  carrier  of  oxygen  from  air  to  sulphur 
dioxide.  .It  has  been  suggested  that  the  action  of  spongy  platinum  or 
colloidal  platinum  rests  on  the  same  process,  and  that  in  the  oxidation  of 
hydrogen,  for  instance,  PtO  or  Pt02  is  formed  and  at  once  reduced  by  the 
hydrogen  with  the  formation  of  water. 

There  is  a  certain  amount  of  experimental  evidence  in  favour  of  this  hypothesis. 
According  to  Engler  and  Wohler,*  platinum  black,  which  has  been  exposed  to  oxygen, 
in  virtue  of  the  gas  which  it  has  occluded,  has  the  power  of  turning  potassium  iodide 
and  starch  blue.  This  power  is  not  destroyed  by  heating  to  260°  in  an  atmosphere  of 
Co2,  or  by  washing  with  hot  water.  On  exposure  of  the  platinum  black  to  hydrochloric 
acid,  a  certain  amount  is  dissolved,  and  the  substance  loses  its  effect  on  potassium 
iodide.  The  amount  dissolved  corresponds  with  the  amount  of  iodine  liberated  from 
potassium  iodide,  and  also  with  the  amount  of  oxygen  occluded,  the  (soluble)  platinum 
and  oxygen  being  in  the  proportions  necessary  to  form  the  compound  PtO. 

But  why  should  a  reaction  take  place  more  quickly  if  it  occurs  in  two 
stages  instead  of  one  ?  As  Ostwald  has  pointed  out,  the  formation  of  an 
intermediate  compound  can  be  regarded  as  a  sufficient  explanation  of  a 
catalytic  process  only  when  it  can  be  demonstrated  by  actual  experiment 
that  the  rapidity  of  formatiou  of  the  intermediate  compound  and  the  rapidity 
of  its  decomposition  into  the  end-products  of  the  reaction  are  in  sum  greater 
than  the  velocity  of«the  reaction  without  the  formation  of  the  intermediate 
body.  In  the  case  of  one  reaction  this  requirement  has  been  fulfilled.  The 
catalytic  effect  of  molybdic  acid  on  the  interaction  of  hydriodic  acid  and 
hydrogen  peroxide  has  been  explained  by  assmning  that  the  first  action 
which  takes  place  is  the  formation  of  permolybdic  acid,  and  that  this  then 
interacts  with  the  hydrogen  iodide  to  form  water  and  iodine.  Now  it  has 
been  actually  shown — (1)  that  permolybdic  acid  is  formed  by  the  action 
of  hydrogen  peroxide  on  molybdic  acid  ;  (2)  that  permolybdic  acid  with 
hydriodic  acid  produces  water  and  iodine  ;  (3)  that  the  velocity  with  which 
these  two  reactions  occur  is  much  greater  than  the  velocity  of  the  inter- 
action of  hydrogen  peroxide  and  hydriodic  acid  by  themselves. 

Although  we  may  find  it  difficult  to  explain  why  a  reaction  should  occur  more 
quickly  in  the  presence  of  a  catalyser  by  the  formation  of  these  intermediate  bodies, 
certain  simple  analogies  may  help  us  to  comprehend  how  a  factor  which  introduces  no 
energy  can  yet  assist  the  process.  Thus  a  man  might  stand  to  all  eternity  before  a 
perpendicular  wall  twenty  feet  high.  Since  he  cannot  reach  its  top  at  one  jump,  he  is 
unable  to  get  there  at  all.  The  introduction  of  a  ladder  will  not  in  any  way  alter  the 
total  energy  he  must  expend  on  raising  his  body  for  twenty  feet,  but  will  enable  him 
to  attain  the  top.  Or  we  might  imagine  a  stone  perched  at  the  top  of  a  high  hill.  The 
passive  resistance  of  the  system,  the  friction  of  the  stone,  and  its  inertia  will  tend  to 
keep  it  at  rest,  even  though  it  be  on  a  sloping  surface  and  therefore  tending  to  slide 
or  roll  to  the  bottom.  If  however  it  be  rolled  to  a  point  where  there  is  a  sudden  increase 
in  the  rapidity  of  slope,  it  may  roll  over,  and  having  once  started  its  downward  course,  its 
*  Quoted  by  Mellor,   "Chemical  Statics." 

11 


162  PHYSIOLOGY 

momentum  will  carry  it  to  the  bottom.  The  amount  of  energy  set  free  by  the  stone  in 
its  fall  will  not  vary  whether  the  course  be  a  uniform  one,  or  whether  it  falls  over  a 
precipice  at  one  time  and  rolls  down  a  gentle  slope  at  another.  It  is  evident  that  by 
a  mere  alteration  of  the  slope  or,  in  the  case  of  a  chemical  reaction,  of  the  velocity  of 
part  of  its  course,  a  change  in  the  system  may  be  initiated  and  brought  to  a  conclusion 
which  without  this  alteration  would  never  take  place. 

vSince  the  action  of  ferments,  like  that  of  catalysts,  consists  essentially 
in  the  quickening  up  of  processes  which  would  otherwise  occur  at  an  in- 
finitely slow  velocity,  it  is  possible  that  in  their  case  also  the  formation 
of  an  intermediate  compound  may  be  involved  in  the  reaction.  Light  may 
be  thrown  upon  this  question  by  a  study  of  the  velocity  of  the  reaction 
induced  by  the  action  of  a  ferment. 

It  is  well  known  that  the  velocity  of  a  rexction  depends  on  the  number  of  molecules 
involved.  As  an  illustration,  we  may  take  first  the  case  of  a  reaction  involving  a 
change  in  one  substance.  If  arseniuretted  hydrogen  be,  heated,  it  undergoes  decom- 
position into  hydrogen  and  arsenic.  This  decomposition  is  not  immediate,  but  takes 
a  certain  time,  and  the  velocity  with  which  the  change  occurs  depends  on  the  tempera- 
ture. At  any  given  temperature  the  amount  of  substance  changed  in  the  unit  of  time 
varies  with  the  concentration  of  the  substance.  If,  for  instance,  one-tenth  of  the  gas 
be  dissociated  in  the  first  minute,  in  the  second  minute  a  further  tenth  of  the  gas  will 
also  be  dissociated.  Thus,  if  we  start  with  1000  grammes  of  substance,  at  the  end 
of  the  first  minute  100  grammes  will  have  been  dissociated,  and  900  of  the  original 
substance  will  be  left.  In  the  second  minute  one-tenth  again  of  the  remaining  substance 
will  be  dissociated,  i.e.  90  grammes,  leaving  810  grammes.  In  the  third  minute  81 
grammes  will  be  dissociated,  leaving  729  grammes.  The  amount  changed  in  the 
unit  of  time  will  always  bear  the  same  ratio  to  the  whole  substance  which  is  to  be 
changed,  and  will  therefore  be  a  function  of  the  concentration  of  this  substance.  Put 
in  the  form  of  an  equation,  we  may  say  that  <^>,  the  amount  changed  in  the  unit  of  time, 
will  be  equal  to  KC,  where  K  is  a  constant  varying  with  the  substance  in  question  and 
with  the  temperature,  and  C  represents  the  concentration  of  the  substance.  The 
equation  <f>   =  KC  applies  to  a  monomolecular  reaction. 

If  two  substances  are  involved,  the  equation  will  be  rather  different.  In  this  case 
the  amount  of  change  in  a  unit  of  time  will  be  a  function  of  the  concentration  of  each 
of  the  substances,  and  the  form  of  the  equation  will  be  <&  =  K(C,  +  Cy).  In  the  case 
of  the  unimolecular  reaction,  halving  the  concentration  of  the  substance  will  halve  the 
amount  of  substance  changed  in  the  unit  of  time.  In  the  case  of  a  bimolecular  reaction, 
halving  each  of  the  substances  will  cause  the  amount  of  change  in  the  unit  of  time  to  be 
reduced  to  one-quarter  of  its  previous  amount.  If  now  either  a  unimolecular  or  a 
bimolecular  reaction  be  quickened  by  the  addition  of  a  catalyser  or  ferment,  and  the 
ferment  enter  into  combination  with  one  of  the  substances  at  some  stage  of  the  reaction, 
it  is  evident  that  our  equation  must  take  account  also  of  the  concentration  of  the 
ferment  or  catalyser.  In  the  case  of  the  catalytic  effect  of  molybdic  acid  on  the  inter- 
action between  hydrogen  peroxide  and  HI,  there  was  definite  evidence  of  a  reaction 
taking  place  between  the  molybdic  acid  and  the  peroxide,  resulting  in  the  formation 
of  an  intermediate  compound,  namely,  permolybdic  acid.  Brode  has  shown  that  the 
interaction  of  the  molybdic  acid  is  revealed  in  the  equation  representing  the  velocity 
of  the  reaction.  '6  Without  the  addition  of  molybdic  acid  the  equation  would  be  : 

4>=K(CH2o2  XCHI) 
After  the  addition  of  molybdic  acid,  the  equation  becomes  : 

4>  =  K(CH,0,  +  y  C  molybdic  <acid)CH!, 
when  y  is  another  constant  depending  on  the  molybdic  acid.     If  ferments  act  in  a 
similar  way  by  the  formation  of  intermediate  compounds,  this  fact  should  be  revealed 
by  a  study  of  the  velocity  at  which  the  ferment  action  takes  place. 


CHEMICAL  CHANGES  IN  LIVING  MATTER.     FERMENTS     163 

Various  methods  may  be  adopted  for  the  study  of  the  velocity  of  ferment 
action.  If,  for  instance,  we  are  investigating  the  action  of  diastase  upon 
starch,  we  should  take  solutions  of  starch  and  of  diastase  of  known  concen- 
trations, keep  them  in  a  water  bath  at  38°C,  and  at  a  certain  point  add, 
say,  20  c.c.  of  ferment  solution  to  every  100  c.c.  of  the  starch  solution. 
At  periods  of  five  or  ten  minutes  after  the  addition  had  been  made,  5  c.c. 
of  the  mixture  might  be  withdrawn  by  a  pipette  and  at  once  run  into  boiling 
Fehling's  solution.  The  precipitated  cuprous  oxide  would  be  dried  and 
weighed,  and  woidd  give  directly  the  amount  of  sugar  formed  by  the  action 
of  the  ferment.  After  obtaining  a  series  of  data  in  this  way,  a  curve  could 
be  drawn,  showing  the  amount  of  change  of  starch  which  had  occurred 
in  each  unit  of  time.  In  the  case  of  the  action  of  invertase  on  cane  sugar 
the  investigation  is  still  easier.  Since  the  change  from  cane  sugar  to  invert 
sugar  is  accompanied  by  a  change  in  the  rotatory  power  of  the  solution 
on  polarised  light,  it  is  necessary  only  to  put  the  mixture  of  ferment  and 
cane  sugar  into  a  polarimeter  tube,  which  is  kept  at  a  constant  temperature 
by  means  of  a  water  jacket,  and  read  off  at  intervals  of  a  few  minutes  the 
change  in  the  rotatory  power  of  the  solution.  From  this  change  can  be 
easily  calculated  the  percentage  of  cane  sugar  still  present,  and  therefore 
the  total  amount  which  has  been  converted  into  fructose  and  glucose. 

In  investigating  the  action  of  proteolytic  ferments,  as,  e.g.  that  of  trypsin 
on  caseinogen,  samples  are  taken  at  five-minute  intervals  and  run  into 
some  substance  such  as  trichloracetic  acid,  which  will  precipitate  all  the 
unchanged  protein,  but  will  leave  in  solution  the  products  of  hydration 
of  the  protein.  From  the  amount  of  nitrogen  in  the  filtrate  from  the  precipi-. 
tate  can  be  determined  the  total  amount  of  protein  which  has  undergone 
hydration  in  the  sample  under  observation.  Or  the  amount  of  albumoses 
and  peptones  present  in  each  sample  may  be  estimated  by  the  intensity  of 
the  biuret  reaction  which  can  be  obtained.  This  method  however  suffers 
from  the  drawback  that  the  albumoses  and  peptones,  at  any  rate  in  the 
action  of  trypsin,  are  formed  merely  as  a  stage  in  the  process,  and  the  in- 
tensity of  the  reaction  will  first  rise  to  a  maximum  and  then  gradually  dis- 
appear. A  very  convenient  method  is  that  employed  by  Henri  and  by 
Bayliss  in  the  investigation  of  the  kinetics  of  tryptic  action,  namely,  the 
determination  of  the  conductivity  of  the  solution.  In  the  disintegration 
of  the  molecule  caused  by  the  action  of  the  ferment,  there  is  a  continuous 
increase  in  the  conductivity  of  the  solution,  and  this  increase  can  be  regarded 
as  an  index  to  the  rate  of  change  in  the  substances  undergoing  disinte- 
gration. 

By  such  methods  it  has  been  found  that,  when  the  quantity  of  ferment 
employed  is  very  small  in  comparison  with  the  substrate  (the  substance 
acted  upon),  the  amount  of  change  in  a  given  time  is  proportional  to  the 
amount  of  ferment  present,  and  is  (within  limits)  independent  of  the  con- 
centration of  the  substrate.  This  is  well  shown  by  the  two  following  Tables 
representing  the  action  of  lactase  upon  lactose  (E.  F.  Armstrong)  : 


L64 


PHYSIOLOGY 


Proportions  Hydrolysed  in  100  CO. 
Solution  of  Lactose 

OF    A    5    PER    CENT. 

Solutions  containing 

1'5  hours 

20  hours 

45  hours 

1  c.c.  lactase  . 

015 

2-2 

3-9 

10  c.c.      „ 

If! 

2:s-:i                  38-6 

•21 »  r.r 

32 

ir.s 

Amount  of 

StroAB  (Lactose)  Hydrolysed 

Solutions  containing — 

-4  hours                                        4  0  hours 

Proportion 

Weight 

Proportion 

Weight 

10  per  cent,  lactose 

14-2 

1-42 

22-2 

2-22 

20 

7-0 

1-40 

10-9 

218 

30 

4-8 

1-44 

7-7 

2-21 

Moreover,  if  we  take  only  the  earlier  stages  of  the  ferment  action,  it  is  found 
that,  with  small  proportions  of  ferment,  equal  amounts  of  substrate  are 
changed  in  successive  intervals  of  time  until  about  10  per  cent,  has  been 
hydrolysed.     This  is  shown  in  the  following  Table  : 


Time 
J  hour 


2  hours 

3  „ 


2  per  cent.  Lactose  with  Lactase 

Amount  hydrolysed 
3.2 
6.4 
9.6 
16.4 
20.8 


These  results  can  be  interpreted  only  by  assuming  that  the  first  stage  in 
the  reaction  is  a  combination  of  ferment  with  substrate.  It  is  only  this 
compound  which  represents  the  active  mass  of  the  molecules,  i.e.  the  mole- 
cules of  substrate  which  are  undergoing  change.  This  compound,  as  soon  as 
it  is  formed,  takes  up  water  and  breaks  down,  setting  free  the  hydrolysed 
substrate  and  the  ferment,  which  is  at  once  ready  to  combine  with  a  further 
portion  of  the  substrate.  In  such  a  case  the  velocity  of  reaction  must  be 
directly  proportional  to  the  amount  of  ferment,  and  the  same  absolute- 
quantity  of  substance  will  continue  t?o  be  changed  in  succeeding  units  of 
time.  Supposing,  for  instance,  we  had  a  load  of  bricks  at  the  bottom  of  a 
hill  which  had  to  be  transferred  to  the  top,  and  five  men  to  effect  the  trans- 
ference. The  rate  of  transference  would  be  directly  proportional  to  the 
number  of  men  employed  ;  we  could  double  the  rate  by  doubling  the  men. 


CHEMICAL  CHANGES  IN  LIVING  MATTER.    FERMENTS    165 

Moreover  the  number  of  bricks  carried  in  each  unit  of  time  would  be  the 
same.  Five  men  would  carry  as  many  bricks  in  the  second  ten  minutes 
as  they  would  in  the  first,  and  so  on.  On  the  other  hand,  the  velocity  with 
which  the  transference  was  effected  would  be  independent  of  the  number — 
that  is,  the  concentration — of  the  bricks  at  the  bottom  of  the  hill.  The 
active  mass  of  bricks  could  be  regarded  as  that  number  carried  at  any  moment 
by  the  transferring  factor,  namely,  the  men.  The  equation  of  change  would 
be  4>  =  KG,  where  C  is  the  concentration  of  the  ferment.  This  concen- 
tration is  always  being  renewed,  and  kept  constant  by  the  breaking  down 
of  the  intermediate  product,  so  that  the  rate  of  change  would  be  continuous 
throughout  the  experiment. 

On  the  other  hand,  when  the  amount  of  ferment  is  relatively  large,  the 
rate  of  change,  though  at  first  very  rapid,  tends  continuously  to  diminish. 
This  is  shown  by  the  following  Table  representing  the  rates  of  change, 
during  succeeding  intervals  of  ten  minutes,  in  a  caseinogen  solution  to  which 
a  strong  solution  of  trypsin  had  been  added  (Bayliss)  . 

Velocity  of  Trypsin  Reaction 

'  N 
6  c.c.  8  per  cent,  caseinogen  +  2  c.c.-r^  AmHO  -f  2  c.c.  2  per  cent. 

trypsin  at  39°C. 
1st  10  minutes K =0-0079 


2nd 

3rd 
4th 
5th 
7  M. 


0-0046 
0-0032 
0-0022 
0-0016 
0-0009 


The  cause  of  this  rapid  diminution  in  the  velocity  of  change  is  probably 
complex.  One  factor  may  be  an  auto-destruction  of  the  ferment,  which  is 
known  to  occur  in  watery  solution.  That  this  is  not  the  only,  or  even  the 
chief,  factor  involved  is  shown  by  the  fact  that,  when  the  action  of  trypsin 
on  caseinogen  has  apparently  come  to  an  end,  it  may  be  renewed  by  further 
dilution  of  the  mixture  or  by  removal  of  the  end-products  of  the  action  by 
dialysis.  It  is  evident  that,  in  this  retardation  of  the  later  stages  of  ferment 
action,  the  end-products  are  concerned  in  some  way  or  other,  and  the  re- 
tardation can  be  augmented  by  adding  to  the  digesting  mixture  the  boiled 
end-products  of  a  previous  digestion.  The  retarding  effect  of  the  end- 
products  resembles  in  many  ways  that  observed  in  a  whole  series  of  reactions 
which  are  known  as  reversible. 

As  an  example  of  such  a  reaction  we  may  take  the  case  of  methyl  acetate  and  water. 
When  methyl  acetate  is  mixed  with  water,  it  undergoes  decomposition  with  the  forma- 
tion of  methyl  alcohol  and  acetic  acid.  On  the  other  hand,  if  acetic  acid  be  mixed 
with  alcohol,  an  interaction  takes  place  with  the  formation  of  methyl  acetate  and 
water.     These  changes  are  represented  by  the  equation  : 

MeC2H302  +  HOH  =  MeOH  +   HC,H3Oa. 
niethylaeetate       water     methylalcohol  acetic  acid 
Each  of  these  changes  has  a  certain  velocity  constant,  and,  since  they  are  in  opposite 
directions,   then-   must   be  some  equilibrium   point  where   no   change   will  occur,   and 


166  JPHYSIOLOGY 

there  will  be  a  definite  amount  of  all  four  substances  present  in  the  mixture,  namely, 
water,  alcohol,  ester,  .and  acid.  This  equilibrium  point  can  be  shifted  by  altering 
the  amount  of  any  of  the  four  substances.  Thus  the  interaction  of  methyl  acetate  and 
water  can  be  diminished  to  any  desired  extent  by  adding  to  the  mixture  the  products 
of  the  interaction,  namely,  methyl  alcohol  and  acetic  acid. 

There  is  evidence  that  some  of  the  ferment  actions  are  reversible.  Thus 
nialtase  acts  on  maltose  with  the  formation  of  two  molecules  of  glucose. 
If  the  maltase  be  added  to  a  concentrated  solution  of  glucose,  we  get  a 
reverse  effect,  with  the  production  of  a  disaccharide  which  has  been  desig- 
nated as  isomaltose  or  revertose.  To  this  reverse  action  may  be  due  a 
certain  amount  of  the  retardation  observed  in  the  action  of  trypsin  on 
coagulable  protein.  A  more  important  factor  is  probably  the  combination 
of  the  ferment  itself  with  the  end-products  and  the  consequent  removal 
of  the  ferment  from  the  sphere  of  action.  Several  facts  speak  for  such  a 
m.ode  of  explanation.  Thus  the  action  of  lactase  on  milk  sugar  is  not 
retarded  by  both  its  end-products,  namely,  glucose  and  galactose,  but  only 
by  galactose.  In  the  same  way  the  action  of  invertase  on  cane  sugar  is 
retarded  by  the  end-product  fructose,  but  not  at  all  by  the  other  end- 
product,  glucose. 

So  far  therefore  a  study  of  the  velocity  of  ferment  actions  would  lead 
us  to  suspect  that  the  ferment  combines  in  the  first  place  with  the  substrate, 
and  that  this  combination  is  a  necessary  step  in  the  alteration  of  the  sub- 
strate. In  the  second  place,  the  ferment  is  taken  up  to  a  certain  extent 
by  some  or  all  of  the  end-products,  and  this  combination  acts  in  opposition 
to  the  first  combination,  tending  to  remove  the  ferment  from  the  sphere 
of  action,  and  therefore  to  retard  the  whole  reaction.  Other  facts  can  be 
adduced  in  favour  of  these  conclusions.  Thus  it  has  been  shown  that 
invertase  ferment,  which  is  destroyed  when  heated  in  watery  solution  at  a 
temperature  of  60°C,  can,  if  a  large  excess  of  its  substrate,  cane  sugar, 
be  present,  be  heated  253  higher  without  undergoing  destruction.  The 
same  protective  effect  is  observed  in  the  case  of  trypsin.  Trypsin  in  watery 
or  weakly  alkaline  solutions  undergoes  rapid  decomposition.  At  37  °C.  it 
may  lose  50  per  cent,  of  its  proteolytic  power  within  half  an  hour.  If,  on 
the  other  hand,  trypsin  be  mixed  with  a  protein  such  as  egg  albumin  or 
caseinogen,  or  with  the  products  of  its  own  action,  namely,  albumoses  and 
peptones,  it  can  be  kept  many  hours  without  undergoing  any  considerable 
loss  of  power. 

It  has  been  found  that,  whereas  maltase  splits  up  all  the  a-glueosides,  it  has  no 
power  on  the  /S-glucosides  ;  that  is  to  say,  maltase  will  fit  into  a  molecule  of  a  certain 
configuration,  but  is  powerless  to  affect  a  molecule  which  differs  from  the  first  only 
in  its  stereochemical  structure.  On  the  other  hand,  emulsin,  which  breaks  up  /S-gluco- 
sides,  has  no  influence  on  a-glucosides.  This  specific  affinity  of  the  ferments  for  optically 
active  groups  of  bodies  suggests  that  the  ferment  itself  may  be  optically  active.  We 
cannot  of  course  isolate  the  ferment  and  determine  its  optical  behaviour ;  but  that 
it  is  optically  active  is  rendered  probable  both  by  these  results  and  certain  results 
obtained  by  Dakin  on  lipase,  the  fat-sphtting  ferment.  Dakin  carried  out  his  experi- 
ments on  the  esters  of  mandelic  aeid.  Mandelic  acid  is  optically  inactive,  but  this 
optically  inactive  modification  consists  of  a  mixture  of  equal  parts  of  dextro-rotatory 


CHEMICAL  CHANGES  IN  LIVING  MATTER.    FERMENTS    167 

and  leevo-rotatory  mandelic  acid.  The  esters  prepared  from  the  optically  inactive 
acids  are  themselves  optically  inactive.  Dakin  found  that,  when  an  optically  inactive 
mandelic  ester  was  acted  upon  by  a  lipase  prepared  from  the.  liver,  the  final  results 
of  the  action  were  also  inactive  ;  but  if  the  reaction  were  interrupted  at  the  half-way 
point,  the  mandelic  acid  which  had  been  liberated  was  dextro-rotatory,  while  the 
remainder  of  the  ester  was  lsevo-rotatory.  Thus  the  rate  of  hydrolysis  of  the  dextro- 
eomponent  of  the  ester  is  greater  than  that  of  the  kevo-component,  a  result  which  can 
be  best  explained  by  the  assumptions  (a)  that  the  enzyme  or  a  substance  closely  associ- 
ated with  it  is  a  powerfully  optically  active  substance  ;  (6)  that  actual  combination 
takes  place  between  the  enzyme  and  the  ester  undergoing  hydrolysis.  Since  the 
additive  compounds  thus  formed  in  the  case  of  the  dextro-  and  kevo-components  of 
the  ester  would  not  be  optical  opposites,  they  would  be  decomposed  with  unequal 
velocity,  and  thus  account  for  the  liberation  of  the  optically  active  mandelic  acid. 

We  may  conclude  that  in  the  action  of  ferments  on  the  food  substances, 
whether  carbohydrate  or  protein,  an  essential  factor  is  the  combination 
of  the  ferment  with  the  substrate.  Only  the  part  of  the  substrate,  which  is 
thus  combined  with  the  ferment,  can  be  regarded  as  the  active  mass  and  as 
undergoing  the  hydrolytic  change.  What  is  the  nature  of  this  combination  ? 
Ferments,  which  are  all  of  a  colloidal  or  semi-colloidal  character,  cannot 
be  dealt  with  in  the  same  way  as  the  catalysts  of  definite  chemical  com- 
position, such  as  molybdic  acid  or  nitric  oxide.  In  many  cases  the  substrate, 
e.g.  starch  or  protein,  is  also  colloidal,  and  the  combination  therefore  falls 
into  the  class  of  combinations  between  colloids.  In  this  we  have  an  inter- 
action between  two  substances  in  which  the  adsorption  by  the  surfaces 
of  the  molecules  of  one  or  both  substances  plays  an  important  part,  though 
this  adsorption  is  itself  determined  or  modified  by  the  chemical  configuration 
of  the  molecules.  The  combination  of  ferments  with  their  substrates  be- 
longs therefore  to  that  special  class  of  interactions,  not  entirely  chemical 
and  not  entirely  physical,  but  depending  for  their  existence  on  a  co-operation 
of  both  chemical  and  physical  factors,  which  we  have  discussed  earlier  under 
the  name  of  adsorption  compounds. 

FERMENTS  AS  SYNTHETIC  AGENTS 
If  maltase,  obtained  from  yeast,  or  from  the  so-called  takadiastase 
(prepared  from  Aspergillus  oryzw),  be  added  to  a  solution  of  maltose,  the 
latter  is  hydrolysed  to  ghicose.  The  process  of  hydrolysis  stops  short  of 
complete  inversion  at  a  point  varying  with  the  concentration  of  the  sugar 
solution.  Thus  in  a  10  per  cent,  solution  of  maltose,  inversion  proceeds 
until  98  per  cent,  otthe  maltose  is  converted  into  dextrose,  whereas  in  a 
40  per  cent,  solution  the  change  stops  short  when  85  per  cent,  sugar  has 
undergone  inversion.  Croft  Hill  showed  that  if  the  maltase  were  added 
to  a  40  per  cent,  solution  of  dextrose,  a  change  took  place  in  the  reverse 
direction,  which  proceeded  until  85  per  cent,  of  the  glucose  was  left.  The 
sugar  formed,  which  is  a  disaccharide,  was  regarded  by  Croft  Hill  as  maltose. 
According  to  Emmerling,  however,  it  is  the  stereoisomeric  sugar,  iso-maltose, 
which  is  formed  ;  and  Croft  Hill  in  his  later  papers  spoke  of  the  sugar  as 
revertose. 

In  the  same  way  it  has  been  shown  by  Castle  and  Loewenhart  that  the 


168  PHYSIOLOGY 

hydrolysis  of  esters  by  lipase  is  a  reversible  read  ion,  the  action  of  lipase 
being  simply  to  hasten  the  attainment  of  the  equilibrium  point  between 
the  four  substances — ester  (or  neutral  fat),  water,  fatty  acid,  and  alcohol. 
Similar  reversible  effects  have  been  described  for  other  ferments.  Thus 
the  addition  of  pepsin  to  a  strong  solution  of  albumoses  causes  the  appear- 
ance of  an  insoluble  precipitate,  which  is  called  plastein,  and  has  been 
regarded  as  produced  by  the  resynthesis  of  the  original  protein  molecule. 

If  all  ferment  actions  are  in  this  way  reversible,  a  possibibty  is  opened 
of  regarding  the  synthetic  processes  occurring  in  the  living  cell,  as  well 
as  the  processes  of  disintegration,  as  determined  by  the  action  of  enzymes. 
It  must  be  noted  that  these  effects  are  obtained  with  distinctness  only 
when  dealmg  with  concentrated  solutions.  The  degree  of  synthesis  which 
would  be  produced  in  the  very  dilute  solutions  of  glucose  &c.  occurring 
in  the  animal  cell  would  therefore  be  infinitesimal.  But  if  a  mechanism 
were  provided  for  the  immediate  separation  of  the  synthetical  product 
from  the  sphere  of  reaction,  either  by  removing  it  to  a  different  part  of  the 
cell  or  by  building  it  up  into  some  more  complex  body  which  was  not  acted 
on  by  the  ferment,  the  process  of  synthesis  might  go  on  indefinitely,  and  the 
infinitesimal  quantities  be  summated  to  an  appreciable  amount. 

Some  experiments  by  Bertrand  on  fat  synthesis  have  been  interpreted  as  showing 
that  the  process  of  synthesis  by  ferments  is  not  the  mere  attainment  of  an  equilibrium 
point  in  a  reversible  reaction.  It  has  long  been  known  that  watery  extracts  of  the 
fresh  pancreas  split  neutral  fats  into  the  higher  fatty  acids  and  glycerine.  This  observer 
has  shown  that,  if  the  pancreas  be  dried  with  alcohol  and  ether  and  powdered,  addition 
of  the  dry  powder  to  a  mixture  of  the  higher  fatty  acids  and  glycerine  brings  about  a 
rapid  synthesis  of  neutral  fat,  The  process  of  synthesis  is  at  once  stopped  by  the 
addition  of  water.  In  this  case  either  there  are  two  ferments  present,  one  a  synthetising, 
the  other  a  hydrolysing,  ferment,  differing  in  their  conditions  of  activity,  or  there  is 
one  ferment  which  may  act  either  as  a  fat-splitting  or  fat-forming  agent  according  to 
the  conditions  under  which  it  is  placed.  In  the  latter  case  the  effect  of  the  addition  of 
water  would  be  simply  to  alter  the  equilibrium  point  of  the  mixture.  It  has  been 
shown  that  in  all  reversible  reactions  the  equilibrium  position  is  the  same  from  which- 
ever side  it  be  approached.  The  action  of  the  ferment  is  to  hasten  the  attainment  of 
equilibrium,  the  position  of  the  latter  being  determined  by  the  relative  concentration 
of  the  reacting  molecules. 


SECTION  V 
ELECTRICAL   CHANGES   IN   LIVING   TISSUES 

The  material  composing  living  cells  and  tissues  is  permeated  throughout 
with  water  containing  electrolytes  in  solution.  All  salts,  as  we  have  seem 
undergo  ionic  dissociation  in  watery  solution — a  dissociation  which,  in  the 
concentrations  occurring  in  the  animal  body,  must  be  nearly  complete. 
When  an  electric  current  passes  through  the  living  tissues  it  is  carried  by  the 
charged  ions  formed  by  the  dissociation  of  the  salts.     Thus,  n/10  solution 

+  - 

of  sodium  chloride  contains  almost  entirely  Na  and  CI  ions.  In  addition  to 
these  charged  inorganic  ions,  the  cell  protoplasm  contains  in  solution  or 
suspension  various  colloidal  particles  which  in  many  cases  are  themselves 
charged.  By  the  presence  of  these  colloidal  particles  marked  differences 
may  be  caused  in  the  distribution  of  the  inorganic  ions  owing  to  the  power 
of  adsorption  possessed  by  the  colloids  for  many  inorganic  salts.  It  is 
evident  that  any  unequal  distribution  of  the  charged  ions  or  colloidal  particles 
in  a  tissue  or  on  the  two  sides  of  a  membrane  may  give  rise  to  corresponding 
unequal  distribution  of  electric  charges,  and  therefore  differences  of  potential 
between  different  parts  of  the  tissue,  which  under  suitable  conditions  may 
find  their  expression  in  an  electric  current.  It  is  therefore  not  surprising  that 
practically  every  functional  change  in  a  tissue  has  been  shown  to  be 
associated  with  the  production  of  differences  of  electrical  potential.  Thus  all 
parts  of  an  uninjured  muscle  are  isopotential,  and  any  two  points  may  be  led 
off  to  a  galvanometer  without  any  cm-rent  being  observed.  If  however  one 
part  of  the  muscle  be  strongly  excited,  as  for  instance  by  injury,  so  that  it 
is  brought  into  a  state  of  lasting  excitation,  it  will  be  found  that,  on  leading 
off  from  this  point  and  a  point  on  the  uninjured  surface  to  a  galvanometer, 
a  current  flows  through  the  latter  from  the  uninjured  to  the  injured  surface. 
Every  beat  of  the  heart,  every  twitch  of  a  muscle,  every  state  of  secretion  of 
a  gland,  is  associated  in  the  same  way  with  electrical  changes.  In  most 
cases  the  electrical  changes  associated  with  activity  have  the  same  general 
character,  the  excited  part  being  found  to  be  negative  in  reference  to  any 
other  part  of  the  tissue  which  is  at  rest.  The  uniform  character  of  the 
electric  response  in  different  kinds  of  tissues  suggests  that  an  accurate  know- 
ledge of  the  changes  in  the  distribution  of  charged  ions  responsible  for  the 
response  ought  to  throw  important  light  on  the  intimate  nature  of  excitation 
generally.      It  may  be  therefore  advisable  to  consider  more  closely  the 

169 


170 


PHYSIOLOGY 


conditions  which  determine  differences  of  potential  in  a  complex  system  of 
electrolytes. 

As  a  simple  case  we  may  take  an  ordinary  concentration  cell.  Two 
vessels  (Fig.  29),  A  and  B,  are  united  by  a  glass  tube  C.  A  contains  a  10 
per  cent,  solution  of  zinc  sulphate  and  B  a  1  per  cent,  solution  of  the  same 
salt.  A  rod  of  pure  zinc  is  immersed  in  each  limb.  On  connecting  the  zinc 
by  a  zinc  wire  to  a  galvanometer  a  current  is  observed  to  flow  from  A  to  B 
through  the  galvanometer,  and  therefore  from  B  to  A  through  the  cell.     A 


solution  of  zinc  sulphate  contains  partly  undissociated  ZnS04  and  partly 

+  — 

dissociated  Zn  and  S04  ions.  If  a  rod  of  zinc  be  immersed  in  a  watery  fluid 
the  zinc  tends  to  dissolve.  The  Zn  passing  into  the  fluid  is  however 
directly  ionised,  and  therefore  carries  a  positive  charge  into  the  fluid,  leaving 
the  zinc  negatively  charged  (Fig.  30).  This  process  of  solution  will  rapidly 
come  to  an  end,  since  the  positively  charged  ions  in  the  fluid  will  repel  back 
into  the  zinc  any  ions  which  may  be  escaping  from  the  zinc.  The  amount  of 
zinc  actually  dissolved  in  the  fluid  is  infinitesimal,  the  process  of  solution 
ceasing  when  the  pressure  (osmotic  pressure)  of  the  Zn  ions  in  the  fluid 
equals  what  may  be  called  the  '  electrolytic  solution  pressure  '  of  the  zinc. 
The  continued  solution  of  the  zinc  is  therefore  possible  only  when  means  are 
supplied  for  the  Zn  ions  in  the  fluid  to  get  rid  of  their  positive  charges. 
In  an  ordinary  Daniell  cell  the  Zn  ions  which  leave  the  zinc  are  dis- 
charged by  combining  with  the  S04  ions  passing  to  the  zinc  from  the  copper 
sulphate  in  the  outer  cell.  It  is  a  well-known  fact  that  pure  zinc  does  not 
dissolve  in  acid  until  some  other  metal,  such  as  copper,  is  brought  into  con- 
tact with  it,  so  as  to  set  up  an  electric  couple,  i.e.  to  provide  means  for  the 
discharge  of  the  Zn  ions  passing  into  the  solution.  When  the  zinc  is 
immersed  in  the  two  solutions  of  zinc  sulphate  in  the  concentration  battery, 
the  same  change  will  occur.     The  ZnS04  solution  in  the  two  limbs  of  the 


ELECTRICAL  CHANGES  IN  LIVING   TISSUES  171 

concentration  cell  already  contains  Zn  ions.  Since  their  pressure  in  the  10  per 
cent,  solution  is  greater  than  in  the  1  per  cent,  solution,  fewer  Zn  ions  will 
leave  the  zinc  in  A  than  in  B.  The  negative  charge  on  the  Zn  in  A  will 
therefore  be  less  than  that  on  the  rod  in  B,  and  positive  electricity  will  there- 
fore flow  from  A  to  B.  This  will  disturb  the  equilibrium  at  the  surface  both 
of  B  and  A,  so  that  Zn  ions  will  be  deposited  from  the  fluid  on  the  surface  of 
the  zinc  in  A  and  will  continue  to  pass  from  zinc  into  solution  in  B.  At  the 
same  time  there  is  a  movement  of  S04  ions,  set  free  at  the  surface  of  A 
towards  B.  The  ultimate  result  therefore  is  that  the  zinc  in  B  dissolves 
and  the  same  amount  of  zinc  is  deposited  on  A.  The  solution  of  zinc 
sulphate  on  A  becomes  progressively  weaker,  while  that  in  B  becomes 
stronger,  until  finally  the  concentrations  in  the  two  limbs  are  identical 
and  the  current  ceases.  In  this  process  no  chemical  energy  is  involved, 
the  energy  set  free  by  the  conversion  of  zinc  into  zinc  sulphate  in  B  being 
exactly  balanced  by  the  energy  lost  by  the  deposition  of  zinc  from  zinc 
sulphate  in  A.  Yet  the  current  which  is  produced  has  a  certain  amount 
of  energy  which  can  be  utilised  for  heating  a  wire  through  which  it  is  made 
to  pass.  Since  this  energy  must  be  taken  from  the  cell,  the  cell  is  cooled 
during  the  passage  of  the  current.  We  have  here  a  close  analogy  with  the 
case  of  compressed  gases.  If  the  10  per  cent,  and  1  per  cent,  solutions 
were  mixed  together  in  a  calorimeter,  no  change  of  temperature  would 
be  produced,  since  no  work  is  done  in  the  process.  In  the  same  way  no  cooling 
effect  is  observed  if  compressed  gas  be  allowed  to  expand  into  a  vacuum. 
If  however  the  compressed  gas  be  allowed  to  expand  from  a  narrow  orifice 
against  the  pressure  of  the  external  air,  so  that  it  does  work  in  the  process, 
it  is  cooled,  and  this  cooling  effect  is  made  use  of  in  the  working  of  refrigerat- 
ing machines  or  for  the  liquefaction  of  gases.  We  may  therefore  regard  the 
concentration  battery  as  a  machine  for  making  the  substances  in  solution 
do  work  as  they  expand  from  a  strong  into  a  dilute  solution. 

The  differences  of  potential  obtained  from  an  ordinary  concentration 
cell  are  very  small  and  would  not  ^ 

suffice    to    account  for  such  a  high 
electromotive  force  as  is  set  up,  e.g. 
in  the  contraction  of  a  muscle.    We 
have  seen  earlier  however  that  even 
in  isosmotic  solutions  differences  of 
pressure  may  be  brought  about  by 
differences  in  diffusibility  of  the  sub- 
stances in  solution,  especially  if  the 
two  solutions  be  separated  by  a  mem- 
brane. Very  large  differences  may  be  Fig.  31. 
produced  if  this  membrane  be  prac- 
tically impermeable  to  one  or  other  of  the  dissolved  substances.    In  the  same 
way  a  semipermeable  membrane,  i.e.  a  membrane  with  different  permeabil- 
ities for  the  different  ions  of  the  two   solutions,  may  suffice  to    bring  the 
differences  of  potential  of  a  concentration  cell  up  to  and  beyond  the  extent 


uv 


B 
UV 


172  PHYSIOLOGY 

which  is  observed  in  living  tissues.  Supposing  we  have  (Fig.  31)  two  solu- 
tions, A  and  B,  each  containing  an  electrolyte, UV,  in  different  concentrations 
separated  by  a  membrane  m.  If  u  represents  the  velocity  of  transmission 
of  U  through  m,  and  v  the  velocity  of  V,  then  the  electromotive  force  of  the 
cell  is  given  by  the  formula 

^^0-0577.1og.1„C2  Volt. 


If  v  is  taken  as  very  small,  the  membrane  may  be  regarded  as  semipermeable 
for  the  corresponding  ion  V.  Supposing  we  take  potassium  chloride  as  the 
solution,  we  should  have  to  make  the  concentration  in  B  eight  times  that  in 
A,  in  order  to  get  a  current  of  strength  equal  to  that  obtained  from  the 
olfactory  nerve  of  the  pike,  for  example.  Macdonald  has  made  such  an 
assumption  in  order  to  explain  the  normal  nerve  current.  He  suggests  that 
the  axis  cylinder  contains  an  electrolyte  which  is  equivalent  to  a  2-6  per 
cent,  solution  of  potassium  chloride.  It  is  unnecessary  however  to  assume 
such  great  differences  of  concentration  if  we  regard  the  membrane  as  itself 
a  solution  of  electrolytes,  as  has  been  suggested  by  Cremer,  or  if  we  take 
different  substances  on  the  two  sides  of  the  membrane.  In  the  case  of  two 
electrolytes,  UiVj,  U2V2  (U  being  the  cation  in  each  case),  separated  by  a 
membrane  with  varying  permeability  for  the  different  ions,  the  electro- 
motive force  of  the  cell  is  given  by  the  following  formula  : 

0-0577  log.,,;'" 


_  +  vt 

where  uu  vlt  «2,  v2,  are  the  velocities  of  the  corresponding  ions.  We  assume 
that  the  concentrations  of  the  two  solutions  are  identical.     Now  it  is  evident 

that  by  making  w2  and  vt  very  small,  the  expression  log.10  — -  may  be 

U2   +   Vj 

made  to  attain  any  quantity,  and  in  the  same  way  by  making  Uj  +  v2 
infinitesimally  small,  the  electromotive  force  of  the  combination  will  also 
become  correspondingly  small.  The  thickness  of  the  membrane  does  not 
come  into  the  formula,  so  that  membranes  of  microscopic  or  even  ultra- 
microscopic  thickness,  which  we  have  seen  reason  to  assume  as  present  in 
and  around  cells  and  their  parts,  could  perform  all  the  functions  required 
of  the  hypothetical  membrane  in  the  above  example.  This  is  also  the  case 
when  V!  is  the  same  as  V2 — that  is  to  say,  there  is  a  common  anion  or  a 
common  cation  on  the  two  sides  of  the  membrane. 

It  must  be  remembered  that  the  passage  of  a  current  through  a  membrane 
impermeable  to  one  or  other  ion  in  the  surrounding  fluid  will  cause  an  accu- 
mulation of  the  ion  at  the  surface  of  the  membrane,  so  that  this  will  become 
polarised.  Such  an  accumulation  at  any  surface  will  naturally  alter  the 
properties  of  the  surface,  including  its  surface  tension.  The  construction  of 
the  capillary  electrometer  depends  on  this  fact.  When  mercury  is  in  contact 
with  dilute  acid  or  mercuric  sulphate  solution  it  takes  a  positive  charge  from 
the  fluid,  and  the  state  of  stress  at  the  surface  of  contact  between  the 
mercury  and  the  negatively  charged  fluid  diminishes  the  surface  tension  of 


ELECTRICAL  CHANGES  IN   LIVING  TISSUES 


173 


the  mercury.  If  the  mercury  be  in  the  form  of  a  drop  in  a  tube  drawn  out 
to  a  capillary,  the  mercury  will  run  down  the  capillary  and  the  drop  will  be 
deformed  until  the  surface  tension  tending  to  pull  the  mercury  into  a 
spherical  globule  is  just  equal  to  the  force  of  gravity  tending  to  make  the 
mercury  run  out  through  the  end  of  the  capillary  (Fig.  3'2). 
If  the  mercury  be  immersed  in  sulphuric  acid  it  will  descend  to 
a  lower  level  in  the  capillary  owing  to  the  diminution  of  its 
surface  tension,  If  now  the  acid  and  the  mercury  be  con- 
nected with  a  source  of  current  so  as  to  charge  the  mercury 
negatively,  the  effect  will  be  to  diminish  the  charge  previously 
taken  up  by  the  mercury.  The  state  of  tension  at  the  contact 
with  the  acid  is  therefore  diminished,  the  surface  tension  is 
increased,  and  the  mercury  withdraws  itself  from  the  point 
of  the  capillary.  If  however  the  mercury  be  connected  with 
the  positive  pole,  its  charge  will  be  increased  and  its  surface 
tension  correspondingly  diminished,  so  that  the  meniscus 
will  move  towards  the  point  of  the  capillary.  The  move- 
ment of  the  meniscus  to  or  away  from  the  point  may  thus  be 
used,  as  in  the  capillary  electrometer,  to  show  the  direction 
and  amount  of  any  moderate  electric  change  occurring  in  a 
tissue,  two  points  of  which  are  connected  with  the  mercury 
and  the  acid  respectively.  It  is  possible  that  this  electrical 
alteration  of  surface  tension  may  be  a  determining  factor 
in  many  of  the  phenomena  of  movement  observed  in  the  animal 
body.  We  shall  have  occasion  to  discuss  this  question  more  fully  when 
endeavouring  to  account  for  the  ultimate  nature  of  muscular   contraction. 


Fig.  32. 


BOOK  II 

THE  MECHANISMS  OF  MOVEMENT  AND 
SENSATION 


CHAPTER  V 
THE   CONTRACTILE    TISSUES 

SECTION   I    • 

THE    STRUCTURE    OF   VOLUNTARY   MUSCLE 

The  most  striking  features  in  the  continual  series  of  adaptations  to  the 
environment,  which  make  up  the  life  of  an  individual,  are  the  movements 
carried  out  by  contractions  of  the  skeletal  muscles.  In  fact,  all  the  mechan- 
isms of  nutrition  can  be  regarded  as  directed  to  the  maintenance  of  the 
neuro-muscular  apparatus,  i.e.  of  the  mechanism  for  adapted  movement. 
With  the  growth  of  the  cerebral  hemispheres,  which  determines  the  rise 
in  the  scale  of  animal  life,  the  skeletal  muscles  become  more  and  more  the 
machinery  of  conscious  reaction.  Even  the  highest  of  the  adaptations 
possessed  by  man,  those  involving  the  use  of  speech,  are  impossible  without 
some  kind  of  movement.  A  man's  relation  to  his  fellows,  and  his  value  in 
the  community,  are  determined  by  these  higher  muscular  adaptations. 
It  is  not  therefore  surprising  that  the  organs  of  the  body  which  present 
in  the  highest  degree  the  reactivity  characteristic  of  all  living  things  should 
have  early  attracted  the  attention  of  physiologists  and  have  been  the  object 
of  numberless  researches  directed  to  determining  the  ultimate  nature,  of  the 
processes  generally  described  as  vital. 

The  movements  of  the  muscles  are  carried  out  in  response  to  changes 
aroused  in  the  central  nervous  system  by  events  occurring  in  the  environ- 
ment and  acting  on  the  surface  of  the  body.  Every  movement  of  an  animal 
is  thus  in  its  most  primitive  form  a  reflex  action,  and  involves  changes  in  a 
peripheral  sense  organ,  in  an  afferent  nerve  fibre,  in  the  central  nervous 
system,  and  in  an  efferent  nerve  fibre,  before  the  actual  process  of  contrac- 
tion occurs  in  the  muscle  itself  and  gives  rise  to  the  resultant  movement 
(Fig.  33).  If  we  are  to  determine  the  nature  of  the  changes  involved  in  this 
reflex  action,  we  must  be  able  to  study  them  as  they  progress  along  the 
different  elements  which  make  up  the  reflex  arc.  This  analysis  is  facilitated 
by  the  fact  that  we  are  able  to  arouse  a  condition  of  activity  in  the  different 
parts  of  the  arc,  even  when  isolated  from  one  another.  Thus  we  can  excite 
anv  given  reflex  movement  by  stimulation  of  the  periphery  of  the  body, 
or  of  the  afferent  nerve  passing  from  the  surface  to  the  central  nervous 

177  12 


178 


PHYSIOLOGY 


system.  We  can  proceed  further  and  cut  the  efferent  nerve  away  from 
the  central  nervous  system  and  still  succeed  in  exciting  a  condition  of  activity 
in  the  efferent  nerve  or  in  its  attached  muscle.  All  parts  of  the  reflex  arc 
possess  the  property  of  excitability,  and  we  are  thus  able  to  arouse  the 
activity  of  each  part  in  turn,  to  study  its  conditions,  its  time  relations,  and 
the  physical  and  chemical  changes  concomitant  with  the  state  of  activity. 
It  will  be  convenient  for  our  analysis  to  begin  with  the  tissue  whose 


Sensory  ll^     Sensory  nerve       9 
Surface  \\M  — * 


Central  Nervous 
System 


Fig.  33.     Diagram  of  a  reflex  arc. 

reaction  forms  an  end  link  in  the  reflex  chain,  namely,  the  muscle,  and  to 
proceed  from  that  to  the  consideration  of  the  processes  occurring  in  the 
conducting  strand  between  central  nervous  system  and  muscle,  namely, 
the  nerve  fibre,  postponing  to  a  future  chapter  the  treatment  of  the  more 
complex  processes  associated  with  the  central  nervous  system. 

In  the  higher  animals  we  may  distinguish  several  varieties  of  muscle. 
All  movements  that  require  to  be  sharply  and  forcibly  carried  out  are 
effected  by  means  of  striated  muscular  tissue  and,  as  these  movements 
are  in  nearly  all  cases  under  the  control  of  the  will,  the  muscles  are  generally 
spoken  of  as  voluntary.  Unstriated  or  involuntary  muscles  form  sheets 
or  closed  tubes  surrounding  the  hollow  viscera.  By  their  slow,  prolonged 
contractions  they  serve  to  maintain  and  regulate  the  flow  of  the  contents 
of  these  organs.  Such  fibres  are  found  surrounding  the  blood-vessels, 
the  alimentary  canal,  the  bladder,  &c.  Intermediate  in  properties  as 
well  as  structure  between  these  two  classes  is  the  heart  muscle.  This, 
like  voluntary  muscle,  is  striated,  but  presents  considerable  variations  both 
in  structure  and  function  from  ordinary  skeletal  muscle.  Many  of  its 
properties  will  be  considered  in  treating  of  the  physiology  of  the  heart. 

The  properties  of  contractile  tissues  have  been  most  fully  investigated  in  the  volun- 
tary muscles,  almost  exclusively  on  the  muscles  of  cold-blooded  animals,  such  as  the 
frog.  The  choice  of  skeletal  muscles  for  this  purpose  is  justified  by  the  fact  that  a 
function  is  most  easily  investigated  in  the  organs  in  which  it  is  most  highly  develojied. 
The  choice  of  cold-blooded  animals  is  guided  by  the  fact  that  it  is  possible  to  isolate 
the  muscle  from  the  rest  of  the  body  and  to  study  its  reactions  during  a  considerable 
time  without  the  research  being  interfered  with  by  the  death  of  the  tissue.  We  may 
therefore  deal  at  length  with  the  properties  of  the  skeletal  muscles,  pointing  out  inei- 


THE  STRUCTURE   OF  VOLUNTARY  MUSCLE  179 

dentally  in  what  respects  the  heart  muscle  and  involuntary  muscle  differ  from   the 
skeletal  muscle. 

The  voluntary  or  striated  muscles  form  a  large  part  of  the  body,  and 
are  known  as  the  flesh  or  meat.  Each  muscle  is  embedded  in  a  layer  of 
connective  tissue,  and  is  made  up  of  an  aggregation  of  muscular  fibres, 
which  are  united  into  bundles  by  means  of  areolar  connective  tissue.  The 
individual  fibres  vary  much  in  length,  and  may  be  as  long  as  4  or  5  cm. 
At  each  end  of  the  muscle  the  fibres  are  firmly  united  to  tough  bundles 
of  white  fibres.,  which  form  the  tendon  of  the  muscle,  and  are  attached  as 


Fio.   34.     Muscular   fibre  of  a   mammal,   examined   fresh  in   serum, 
highly  magnified.     (Schafer.) 

a  rule  to  bones.  Running  in  the  connective  tissue  framework  of  the  muscle 
we  find  a  number  of  blood-vessels,  capillaries  and  nerves. 

On  examination  of  a  living  muscle,  each  fibre  is  seen  to  consist  of  a 
series  of  alternate  light  and  dark  strise,  arranged  at  right  angles  to  its  long 
axis,  and  enclosed  in  a  structureless  sheath — the  sarcolemma.  Lying  under 
the  sarcolemma  are  a  number  of  oval  nuclei  embedded  in  a  small  amount 
of  granular  protoplasm.  In  some  animals  these  nuclei  occupy  a  central 
position  in  the  fibre.  Each  band  may  be  considered  to  be  made  up  of  a 
number  of  prisms  (sarcomeres)  side  by  side,  with  interstitial  substance 
(sarcoplasm)  between  them.  The  muscle  prisms  of  adjacent  discs  are 
connected  to  form  long  columns  (primitive  fibrillse,  or  sarcostyles).  Each 
muscle  prism  is  more  transparent  at  the  two  ends  than  in  the  middle,  thus 
giving  rise  to  the  appearance  of  light  and  dark  strise.  In  the  middle  of 
the  light  band  is  a  line  or  row  of  dots  (often  appearing  double),  called  Krause's 
membrane. 

The  development  of  this  regular  cross  and  longitudinal  striation  is 
closely  connected  with  the  evolution  and  specialisation  of  the  muscular 
function,  i.e.  contraction.  Contractility  is  among  others  a  function  of  all 
undifferentiated  protoplasm.  Undifferentiated  cells,  such  as  the  amoeba, 
can  effect  only  slow  and  weak  contractions.  Directly  a  specialisation  of 
function  is  necessary  and  some  cell  or  part  of  a  cell  has  to  contract  rapidly 
in  response  to  some  stimulus  from  within  or  without,  we  find  a  differentiation 
both  of  form  and  of  internal  structure.  In  many  cases,  as  in  the  developing 
muscle  of  the  embryo  or  the  adult  muscles  of  many  invertebrates,  this 
differentiation  affects  only  part  of  the  cell,  so  that  while  one  part  presents 
the  ordinary  granular  appearance,  the  other  half  is  finely  and  longitudinally 


180. 


PHYSIOLOGY 


striated,  the  striatum  being  apparently  due  to  the  development  of  special 
contractile  fibrillae.  In  the  slowly  contracting  unstriated  muscle  of  the 
vertebrate  intestine,  the  longitudinal  striation  is  with  difficulty  made  cut, 
but  as  the  muscle  rises  in  the  scale  of  efficiency,  the  longitudinal  striation 
becomes  more  apparent,  and  in  the  striated  muscle  of  vertebrates,  and  still 
more  in  the  wonderful  wing-muscles  of  insects,  which  can  perform  three 
hundred  complete  contractions  in  a  second,  the  longitudinal  is  associated 


Fig.  35.     Muscle  fibre  of  an  ascaris.     a,  the  differentiated  contractile  portion  of  the 

cell.     (After  Hertwig.) 
Fig.  3(5.     Muscle  fibres  from  the  small  intestine,  showing  the  fine  longitudinal  stria- 
tion.    (Schafee.) 

with  and  often  apparently  subordinated  to  a  transverse  striation,  due  to 
the  regular  segmentation  of  the  contractile  fibrillae  or  sarcostyles.  Every 
muscular  fibre,  which  presents  any  trace  of  histological  differentiation,  may 
be  said  to  consist  of  contractile  fibrillse  (sarcostyles),  each  composed  of  a 
series  of  contractile  elements  (sarcous  elements  or  sarcomeres),  and  embedded 
in  a  granular  material  known  as  sarcoplasm.  The  great  divergence  in  the 
aspect  of  muscular  fibres  from  different  paits  of  the  animal  kingdom  is 


THE  STRUCTURE   OF  VOLUNTARY  MUSCLE 


181 


largely  conditioned  by  the  varying  relations,  spatial  and  quantitative,  cf 
the  sarcoplasm  to  the  sacostytes.  Thus  in  the  higher  vertebrates,  two 
types  of  voluntary  muscular  fibre  are  distinguished,   according  to  the 


Fig.  37.  Transverse  sections  of  the  ])ectoral  muscles  of  «,  the  falcon,  b.  the  goose,  and  c, 
the  domestic  fowl.  It  will  be  noticed  that  the  relative  amount  of  granular  or  red  fibres 
present  varies  directly  as  the  bird's  power  of  sustained  flight.     (After  Knoll.) 

amount  of  sarcoplasm  they  contain  :   one  rich  in  sarcoplasm,  more  granular 

in  cross-section,  and  generally  containing  haemoglobin  ;   and  the  other  poor 

in  sarcoplasm,  clear  in  cross-section,  and  containing  no  ha?moglobin.      From 

the  fact  that  the  granular  fibres  are  B 

found  chiefly  in  those  muscles  which 

have   to   carry    out    long-continued 

and  powerful  contractions,  it  seems 

reasonable  to  regard  the  interstitial 

sarcoplasm  as  the  local  food-supply 

of  the  active   sarcostyles,    although 

some    authors  have    endowed    the 

sarcoplasm  with  a  contractile  power 

of   its  own,   differing    onlv   bv    its 

extremely  p  olonged  character  from 

the  quick  twitch  of  the  sarcostyles. 

The  connection    between   structure 

and  activity  of  the  muscle-fibres  is 

well  shown  by  Fig.  37. 


S 

flfett 
gmSL 

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In  some  animals,  such  as  the  rabbit, 
we  find  muscles  consisting  almost  entirely 
of  one  or  other  of  these  varieties  ;  but  in 
most  animals  (amongst  which  we  may 
reckon  frog  and  man)  the  two  varieties 
occur  together  in  one  muscle,  so  that  what 
we  have  to  say  about  the  properties  of 
voluntary  muscle,  which  rests  nearly  Fig.  38 
entirely  on  experiments  with  frog's 
muscle,  really  has  reference  to  a  mixed 
muscle,  i.e.  muscle  containing  both  red 
and  white  fibres. 

Since  the  sarcous  element  represents  the 
contractile  unit   of   the  muscle,  a  know- 
ledge of  its  intimate  structure  should  be  of  great  importance  for  the  theory  of  muscular 
contraction.       Unfortunately  however  we  are  here  at  the  limits  of  the  demonstrably 


Fibrils  of  the  wing-muscles  of  a  wasp, 
prepared  by  Rollet's  method.  Highly 
magnified.     (E.  A.  Schafer.) 

a,  a  contracted  fibril.  B,  a  stretched 
fibril,  with  its  sarcous  elements  separated 
at  the  line  of  Hensen.  c,  an  uncon- 
tracted  fibril,  showing  the  porous  struc- 
ture of  the  sarcous  elements. 


182 


PHYSIOLOGY 


SJS. 


Fio.  30.  Diagram  of  a  sarcomere  in 
a  moderately  extended  condition, 
A,  and  in  a  contracted  condition,  B  ; 
k,  K,  membranes  of  Krause :  h, 
line  or  plane  of  Hensen  ;  SE, 
poriferous  sarcous  elements. 
(Si  rafer.) 


visible.     It  becomes  difficult  to  determine  how  far  the  appearances  observed  under 
the  microscope  are  due  to  actual  structural  differences  or  are  produced  by  the  unequal 
diffraction  of  light  by  the  Various  elements  of  the  muscle  fibre.     All  observers  are  agreed 
thai  the  essential  contractile  element  is  the  row 
A  B  of  sarcous  elements  forming  the  muscle  fibril  or 

sarcostylc.  Schafer,  working  on  the  highly 
differentiated  wing-muscle  of  the  wasp,  concludes 
that  each  sarcostyle  is  divided  by  Krause's 
membranes  (the  lines  in  the  middle  of  each  light 
stripe)  into  sarcomeres.  Each  sarcomere  contains 
a  darker  substance  near  the  centre  divided  into 
two  parts  by  Hensen's  disc.  At  each  end  of  the 
sarcomere  the  contents  are  clear  and  hyaline. 
In  the  act  of  contraction,  the  clear  material  flows, 
according  to  Schafer,  into  tubular  pores  in  the 
central  dark  material. 

Most  histologists  agree  in  assigning  to  the 
middle  part  of  the  sarcous  clement  (the  sarco- 
mere) a  denser  structure  than  to  the  two  ends. 
According  to  Macdougall,  however,  the  lighter  appearance  at  each  end  of  the  sarco- 
mere is  an  optical  illusion.  He  regards  the  sarcous  element  as  a  cylindrical  bag  with 
homogeneous  contents,  crossed  only  by  one  or 
three  delicate  transverse  membranes.  Krause's 
membrane  would  be  rigid,  while  the  lateral  wall  of 
the  sarcous  element  is  extensible,  and  is  folded  longi- 
tudinally, so  that  it  can  bulge  out  and  produce 
a  shortening  and  thickening  of  the  whole  sarcous 
element  if  by  any  means  the  pressure  be  raised 
in  its  interior.  In  favour  of  a  differentiation 
within  the  sarcomere  itself  is  the  fact  that 
under  certain  conditions  it  is  possible  to  produce 
a  precipitate,  limited  only  to  central  part,  i.e. 
to  the  sarcous  element  to  which  Schafer  assigns 
a  tubular  structure. 

When  a  muscle  fibre,  killed  by  osmic  acid  or 
alcohol,  is  examined  under  the  microscope  by  pol- 
arised light,  it  is  seen  to  be  made  up  of  alternate 
bands  of  singly  and  doubly  refracting  material. 
The  doubly  refracting  {anisotropous)  substance 
corresponds  to  the  dark  band,  and  the  singly  re- 
fracting (isotropous)  to  the  light  band.  If  the 
living  fibre  be  examined  in  the  same  way,  it  is 
found  that  nearly  the  whole  of  it  is  doubly  re- 
fracting, the  singly  refracting  substance  appearing 
only  as  a  meshwork  with  long  parallel  meshes 
corresponding  to  the  muscle  prisms.  In  short,  in 
a  living  fibre  the  muscle  prisms  are  anisotropous, 
the  sarcoplasm  isotropous. 

When  a  muscle  fibre  contracts,  there  is  an  ap- 
parent reversal  of  the  situations  of  the  light  and 
dark  stripes,  owing  to  the  fact  that  the  interstitial 
sarcoplasm  is  squeezed  out  from  between  the 
bulging  sarcomeres,  and  accumulates  on  each  side 
of  the  membranes  of  Krause.  The  accumulation  of  sarcoplasm  in  this  situation 
makes  the  previously  light  striae  appear  dark,  and  the  dark  striae  by  contrast  lighter 


Fw.  40.  Motor  end-organ  of  a 
lizard,  gold  preparation.  (Ktjhnb.) 
n,  nerve  fibre  dividing  as  it  ap- 
proaches the  end-organ  ;  r,  ramifi- 
cation of  axis  cylinder  upon  b,  gran- 
ular bed  or  sole  of  the  end-organ  ; 
m,  clear  substance  surrounding  the 
ramifications  of  theaxis  cylinder. 


THE  STRUCTURE  OF  VOLUNTARY  MUSCLE  183 

than  they  were  before.  That  there  is  no  true  reversal  of  the  striae  is  shown  by  exam- 
ining the  muscle  by  polarised  light,  the  two  substances,  isotropous  and  anisotropous, 
retaining  their  relative  positions. 

Every  skeletal  muscle  is  connected  with  the  central  nervous  system 
by  nerve  fibres,  some  conveying  impressions  from  the  muscle  to  the  centre, 
the  others  acting  as  the  path  of  the  motor  impulses  from  the  centre  to  the 
muscle.  These  latter — the  motor  nerves — end  in  the  muscular  fibre  itself, 
by  means  of  a  special  end-organ — the  motor  end-plate.  The  neurilemma 
ofthe  nerve  fibre  becomes  continuous  with  the  sarcolemma,  the  medullary 
sheath  ends  suddenly,  while  the  axis  cylinder  ramifies  in  a  mass  of  un- 
differentiated protoplasm,  containing  nuclei,  and  lying  in  contact  with  the 


Tendo  Aehillis 


Fio.  41.     Muscles  of  hinder  extremity  of  frog.     (After  Ecker.) 

contractile  substance  of  the  muscle  immediately  under  the  sarcolemma 
(Fig.  40).  This  mass  of  protoplasm  is  known  as  the  '  sole  plate.'  It  is  not 
marked  in  all  animals.  Thus  in  the  frog  the  axis  cylinder  ends  in  a  series  of 
branches  at  right  angles  to  one  another,  distributed  over  a  considerable  length 
of  the  muscle  fibre.  The  sole  plate  in  this  case  seems  to  be  limited  to  scat- 
tered nuclei  lying  in  close  contact  with  the  terminal  branches  of  the  nerve 
fibre.  So  far  as  we  can  tell  at  present,  the  ultimate  ramifications  of  the 
axis  cylinder  end  freely  and  do  not  enter  into  organic  connection  with  the 
contractile  substance  itself. 


184  PHYSIOLOGY 

Musi  nf  our  knowledge  on  the  subject  of  muscle  has  been  derived  from  the  study 
ill  i In-  gastrocnemius  and  saitorius  muscles  of  the  frog.  The  position  of  these  muscles 
is  shown  in  I  In'  accompanying  diagram  (Fig.  41).  The  gastrocnemius  which,  with 
the  attached  sciatic  nerve,  is  must  frequently  employed  as  a  nerve-muscle  preparation, 
forms  a  thick  belly  immediately  under  the  skin  at  the  back  of  the  leg,  and  arises  by 
t  \vi  i  tendons  from  the  lower  end  of  the  femur  and  the  outer  side  of  the  knee-joint.  The 
two  tendons  converge  towards  the  centre  of  the  muscle,  uniting  about  its  middle,  and 
from  them  a  number  of  short  muscular  fibres  arise,  passing  backwards  and  dorsally  to 
be  inserted  into  a  flat  aponeurosis  covering  the  lower  half  of  the  muscle,  which  ends 
in  the  tendo  Achillis.  On  account  of  this  irregular  arrangement  of  the  muscular  fibres, 
tin  gastrocnemius  can  be  employed  only  when  the  contraction  of  the  muscle  as  a  whole 
is  the  object  of  investigation.  The  effective  cross-area  of  the  fibres  is  much  greater 
than  the  actual  cross-section  of  the  muscle,  so  that,  while  the  actual  shortening  of  the 
gastrocnemius  is  but  small,  its  strength  of  contraction  is  considerable. 

The  sartorius  muscle  consists  of  a  thin  band  of  muscle  fibres  running  parallel  from 
one  end  of  the  muscle  to  the  other.  It  lies  on  the  ventral  surface  of  the  thigh,  arising 
from  the  symphysis  puhlis  by  a  thin  Hat  tendon,  and  is  inserted  by  a  narrow  tendon 
into  the  inner  side  of  the  head  of  the  tibia.  On  account  of  the  regularity  with  which 
its  fibres  are  disposed,  this  muscle  is  of  especial  value  in  experiments  on  the  local  con- 
ditions of  a  muscle  fibre  accompanying  its  activity.  When  a  greater  mass  of  approxi- 
mately parallel  fibres  is  necessary,  recourse  may  be  had  to  a  preparation  consisting  of 
the  gracilis  and  semi-membranosus  muscles  together.  This  latter  muscle  lies  dorsally 
to  the  gracilis  muscle  which  is  shown  in  the  illustration. 

Other  muscles  in  the  frog  used  for  particular  purposes  are  the  mylohyoid  and  the 
dorsocutaneous  muscles.  The  mylohyoid  muscle  of  the  frog,  which  lies  on  the  ventral 
surface  of  the  tongue,  has  the  advantage  that  its  fibres  lie  in  close  contact  with  a  lymph- 
space  occupying  the  centre  of  the  tongue.  Tf  any  drug  be  injected  into  this  lymph- 
space  it  ails  with  extreme  rapidity  on  the  muscle  fibres,  so  that  the  tongue-preparation 
of  the  frog  is  a  useful  one  for  the  study  of  the  action  of  different  substances  on  muscle- 
fibres. 


SECTION  II 

EXCITATION    OF   MUSCLE 

A  MUSCLE  may  be  caused  to  contract  in  various  ways.  Normally  it  con- 
tracts only  in  response  to  impulses  starting  in  the  central  nervous  system 
and  transmitted  down  the  nerves.  But  contraction  may  be  artificially 
excited  in  various  ways  in  a  muscle  removed  from  the  body.  If  we  make 
a  muscle-nerve  preparation  {i.e.  a  muscle  with  as  long  a  piece  of  its  nerve 
as  possible  attached  to  it),  such  as  the  gastrocnemius  of  the  frog  with  the 
sciatic  nerve,  we  find  we  can  cause  contraction  by  various  forms  of  stimuli — 
mechanical,  thermal,  or  electrical — applied  to  the  muscle  or  the  nerve 
(direct  and  indirect  stimulatiou).  Thus  the  muscle  responds  with  a  twitch 
if  we  pass  an  induction  shock  through  it  or  its  nerve,  or  pinch  either  with  a 
pail  of  forceps.  Or  we  may  use  chemical  stimuli,  and  cause  contraction 
by  the  application  of  strong  glycerin  or  salt  solution  to  the  nerve. 

These  experiments  do  not  prove  conclusively  that  muscle  itself  is  irritable. 
It  might  tie  urged  that,  when  we  pinched  or  burnt  the  muscle  we  stimu- 
lated, nut  Hie  muscle  substance  itself,  but  the  terminal  ramifications  of 
the  nerve  in  the  muscle,  and  that  these  in  their  turn  incited  the  muscle  to 
contract.  But  the  independent  excitability  of  muscle  is  shown  clearly  by 
the  following  experiment  by  Claude  Bernard. 

A  frog,  whose  brain  has  been  previously  destroyed,  is  pinned  on  a  board, 
and  the  sciatic  nerves  on  each  side  exposed.  A  ligature  is  then  passed 
round  the  right  thigh  underneath  the  nerve,  and  tied  tightly  so  as  effectually 
to  close  all  the  blood-vessels  supplying  the  limbs,  without  interfering 
with  the  blood-supply  to  the  nerve.  Two  drops  of  a  1  per  cent,  solution 
of  curare  are  then  injected  into  the  dorsal  lymph-sac.  After  the  lapse  of  a 
quarter  of  an  hour  n  is  found  that  the  strongest  stimuli  may  be  applied 
to  the  left  sciatic  nerve  without  causing  any  contraction  of  the  muscles  it 
supplies.  On  the  right  side,  stimulation  of  the  nerve  is  as  efficacious  as 
before.  Both  gastrocnemii  respond  readily  to  direct  stimulation,  showing 
that  the  muscles  are  not  affected  by  the  drug.  Since  both  sciatic  nerves 
have  been  exposed  to  the  influence  of  the  curare,  it  is  evident  that  the 
difference  on  the  two  sides  cannot  be  due  to  any  deleterious  effect  on  them 
by  the  curare.  We  have  also  excluded  the  muscles  themselves  ;  so  we  must 
conclude  that  the  curare  paralyses  the  muscles  by  affecting  the  terminations 
of  the  nerve  within  the  muscle,  and  probably  the  end-plates  themselves. 

185 


186 


PHYSIOLOGY 


This  experiment  teaches  us  that  muscle  can  be  excited  to  contract  by 
direct  stimulation,  even  when  the  terminal  ramifications  of  the  nerve  within 
it  are  paralysed,  so  that  stimulation  of  them  would  be  without  effect. 

The  same  fact  may  be  demonstrated  in  a  different  way  by  means  of 
chemical  stimuli.  It  is  found  that  whereas  strong  glycerin  excites  nerve 
fibres,  it  is  without  effect  on  muscle  fibres,  while  on  the  other  hand  weak 
ammonia  is  a  strong  excitant  for  muscle,  but  is  without  effect  on  nerve. 
If  the  frog"s  sartorius  be  dissected  out  and  the  lower  end  dipped  in  glycerin, 
no  twitch  is  produced.  On  snipping  off  the  lower  third  of  the  muscle  and  then 
immersing  the  cut  end  in  glycerin,  a  twitch  at  once  occurs.  The  lower 
end  contains  no  nerve  fibres  (Fig.  42),  and  it  is 
only  when  a  section  containing  nerve  fibres  is  ex- 
posed to  the  action  of  glycerin  that  contraction  takes 
place.  On  the  other  hand,  mere  exposure  of  muscle 
to  the  vapour  of  dilute  ammonia  causes  contraction 
(and  subsequent  death),  although  the  nerve  to  the 
muscle  can  be  immersed  in  the  solution  without 
any  excitation  being  produced. 

Of  all  the  different  stimuli  capable  of  exciting 
muscular  contraction,  the  electrical  is  that  most 
frequently  employed.  It  is  easy,  using  this  form, 
to  graduate  accurately  the  intensity  and  duration 
of  the  stimulus.  At  the  same  time  the  stimulus 
may  be  applied  many  times  to  any  point  on  the 
of  the  nerve  fibres  within  muscle  or  nerve  without  killing  the  part  stimulated, 
the  sartnrius  muscle  of  whereas  with  other  forms  of  stimulus  it  is  difficult 

the  frog,  showing  the  free-  .  ■  .... 

doni  of  the  lower  portion  to  obtain  excitatory   effects  without  injuring  to  a 

of  the  muscle  from  nerve  greater  or  less  extent  the  part  stimulated, 
fibres.     (Kuhne.)  * 

METHODS  EMPLOYED  FOR  THE  STIMULATION  OF  MUSCLE  AND  NERVE 
The  two  commonest  forms  of  electrical  stimuli  employed  are  (1)  the  make  and  break 
of  a  constant  current,  (2)  the  induction  currents  of  high  intensity  and  short  duration 
obtained  from  an  induction  coil.  « 

(1)  Constant  Current.  As  a  source  of  constant  current  a  Daniell's  cell  is  generally 
employed.  This  consists  of  an  outer  pot  containing  a  saturated  solution  of  copper 
sulphate,  in  which  is  immersed  a  copper  cylinder.  To  the  cylinder  at  the  top  a  binding 
screw  is  attached,  by  which  the  connection  of  the  copper  with  a  wire  terminal  is  effected. 
Within  the  copper  cylinder  is  a  second  pot.  of  porous  clay,  filled  with  dilute  sulphuric 
acid,  in  which  is  immersed  a  rod  of  amalgamated  zinc.  In  this  cell  the  zinc  is  the 
positive  and  the  copper  the  negative  element.  Hence  the  current  flows  (in  the  cell) 
from  zinc  to  copper,  and  if  the  binding  screws  of  the  two  elements  are  connected  by 
a  wire,  the  current  flows  in  the  wire  (outer  circuit)  from  copper  to  zinc,  thus  completing 
the  circuit.  Since  in  the  outer  circuit  the  current  flows  from  copper  to  zinc,  the  terminal 
attached  to  the  copper  is  called  the  positive  pole,  and  that  to  the  zinc  the  negative 
pole.  When  the  current  is  required  to  be  very  constant,  the  zinc  may  be  immersed 
in  a  saturated  solution  of  zinc  sulphate  instead  of  dilute  sulphuric  acid.  A  Daniell's 
cell,  though  very  constant,  gives  only  a  small  current,  owing  to  its  small  electromotive 
force  and  high  internal  resistance. 

When  a  stronger  current  is  required  it  is  best  to  use  a  storage  battery.      In  this, 


Fia.  42.     The  ramification 


EXCITATION  OF  MUSCLE  187 

when  charged,  the  two  elements  are  lead  and  lead  oxide,  Pb02.  It  has  the  advantage 
that  it  may  be  used  over  and  over  again,  being  recharged  through  a  resistance  from  the 
electrical  mains  when  it  has  run  down. 

Another  useful  type  of  cell  is  the  Leclanche  cell.  This  consists  of  a  glass  jar  con- 
taining a  solution  of  sal  ammoniac.  Into  this  dips  an  amalgamated  rod  of  zinc,  which 
is  the  positive  plate.  A  piece  of  gas  carbon  forms  the  negative  plate.  This  is  sur- 
rounded by  peroxide  of  manganese  (Mn02)  which  is  kept  in  contact  with  the  surface  of 
the  carbon  by  being  placed  in  a  porous  pot.  In  some  forms  of  Leclanche  the  manganese 
and  carbon  are  ground  up  together  and  pressed  into  a  cylinder  which  surrounds  the 
zinc  rod.  When  the  cell  is  on  open  circuit — that  is,  when  the  terminals  are  not  con- 
nected and  no  current  is  passing — very  little  action  takes  place  ;  but  when  the  circuit 
is  closed  and  the  current  passes,  the  zinc  dissolves  in  the  sal  ammoniac,  forming  a  double 
chloride  of  zinc  and  ammonia,  while  ammonia  gas  and  hydrogen  are  liberated  at  the 
carbon  pole.  The  nascent  hydrogen  reduces  the  peroxide  of  manganese  and  so  polarisa- 
tion is  prevented.  On  account  of  its  great  solubility  in  water  the  ammonia  has  no 
polarising  action.  The  Leclanche  is  a  convenient  form  of  cell,  as  when  once  set  up  it 
requires  a  minimum  of  attention.  If  it  is  worked  through  a  considerable  resistance, 
it  will  keep  in  order  for  some  time,  particularly  if  the  work  is  intermittent ;  but  if  it  is 
used  with  a  small  resistance  in  circuit  it  polarises  very  rapidly.  The  E.M.F.  of  one 
Leclanche  cell  is  l-4  volt  in  the  external  circuit.  The  positive  current  is  conventionally 
said  to  run  from  the  zinc  to  the  carbon  in  the  cell,  and  from  the  carbon  to  the  zinc 
in  t  he  circuit  outside.  The  wire  attached  to  the  carbon  is  the  positive  pole,  that  to  the 
zinc  the  negative  pole.  Dry  cells  are  usually  Leclanche  cells,  in  which  the  solution  of 
sal  ammoniac  is  prevented  from  spilling  by  absorption  with  sawdust  or  plaster  of  Paris. 
The  E.M.F.  is  the  same  as  the  Leclanche,  but  they  polarise  much  more  readily. 

If  the  poles  of  a  Daniell's  cell  be  connected  by  wires  with  a  nerve  or  muscle  of  a 
nerve-muscle  preparation  (as  in  Fig.  43),  the  current  will  flow  from  copper  to  the  nerve 
at  a,  and  along  the  nerve  from  a  to  K. 
At  K  the  current  will  leave  the  nerve  to 
flow  to  the  zinc  of  the  battery,  so  com- 
pleting the  circuit.  The  point  at  which 
the  current  enters  the  nerve  {i.e.  the 
point  of  the  nerve  connected  with  the 
positive  pole  of  the  battery)  is  called  the 
anode,  and  the  point  at  which  the  current 
leaves  the  nerve  is  called  the  cathode.  The 
wires  by  which  the  current  is  conducted 
to  and  from  the  nerve  are  called  the  electrodes.  As  electrodes  we  generally  employ 
two  platinum  wires  mounted  together  on  a  piece  of  vulcanite. 

For  the  purpose  of  making  or  breaking  the  current  at  will,  various  forms  of  keys 
are  employed.  The  ordinary  make  and  break  key  consists  of  a  hinged  wire  dipping 
into  a  mercury  cup.  When  the  wire  is  depressed  so  that  it  dips  into  the  mercury, 
the  circuit  is  complete.  On  raising  the  wire  by  means  of  the  handle,  the  circuit  is 
broken. 

Du  Bois  Reymond's  key  consists  of  two  pieces  of  brass,  each  of  which  has  two  bind- 
ing screws  for  the  attachment  of  wires.  These  are  connected  by  a  third  piece,  or 
bridge,  which  is  jointed  to  one  of  the  two  side  bits,  so  that  it  may  be  raised  or  lowered 
at  pleasure  {v.  Fig.  44).  It  may  be  used  either  as  a  simple  make-and-break  key,  or, 
as  is  more  usual,  as  a  short-circuiting  key.  In  the  first  case  one  brass  bank  is  attached 
to  one  terminal,  the  other  to  the  other  terminal.  If  the  bridge  be  now  lowered,  the 
connection  is  made  and  the  current  passes.  If  the  bridge  be  raised,  the  current  is 
broken.  Fig.  44  a  and  B  shows  the  way  in  which  the  key  is  arranged  for  short-circuit- 
ing. It  will  be  seen  that  four  wires  are  attached  to  the  key  ;  two  going  to  the  battery, 
and  two  we  may  suppose  going  to  a  nerve.  When  the  bridge  is  down,  as  in  Fig.  44  A, 
the  current  from  the  cell  on  coming  to  the  key  has  a  choice  of  two  routes.  It  may  either 
go  through  the  brass  bridge,  or  through  the  "other  wires  and  nerve.     The  resistance  of 


J! 


PHYSIOLOGY 


I  lie  nerve  however  is  about  100,000  ohms,  whereas  that  of  the  bridge  is  not  the  thou- 
sandth part  of  an  ohm.  When  a  current  divides,  the  amount  of  current  that  goes  along 
any  branch  is  inversely  proportional  to  the  resistance.  Here  the  resistance  in  the  nerve- 
circuit  is  practically  infinite  compared  with  that  in  the  brass  bridge,  and  so  all  the 
A  B 


Fig.  44.     Du  Bois  key.  closed. 


Du  Bois  key.  open. 

We  say  then  that  the 


current  goes  through  the  bridge  and  none  through  the  nerve. 
current  is  shorl-circuitnl. 

It  is  often  necessary  to  reverse  the  direction  of  a  current  through  a  nerve-muscle 
preparation  or  a  galvanometer  in  the  course  of  an  experiment.  For  this  purpose 
Polil's  reverser  may  be  used.  It  consists  of  a  slab  of  ebonite  or  paraffin  or  other  in- 
sulating material,  in  which  are  six  small  holes  filled  with  mercury.  A  binding  screw  is 
in  connection  with  the  mercury  in  each  of  these  holes.  Two  cross-wires  (not  in  contact 
with  one  another)  join  two  sets  of  pools  together,  as  shown  in  Fig.  45.  A  cradle  con- 
sisting of  two  wires  joined  by  an  insulating  handle  carries  two  arcs  of  wire  by  which 
the  pools  at  a  and  b  may  be  put  into  connection  with  either  x  and  y,  or  the  corresponding 

pools  on  the  opposite  side.  It  will  be  seen 
that  with  the  cradle  tipped  to  one  side,  as  in 
Fig.  45  a,  the  current  from  the  battery  enters 
the  reverser  at  a  ;  this  proceeds  up  the  wire 
of  the  cradle,  down  towards  the  right,  then 
along  the  cross-wire  to  the  pool  at  x.  x  is 
therefore  the  anode,  and  y  the  cathode.  In 
Fig.  45  B  the  cradle  has  been  swung  over  to 
the  other  side.  Here  the  cross-wires  are  not 
used  at  all  by  the  current,  which  passes  from  o 
up  the  sides  and  down  the  curved  wire  to  y. 
In  this  case  y  is  now  the  anode  and  x  the 
cathode,  and  the  direction  of  the  current 
through  the  circuit  connected  with  X  and  y  is 
reversed.  By  taking  out  the  cross-wires, 
Polil's  reverser  may  be  used  as  a  simple 
switch,  by  which  the  current  may  be  led  into 
two  different  circuits  in  turn. 

With  this  form  of  reverser  difficulty  is  often 
experienced  owing  to  dirt  accumulating  on  the 
mercury  and  forming  an  insulating  layer  be- 
tween it  and  the  binding  screw  or  copper 
wire.  Several  improved  forms  of  reverser 
are  now  made  where  the  mercury  poles  are  replaced  by  brass  banks,  and  these  are 
generally  to  be  preferred  in  practice. 

(2)  Induced  Currents.  In  using  these  the  muscle  or  nerve  is  stimulated  by  the 
current  of  momentary  duration  produced  in  the  secondary  circuit  of  an  induction-coil 
by  the  make  or  break  of  a  constant  current  in  the  primary. 

The  construction  of  the  induction-coil  or  inductorium  is  founded  on  the  fact  that  if 
a  coil  of  wire  in  connection  with  a  galvanometer  be  placed  close  to  (but  insulated  from) 


Fig.  45.     Diagram  of  Pohl's  reverser. 


EXCITATION  OF  MUSCLE 


189 


another  coil  through  which  a  current  may  be  led  from  a  battery,  it  is  found  that  on 
make  and  break  of  the  current  of  the  second  coil  a  momentary  current  Is  induced  in  the 
first.     The  induced  current  on  make  is  in  the  reverse  direction,  that  on  break  in  the 
same  direction  as  the  primary  current.     The  electromotive  force  of  the  induced  current 
is  proportional  to  the  number  of  turns  of  wire  in  the  coils.     The  induction-coil  consists 
of  two  coils,  each  containing   many 
turns  of  wire.     The  smaller  coil  {nr, 
Fig.  46),  consisting  of  a  few  turns  of 
comparatively  thick  wire,  is  the  pri- 
mary coil,  and  is  put  into    connec- 
tion with  a  battery.     It  has  within 
it  a  core  of  soft   iron  wires,  which 
has    the     effect    of    attracting   the 
lines  of  force,   concentrating   them, 
and  so  increasing  its   power  of   in- 
ducing  secondary   currents.       The 
secondary  coil.  r2,  of  a  large  num- 
ber   of    turns   of    very   thin    wire, 
is  arranged  so  as  to  shde  over  the 
primary  ooil.     It  is   provided  with 
two   terminals,  which  may  be  con- 
nected   with    the    nerve     or    other  Fl0  46      Diagram  of  inductorium.     R[,     primary: 
tissue  that   we   wish   to   stimulate.      e2,  secondary  coil,  m,  electro-magnet  of  Wagner's 
Since  the  electromotive  force  of  the      hammer,     w,  Helmholtz's  side  wire. 
induced  current  is  proportional  to 

the  number  of  turns  of  wire,  it  is  evident  that  the  electromotive  force  of  the  current 
delivered  by  the  induction  coil  may  be  many  thousand  times  that  of  the  battery  cur- 
rent flowing  through  the  primary  coil.  The  induced  currents  increase  rapidly  in 
strength  as  the  coils  are  approached  to  one  another ;  the  strength  of  these  therefore 
may  be  regulated  by  shoving  the  secondary  up  to  or  away  from  the  primary  coil. 

A  short-circuiting  key  is  always  placed  between  the  secondary  coil  and  the  nerve 
to  be  stimulated.  If  only  single  induction  shocks  are  to  be  used,  a  make-and-break 
key  is  put  in  the  primary  battery  circuit,  and  the  two  wires  from  the  battery  and  key- 
are  attached  to  the  two  top  screws  of  the  primary  coil  (c  and  d.  Pig.  46).  It  is  then 
found  that  the  shock  given  by  the  induced  current  on  break  of  the  primary  current 
is  much  stronger  than  that  on  make. 

In  endeavouring  to  explain  this  difference  in  the  intensity  of  the  make-and-break 
induction  shocks,  it  must  be  remembered  that  the  intensity  of  the  momentary  current 
induced  in  the  secondary  coil  at  make  or  break  of  the  primary  current  is  proportional 
il )  to  the  number  of  turns  of  wire  in  each  coil ;  (2)  inversely  to  the  mean  distance  between 
the  coils  (i.e.  the  nearer  the  coils,  the  stronger  the  induced  current)  ;  (3)  to  the  rate  of 
change  in  strength  of  the  primary  current.  Now,  when  a  current  is  made  through  the 
primary  coil,  induction  takes  place,  not  only  between  primary  and  secondary  coils, 
hut  also  between  the  individual  turns  of  the  primary  coil  itself.  This  current  of  self- 
induction,  being  opposed  in  direction  to  the  battery  current,  hinders  and  delays  the 
attainment  by  the  latter  of  its  full  strength,  and  so  slows  the  rate  of  change  of  current 
in  the  primary  coil.  Hence  the  intensity  of  the  momentary  current  induced  in  the 
secondary  coil  is  less  than  it  would  have  been  without  the  retarding  effect  of  self-induc- 
tion. At  break  of  the  current,  an  extra  current  is  also  produced  in  the  primary  coil 
in  the  same  direction  as  the  battery  current,  and  therefore  tending  to  reduce  the  rate 
of  change  of  the  current  from  full  strength  to  nothing.  In  this  case  however  the 
primary  circuit  being  broken,  the  current  of  self-induction  cannot  pass  without  jumping 
the  great  resistance  offered  by  the  air,  so  that  its  retarding  effect  on  the  rate  of  dis- 
appearance of  the  primary  current  may  be  practically  disregarded.  In  Fig.  47  the  line, 
a,  6,  c,  d,  will  represent  the  changes  occurring  in  the  primary  current  at  make  and 
break,  a  b  corresponding  to  the  make  and  c  d  to  the  break.     The  lower  line  represents 


190 


PHYSIOLOGY 


the  momentary  currents  induced  in  the  secondary  circuit,  m  being  the  current  of  low 
intensity  and  long  duration  produced  by  the  make,  and  \  the  shock  of  high  intensity 
and  short  duration  caused  by  the  sharp  break  of  the  primary  current. 

When  we  desire  to  use  faradic  stimulation — that  is,  secondary  induced  shocks 
rapidly  reputed  .VI  to  100  times  a  second — -we  make  use  of  the  apparatus  attached 

to  the  coil,  known  as  Wagner's 
hammer  (Figs.  48a  and  48b). 
In  this  case  the  wires  from  the 
battery  are  connected  to  the 
two  lower  screws  (a  and  b,  Fig. 
46).  Fig.  48a  shows  the  direc- 
tion of  the  current  when  Wag- 
ner's hammer  is  used.  The  cur- 
rent enters  at  a.  runs  up  the 
pillar  and  along  the  spring  to  the 
screw  x.  Here  it  passes  up 
through  the  screw,  and  through 
the  primary  coil  Br  From  the 
primary  coil  it  passes  up  the 
small  coil  m,  and  from  this  to 
the  terminal  h  and  back  to  the 
battery.  But  in  this  course 
the  coil  m  is  converted  into  an 
electro-magnet.  The  hammer  h 
attached  to  the  spring  is  attracted  down,  and  so  the  spring  is  drawn  away  from  the 
screw  x,  and  the  current  is  therefore  broken.  The  break  of  the  current  destroys  the 
magnetic  power  of  the  coil,  the  spring  jumps  up  again  and  once  more  makes  circuit 
with  the  screw  x,  only  to  be  drawn  down  again  directly  this  occurs.  In  this  way  the 
spring  is  kept  vibrating,  and  the  primary  circuit  is  continually  made  and  broken,  with 
the  production  at  each  make-and-break  of  an  induced  current  in  the  secondary  coil. 

It  is  evident  that,  when  the  primary  current  is  made  and  broken  fifty  times  in  the 
second,  there  will  be  a  hundred  momentary  currents  produced  during  the  same  period 
in  the  secondary  coil.     Every  alternate  one  of  these  produced  by  the  break  of  current 

-  T 


^7- 


Fig.  47 


T 


Uq 


Fig.  48a.  Diagram  showing  course  of 
current  in  inductorium  when  Wagner's 
hammer  is  used. 


Fio.  48b.  Diagram  showing  course  of 
current  when  the  Helmholtz  side  wire 
is  used. 


in  the  primary  will  be  much  stronger  than  the  intervening  currents  produced  by  the 
make.  In  order  to  equalise  make  and  break  induction-shocks,  so  that  a  regular  series 
of  momentary  currents  of  nearly  equal  intensity  may  be  produced,  the  arrangement 
known  as  Helmholtz's  is  used.  In  this  arrangement  the  side  wire  w,  shown  in  Fig.  46, 
and  diagrammatically  in  Fig.  48b,  is  used  to  connect  the  binding  screw  o  with  the 
binding  screw  c  at  the  top  of  the  coil.  The  screw  x  is  raised,  so  as  not  to  touch  the 
spring,  and  the  lower  screw  y  is  moved  up  till  it  comes  nearly  in  contact  with  the  under 


EXCITATION  OF  MUSCLE 


191 


surface  of  the  spring.  If  we  consider  the  direction  of  the  current  now,  we  see  that 
it  enters  as  before  at  the  terminal,  travels  up  the  Helmholtz  wire  w  to  the  screw  c, 
thence  through  the  primary  coil  Rx,  then  through  the  coil  to  of  the  Wagner's  hammer, 
and  so  back  to  the  battery.  The  coil  to,  thus  becoming  an  electro-magnet,  draws 
down  the  hammer  h.  In  this  act  the  under  surface  of  the  spring  comes  in  contact  with 
the  screw  y.  The  current  then  has  a  choice  of  two  ways.  It  may  either  go  through 
the  coil  as  before,  or  take  a  short  cut  from  the  terminal  a,  up  the  pillar,  along  the  spring, 
through  the  screw  y,  and  down  to  the  terminal  b  back  to  the  battery.  As  the  resistance 
of  this  latter  route  is  very  small  compared  with  the  resistance  of  the  primary 
coil,  &c,  the  greater  part  of  the  current  takes  this  way.  The  infinitesimal 
current  which  now  passes  through  the  coil  of  Wagner's  arrangement  is  insufficient  to 
magnetise  this,  and  the  hammer  springs  up  again  ;  thus  the  process  is  restarted,  and  the 
•  spring  vibrates  rhythmically.  With  this  arrangement  the  primary  current  is  never 
broken,  but  only  short-circuited,  and  so  diminished  very  largely.  Hence  the  retarding 
influence  of  self-induction  is  as  potent  with  break  as  with  make  of  the  current,  and  the 
effects  on  the  secondary  coil  in  the  two  cases  are  approximately  equal.  In  Fig.  47  ce 
represents  the  change  in  the  primary  current  when  the  current  is  short-circuited  instead 
of  being  broken,  and  6  represents  the  effect  produced  in  the  secondary  coil.  It  will  be 
seen  that  the  currents  to  and  b  are  practically  identical  in  intensity  and  duration. 

When  the  induction-coil  is  used  for  stimulating,  it  is  usual  to  graduate  the  strength 
of  the  shock  administered  to  the  excitable  tissue  by  moving  the  secondary  coil  nearer 
to  or  further  away  from  the  primary  coil.  It  must  be  remembered  that  the  strength 
of  the  induced  current  does  not  vary  in  numerical  proportion  with  the  distance  of  the 
two  coils  from  one  another.  If  one  coil  is  some  distance,  say,  20  cms.  from  the  primary 
coil,  the  induced  current  produced  by  make  or  break  of  the  primary  current  is  very 
small,  and  on  moving  the  secondary  from  20  up  to  10  cms.  the  increase  in  strength  of 
the  current  will  not  bo  very  rapid.  The  increase  will  however  become  more  and  more 
rapid  as  the  two  coils  are  brought  closer  together.  Usiog  the  same  strength  of  current 
in  the  primary  coil  and  the  same  resistance  in  the  secondary  coil,  we  can  say  that  the 
make  or  break  current  will  be  uniform  so  long  as  the  distance  of  the  coils  remains 
constant.  We  are  not  able  however  to  say  by  how  much  the  current  will  increase 
as  the  secondary  coil  is  moved,  say,  from  11  to  10  cms.  distant  from  the  primary  coil. 
If  it  is  required  to  know  the  exact  increment  in  the  exciting  current  which  is  used,  it 
is  necessary  to  graduate  the  induction-coil  by  sending  the  induction  shocks,  obtained 
at  different  distances  of  secondary  from  primary  coil,  through  a  ballistic  galvanometer. 

Another  method  which  may  be  adopted  for  the  excitation  of  muscle  or  nerve  is  the 
discharge  of  a  condenser.  The  advantage  of  this  method  is  that  we  can  determine 
not  only  the  amount  of  electricity  discharged  through 
the  preparation,  but  the  actual  energy  employed.  If 
two  plates  of  metal  separated  from  one  another  by  a  thin 
insulating  layer  of  dielectric  such  as  air,  glass,  mica,  or 
paraffined  paper,  be  connected  with  the  two  poles  of  a 
battery,  each  plate  acquires  the  potential  of  the  pole  of 
the  battery  with  which  it  is  connected,  and  receives 
therefrom  a  charge  of  electricity  (positive  or  negative). 
If  the  connections  be  broken  the  two  plates  retain  their 
charge.  If  now  they  be  connected  by  a  wire  they 
discharge  through  the  wire,  and  if  a  nerve  be  inserted  in 
the  course  of  the  wire,  it  may  be  excited  by  the  discharge. 

The  amount  of  electricity  that  may  be  stored  up  in 
tills  way  will  depend  on  the  extent  of  .the  plates  and 
their  proximity  to  one  another,  as  well  as  on  the  e.m.f.  Fir..  49.  Diagram  to  show 
of  the  charging  battery.  In  order  to  get  great  extent  t,le  mo,,e  of  construction  of 
of  surface,   a   condenser  is   built  up,  as  in  the  diagram  '  '     ' 

(Fig.  49),  of  a  very  large  number-  of  plates  of  tinfoil, 
separated  by  discs  of  mica  or  paraffined  paper.   Alternate  discs  are  connected  together  : 


L92  PHYSIOLOGY 

thus,  1,  3,  5  are  connected  to  one  polo,  while  2,  -I,  6  are  connected  to  the  other. 
The  rheocord  is  used  to  modify  the  amount  or  strength  of  current  flowing  through 
a  preparation.  One  form  of  it  is  represented  in  fig.  50.  A  constant  source  of  current 
at  B  causes  a  flow  of  electricity  from  n  to  6  through  a  straight  wire.  As  the  resistance 
of  this  wire  is  the  same  throughout  its  length,  the  fall  of  potential  from  a  to  6  must 
be  constant.  The  nerve,  or  w  li.it. >\  rr  preparation  is  used,  is  connected  with  the  straight 
wire  at.  two  points,  a<  »  and  at  c,  by  means  of  a  sliding  eontaot  or  rider.  Supposing 
thai  there  is  an  eleotromotii  e  difference  <>f  one  volt  between  </  and  A,  it  is  evident  that 
if  c  is  pushed  close  to  b,  the  e.m.f.  acting  on  the  nerve  will  be  also  one  volt.      The  e.m.f. 

however  may  be  made  as  small  as  we  like 
by  sliding  c  nearer  to  a.  Thus  it  nli  is  one 
metre,  and  there  is  a.  difference  of  one  volt 
between  the  two  <'iids,  then  if  c  be  one 
centimetre  from  n,  the  e.m.f.  acting  on 
the  nerve  will  be  ,  ,', ,,  volt.  Thus  we 
alter  the  current  passing  through  the 
nerve  by  altering  the  e.m.f.  which  drives 
the  current. 

If  a  weak  current  from  a  Daniell's 

cell  (or  any  other  form  of  battery; 
lie  passed  through  a  muscle  or  any  part  of  its  nerve,  at  the  make  of  the 
current  the  muscle  gives  a  single  sharp  contraction — a  muscle  twitch.  In 
this  contraction  the  whole  of  the  muscle  fibres  may  be  involved.  During  the 
passage  of  the  current  no  effect  is  apparently  produced  and  the  muscle  seems 
to  be  quiescent,  though  on  careful  observation  we  may  see  that  there  is  a 
state  of  continued  contraction  limited  to  the  immediate  neighbourhood  of 
the  cathode,  which  lasts  as  long  as  the  current  is  passing  through  the  muscle, 
and  is  not  propagated  to  the  rest  of  the  muscle.  If  the  current  be  now 
broken,  the  muscle  may  remain  epiiescent.  If  however  the  current  is  above 
a  certain  strength,  the  muscle  responds  to  the  break  of  the  current  with 
another  single  rapid  contraction.  With  a  current  of  moderate  strength  we 
may  get  a  contraction  both  at  make  and  break  of  the  current,  but  the  make- 
contraction  may  be  stronger  than  the  break  contraction.  Thus  stimulation 
is  caused  by  the  make  and  break  of  a  constant  current,  the  make  stimulus 
being  more  effective  than  the  break  stimulus.  If  the  duration  of  the  passage 
of  the  current  is  sufficiently  short,  no  contraction  is  produced  at  the  break 
of  the  current,  however  strong  this  may  be.  The  same  phenomenon  of  a 
single  twitch  may  be  evoked  by  the  passage  of  an  induction  shock.  This 
is  the  current  of  momentary  duration  produced  in  the  second  circuit  of 
an  induction-coil  by  the  make  or  break  of  a  constant  current  in  the  primary. 
Using  this  mode  of  stimulus,  it  is  found  that  the  contraction  on  break  of 
the  primary  current  is  much  stronger  than  that  on  make. 

It  must  not  be  imagined  however  that  there  is  any  contradiction  between 
this  and  the  fact  that  the  make  of  a  constant  current  is  a  stronger  stimulus 
than  the  break.  When  we  put  a  muscle  in  the  secondary  circuit  and  make 
a  current  in  the  primary,  there  is  a  current  of  momentary  duration  induced 
in  the  secondary,  so  that  there  is  a  current  made  mid  broken  through  the 
muscle  ;  and  the  same  thing  takes  place  again  when  the  primary  circuit 
is  broken.     It  has  been  shown  that,  when  we  use  currents  of  such  short 


EXCITATION  OF  MUSCLE  193 

duration,  the  break  stimulus  is  ineffective  ;  so  in  both  cases,  whether 
we  make  or  break  the  current  in  the  primary  circuit,  we  are  dealing  with 
a  make  stimulus  in  the  muscle.  The  difference  in  the  efficacy  of  make  and 
break  induction  shocks  is  purely  physical,  and  depends  on  the  fact  that  the 
current  induced  in  the  secondary  coil  on  make  is  of  slower  rise  and  smaller 
potential  than  that  produced  at  break. 

In  using  cither  of  these  modes  of  stimulation  we  find  that  there  is  a  certain  intensity 
which  the  stimulating  current  must  possess  in  order  that  any  effect  shall  be  produced. 
Any  strength  of  stimulus  below  this  is  known  as  a  subminimal  stimulus.  A  minimal 
stimulus  (sometimes  known  as  liminal  or  threshold  stimulus)  is  the  weakest  stimulus 
that  will  produce  any  result,  i.e.  in  muscle  a  contraction.  A  maximal  stimulus  is 
one  that  produces  the  strongest  contraction  a  muscle  is  capable  of  under  the  effects 
of  a  single  stimulus.  A  svbmaximal  stimulus  is  any  strength  of  stimulus  between  these 
two  extremes. 


SECTION   III 

THE   MECHANICAL  CHANGES   THAT    A   MUSCLE 
UNDERGOES   WHEN   IT   CONTRACTS 

If  a  skeletal  muscle,  such  as  the  gastrocnemius,  be  stimulated  either  directly 
or  by  the  intermediation  of  its  nerve  by  any  of  the  means  mentioned  in  the 
foregoing  chapter,  it  responds  by  a  single  short  sharp  contraction,  followed 
immediately  by  a  relaxation.  The  volume  of  the  muscle  does  not  alter  in  the 
slightest  degree,  but  each  muscle-fibre  and  the  whole  muscle  become  shorter 
and  thicker.  At  the  same  time,  if  a  weight  be  tied  on  to  the  tendon  of  the 
muscle,  the  muscle  during  contraction  may  raise  the  weight  and  thus  perform 
mechanical  work.  In  order  to  determine  the  time  relations  of  the  simple 
muscle  contraction  or  the  muscle-twitch,  and  to  study  its  conditions,  it  is 
necessary  to  employ  the  graphic  method^  so  as  to  obtain  a  record  of  the 
changes  in  shape  of  the  muscle  during  contraction.  We  may  use  the  graphic 
method  either  for  recording  the  changes  in  shape  or  for  registering  changes  in 
tension  of  a  muscle  which  is  prevented  from  contracting. 

In  order  to  record  the  contraction  of  the  frog's  gastrocnemius,  the  muscle  is  excised 
together  with  a  portion  of  the  femur  to  which  it  is  attached,  and  the  whole  length 
of  the  sciatic  nerve  from  its  origin  in  the  spinal  canal  to  its  insertion  into  the  muscle. 
The  femur,  to  which  the  gastrocnemius  is  attached,  is  clamped  firmly,  and  the  tendo 
Achillis  attached  by  a  thread  to  a  light  lever,  free  to  move  round  an  axis  at  one  end. 
The  point  of  this  lever  is  armed  with  a  bristle  (anything  that  is  stiff  and  pointed  will 
do),  which  just  touches  the  blackened  surface  of  a  piece  of  glazed  paper.  This  paper 
is  stretched  round  a  cylinder  (drum)  which  can  be  made  to  rotate  at  any  constant 
speed  required.  If  the  drum  is  moving,  the  point  of  the  bristle  draws  a  horizontal 
white  line  on  the  smoked  paper. 

If  a  single  induction  shock  be  sent  through  the  nerve  of  the  preparation  the  lever 
is  jerked  up,  falling  again  almost  directly,  and  a  curve  is  drawn  like  that  shown  in 
Fig.  52.     A  similar  curve  is  obtained  if  the  muscle  be  stimulated  directly. 

In   all  such  graphic  records  we   should   have  also — 

(1)  A  time  record.  This  is  furnished  by  means  of  a  small  electro-magnet,  armed  with 
a  pointed  lever  writing  on  the  smoked  surface.  This  electro-magnet  (time  marker  or 
signal)  is  made  to  vibrate  100  times  a  second  (more  or  less  as  may  be  required)  by 
putting  it  in  a  circuit  which  is  made  and  broken  100  times  a  second  by  means  of  a 
tuning-fork  vibrating  at  that  rate.  The  tuning-fork  is  maintained  in  vibration  in  the 
same  way  as  the  Wagner's  hammer  of  an  induction-coil. 

(2)  A  record  of  the  exact  point  at  which  the  nerve  or  muscle  is  stimulated.  This  may 
be  obtained  in  two  ways  : 

(a)  When  using  the  pendulum  or  trigger  myograph,  in  both  of  which  the  recording 
surface  is  a  smoked  flat  surface  on  a  glass  plate,  this  flatter  is  so  arranged  that  it  knocks 

194 


THE  MECHANICAL  CHANGES   OF  MUSCLE' 


195 


over  a  key  as  it  shoots  across,  and  so  breaks  the  primary  circuit  and  excites  the  nerve 
or  muscle  of  the  preparation.  As  we  know  the  exact  point  that  the  plate  reaches 
when  it  knocks  over  the  key,  we  can  mark  on  the  contraction  curve  the  exact  moment 
at  which  stimulation  took  place. 

(b)  If  we  wish  to  make  and  break  the  primary  circuit  at  will  by  means  of  a  key,  a 
small  electro-magnetic  signal,  interposed  in  the  circuit,  is  arranged  to  write  on  the 
revolving  drum,  and  so  mark  the  point  of  stimulation. 


Fia.  51.     Arrangement,  of  apparatus  for  recording  simple  muscle-twitch. 

In  the  figure  (Fig.  52)  the  upper  line  is  the  curve  drawn  by  the  lever  of  the  muscle 
as  it  contracts  ;  the  small  upright  line  shows  the  point  at  which  the  muscle  was  stimu- 
lated ;  and  the  second  line  is  the  tracing  of  the  chronograph,  every  vibration  repre- 
senting ,j4   of  a  second. 

In  the  pendulum  myograph  (Fig.  53)  a  smoked  glass  plate  is  carried  on  a  heavy 
iron  pendulum.     At  each  side  the  pendulum  is  armed  with  a  catch,  which  fits  on  to 


Fig.  52.     Curve  of  single  muscle-twitch  taken  on  a  rapidly  moving  surface 
(pendulum  myograph).     (Yeo.) 

other  catches  at  the  side  of  the  triangular  box,  from  the  apex  of  which  the  pendulum 
is  suspended.  At  its  lower  part  the  pendulum  carries  a  projecting  piece  which  can 
knock  over  the  '  kick-over '  key  k,  thus  breaking  a  circuit  in  which  is  included  the 
primary  coil  of  an  induction-coil.  The  lever  attached  to  the  muscle  is  arranged  so  as 
to  write  lightly  on  the  glass  plate.  Everything  being  ready,  and  the  key  k  closed,  the 
pendulum  is  raised  to  A,  the  catch  A  is  then  released,  arid  the  pendulum  falls  at  an 
ever-accelerating  rate  and  then  rises  again,  gradually  slowing  off  until  it  is  caught 
again  at  B.  As  it  passes  by  the  key  it  breaks  the  circuit.  A  break  induction  shock 
is  sent  into  the  muscle  or  nerve,  which  contracts,  and  a  curve  is  obtained  similar  to  that 
shown  in  Fig.  52.  Since  the  rate  of  the  pendulum  is  constantly  varying  throughout  its 
course,  it  is  necessary  to  have  a  tuning-fork,  or  time-marker  actuated  electrically  by  a 
tuning-fork,  writing  just  below  the  muscle-lever. 

In  the  spring  myograph,  otherwise  known  as  the  trigger  or  shooter  myograph 
(Fig.  54),  a  smoked  glass  plate  is  also  used.  "  The  frame  supporting  the  glass  plate 
slides  on  two  horizontal  steel  wires.  To  make  the  instrument  ready  for  use,  the  frame 
is  moved  to  one  side,  which  compresses  a  short  spring.  When  the  catch  holding  it  in 
this  position  is  released  by  the  trigger,  the  spring,  which  only  acts  for  a  short  space, 


1% 


PHYSIOLOGY 


gives  the  frame  and  the  glass  plate  a  rapid  horizontal  motion;    and  the  momentum 
carries  the  glass  plate  through  the  rest  of  the  distance,  till  stopped  hy  the  huffers.     Tho 


Fig.  53.     Simple  form  of  pendulum  myograph. 

velocity  during  this  time  is  nearly  constant,  as  the  friction  of  the  guides  is  small.  Two 
keys  are  knocked  over  by  pins  on  the  frame  and  break  electric  circuits.  The  relative 
positions  at  which  the  circuits  are  broken  can  be  altered  by  a  convenient  adjustment. 


(7T\ 


Fig.  54.     Diagram  of  spring  myograph,  or  '  shooter.' 

A  tuning-fork  vibrating  abont  100  per  second  fixed  to  the  base  of  the  instrument  marks 
the  time  ;  its  prongs  are  sprung  apart  by  a  block  between  their  ends,  and  the  same 
action  which  releases  the  glass  plate  also  frees  the  fork  by  removing  the  block  and  allows 
it  to  vibrate  ;  a  writing  style  then  draws  a  sinuous  line  on  the  smoked  surface  of  the 
moving  glass  plate.  A  muscle  lever  with  a  scale-pan  attached  also  forms  part  of  the 
instrument." 

The  record  obtained  in   either  of  these  ways  may,  in  consequence  of  instrumental 


THE  MECHANICAL  CHANGES  OF  MUSCLE 


197 


inertia,  be  a  very  inaccurate  reproduction  of  the  true  events  occurring  in  the  muscle 
itself.  When  the  muscle  begins  to  contract  it  imparts  a  very  rapid  movement  to  the 
lr\  ei .  which  therefore  tends  to  overshoot  the  mark  and  deform  the  curve.  This  source 
of  error  may  be  almost  avoided  by  making  the  lever  as  light  as  possible,  and  hanging  the 
extending  weight  in  close  proximity  to  the  axle  of  the  lever,  as  shown  in  Fig.  55.  Since 
the  energy  of  a  moving  mass  is  proportional  to  the  square  of  the  velocity  (  =  £  rai>2,) 
and  the  tension  due  to  the  weight  as  well  as  the  velocity  on  contraction  is  directly 
proportional  to  the  distance  of  the  weight  from  the  axis,  it  follows  that  it  is  better  to 


Fig.  55.  151ix  apparatus  for  recording  isometric  and  isotonic  curves  synchronically.  (Miss 
Buchanan.)  p,  the  steel  C3'lindrical  support  with  jointed  steel  arm  to  bear  the  isotonic 
lever  I,  which  consists  of  a  strip  of  bamboo  with  an  aluminium  tip.  t,  the  isometric 
lever,  also  of  bamboo,  except  for  a  short  metal  part  (',  in  which  are  holes  for  fixing  the 
muscle.  The  two  wires  from  an  induction  coil  are  brought,  one  to  x,  which  is  in  con- 
nection with  the  support  and  hence  with  the  metal  bar  t',  the  other  to  y,  which  is  insulated 
from  the  support  but  connected  by  a  copper  wire  with  a  thin  piece  of  copper  surrounding 
the  isotonic  lever  at  the  point  where  the  muscle  is  attached  to  it.  CI,  clamp  for  fixing 
the  lower  end  of  the  muscle  when  an  isometric  curve  is  to  be  taken.  The  axis  of  the 
isotonic  lever  is  at  X,  close  to  which  is  hung  the  weight  of  50  grin. 

load  the  muscle  with  40  grams  1  milhmetre  from  the  axis  than  with  1  gram  40  milli- 
metres from  the  axis,  though  the  tension  put  on  the  muscle  will  be  the  same  in  both 

rases. 

In    tlie    first     ease    the    energy    of    the    moving    mass    will    be    proportional    to 

■_'li,  and  in  the  second  to  — _ — -  =  800,  and  it  is  this  energy  which  deter- 

2  2 

mines  the  overshooting  of  the  lever  and  the  deformation  of  the  curve.  Since  throughout 
the  contraction  in  the  latter  arrangement  the  lever  follows  the  muscle  in  its  movement, 
the  tension  on  the  muscle  remains  the  same  throughout,  and  the  method  is  therefore 
known  as  the  isotonic  method. 

It  is  of  importance  to  be  able  to  record  the  development  of  the  energy  (i.e.  the  ten- 
sion) of  the  active  muscle  apart  from  any  changes  in  its  length.  For  this  purpose  the 
muscle  is  allowed  to  contract  against  a  strong  spring,  the  movements  of  which  are 
magnified  by  means  of  a  very  long  lever.  Thus  the  shortening  of  the  muscle  is  almost 
entirely  prevented,  but  the  increase  in  its  tension  causes  a  minute  but  proportionate 
movement  of  the  spring,  which  is  recorded  by  means  of  the  lever.  Since  in  this  case 
the  length  or  measurement  of  the  muscle  remains  approximately  constant,  while  the 
tension  is  continually  varying  throughout  the  contraction,  it  is  known  as  the  isometric 
method.  Tin'  great  magnification  necessary  in  this  method  introduces  serious  sources  of 
error  ;  but  it  seems  that  if  all  due  precautions  be  taken  to  avoid  these  errors,  the  isometric 


PHYSIOLOGY 


curve  differs  very  little  in  form  from  the  isotonic,  displaying  only  a  somewhat  quicker 
development  of  energy  at  the  beginning  of  contraction.  It  is  better  to  eliminate 
the  lever  altogether  and  magnify  the  minute  movements  of  the  spring  by  attaching 
to  it  a  small  hinged  mirror  by  which  a  ray  of  light  is  reflected  through  a  slit  on  to  a 
travelling  photographic  plate.  Since  the  ray  of  light  has  no  inertia,  magnification 
of  the  movements  may  be  carried  to  any  extent  without  increasing  the  instrumental 
deformation  of  the  curve  (Fig.  56). 

A  simple  muscular  contraction  or  twitch,  such  as  that  in  Fig.  52, 
1  in  ill  need  by  a  momentary  stimulus,  consists  of  three  main  phases: 

(1)  A  phase  during  which  no  apparent  change  takes  place  in  the  muscle, 
or  at  any  rate  none  which  gives  rise  to  any  movement  of  the  lever.  This 
is  called  the  latent  'period. 


Fio.  50.     Myograph  for  optical  registration  of  muscular 
contraction.     (K.  Lttcas.) 

(2)  A  phase  of  shortening,  or  contraction. 

(3)  A  phase  of  relaxation,  or  return  to  the  original  length. 

The  small  curves  seen  after  the  main  curve  are  due  to  elastic  vibrations 
of  the  lever,  and  do  not  indicate  any  changes  occurring  in  the  muscle  itself. 
From  the  time-marking  below  the  tracing  we  see  that  the  latent  period 
occupies  about  yJ)Tr  second,  the  phase  of  shortening  TTt  ff,  and  the  relaxation 
t^q  second. 

Thus  a  single  muscle-twitch  is  completed  in  about  ^  second.  It  must 
be  remembered  however  that  this  number  is  only  approximate,  and  varies 
with  the  temperature  of  the  muscle  and  its  condition,  being  much  longer  in 
a  fatigued  muscle.  ■  Moreover  it  is  almost  impossible  to  avoid  some  deforma- 
tion of  the  curve  due  to  defects  of  the  recording  instruments  used.  Thus  the 
relative  period  during  which  no  mechanical  changes  are  taking  place  in 
the  muscle  must  always  be  shorter  than  is  apparent  from  a  curve  obtained 


THE  MECHANICAL  CHANGES   OF  MUSCLE 


199 


bv  the  foregoing  method.  The  elasticity  and  extensibility  of  the  muscle  must 
prolong  the  apparent  latent  period,  since  the  first  effect  of  contraction  of  any 
part  of  the  muscle  will  be  to  stretch  the  adjacent  part,  and  only  later  to 


Fig.  57.     Burdon  Sanderson's  method  for  photographic  record  of  muscle-twitch. 
The  exciting  shock  is  sent  into  the  muscle  by  the  wires  d  and  d'. 

move  the  tendon  to  which  the  lever  is  attached.  Thus  if  we  have  a  weight 
supported  by  a  rigid  wire,  and  suddenly  pull  the  upper  end  of  the  wire  so  as  to 
raise  the  weight,  the  latter  will  rise  instantaneously.  If  however  the 
weight  be  suspended  by  a  piece  of  elastic,  it  will  not  follow  the  pull  exactly, 
but  will  lag  behind,  the  first  part  of  the  pull  being  occupied  with  stretching 
the  india-rubber,  and  only 
when  this  is  stretched  to  a 
certain  degree  will  the  weight 
begin  to  rise.  The  same  re- 
tardation of  the  pull  would  be 
observed  if,  instead  of  india- 
rubber,  we  used  a  piece  of 
living  muscle. 

It  is  possible  to  obviate 
this  instrumental  inertia  by 
employing  solely  photographic 
methods  for  the  record  and 
magnification  of  the  muscle- 
twitch.  In  the  experiments 
of  Sanderson  and  Burch 
the  thickening  of  the  muscle 
at  the  point  stimulated  was 
recorded  graphically  by  photo- 
graphing the  movement  on  a  Fig.  58.  Photographic  record  of  muscle-twitch  . 
l-i.  fi?-  rt\  -U  l:„j  „l,;„i,  (B.  Sanderson.)  The  upper  curve  is  the  move- 
slit  (Fig.    57),   behind  which     ^ent  of  the  J^  the'middle  curve  the  9ignal 

was  a    moving  sensitive  plate.       showing  the  moment  of    excitation,  and  the  lower 

Thus  avoiding  all  instrumental  ™™Jd  that  °f  a  tuning-fork  vibrating  50°  time8 
inertia,   and    diminishing   the 

inertia  of  the  muscle  to  a  minimum,  the  mechanical  latent  period  was 
found  to  be  only(H>025  second  (Fig.  58).  This  figure  we  can  take  as  the 
average  latent  period  for  the  skeletal  muscle  of  the  frog  at  the  ordinary 
temperature  of  the  laboratory  (about  16°C.).     We  shall  have  occasion  later 


-I  Ml 


nnsioi,<>(;\ 


on  to  consider  the  changes  which  occur  in  the  muscle  between  the  application 
of  the  stimulus  and  the  moment  at  which  the  first  mechanical  change  makes 
its  appearance. 

The  relaxation  of  muscle  is  helped  by  a  moderate  load,  and  in  a  normal 
condition  is  complete.     It  is  not  active — that  is  to  say,  is  not  due  to  a  con- 


Fig.  50. 


V.   Krics'  apparatus  for  taking  'after-loading'  and   'arrested  con- 
traction curves.' 


traction  in  the  transverse  direction — but  is  a  passive  effect  of  extension  and 
elastic  rebound.  This  may  be  shown  by  allowing  a  muscle  to  contract  while 
floating  on  mercury.  The  subsequent  lengthening  on  relaxation  is  very 
incomplete. 

Even  with  the  most  careful  arrangements  for  securing  isotonicity  in  the 
record  of  the  contraction  there  is  probably  a  certain  amount  of  over-shoot 
of  the  lever  whenever,  as  at  high  temperatures,  the  contraction  is  sufficiently 
rapid.  The  effect  of  this  is  that  one  cannot  assume  the  existence  of  an  actual 
pull  on  the  lever  during  the 
whole  time  of  the  ascent  of  the 
latter.  We  can  therefore  speak 
of  a  period  during  which  there 
is  contractile  stress — that  is  to 
say,  when  the  muscle  is  actu- 
ally pulling  on  the  lever,  which 
will  occupy  only  a  part  of  the 
ascent  of  the  curve.  The  dura- 
tion of  this  period  of  contrac- 
tile stress  may  be  shown  by 
recording  what  is  known  as  '  arrested  '  contractions.  One  mechanism 
for    this   purpose    is  shown    in  the  figure    (Fig.    59).      The  stop    Su    is 


AAAAAAAAAAAAAAAAAAAAA 

.   60.     Curves  of  isotonic  and  arrested  contractions 
of  an  unloaded  muscle,     (Kaiser.) 


THE  MECHANICAL  CHANGES   OF  MUSCLE  201 

used  simply  for  after-  loading  the  muscle  so  that  the  weight  shall  not 
act  upon  the  muscle  until  it  begins  to  contract.  The  stop  So  may  be  regu- 
lated so  that  it  suddenly  checks  the  movement  of  the  lever  at  any  desired 
height  above  the  base  line.  We  may  thus  get  a  series  of  contractions  such 
as  those  shown  in  Fig.  60.  It  will  be  seen  that  at  the  points  x',  x",  and  x"' 
the  muscle  was  still  pulling  on  the  lever,  and  therefore  held  it  up  against 
the  stop.  At  the  point  X  the  arrested  twitch  returns  rapidly  to  the  base 
line,  showing  that  the  movement  of  the  lever  in  the  unarrested  curve  above 
this  point  was  due  to  the  inertia  of  the  moving  parts  and  not  to  the  actual  pull 
of  the  muscle.  In  this  case  the  period  of  contractile  stress  was  about  0'02 
seconds. 

THE  ENERGY  OF  CONTRACTION.  When  a  muscle  contracts  we  may 
conceive  of  it  as  converted  into  a  body  with  elastic  properties  other  than 
those  which  it  possesses  during  rest.  Directly  after  it  has  been  excited 
it  possesses  potential  energy  which  can  be  measured  by  the  isometric  method 
as  tension  and  which  will  degenerate  in  a  few  hundredths  of  a  second  into 
heat,  or  can  be  turned  into  work  by  allowing  the  muscle  to  shorten  and  to 
raise  a  weight,  as  in  the  isotonic  method  of  recording  muscular  contractions. 
Under  the  conditions  of  an  ordinary  physiological  experiment,  a  contracted 
muscle  loaded  only  by  a  light  lever  is  shorter  than  the  non-contracted, 
but  can  be  stretched  to  the  length  of  the  latter  by  a  certain  weight,  when 
it  will  be  in  a  condition  of  tension.  In  their  natural  position  in  the  body 
muscles  may  possess  any  length  between  extreme  shortening  and  extreme 
elongation  whether  they  are  in  a  resting  or  in  an  excited  condition.  Since 
the  relaxed  muscle  requires  only  a  minimal  force  to  extend  it  to  the  maximal 
length  possible  in  its  natural  relationships  in  the  body,  it  is  usual  to  speak 
of  the  different  lengths  of  an  excited  and  unexcited  muscle,  the  lengths  being 
in  this  case  those  which  are  impressed  on  the  muscle  by  a  minimal  load. 
When  we  measure  by  means  of  the  isometric  method  the  maximum  energy 
set  free  in  a  muscle  as  the  result  of  excitation,  we  find,  as  Blix  first  pointed 
out,  that  this  energy  depends  on  the  length  of  the  muscle  fibres  during 
the  period  of  contractile  stress  set  up  by  the  excitation.  With  increase 
in  the  length  of  the  muscle  the  tension  developed  on  excitation  increases 
until  the  length  of  the  muscle  is  somewhat  greater  than  that  which  it  possesses 
in  its  normal  relationships  in  the  body.  To  lengthen  the  muscle  beyond 
this  point  a  certain  stretching  force  must  be  applied  to  it  which  rapidly 
increases.  The  tension  developed  on  excitation  however  soon  begins  to 
diminish. 

These  relationships  are  shown  by  the  diagram  (Fig.  61),  where  the  ordinates  repre- 
sent the  length  of  the  muscle  and  the  abscissa  the  tension  on  the  muscle.  The  left- 
hand  thick  line  represents  the  muscle  in  a  state  of  rest,  the  right-hand  curved  line 
the  muscle  in  a  state  of  excitation.  The  horizontal  distance  between  the  two  lines 
gives  the  increase  of  tension  (as  measured  by  the  isometric  method)  produced  when  the 
muscle  passes  from  the  resting  into  the  excited  state  as  the  result  of  stimulation  by  a 
single  induction  shock. 

Since  the  tension  set  free  on  excitation  depends  on  the  length  of  the 


202 


PHYSIOLOGY 


muscle  fibres  during  the  production  of  the  condition  of  tension,  the  tension 
developed  will  be  diminished  if  the  muscle  be  allowed  to  shorten  before  its 
maximum  tension  has  been  reached.  This  is  the  case  with  all  isotonic 
records  of  muscular  contraction,  so  that  it  becomes  difficult  to  give  any 
exact  expression  for  the  total  energy  changes  in  a  muscle  which  is  allowed 
to  shorten.  On  the  other  hand,  in  the  body  the  bony  levers  are  so  arranged 
that  the  muscles  at  their  greatest  length  work  at  a  maximum  mechanical 
disadvantage  which  lessens  continuously  as  the  muscles  shorten  and  approxi- 
mate their  points  of  attachment.     The  load  on  a  muscle  is  thus  lessened 


-J 

i 

SB 

r 

Tension  > 

Fig.  61.  Diagram  to  show  the  relation  between  the  initial  length  of  a 
muscle  and  the  tension  developed  in  it  during  excitation  (as  measured 
by  the  isometric  method).  The  tension  developed  at  each  initial 
length  is  measured  by  the  horizontal  distance  between  the  two  thick 
lines,  the  left  line  representing  the  resting  muscle,  and  the  curved  thick 
line  on  the  right  the  contracted  muscle.     (From  Blix.) 

continuously  as  the  muscle  contracts.  A  muscle  is  a  machine  primarily 
for  developing  tension,  and  the  potential  energy  thus  set  up  may  be  used 
for  the  production  of  work  to  any  degree  the  conditions  of  loading  allow. 
The  work  done  by  a  muscle  when  it  contracts  is  measured  by  multiplying 
the  weight  lifted  by  the  height  through  which  it  is  lifted,  w  X  h.  Since 
however  the  result  will  vary  according  to  the  conditions  of  loading  of  the 
muscle,  a  much  more  useful  quantity  is  obtained  by  measuring  the  tension 
produced  in  a  muscle  which  is  stimulated  but  not  allowed  to  shorten.  The 
potential  erjergy  available  due  to  the  new  elastic  conditions  of  the  fibres  is 
found  to  be  approximately  1 IV,  where  T  is  the  maximum  tension  developed 
in  the  twitch  and  I  is  the  length  of  the  muscle  (A.  V.  Hill). 


THE   MECHANICAL   CHANGES  OF  MUSCLE 


203 


Living  muscle 


1 


THE  EXTENSIBILITY  OF  MUSCLE 

a  perfectly  normal  condition  is  distinguished  by  its  slight  but 
perfect  elasticity ;   that  is  to  say,  it  is  con- 
siderably stretched  by  a  slight  force  (in  the 
longitudinal    direction),  but  returns  to  its 
original  length  when  the  extending  weight 
is  removed.     The  length  to  which  muscle  is 
stretched  is  not  proportional  to  the  weight 
used,    but  any  given  increment  of  weight 
"N   gives  rise  to  less  elongation  the  more  the 
Fig.  62,     Extensibility  of  india-rubber   («)  musc]e  is  already  stretched.     The  accom- 
comparcd  with  that  <>f  a    frogs    gastroc-  .  '  .,       , 

nemius  muscle  (6).  panymg  curves  show  ^grammatically  the 

elongation  of  muscle   as  compared   with  a 
piece  of  india-rubber  when  the  weight  on  it  is  uniformly  increased. 

Dead  muscle  is  less  extensible  and  its  elasticity  is  less  perfect.  A  given  weight 
applied  to  a  dead  muscle  will  not  stretch  it  so  much  as  when  the  muscle  was  alive,  but 
the  de'ad  muscle  does  not  return  to  its  original  length  when  the  weight  is  removed. 
A  contracted  muscle,  on  the  other  hand,  is  more  extensible  than  a  muscle  at  rest. 
A  gramme  applied  to  a  contracted  gastrocnemius  will  cause  greater  lengthening  than 
if  it  were  applied  to  the  ^  ^ 

same  muscle  at  rest.  The 
relation  between  the  exci- 
tability of  a  muscle  under 
the  two  conditions  of  ) 
contraction  and  rest  are 
shown  in  the  diagram  in 
Fig.  03. 

At  the  point  y  the 
muscle  is  unable  to  shor- 
ten at  all  against  a 
weight.  /  It  is  evident 
from  this  diagram  that  Fio.  63.  Curve  allowing  the  length  of  a  muscle  under  various 
the  height  of  contraction  loads  in  the  contracted  condition  by,  and  uncontracted 
of  a  muscle  diminishes  as  c°nditiot>  CV-  The  double  lines  a,  b,  &c,  represent  the  con- 
tracted muscle,  while  the  long  single  lines  a  c,  Sec.,  show  the 
the  load  is  increased, .very,      length  of  the  inactive  muscle. 

riipjrl1yjf__thp    mpse,|e  _js 

after-loaded,  less  rapidly  if  the  weight  applied  to  the  muscle  be  allowed  to  extend  it 
at  rest.  It  is  evident  however  that  in  either  case  the  diminution  in  height  is  nut  in 
proportion  to  the  load,  and  that  the  work  done  by  the  muscle,  w  X  h,  as  the  weight  is 
ineivasrd.  rises  at  first  quickly,  then  more  slowly  to  a  maximum  to  sink  finally  to 
zero.  \  By  inspection  of  diagram  (Fig.  63)  it  will  be  seen  that 

\_  O.h0  <10.h1  <20.h2<  30.h3  >  40.h4  >  50.h6, 

so  that  in  this  case  the  maximal  mechanical  work  is  obtained  when  the  muscle  is  loaded 
with  about  30  gms. 


PROPAGATION  OF  CONTRACTION.  THE  CONTRACTION  WAVE 
The  whole  muscle  does  not  as  a  rule  contract  simultaneously.  When 
excited  from  its  nerve  the  contraction  begins  at  the  end-plates  and  spreads 
in  both  directions  through  the  muscle.  The  rate  of  propagation  of  the  con- 
traction wave  ran  only  be  measured  by  employing  a  curarised  muscle,  so  as 
to  avoid  the  wide  spreading  of  the  excitatory  change  by  means  of  the  intra- 
muscular nerve-endings.     For  this  purpose  a   curarised  saitorius  muscle 


204  PHYSIOLOGY 

is  taken,  stimulated  at  one  end,  and  the  thickening  of  the  muscle  recorded  by 
means  oftwo  levers  placed  one  near  the  exciting  electrodes  and  the  second 
at  the  other  end  of  the  muscle,  as  shown  in  the  diagram  (Fig.  04).  The 
difference  between  the  latent  periods  of  the  two  curves  represents  the  time 
taken  by  the  contraction  wave  in  travelling  from  a  to  b.  By  measurements 
carried  out  in  this  way  it  is  found  that  the  rate  of  propagation  of  the  con- 
traction in  frog's  muscle  is  :>  to  4  metres  per  second  ;  in  the  muscle  of 
warm-blooded  animals  it  may  amount  to  6  metres. 


Fig.  04.     Diagram  of  arrangement  for  recording  the  contraction  wave  in  a 
curariaed  sartorius. 

The  actual  duration  of  the  shortening  at  any  given  point  is  necessarily 
smaller  than  that  of  the  whole  muscle,  and  amounts  in  frog's  muscle  to  only 
005-009  sec,  about  half  the  duration  of  the  contraction  of  a  whole  muscle 
of  moderate  length.  The  length  of  the  wave  is  obtained  by  multiplying  the 
rate  of  transmission  by  the  duration  of  the  wave  at  any  one  point.  It  varies 
therefore  in  frog's  muscle  between  3CC0  x  -05  (  =  150)  and  4CC0  x  -C9 
(=  360)  millimetres.  Thus  the  muscle  fibres  in  the  frog  are  much  too  short 
to  accommodate  the  whole  length  of  the  wave,  and  the  contraction  of  the 
whole  muscle  must  be  made  up  of  the  summated  effects  of  the  contraction 
wave  as  it  passes  from  point  to  point.  Hence  the  longer  the  muscle,  the 
more  must  the  contraction  be  lengthened  by  the  time  taken  up  in  propagation 
from  one  end  to  another. 


SECTION  IV 


THE   CONDITIONS   AFFECTING   THE    MECHANICAL 
RESPONSE    OF    A   MUSCLE 

STRENGTH  OF  STIMULUS.  If  a  series  of  single  break-shocks  be  applied 
to  a  muscle  or  nerve  at  intervals  of  not  less  than  five  seconds,  it  will  be  found 
that  beyond  a  certain  distance  of  the  secondary  from  the  primary  coil  no 
effect  at  all  is  produced.  The  shocks  are  said  to  be  subminimal. 
On  pushing  the  secondary  coil  nearer  the  primary  a  point  will 
be  reached  at  which  a  small  contraction  will  be  observed. 
On  then  pushing  in  the  coil  a  millimetre  at  a  time  the  contrac- 
tion will  become  greater  for  the  next  couple  of  centimetres 
(e.g.  as  the  coil  is  moved  from  12  to  10  cm.  distance).  Further 
increase  of  current  by  approximation  of  the  coils  is  without 
effect,  although  the  current  actually  used  may  be  increased 
a  hundred  times  in  moving  the  coil  from  10  to  0.  It  was 
formerly  thought  that  this  limited  gradation  of  the  muscular 
response  according  to  strength  of  stimulus  was  due  to  a  similar 
gradation  in  the  response  of  each  individual  muscle  fibre  of 
which  the  muscle  is  composed.  It  seems  more  probable  how- 
ever that,  when  a  minimal  or  subminimal  response  is  obtained, 
not  all  the  fibres  making  up  the  muscle  are  contracting.  A  min- 
imal contraction  is  in  fact  a  contraction  in  which  some  fibres 
of  the  whole  muscle  are  stimulated.  A  maximal  contraction 
is  one  in  which  all  the  fibres  are  stimulated.  So  far  as  concerns 
each  individual  muscle  fibre  every  contraction  is  a  maximal 
contraction.  The  fibre  either  contracts  to  its  utmost  or  it  does 
not  contract  at  all.     The  rule  of  all  or  none '  which  was  first    ^  o 

enunciated  for  heart-muscle  is  probably  true  for  every  con- 
tractile  element.  The  difference  between  skeletal  and  heart 
muscle  lies  in  the  fact  that  in  the  former  the  excitatorv  process  does  not 
spread  from  one  fibre  to  its  neighbours.  If  for  instance  we  take  a  curarised 
sartorius  and  split  its  lower  end,  as  in  Fig.  65,  the  stimulus  applied  to  a 
causes  a  contraction  only  of  the  left  side  of  the  muscle,  while  a  stimu- 
lus applied  to  b  is  in  the  same  way  limited  to  the  right  side.  If  a  piece 
of  ventricular  or  auricular  muscle  of  the  frog  or  tortoise  were  treated  in  the 
same  way,  a  stimulus  applied  at  a  would  cause  a  contraction  which  would 
travel  across  the  bridge  at  the  upper  end  and  extend  to  b.  « 

205 


206 


I'HYKIOI-Om 


It    was  shown  by  Gotch  that,  if  eaofa  <>f  the  three  roots  which   make   up  thr  sciatic 

nerve  and  send  fibres  to  the  gastrocnemius  be  stimulated  in  turn,  it  is  often  impossible 
in  evoke  a  maximal  contraction  of  I  he  gastrocnemius,  however  strongly  each  root 
be  stimulated.  Keith  Lucas  has  shown  that  if  stimuli  in  gradually  increasing  strength 
lie  applied  to  the  motor  nerve  (containing  only  seven  to  nine  fibres),  which  supplies 
the  dorso-cutaneous  muscle  of  tin-  frog,  the  contraction  of  the,  muscle  increases,  not 
gradually,  but  by  a  series  of  sic ps.  This  can  be  explained  only  by  assuming  that  the 
smallest  effective  stimulus  excites  perhaps  four  out  of  the  seven  nerve  fibres,  those 
immediately  in  contact  with  the  electrodes.  With  increasing  strength  of  current 
the  stimulus  becomes  effective  for  the  three  lilacs  lying  next  to  these,  and  finally  still 
further  increase  of  current   may  excite  all  the  fibres  making  up  the  nerve  (Fig.  66). 


'  '1                                          T 

. 

r 

Fig.  66.     Curve  showing  relation  of  height  of  contraction  of  dorso-cutaneous  muscle 
to   strength   of   stimulus.        Ordinates  =  height   of   contraction  ;    abscissa  = 
strength  of  stimulus.     (K.  Lucas.) 

THE  REPETITION  OF  STIMULUS 
SUMMATION.  The  response  of  a  muscle  fibre  to  a  single  shock,  whether 
measured  by  the  isotonic  or  the  isometric  method,  i.e.  as  shortening  or  as 
tension,  is  independent  of  the  strength  of  stimulus  and  varies  only  with  the 
length  of  the  fibre  during  the  rise  of  the  excitatory  condition.  If  however 
a  second  shock  is  sent  in  during  this  period  a  further  evolution  of  energy  is 
possible,  and  the  effect  is  still  further  increased  by  putting  a  series  of  stimuli 
into  the  muscle  or  its  attached  nerve  before  the  development  of  the  contractile 
stress  due  to  the  first  stimulus  has  reached  its  maximum.  If  two  shocks  at 
intervals  of  one  hundredth  of  a  second  be  sent  into  a  muscle,  the  response, 
whether  shortening  or  rise  of  tension,  will  be  greater  than  that  produced  by 
one  shock.  If  a  series  of  shocks  be  sent  in,  the  excitatory  condition  is  main- 
tained, so  that  instead  of  a  simple  muscle  twitch  rising  to  a  maximum  and 
then  falling,  the  muscle  lever  rises  to  a  given  point,  which  in  the  muscle  con- 
tracting isometrically  may  be  double  that  due  to  a  single  stimulus,  and  then 
remains  at  this  height  during  the  continuation  of  the  repeated  excitations. 
If  the  muscle  be  allowed  to  contract  isotonically,  the  continued  contraction 
produced  by  a  series  of  stimuli  may  with  a  heavy  load  be  three  or  four  times 
as  considerable  as  that  produced  by  a  single  stimulus.  This  condition  of 
apparently  continued  stimulation  brought  about  by  continued  application  of 
stimuli  is  said  to  be  summated. 

REFRACTORY  PERIOD.  If  the  interval  between  two  stimuli  sent  into 
a  muscle  be  successively  shortened  in  a  series  of  observations,  we  finally 
yrrive  at  a  point  at  which  summation  is  no  longer  apparent,  i.e.  the  effect  of 


THE  MECHANICAL  RESPONSE  OF  MUSCLE 


207 


r  it 


Fig.  67.  Muscle  curves  showing  summation  of 
stimuli,  r  and  r'.  the  points  at  which  the 
stimuli  were  sent  into  the  nerve.  From  the 
first  stimulus  alone  the  curve  abc  would  be 
obtained.  From  r'  the  curve  def  is  obtained. 
These  two  curves  are  stimulated  to  form  the 
curve  aejhik  when  both  stimuli  are  sent  in  at 
the  interval  r  r'. 


the  two  .stimuli  is  no  greater  than  the  effect  of  a  single  .stimulus.  This 
means  that  the  second  stimulus  has  become  ineffective,  and  this  ineffective- 
ness we  must  ascribe  to  the  condition  set  up  in  the  muscle  as  the  result 
of  the  first  stimulus.  For  a  very  short  period  of  time  after  stimulation  a 
muscle  is  inexcitable  to  a  second  stimulus.  The  period  during  which  it  is 
inexcitable  is  known  as  the  refractory  period  and  amounts  in  skeletal  muscle 
to  about  -0015  second.  The  same  phenomenon  is  better  marked  in  certain 
other  excitable  tissues,  such  as  the  heart  muscle,  but  it  seems  to  be  a  common 
property  of  excitable  tissues  generally. 

When  a  loaded  muscle  is  made  to  record  its  contractions  isotonically  we  may  get 
summation  of  effects,  though  the  interval  between  the  stimuli  is  greater  than  that 
which  corresponds  to  the  duration  of 
the  rise  of  contractile  stress.  Thus  if 
the  interval  is  just  so  long  that  the 
second  becomes  effective  just  as  the 
contraction  due  to  the  first  has  com- 
menced to  die  away,  the  second  con- 
traction seems  to  start  from  the  point 
to  which  the  muscle  has  been  raised 
by  the  first  (Fig.  67).  By  repeating 
these  stimuli  in  a  heavily  loaded 
muscle,  the  contraction  may  be  made 
three  or  four  times  as  extensive  as  a 
single  twitch.  With  slow  stimuli  the 
summation  is  however  rather  mechan- 
ical than  physiological.  The  period  of  contractile  stress,  which  lasts  only  about 
03  second,  is  so  short  that  it  has  no  time  to  raise  the  weight  to  the  maximum  height 
before  it  has  passed  away.  This  is  shown  by  the  fact  that  if  the  muscle  be  after- 
loaded,  so  that  the  lever  is  raised  to  the  top  of  the  curve  of  a  single  twitch,  application 
of  the  stimulus  will  make  it  shorten  still  more,  and  by  repeated  after-loading  in  this 
fashion,  it  is  possible  to  make  the  muscle  raise  a  weight  in  response  to  a  single  stimulus 

to  the   same   height  that 
it  would   if   excited  by  a 
series    of    stimuli.      This 
mechanical  factor  in  sum- 
mation is  shown  in  Fig. 
68.        It   will    be    noted 
however  that  the  tetanus 
is  not   a  steady  one  and 
is  probably  due  to  stimuli 
Fig.  68.     Contractions  of  a  frog's  muscle.     Two  single  (witches     repeated    at   intervals    of 
are  followed  by  a  tetanus,  which  is  almost  twice  as  high  as  a     about    *    of  a  second      If 
single  contraction.     After  two  more  single  twitches,  the  drum      ,,  '" 

was  made  to  rotate  more  slowly,  and  single  shocks  employed,  tbe  r.  of  stimulation 
at  the  same  time  as  the  '  after-loading  '  was  continually  were  increased  to  50  or 
increased.  It  can  be  seen  that  the  curve  obtained  in  this  way  100  per  second,  a  tetanus 
is  as  high  as  the  original  tetanus.     (V.  Frey.)  wouM    bo    produoed   and 

the  curve  would  be  prob- 
ably twice  as  high  as  that  represented  in  the  figure.  We  thus  see  that  for  the  over- 
coming of  a  resistance  a  single  twitch  is  not  economical.  It  is  doubtful  whether  any 
contractions  of  muscles  which  occur  in  the  body  are  other  than  tetani  of  varying 
duration. 


TEMPERATURE.     Speaking  generally,  the  effect  of  warming  a  muscle 


208 


PHYSIOLOGY 


is  to  quicken  all  its  processes.     The  latenl  period  becomes  shorter  and  the 
muscle  curve  steeper  and  shorter. 

It  is  very  often  observed  that  the  height  of  contraction  of  the  warmed  muscle  is 
greater  than  that  obtained  at  ordinary  temperatures.  It  seems  that  this  apparent 
increase  in  height  is  really  instrumental  in  origin,  the  quicker-moving  muscle  jerking 
the  lever  beyond  the  real  extent  of  the  contraction.  If  proper  means  are  taken  to 
eliminate  this  overshooting  of  the  lever,  it  is  found  that  the  height  of  contraction  is 
unaltered  between  5°  and  20°C,  the  only  change  being  in  the  time-relations  of  the 
curves.     This  is  especially  well  shown  in  the  so-called  '  arrest '  curves  (Fig.  69). 


Fig.  69.  Isotonic  and  'arrest '  curves  of  muscle-twitch  :  (1)  unloaded  at  14  ('.  . 
(2)  at  25°C.  ;  (3)  at  0°C.  ;  (4)  loaded  at  14°C.  Note  that  the  arrest  curves 
attain  the  same  height  throughout.     (Kaiser.) 

If  a  muscle  be  heated  gradually  (without  stimulation)  up  to  about  45°C., 
it  begins  to  contract  slowly  at  about  34°0,  and  this  contraction  reaches  its 
maximum  at  45°C,  at  which  point  the  muscle  has  entered  into  pronounced 
rigor  mortis. 

Cold  has  the  reverse  effect.  The  intra-molecular  processes  which  lie  at 
the  root  of  the  muscular  activity  are  slowed,  so  that  the  latent  period  and  the 
contraction  period  are  prolonged.  The  action  of  cold  on  the  excitability  <>l 
muscle  is  to  increase  it,  so  that  any  form  of  stimulus  is  more  effective  at  5°C. 
than  at  25°C.  Moreover,  when  maximal  stimuli  are  being  used,_and  the 
muscle  is  heavily  loaded,  the  first  effect  of  the  application  of  cold  may  be  to 
increase  the  height  as  well  as  the  duration  of  contraction,  for  the  same 
reason  that  a  gentle  push  is  more  efficacious  in  closing  a  door  than  would  be 
a  heavy  blow  with  a  hammer.  If  however  a  muscle  be  cooled  for  a  short 
time  to  zero  or  a  little  below,  it  loses  its  irritability,  which  returns  if  the 
muscle  be  gradually  warmed  again.  Prolonged  exposure  to  severe  cold 
irrevocably  destroys  its  irritability.  Warming  the  muscle  will  now  simply 
bring  about  rigor  mortis. 

FATIGUE.  A  muscle  will  not  go  on  contracting  indefinitely.  If  it 
be  repeatedly  stimulated,  changes  soon  become  apparent  in  the  curve  of 
contraction.  The  latent  period  is  prolonged,  as  well  as  the  length  of  the 
contractions  ;  the  absolute  height  and  work  done  are  diminished.  At 
the  same  time  the  muscle  does  not  return  to  its  original  length  ;  the  shorten- 


THE  MECHANICAL  RESPONSE   OF  MUSCLE 


209 


ing  which  remains  is  spoken  of  as  '  contraction  remainder.''  After  an  initial 
rise  during  the  first  few  contractions,  these  diminish  uniformly  in  height 
till  they  are  no  longer  apparent,  so  that  the  muscle  is  now  said  to  have  lost 
its  irritability.  At  the  same  time  there  is  a  great  prolongation  of  the  curve, 
occasioned  almost  entirely  by  a  retardation  -of  the  relaxation,  so  that  after 
forty  or  fifty  contractions  several  seconds  may  elapse  before  the  lever  returns 
to  the  base  line  (Fig.  70). 


fro.  70.  Muscle  curves  showing  fatigue  in  consequence  "!'  repealed  stimulation. 
The  first  six  contractions  are  numbered,  and  show  the  initial  increase  of  the 
first  three  contractions.     (Brodik.) 

The  fact  that  I  he  relaxation  part  of  the  muscle  curve  is  affected  by  various  conditions, 
especially  fatigue,  apparently  independently  of  the  contraction  part,  led  Fick  to  put 
forward  a  theory  that  two  distinct  processes  were  concerned  in  the  response  of  a  muscle 
to  excitation,  one  process  causing  the  active  shortening  and  the  other  the  relaxa- 
tion. (It  must  be  noted  that  this  is  not  the  same  as  saying  that  the  lengthening  is 
an  active  process,  a  statement  negatived  by  the  behaviour  of  a  muscle  when  caused 
to  contract  on  mercury.)  He  suggested  that  the  disintegration  associated  with  activity 
might  be  conceived  as  occurring  in  two  stages  :  the  first  resulting  in  the  production 
of  sarcolactic  acid  and  the  active  shortening  of  the  muscle  ;  the  second  in  the  further 
conversion  of  the  acid  into  C02,  with  a  consequent  relaxation.  A  retardation  of  this 
second  phase  would  cause  the  prolonged  curve  with  '  contraction  remainder '  observed 
in  a  fatigued  muscle.  We  shall  return  to  this  point  when  discussing  the  chemical 
and  heat  changes  which  accompany  contraction. 

If  left  to  itself,  the  muscle  which  has  been  exhausted  by  repeated  stimula- 
tion will  recover.  The  recovery  is  hastened  by  passing  a  stream  of  blood, 
or  even  of  salt  solution,  through  the  blood-vessels  of  the  muscle.  Recovery 
in  a  muscle  outside  the  body  is  never  complete. 

The  phenomena  of  fatigue  probably  depend  on  two  factors  : 

(1)  The  consumption  of  the  contractile  material  or  the  substances  avail- 
able for  the  supply  of  potential  energy  to  this  material. 

(2)  A  more  important  factor  is  the  accumulation  of  waste  products  of 
contraction.  Among  these  waste  products  the  lactic  acid  is  probably  of  great 
importance.  Fatigue  may  be  artificially  induced  in  a  muscle  by  '  feeding  ' 
it  with  a  dilute  solution  of  lactic  acid,  and  again  removed  by  washing  out 
the  muscle  with  normal  saline  solution  containing  a  small  percentage  of  alkali. 

14 


210 


PHYSIOLOGY 


THE  ACTION  OF  SALTS 

The  action  of  sodium  salts  on  muscle  is  of  considerable  interest.     We 

are  accustomed  to  use  a  0-6  per  cent,  solution  of  Nat 'I  as  a  '  normal  fluid  ' 

to   keep  muscle   preparations  moist.     If    however    the  solution  be  made 

with  distilled  water,  it  has  a  distinctly  excitatory  effect   upon  the  muscle. 


Fio.  71.  A.  Tracing  of  the  contraction  of  a  frog's  sartorius,  poisoned  with  veratrin, 
in  response  to  a  momentary  stimulus.  The  time-marking  indicates  seconds. 
B.  Tetanic  contraction  of  normal  sartorius  in  response  to  rapidly  interrupted 
stimuli.  (The  duration  of  the  stimulus  is  indicated  by  the  words  '  on  '  and 
'off.')  It  will  bo  noticed  that  the  two  curves  are  practically  identical.  (Miss 
Buchanan.) 

so  that  single  induction  shocks  may  cause  tetaniform  contractions.  The 
same  excitatory  effect  is  still  better  marked  with  solutions  of  Na2C08'.  If 
a  thin  muscle,  such  as  a  frog's  sartorius,  be  immersed  in  a  solution  con- 
taining 0-5  per  cent.  NaCl,  0-2  per  cent.  Na2HP04,  and  0-04  per  cent.  Na2C03 
(Biedermann's  fluid),  the  muscle  enters  into  a  series  of  frequent  contractions, 
so  that  it  may  wriggle  from  side  to  side,  or 
may  even  '  beat '  for  a  time  with  the  regularity 
of  heart-muscle,  though  at  a  much  greater 
rate. 

This    excitatory    action    of    sodium    salts 

is   neutralised    by    the    addition  of    traces  of 

calcium  salts.     Hence  the    normal  saline  used 

in  the  laboratory  should   always  be 

made   with   tap   water,    containing 

'Excitation.        calcjum  salts. 
*  jjuULaAj»j\jAj_louLaj_jlaAjljljlji  Seconds. 

Fig.    72.     Tracing    of    the    contraction    of    a  Potassium   salts,  although   form- 

muscle  poisoned  by  the  injection  of  a  strong     ing   SO   important    a     constituent   of 
solution    of   veratrin.    showing   the    double     ,-,  ■,        r  ,  ,  , 

contraction   due   to   unequal  poisoning   of    the  ash    of    muscle,    act    as    muscle 
different  fibres.    (Biedermann.)  poisons,   quickly    and   permanently 

destroying  its  irritability.  If  a 
muscle  be  transfused  with  normal  fluids  containing  minute  traces  of  potas- 
sium salts,  it  at  once  shows  all  the  signs  of  fatigue,  signs  which  may  be 
removed  by  washing  out  the  potassium  salts  by  means  of  0-6  per  cent.  NaCl 
solution.  It  is  possible  that  the  setting  free  of  potassium  salts  may  be  one  of 
the  factors  involved  in  the  development  of  the  normal  fatigue  of  muscle. 


THE   MECHANICAL   RESPONSE   OF  MUSCLE  211 

THE  ACTION  OF  DRUGS 

Of  the  drugs  that  have  a  direct  action  on  muscle,  the  most  remarkable  is  veratrin. 
which  causes  an  excessive  prolongation  of  a  muscular  contraction  (produced  by  a 
single  stimulus).  Thus  the  'twitch'  of  a  muscle  poisoned  with  veratrin  may  last 
fifty  or  sixty  seconds,  instead  of  the  normal  one-tenth  of  a  second  (Fig.  71). 

Barium  salts  have  a  similar,   though   less   marked  effect. 

Tn  order  to  carry  out  the  poisoning  with  veratrin,  very  weak  solutions  (1  in  100,000 
or  1  in  1,000,000  of  normal  saline)  should  be  used  and  the  muscle  exposed  to  its  action 
for  some  time.  We  get  then  on  a  single  stimulus  a  response  lasting  many  seconds 
and  exactly  similar  in  height  and  form  to  a  tetanus  obtained  by  discontinuous  stimu- 
lation. If  stronger  solutions  be  used,  the  action  of  the  drug  is  apt  to  affect  the  fibres 
unequally,  so  that  we  may  have  a  sharp  normal  twitch  preceding  the  prolonged  con- 
traction (Fig.  72).  If  the  muscle  be  excited  several  times  immediately  after  the  pro 
longed  contraction  has  passed  away,  it  responds  with  twitches  like  those  of  a  normal 
muscle,  but  if  allowed  to  rest  a  few  minutes,  stimulation  is  again  followed  by  the  peculiar 
long-drawn-out  contraction. 


SECTION  V 

CHEMICAL   CHANGES   IN   MUSCLE 

CHEMICAL  COMPOSITION  OF  VOLUNTARY  MUSCLE 

Voluntary  muscle  consists  of  elongated  cells,  the  muscle  fibres  being 
embedded  in  a  connective  tissue  framework;  and.  as  in  all  cellular  tissues, 
proteins  form  its  chief  chemical  constituents.  The  contents  of  the  fibres 
are  semi-fluid  and  can  be  expressed  from  the  finely  divided  muscle  as  a 
viscous  fluid  known  as  muscle-plasma. 

Muscle- plasma  is  obtained  in  the  following  way.  The  living  muscle  of  frogs  is 
frozen,  minced  with  ice-cold  knives  and  pounded  in  a  mortar  with  four  times  its  weight 
of  sand  containing  •(>  of  common  salt.  The  mixture  is  then  thrown  on  to  a  filter  kept 
at.  (V  ('.  when  an  opalescent  fluid  filters  through.  The  filters  soon  become  clogged 
and  therefore  must  be  freipifiil  l\  changed,  and  their  temperature  must  not  be  allowed 
to  rise  above  2°  to  3°C. 

If  the  temperature  of  the  muscle-plasma  be  allowed  to  rise,  clotting 
takes  place,  the  clot  later  on  contracting  and  squeezing  out  a  serum,  as  is 
the  case  with  blood-plasma. 

The  muscle-plasma  is  neutral  or  slightly  alkaline.  When  coagulation 
takes  place  however,  it  becomes  distinctly  acid,  and  this  acidity  is  due  to 
the  formation  of  sarcolactic  acid  in  the  process.  Arguing  chiefly  from 
analogy  with  the  blood-plasma,  the  muscle-plasma  has  been  said  to  contain 
a  body,  myosinogen,  which  is  converted  when  clotting  takes  place  into 
myosin. 

The  exact  nature  of  the  proteins  in  muscle-plasma,  as  well  as  of  the  protein  con- 
stituent of  the  clot,  which  we  have  called  myosin,  is  still  a  subject  of  debate.  Kiihne. 
to  whom  we  owe  our  first  acquaintance  with  muscle-plasma,  described  the  clot  as 
consisting  of  myosin,  a  globulin,  soluble  in  5  per  cent,  solutions  of  neutral  salts,  such 
as  NaCl  or  MgS04.  precipitated  by  complete  saturation  with  MgS04,  and  coagulated 
on  heating  to  56°  C.  In  the  muscle-serum,  obtained  after  separation  of  the  clot,  he 
found  three  proteins,  one  coagulating  at  45  ( '.,  one  he  called  an  albumate  (i.e.  a  derived 
albumen  or  metaprotein),  and  the  third  coagulating  about  75°C.  and  apparently 
identical  with  serum  albumen.  Halliburton  extended  these  researches  to  the  muscles 
of  warm-blooded  animals.  He  described  four  proteins  as  existing  in  muscle-plasma, 
of  which  two,  paramyosinogen  and  myosinogen,  gave  rise  to  the  clot  of  myosin. 

In  no  case  however  is  it  possible  entirely  to  dissolve  up  the  clot  when  once  formed, 
and  it  seems  that  the  so-called  solution  in  dilute  salt  solutions  was  merely  an  extraction 
of  still  soluble  protein  in  the  meshes  of  the  clot.  Von  Fiirth  has  shown  that  if  the 
muscles  of  a  mammal  are  washed  free  of  adherent  lymph  and  blood,  the  plasma  obtained 
by  extraction  with  normal  salt  solution  contains  only  two  proteins.  These  proteins 
are  extremely  unstable,  and    are  gradually  transformed  on  standing  into  insoluble 

212 


CHEMICAL  CHANGES  IN  MUSCLE  213 

protein,   giving  rise  to  a  precipitate  in  dilute  solutions,  or  forming  a  jelly-like  clot  in 
strong  solutions.     The  properties  of  these  proteins  may  be  summarised  as  follows  : 

(1)  Myosin  (paramyosinogen  of  Halliburton).  A  globulin,  coagulating  at  about  47°- 
50°C,  precipitated  by  half  saturation  with  ammonium  sulphate  or  on  dialysis.  Trans- 
formed slowly  in  solution,  rapidly  on  precipitation,  into  an  insoluble  protein,  myosin 
fibrin. 

(2)  Myogen  (myosinogen  of  Halliburton).  A  protein  allied  to  the  albumens  in 
that  it  is  not  precipitated  by  dialysis.  Coagulates  on  heating  at  55°-60°C.  It  changes 
slowly  into  an  insoluble  protein,  myogen  fibrin,  but  passes  through  an  intermediate 
soluble  stage  called  soluble  myogen  fibrin.  This  latter  body  coagulates  on  heating  to 
40°C,  being  instantly  converted  at  this  temperature  into  insoluble  myogen  fibrin. 
It  'Iocs  not  seem  that  any  ferment  action  is  associated  with  these  changes,  which  we 
may  represent  by  the  following  schema  : 

Muscle-plasma. 


\  myosin  or  paramyosinogen.  1  myogen  (myosinogen  of   Halliburton, 

albumate  of  Kiihne). 

I 
Soluble  myogen  fibrin. 

I     ' 
Myosin  fibrin.  Insoluble   myogen  fibrin. 

Muscle  clot. 

Soluble  myogen  fibrin,  which  in  mammalian  muscle-plasma  forms  only  on  standing, 
exists  apparently  preformed  in  frog's  muscle.  Hence  the  instantaneous  clotting  of 
frog's  muscle-plasma  on  warming  to  40°C. 

The  residue  left  after  the  expression  of  the  muscle-plasma  consists 
chiefly  of  connective  tissue,  sarcolemma,  and  nuclei,  and  as  such  contains 
gelatin  (or  rather  collagen),  mucin,  nuclein,  and  adherent  traces  of  the 
proteins  of  the  muscle-plasma  itself. 

The  muscle-serum  contains  the  greater  part  of  the  soluble  constituents 
of  muscle. 

OTHER  CONSTITUENTS  OF  MUSCLE.  A  number  of  other  sub- 
stances are  found  in  muscle  in  small  quantities,  those  which  are  soluble 
being  contained  to  a  great  part  in  the  muscle-serum.  It  will  suffice  here 
to  enumerate  the  chief  of  these. 

(a)  Colouring- matter.  All  red  muscles  contain  a  considerable  amount  of  heemo- 
globin.  A  special  muscle  pigment  allied  to  haemoglobin  has  been  described  by  MacMunn 
as  myohaematin.     The  only  evidence  for  its  existence  is  spectroscopic. 

(b)  Nitrogenous  extractives.  Of  these,  the  most  important  is  creatine  (CH9N30.2) 
of  which  0-2  to  03  per  cent,  may  be  found  in  muscle.  Its  significance  will  be  the  subject 
of  consideration  later.  Other  nitrogenous  bodies  occurring  in  smaller  quantities  are 
hypoxanthine,  xanthine,  and  traces  of  urea  and  amino-acids. 

(c)  Non-nitrogenous  constituents. 
Fats,  in  variable  amount. 

Glycogen.  This  substance  is  invariably  found  in  healthy  muscle.  Fresh  skeletal 
muscle  contains  about  1  per  cent.  In  the  embryo  the  muscles  may  contain  many 
times  this  quantity  of  glycogen. 

Glucose  is  present  in  fresh  muscle  in  minimal  quantities,  about  -01  per  cent. 

When  muscle  is  allowed  to  stand,  especially  in  a  warm  place,  the  glycogen  under- 
goes partial  conversion  into  glucose,  so  that  the  latter  increases  at  the  expense  of  the 
former. 


214  PHYSIOLOGY 

Inosit  (C6H12O0  2H,0)  or  '  muscle  sugar '  occurs  in  minute  traces  in  muscle. 
It  does  not  belong  to  the  group  of  carbohydrates  at  all,  being  a  hexahydrobenzene. 
It  is  nonfermentable  and  does  not  rotate  polarised  light  nor  does  it  reduce  Fehling's 
solution.     Its  significance  is  quite  unknown. 

(d)  Inorganic  constituents.  Muscle  contains  about  75  per  cent,  of  water.  Ash 
forms  1  to  1-5  per  cent,  and  consists  chiefly  of  potassium  and  phosphoric  acid,  with 
traces  of  calcium,  magnesium,  chlorine  and  iron. 

RIGOR  MORTIS 
All  muscles  after  removal  from  the  body,  or  if  left  in  the  body  after 
general  death,  lose  after  a  time  their  irritability,  and  this  loss  is  succeeded 
by  the  phenomenon  known  as  rigor  mortis.  The  muscle,  which  was  pre- 
viously flaccid,  contracts,  though  the  shortening  is  not  very  powerful  and 
can  be  prevented  by  a  moderate  load  on  the  muscle.  Whereas  the  living 
muscle  is  translucent,  supple,  and  extensible,  it  becomes  in  the  process  of 
rigor  opaque,  rigid  and  inextensible.  When  rigor  has  been  established, 
the  reaction  of  the  muscle  is  also  found  to  have  changed  from  a  slightly 
alkaline  to  a  distinctly  acid  one,  the  acid  being  due  to  the  presence  of  sarco- 
lactic  acid.  From  this  condition  of  rigor  there  is  no  recovery.  There  can 
be  no  doubt  that  the  change  in  consistence  of  the  muscle  and  probably  also 
its  shortening  in  rigor  are  due  to  the  coagulation  of  the  muscle  proteins.  Both 
changes  can  be  imitated  by  heating  the  muscle,  as  is  indicated  by  Brodie's 
experiments.  This  observer  found  that,  if  a  living  muscle  be  lightly  loaded 
and  then  warmed  very  gradually,  a  series  of  stages  in  the  heat  contraction 
could  be  distinguished  corresponding  to  the  coagulation  temperatures  of 
the  different  proteins  described  by  von  Fiirth  in  muscle  plasma.  It  seems 
likely  however  that  the  main  contraction  at  all  events,  that  which  comes 
on  spontaneously  after  death  or  immediately  on  warming  the  muscle  to 
45°C.,  has  another  component.  In  the  coagulation  of  the  separated  muscle 
proteins  there  is  no  evidence  of  any  appreciable  formation  of  sarcolactic  acid, 
whereas  the  formation  of  this  substance  seems  to  bear  an  important  relation 
to  the  occurrence  of  rigor.  Thus  after  severe  muscular  fatigue,  as  in  hunted 
animals,  where  there  has  already  been  a  considerable  formation  of  the  waste 
products  of  muscular  contraction,  rigidity  may  come  on  almost  imme- 
diately after  death.  If  a  thin  living  muscle  be  plunged  into  boiling  water, 
it  undergoes  instant  coagulation,  but  no  chemical  change.  The  reaction 
of  the  scalded  muscle,  like  that  of  fresh  muscle,  is  slightly  alkaline  to 
litmus.  No  sarcolactic  acid  or  carbonic  acid  is  produced.  On  the  other 
hand,  in  surviving  muscle,  after  the  cessation  of  the  circulation,  there  is  a 
steady  formation  of  lactic  acid  which  accumulates  in  the  muscle.  The 
actual  coagulation  of  the  muscle  proteins  occurring  in  rigor  is  largely,  if  not 
entirely,  determined  by  the  increasing  acidity  of  the  muscle  thereby  pro- 
duced. In  fact,  it  is  the  production  of  the  acid  which  causes  the  onset 
of  rigor,  and  not  the  rigor  which  causes  a  sudden  formation  of  acid.  Hence 
if  the  accumulation  of  lactic  acid  be  prevented  by  perfusing  the  muscle 
with  salt  solutions,  the  onset  of  rigor  may  be  postponed  indefinitely,  and 
the  muscle  may  begin  to  putrefy  without  having  undergone  rigor. 


CHEMICAL  CHANGES   IN  MUSCLE  215 

THE  PRODUCTION  OF  LACTIC  ACID  IN  SURVIVING  MUSCLE 

The  lactic  acid  formed  in  muscle  (sarcolactic  acid)  is  a  physical  isomer  of  the  lactic 
acid  formed  in  the  fermentation  or  souring  of  milk.  They  both  have  the  formula 
CH3.CH(OH).COOH,  i.e.  they  are  ethylidene  lactic  acids.  The  lactic  acid  of  fermenta- 
tion is  optically  inactive  ;  sarcolactic  acid  rotates  polarised  light  to  the  right ;  while 
a  third  isomer  which  is  laevo-rotatory  is  produced  by  the  action  of  various  bacilli  and 
vibriones  on  cane  sugar.  The  sarcolactic  acid  can  be  extracted  from  the  muscle  by 
means  of  alcohol. 

It  was  pointed  out  by  Hopkins  and  Fletcher  that  most  of  the  methods  previously 
used  for  the  extraction  of  lactic  acid  from  muscle  caused  the  formation  of  lactic  acid 
in  this  tissue.  To  obviate  this  difficulty,  they  adopted  the  precaution  of  cooling 
the  muscles  before  cutting  them  out  of  the  body  and  then  dropping  them  into  alcohol 
cooled  to  0°C.  While  in  this  ice-cold  alcohol  they  were  finely  divided  with  scissors 
and  then  pounded  up  in  a  cooled  mortar.  In  this  way  the  tissue  was  destroyed  at 
a  temperature  which  did  not  allow  of  the  changes  responsible  in  surviving  muscle 
for  the  production  of  lactic  acid.  It  is  generally  separated  in  the  form  of  the  zinc 
sarcolactate,  by  boiling  its  partially  purified  solution  with  zinc  carbonate.  Its  presence 
may  be  tested  for  by  means  of  Uffelmann's  reagent,  which  is  made  by  the  addition  of 
ferric  chloride  to  dilute  carbolic  acid.  The  purple  solution  thus  produced  is  at  once 
changed  to  yellow  by  the  addition  of  even  traces  of  lactic  acid. 

A  much  more  definite  colour  reaction  for  lactic  acid  has  been  introduced  by  Hopkins. 
The  test  is  carried  out  in  the  following  way.  About  5  c.c.  of  strong  sulphuric  acid 
are  placed  in  a  test-tube  together  with  one  drop  of  saturated  solution  of  copper  sulphate, 
which  serves  to  catalyse  the  oxidation  that  follows.  To  this  mixture  a  few  drops  of 
the  solution  to  be  tested  are  added,  and  the  whole,  well  shaken.  The  test-tube  is  now 
placed  in  a  beaker  of  boiling  water  for  one  or  two  minutes.  The  tube  is  then  cooled 
under  a  water-tap,  and  two  or  three  drops  of  a  very  dilute  alcoholic  solution  of  thiophene 
(ten  to  twenty  drops  in  100  c.c.)  are  added  from  a  pipette.  The  tube  is  replaced  in 
the  boiling  water  and  the  contents  immediately  observed.  If  lactic  acid  is  present  the 
fluid  rapidly  assumes  a  bright  cherry  red  colour,  which  is  only  permanent  if  the  tube  be 
cooled  the  moment  after  its  appearance. 

A  study  of  the  lactic  acid  content  of  muscle  by  Fletcher  and  Hopkins, 
using  the  precautions  described  above,  has  shown  that  fresh  muscle  contains 
only  minimal  amounts  of  lactic  acid,  the  quantity  being  smaller,  the  greater 
the  care  that  is  taken  to  avoid  injury  to  the  muscle  and  to  keep  its  tempera- 
ture low  until  sufficient  time  has  elapsed  for  its  vital  chemical  processes  to  be 
destroyed  by  the  action  of  the  cold  alcohol.  If  the  muscle  be  left  in  the 
body  after  the  death  of  the  animal  or  be  excised,  a  steady  formation  of 
lactic  acid  takes  place,  which  is  more  rapid  in  the  first  few  hours  after 
death,  but  continues  until  the  muscle  passes  into  rigor.  With  the  complete 
onset  of  rigor,  frog's  muscles  are  found  to  contain  about  4  per  cent,  lactic 
acid.  After  this  time  the  amount  does  not  increase.  The  onset  of  rigor 
and  the  rate  of  production  of  lactic  acid  are  quickened  if  the  muscle  be 
kept  warm.  It  is  interesting  to  note  that  the  amount  of  lactic  acid  found 
in  rigid  muscle  is  almost  invariable  whatever  the  j^revious  history  of  the 
muscle.  Thus,  if  the  muscle  be  finely  minced  and  then  extracted  with 
cold  alcohol,  it  is  found  to  contain  about  -2  per  cent,  lactic  acid.  If  how- 
ever it  be  allowed  to  stand  after  mincing,  there  is  a  slow  production  of 
lactic  acid  up  to  the  maximum  4  per  cent.  Again,  a  muscle  which  has  been 
tetanised  to  exhaustion  contains  about  -2  per  cent,  lactic  acid.  When 
allowed  to  undergo  rigor,  the  amount  rises  to  about  4  per  cent. 


216  PHYSIOLOGY 

It  has  long  been  known  that  the  onset  of  rigor  is  associated  with  an  evolu- 
tion of  carbonic  acid  by  the  muscle.  Fletcher  has  shown  that  this  increased 
output  of  carbonic  acid  by  a  surviving  muscle  is  due  simply  to  the  driving 
off  of  carbonic  acid  from  the  carbonates  in  the  muscle  as  a  result  of  the 
production  of  lactic  acid.  There  is  no  evidence  of  a  new  formation  of  carbonic 
acid  in  the  dying  muscle  as  a  result,  for  instance,  of  oxidative  changes. 

THE  CHEMICAL  CHANGES  WHICH  ACCOMPANY  ACTIVITY 

The  principle  of  the  conservation  of  energy  teaches  us  that  the  energy 
of  the  contraction  of  muscle  must  be  derived  from  chemical  changes,  probably 
processes  of  decomposition  and  oxidation,  occurring  in  the  muscle  itself. 
In  seeking  out  the  nature  of  these  changes  three  methods  are  open  to  us : 

(1)  We  can  examine  the  changes  in  the  muscle  itself,  avoiding  so  far 
as  possible  reintegrative  changes  by  working  on  excised  muscles. 

(2)  We  can  investigate  the  changes  in  the  medium  surrounding  the 
muscle.  Muscle  may  be  exposed  in  a  vacuum  or  in  a  confined  space  of 
air,  and  its  gaseous  interchanges  during  rest  and  activity  compared.  Or 
we  may  lead  a  current  of  defibrinated  blood  through  excised  muscles,  and 
determine  the  change  in  the  composition  of  the  blood  in  passing  through  the 
muscle  under  various  conditions. 

(3)  A  method,  which  although  apparently  complex  has  rendered  the 
utmost  service  to  the  physiology  of  muscle,  is  to  use  the  changes  in  the  total 
metabolism  of  the  animal  during  rest  and  muscular  work  as  a  clue  to  the 
muscular  metabolism  itself.  In  such  a  case  the  respiratory  exchanges  of 
the  animal  are  determined  (viz.  its  oxygen  intake  and  its  C02  output), 
and  the  urine  and  faeces  are  carefully  analysed,  in  order  to  judge  of  the 
action  of  muscular  work  on  the  carbon  and  nitrogen  metabolism  of  the  body. 

By  the  third  of  these  methods  we  may  show  that  muscular  exercise 
increases  largely  the  intake  of  oxygen  and  the  output  of  carbon  dioxide 
by  the  body.  No  corresponding  changes  are  found  in  the  nitrogenous 
metabolism,  so  that  ultimately  we  may  regard  the  energy  of  the  muscular 
contraction  as  derived  from  the  oxidation  of  the  food-stuffs  and  especially 
the  carbohydrates.  That  it  is  this  class  of  bodies  which  is  the  immediate, 
or  at  any  rate  the  most  accessible,  source  of  muscular  energy,  is  shown  by 
the  rise  in  the  respiratory  quotient  which  occurs  during  muscular  exercise, 
When  the  exercise  is  moderate  there  is  no  evidence  of  the  production  of  any 
other  substance  than  carbon  dioxide  as  a  result  of  the  muscular  metabolism, 
but  with  violent  exercise  it  can  be  shown  that  lactic  acid  is  not  only  pro- 
duced in  the  muscle,  but  appears  in  the  blood  and  is  excreted  in  the  urine. 

It  has  been  shown  by  Ryffel  that  normal  urine  contains  3  —  4  mg.  of  lactic  acid 
per  hour.  In  one  experiment  the  urine  passed  after  the  observer  had  run  one  third 
of  a  mile  with  the  production  of  severe  breathlessness  contained  454  mg.  of  lactic  acid. 
In  another  experiment  blood  obtained  before  running  contained  12-5  mg.  per  100  c.c, 
and  that  obtained  immediately  after  running  one  third  of  a  mile  contained  70  mg. 
lactic  acid  per  100  c.c.  On  the  other  hand,  the  examination  of  the  urines  of  com- 
petitors in  a  twenty-four  hours  track  walking  race  showed  no  increase  in  the  output 
of  lactic  acid  above  the  normal  4  mg.  per  hour. 


CHEMICAL  CHANGES  IN  MUSCLE  217 

The  appearance  of  lactic  acid  thus  seems  to  be  attendant  on  a  relative 
deficiency  in  the  oxygen  supply  to  the  contracting  muscle.  The  same 
conclusion  may  be  drawn  from  experiments  made  many  years  ago  by  Araki, 
in  which  lactic  acid  was  observed  in  quantities  in  the  urine  in  cases  where 
the  oxidative  processes  of  the  body  were  interfered  with  by  CO  poisoning. 

Similar  results  are  obtained  when  we  investigate  the  chemical  changes 
accompanying  the  contraction  of  excised  muscles  of  the  frog.  If  frogs' 
muscle  be  hung  up  in  an  atmosphere  of  nitrogen  and  stimulated  repeatedly 
with  single  shocks,  it  will  give  a  series  of  contractions  gradually  diminishing 
in  size  (v.  p.  209).  After  a  time  the  muscle  is  completely  fatigued,  and 
no  further  response  can  be  elicited  on  stimulation.  On  now  examining  it, 
it  is  found  to  be  acid  in  reaction  and  to  contain  about  2  per  cent,  lactic 
acid.  There  is  no  evidence  that  under  these  conditions  any  carbonic  acid 
is  produced,  though  a  certain  amount  may  be  liberated  in  consequence  of  the 
acidification  of  the  muscle.  Almost  the  -same  results  are  obtained  when 
the  muscle  is  stimulated  in  ordinary  atmospheric  air.  The  penetration 
of  oxygen  from  the  air  through  the  body  of  the  muscle  is  so  slow  that  all 
the  muscle  except  the  thin  layer  on  the  surface  may  be  regarded  as  cut  off 
from  the  action  of  oxygen.  By  hanging  the  muscle,  especially  a  thin  muscle 
such  as  the  sartorius,  in  an  atmosphere  of  pure  oxygen,  the  results  are  quite 
different.  In  the  first  place  the  muscle  does  not  fatigue  so  soon.  More- 
over, a  muscle  which  has  been  stimulated  to  exhaustion  in  an  atmosphere  of 
nitrogen,  if  restored  to  one  of  pure  oxygen,  will  rapidly  recover  its  power 
of  contraction.  In  pure  oxygen  no  lactic  acid  is  produced,  and  a  muscle 
stimulated  to  exhaustion  contains  very  little  more  lactic  acid  than  does 
resting  muscle.  On  the  other  hand,  the  intake  of  oxygen  and  the  output 
of  carbonic  acid  by  the  muscle  is  increased  at  each  contraction.  We  thus 
find  that  a  muscle  during  contraction  may  produce  lactic  acid  or  carbonic 
acid  according  as  oxygen  is  absent  or  present.  In  both  cases  contraction 
takes  place  apparently  normally,  but  fatigue  supervenes  much  more  rapidly 
in  the  absence  of  oxygen.  The  question  arises  whether  we  should  regard 
the  formation  of  lactic  acid  and  carbonic  acid  as  alternative  processes,  or 
whether  lactic  acid  is  first  formed  and  is  then  removed  under  the  action  of 
oxygen,  undergoing  partial  or  complete  oxidation  to  carbonic  acid  in  the 
process.  The  evidence  is  distinctly  in  favour  of  the  second  hypothesis. 
Thus  Hopkins  and  Fletcher  have  found  that  muscle  possesses  in  itself  a 
chemical  mechanism  for  the  removal  of  lactic  acid.  If  a  fatigued  muscle 
be  exposed  to  pure  oxygen,  30  per  cent,  of  the  lactic  acid  present  in  the 
muscle  may  disappear  within  two  hours  and  50  per  cent,  within  six  to 
ten  hours.  Thus,  even  apart  from  the  circulation  which  of  course  would 
remove  large  quantities  of  any  lactic  acid  which  might  be  produced  in 
the  muscles,  these  can  deal  with  this  metabolite  locally.  It  has  been  found 
that  a  muscle  may  be  fatigued  several  times  and  then  placed  in  oxygen 
to  recover,  so  that  lactic  acid  is  produced  and  removed  also  several  times. 
If  at  the  end  the  muscle  be  allowed  to  undergo  rigor,  it  is  found  to  contain 
•4  per  cent,  lactic  acid,  i.e.  exactly  the  same  amount  as  if  it  had  given 


218  PHYSIOLOGY 

110  contractions  at  all.  Fletcher  and  Hopkins  interpreted  this  result  as 
showing  that  under  the  influence  of  oxygen,  lactic  acid  is  put  back  into 
the  precursor  from  which  it  arose,  anil  would  assume  that  part  of  the  lactic 
acid  is  completely  oxidised  to  carbonic  acid  and  water,  the  energy  so  evoh  ed 
being  employed  in  the  building  up  of  the  precursor  from  the  rest  of  the  lactic 
acid.  On  the  other  hand  it  is  possible  that  the  lactic  acid  produced  in  the 
initial  stage  of  contraction  may  be  ui.der  normal  circumstances  completely 
removed  by  oxidation,  and  that  the  energy  or  part  of  the  energy  so  made 
available  is  used  to  build  up  some  precursor  substance,  not  out  of  the  lactic 
acid,  but  out  of  the  glycogen  already  present  in  the  muscle  (Parnas).  It 
is  certain  that  prolonged  activity  of  muscle,  especially  in  the  presence  of 
oxygen,  may  be  associated  with  a  diminution  in  the  glycogen  store  of  the 
muscle.  We  cannot  however  discuss  this  question  further  without  refer- 
ence to  the  total  energy  changes  in  muscle  contracting  with  or  without 
oxygen,  and  the  clue  to  these  changes  is  given  by  a  study  of  the  heat 
production  in  muscle. 


SECTION  VI 

THE    PRODUCTION   OF    HEAT   IN   MUSCLE 

The  experience  of  everyday  life  teaches  us  that  muscular  exercise  is 
associated  with  increased  production  of  heat.  Thus  a  man  walks  fast  on  a 
frosty  day  to  keep  himself  warm.  In  large  animals  the  production  of  heat 
in  muscular  contraction  can  be  easily  shown  by  inserting  the  bulb  of  a 
thermometer  between  the  thigh  muscles,  and  stimulating  the  spinal  cord. 
The  rise  of  temperature  produced  in  this  way  may  amount  to  several  degrees. 
This  observation  is  confirmed  when  we  investigate  the  contraction  of  an 
isolated  muscle  outside  the  body.  If  a  frog's  muscle  is  tetanised,  its  tem- 
perature rises  from  0-14"'  to  0-18°C,  and  for  each  single  twitch  from  0-001° 
to  0'C05°C. 

It  is  evident  that  such  small  changes  in  temperature  as  0001°  cannot  be  estimated 
by  ordinary  thermometric  methods.     By  converting  a  heat  change  into  an  electrical 
change  however,  we  can  estimate  differences  of  temperature  with  much  greater  accuracy 
and    fineness  than  by  the  use  of   a   thermometer. 
Two    main  principles  are    employed    in    measuring 
temperature    by   electrical  methods.      The  thermo- 
electrical   method  depends  on   the   fact   that,   when 
the  junctions  of   a   circuit   made   of  two  metals  are   Antimony 
at    different   temperatures,    a   current   of  electricity  "^^-<// 

generally  flows  through  the  circuit.     This  current  can  ^^^^^ 

be  measured    by  means   of   a   galvanometer,  and  is  warm 

proportional  to  the  difference  of  temperature  between  Fig.  73. 

i!i.    two  junctions.     Thus    in    the    circuit    (Fig.  73) 

composed  of  two  metals,  antimony  and  bismuth,  if  the  upper  junction  be  cooled,  there 
will  be  a  current  flowing  from  antimony  to  bismuth  in  the  direction  of  the  arrow, 
and  this  current  will  within  limits  be  proportional  to  the  difference  of  temperature. 
To  measure  the  production  of  heat  during  muscular  contraction,  a  small  flat  thermo- 
pile (containing  four  or  six  elements  composed  of  iron  and  German  silver,  or  copper 
and  '  eonstantan ' )  is  iixed  with  one  of  its  ends  between  two  frogs'  gastrocnemii. 
Another  exactly  similar  pile,  but  reversed,  is  placed  between  two  other  gastrocnemii, 
which  are  kept  resting  and  at  a  perfectly  constant  temperature.  .So  long  as  the  two 
piles  are  at  the  same  temperature  no  current  flows  ;  but,  with  a  sensitive  galvano- 
meter, the  slightest  difference  of  temperature,  such  as  that  caused  by  the  contraction 
of  one  pair  of  muscles,  at  once  causes  a  deflection  of  the  galvanometer,  the  extent  and 
direction  of  which  enable  us  to  estimate  exactly  the  seat  and  amount  of  heat  produced. 
When  we  are  using  such  delicate  detectors  of  temperature  difference,  we  are  met 
bv  t  he  difficulty  that  every  junction  in  the  circuit  tends  to  become  the  seat  of  an  electro- 
motive force  in  consequence  of  slight  changes  of  temperature  due  to  currents  oi  air,  &c. 
It  is  therefore  advisable  to  use  a  plan  adopted  by  Blix,  of  placing  all  the  apparatus, 
the  muscle  included,  within  the  galvanometer  case.  The  arrangements  of  such  an 
experiment  as  employed  by  A.  V.  Hill  are  shown  in  the  diagram  (Fig.  74). 

219 


COOL 

Q 


220 


PHYSIOLOGY 


In  this  instrument  the  junction  of  copper  with  the  alloy  constantan  constitutes 
a  thermo-electric  couple.  The  magnet  and  mirror  chamber  are  entirely  separated  off 
from  the  rest  of  the  instrument  by  the  walls  of  the  tube  containing  the  magnet.  The 
grooves  are  usually  filled  with  plasticine,  and  into  them  fit  the  edges  of  an  outer  case 
of  brass  constituting  the  walls  of  the  muscle  chamber.  The  inside  of  this  case  is  lined 
with  wet  blotting-paper.  The  copper  coil  consists  of  many  more  turns  than  are  shown 
in  the  figure  ;  its  ends,  aa  and  bb,  are  separated  by  the  celluloid  plate,  and  are  con- 
nected by  the  constantan  plug ;  the  points  where  the  copper  meets  the  constantan 
constitute   the   thermo-electric   junctions.     The   tube   containing  the  magnet  hangs 


'agnet  &  Mirror  Chamber 


ra: 


Quartz  Fibre 

Mirror 
Groov, 


Constantan  Plug 


Fig.  74. 

down  through  holes  bored  in  the  broad  copper  coil.  The  two  semimembranosus  muscles 
ride  astride  of  the  celluloid  plate,  one  in  contact  with  each  end  of  the  constantan  plug. 
The  small  piece  of  bone  at  their  upper  ends  which  has  been  left  connecting  the  two  muscles 
is  placed  exactly  on  the  top  of  the  celluloid  plate  at  x  and  held  in  position  by  a  clamp 
(not  shown  in  the  figure).  The  copper  terminals  of  the  coil  are  coated  with  celluloid 
varnish  to  prevent  short  circuiting  of  the  thermo-electric  currents,  and  to  prevent 
poisoning  of  the  muscles.  Each  muscle  is  in  contact  with  a  pair  of  electrodes,  made 
of  fine  platinum  wire  :  the  muscle  lies  over  the  upper  end  beneath  the  lower  of  these 
electrodes,  as  .shown  in  the  figure.  The  tendons  at  the  lower  ends  of  the  muscles  are 
tied  to  silk  threads  which  pass  through  holes  in  the  base  of  the  instrument.  These  are 
then  attached  to  recording  levers  which  write  on  a  drum  beneath  the  table.  When 
all  is  ready  three  heavy  soft-iron  cylinders  are  placed  over  the  instrument  :  the  latter 
is  screwed  to  a  wooden  block  which  is  fixed  to  a  thick  iron  plate  attached  to  the  table. 
In  the  cylinders  holes  are  bored  to  admit  and  let  out  after  reflexion  the  light  from  a 
Nemst  lamp.  The  lamp,  which  is  about  three  metres  away,  shines  upon  the  mirror, 
and  a  line  in  it,  after  reflexion,  is  focussed  on  to  the  screen,  which  is  also  three  metres 
away.  The  line  is  brought  on  to  the  scale  by  the  small  field  exerted  by  a  control  magnet 
placed  outside  the  cylinders  at  a  suitable  position  on  the  table  :  its  position  may  be 
read  easily  to  half  a  millimetre,  and  the  movement  due  to  a  twitch  is  usually  of  the  order 
of  80  mm.  These  soft-iron  cylinders  cut  off  entirely  all  external  magnetism  sufficient 
to  cause  harmful  disturbance  during  an  experiment.     They  lower  very  largely  the 


PRODUCTION   OF  HEAT  IN  MUSCLE 


221 


strength  of  the  constant  external  field  in  which  the  magnet  lies,  and  leave  it  chiefly 
supported  in  any  position  by  the  quartz  fibre.  Thus  all  the  movements  set  up  in 
the  magnet  by  the  thermo-electric  currents  are  working  against  little  more  than  the 
torsion  of  a  quartz  fibre  only  6^,  thick.  This  explains  the  great  sensitivity  of  the 
instrument. 

A  second  method  depends  on  the  fact  that  rise  of  temperature  increases  the  resistance 
of  a  wire  to  the  passage  of  an  electric  current.  A  current  detector  consists  of  a  small 
grid  of  fine  platinum  wire  which  is  placed  against  the  muscle  between  two  muscles. 
This  grid  is  then  made  one 
limb  of  .1  Wheatstone's  bridge 
(Fig.  74a).  A  small  current 
is  passed  through  the  circuit, 
and  the  resistances  are  so 
adjusted  that  no  current 
flows  through  the  galvano- 
meter. Any  alteration  in 
temperature  of  the  grid  will 
alter  the  balance  of  the  re- 
sistance and  will  cause  a 
current  to  flow  through  the 
galvanometer  in  a  direction 
which  will  vary  according 
as  the  resistance  in  the  grid 
is  increased  or  diminished.  It 
is  possible  to  calibrate  the 
nrrangemenl  so  (hat  a  deflection  of  the  galvanometer  over  one  degree  will  correspond 
lo  a  certain  fraction  of  a  degree  of  difference  in  temperature  of  the  grid.  This 
method  is  employed  in  Callender's  recording  thermometers,  and  has  been  made  by 
Gamgee  the  basis  of  an  arrangement  for  the  continuous  record  of  the  temperature  of 
the  human  bodv. 


Fig.  74a.     Arrangement  of  apparatusfor 

small  differences  of  temperature. 


Most  of  the  earlier  work  on  the  development  of  heat  in  muscle  had  as 
its  leading  motive  the  discovery  of  the  relation  between  the  heat  produced 
and  the  work  performed  by  a  muscle  under  varying  conditions  of  load. 
When  a  loaded  muscle  contracts  however,  it  is  not  easy  to  analyse  its 
mechanical  conditions,  since  part  of  the  shortening  of  the  muscle  during 
contraction  can  be  regarded  merely  as  a  recovery  from  the  condition  of 
extension  induced  by  the  weight,  and  the  amplitude  of  the  excursion  may 
be  largely  conditioned  by  the  inertia  of  the  weight  moved.  Working  on 
these  lines,  Heidenhain  discovered  that  the  heat  production  in  muscle 
during  contraction  is  not  an  invariable  quantity,  but  varies  according  to 
the  condition  of  the  muscle  and  especially  according  to  the  tension  developed 
in  it  during  contraction.  It  was  therefore  at  its  maximum  under  isometric 
conditions  when  it  was  not  allowed  to  shorten  at  all  during  contraction. 
\~  we  have  seen,  the  muscle  changes,  as  the  result  of  excitation,  from  a  body 
having  certain  elastic  properties  to  one  having  other  elastic  properties. 
The  whole  energy  of  the  contraction  is  converted  for  a  short  period  into  a 
state  of  tension  which  can  be  used  to  do  work  by  raising  a  weight.  If  it 
be  not  allowed  to  shorten,  the  state  of  tension  passes  off  and  the  whole 
energy  which  has  been  set  free  must  appear  as  heat.  The  potential  energy 
developed  in  a  muscle  twitch  is  approximately  equal  to  J;  T/,  where  T  is  the 


222  PHYSIOLOGY 

tension  developed  and  /  the  length  of  the  muscle,  and  it  is  this  amount 
which  must  be  compared  with  the  heat  production  measured  in  the  muscle 
by  one  of  the  methods  described.  A.  V.  Hill  has  shown  that  the  heat 
production  in  a  contracting  skeletal  muscle  occurs  in  two  phases,  a  rapid 
production  of  heat  which  apparently  is  synchronous  with  the  contraction 
itself,  and  a  slow  production  of  heat  which  continues  for  some  time  after 
fehe  muscle  has  relaxed.  The  second  phase  of  heat  production  depends  on 
the  presence  of  oxygen,  and  is  observed  at  its  best  when  the  muscle  is  kepi 
in  pure  oxygen.  If  the  muscle  be  allowed  to  contract  in  nitrogen  only 
the  initial  heat  production  is  observed.  The  heat  production  of  the  second 
phase  is  stated  by  Hill  to  be  approximately  equal  to  that  in  the  first  phase. 
These  results  have  been  interpreted  as  showing  that  the  initial  change  in 
muscular  contraction  is  the  development  of  lactic  acid.  The  appearance 
of  this  lactic  acid  in  some  way  changes  the  muscle  and  sets  up  potential 
energy  at  the  surface  of  its  ultimate  fibrils,  which  will  result  in  a  shortening 
of  the  muscle  if  any  movement  of  its  ends  be  allowed.  A  comparison  of 
the  energy  of  the  tension  set  up  with  the  actual  heat  evolved  in  the  initial 
stage  when  a  muscle  is  not  allowed  to  contract  shows  that  the  two  quantities 
are  approximately  equal.  In  a  series  of  experiments  Hill  found  that  the 
ratio  (V  Tl. :  H  in  the  sartorius  muscle,  under  low  initial  tensions  and  in 
comparatively  weak  contractions  approximated  to  the  value  1,  the  mean 
value  being  -91.  Under  high  initial  tensions  and  in  strong  contractions 
of  the  sartorius  muscle,  it  is  lower,  being  roughly  from  0-4  to  0-6.  He 
concludes  from  this  that  under  certain  conditions  the  initial  process  of  con- 
traction consists  largely,  if  not  entirely,  of  the  liberation  of  free  potential 
energy  manifested  as  tension  in  the  muscle.  This  potential  energy  may  be 
used  for  the  accomplishment  of  work  or  for  the  production  of  heat.  The 
efficiency  of  the  initial  stage  of  contraction  is  therefore  almost  100  per  cent. 
If  however  a  muscle  is  to  go  on  contracting  without  rapidly  showing 
signs  of  fatigue,  it  must  be  kept  in  oxygen,  so  that  the  processes  of  replace- 
ment or  of  removal  of  the  lactic  acid  may  take  place.  Under  these  circum- 
stances there  is  a  further  evolution  of  heat  after  the  contraction,  equal  to 
that  set  free  during  the  initial  stage.  So  that  the  total  efficiency  of  a  muscle 
kept  in  oxygen  would  not  be  more  than  50  per  cent. 

This  is  assuming  that  the  process  of  oxidation  of  the  lactic  acid  and  its  replace- 
ment in  whole  or  in  part  in  the  muscle  molecule  is  completely  carried  out  during  the 
time  of  the  ob?ervation.  It  is  improbable  that  such  is  the  case,  and  it  seems  possible 
that  the  evolution  of  heat  during  the  jo-called  recovery  stage  of  the  muscle  has  been 
under-estimated. 

If  a  series  of  observations  of  the  heat  production  and  tension  developed 
during  isometric  contractions  be  made  with  varying  initial  length  of  the 
muscle,  it  is  found  that  while  the  ratio  of  tension  developed  to  heat  produced 
is  approximately  constant,  both  these  quantities  first  increase  and  then 
finally  diminish.  The  optimum  of  the  heat  production  in  some  experiments 
seems  to  fall  later  than  the  optimum  of  the  tension  developed.  Thus  the 
longer  the  muscle  fibre,  within  limits,  when  it  is  excited,  the  greater  the  ten- 


PRODUCTION  OF  HEAT  IN  MUSCLE  223 

sion  and  the  greater  the  heat  production  developed,  i.e.  we  may  assume  that 
increased  length  of  muscle  fibre  increases  the  chemical  changes,  ensuing  on 
excitation,  which  are  responsible  both  for  the  development  of  mechanical 
energy  and  the  production  of  heat.  The  significance  of  these  results  for  the 
essential  nature  of  muscular  contraction  we  shall  discuss  in  a  later  chapter. 


.SECTION  VII 


ELECTRICAL  CHANGES   IN   MUSCLE 

If  a  current  from  a  battery  be  passed  between  i»"  plates  of  platinum  immersed  in 
acidulated  water  or  salt  solution,  electrolysis  of  the  water  takes  place,  bubbles  of  oxygen 
appearing  on  the  positive  plate  (anode),  and  bubbles  of  hydrogen  on  the  negative 
plate  (cathode).  If  now  we  remove  the  battery,  and  connect  the  two  plates  (electrodes) 
by  wires  with  a  galvanometer,  a  current  passes  through  the  galvanometer  and  water 
in  the  reverse  direction  to  the  previous  battery  current. 
This  current  is  called  the  polarisation  current,  and  is  due 
to  the  electrolysis  of  the  water  that  has  taken  place. 
The  vessel  in  which  the  electrodes  are  immersed  has  in 
fact  become  a  galvanic  cell,  the  platinum  covered  with 
oxygen  bubbles  being  the  positive  element,  and  that  covered 
with  hydrogen  bubbles  the  negative  element.  Exactly  the 
same  process  of  electrolysis  or  polarisation  takes  place 
when  we  pass  currents  through  the  tissues  of  the  body  by 
means  of  metallic  electrodes. 

Hence  before  we  can  study  accurately  the  delicate 
electrical  changes  that  may  occur  normally  in  living 
tissues,  it  is  necessary  to  have  some  form  of  electrodes  in 
o.covered  wire;  b,  amal-  which  this  polarisation  will  not  occur.  The-  '  non-polari- 
gamated  zinc  rod  ;  e,  sable  '  electrodes  which  are  most  generally  used  for  this 
glass  tube  ;  d,  saturated  purp0Be  are  made  in  the  following  way.  A  glass  tube 
ZnS04  solution  ;  cplug  ot  )  „.,  •       ,        ,      .  ,      .,,    °     ,   J     .  ,      ,.  , 

zinc  sulphate  clay  ; f  plug  '  &•  7'5'  ls  closetl  at  one  end  with  a  plug  of  kaolin  made 
of  normal  saline  clay.  into  a  paste  with  a  saturated  solution  of  zinc  sulphate. 
The  rest  of  the  tube  is  filled  with  a  similar  solution.  Dip- 
ping into  the  zinc  sulphate  solution  is  a  rod  of  pure  zinc,  amalgamated.  Just  before 
use.  a  plug  of  china  clay  made  with  normal  saline  solution  is  put  on  the  end  of  the 
tube,  so  as  to  effect  a  connection  between  the  zinc  sulphate  clay  and  the  nerve  or  muscle 
which  it  is  desired  to  stimulate  or  lead  off.  In 
these  electrodes  there  is  no  contact  of  metals  with 
fluids  that  can  produce  dissimilar  ions  (e.g.  hy- 
drogen or  oxygen)  at  the  surface  of  contact,  and 
hence  they  may  be  regarded  as  practically  non- 
polarisable.  A  more  convenient  form  is  that 
employed  by  Burdon  Sanderson,  in  which  the  glass 
t  ube  is  bent  into  a  U  (Fig.  76).  The  mouth  of  the 
tube  is  closed  by  a  smaller  glass  tube  plugged  with 
clay,  and  bearing  a  plug  of  normal  saline  clay. 
In  such  electrodes  the  conduction  of  the  cur- 
rent through  the  nerve  or  muscle  to  the  metallic 
part  of  the  circuit  may  be  represented  as  shown  on  the  opposite  page  (see  Fig.  77). 

If  a  muscle  such  as  the  sartorius  be  removed  from  the  body,  and  two  non- 
polarisable  electrodes  connected  with  a  delicate  galvanometer  be  applied 
to  two  points  of  its  surface,  there  will  be  a  deflection  of  the  mirror  attached 
to  the  galvanometer,  showing  the  presence  of  a  current  in  the  muscle  from 


Fia.  75.     Diagram  of   non 
polarisable  electrode. 


U  -Imped  non-polaricable 
electrodes. 


ELECTRICAL  CHANGES   IN  MUSCLE 


225 


the  ends  to  the  middle,  and  in  the  external  circuit  from  the  middle  (or  equator) 
to  the  ends.  It  was  formerly  thought  that  this  current  was  always  present 
in  all  normal  muscles,  and  it  was  spoken  of  as  the  '  natural  muscle  current '  ; 
the  muscle  was  said  to  be  made  up  of  a  series  of  electromotive  molecules,  the 
equator  of  each  molecule  being  positive  to  the  two  poles  (du  Bois  Raymond). 
It  has  been  conclusively  shown  however  (by  Hermann  and  others)  that  this 


Zn 


+         + 

Zn       Na 

SO*     CL 


+ 
Na 


+ 
Zn 


— — 
Tissue 


CL        SO* 


+ 

Zn 

+ 


Current  of  rest. 


current  of  resting  muscle  is  not  a  natural  current  at  all,  but  is  due  to  the 
effects  of  injury  in  making  the  preparation.  The  less  the  preparation  is 
injured,  the  smaller  is  the  current  to  be  obtained  from  it,  and  in  some  con- 
tractile tissues,  such  as  the  heart,  there  may  be  absolutely  no  current  during 
quiescence. 

Hermann  describes  the  fact  of  the  existence  of  currents  of  rest  thus  ; 
"  In  partially  injured  muscles  every  point  of  the  injured  part  is  negative 
towards  the  points  of  the  uninjured  surface."     Fig.  78  shows  the  direction 

of  the  current  in  a  muscle  with  two  cut  ends.    

When  the  whole  muscle  is  quite  dead,  this  cur-  f +   £  *  *   + 

rent  of  rest,  or    '  demarcation   current '  (Her-    — 1 ;* 

mann),  disappears.      The  current  is  due  to  the  *A       ""^-       " 

electrical  differences  at  the  junction  of  living 
and  dying  (not  dead)  tissue.  If  the  sartorius 
of  the  frog  be  cut  out  and  immersed  for  twenty- 
four  hours  in  0-6  per  cent.  NaCl  solution  made  with  tap  water  (i.e.  con- 
taining lime),  all  the  injured  fibres  die.  and  the  uninjured  fibres  are  then 
found  to  be  iso-electric  and  therefore  currentlefs. 

The  existence  of  this  current  may  be  demonstrated  without  using  a  galva- 
nometer. If  the  nerve  of  a  sensitive  muscle-nerve  preparation  a,  (Fig.  79)  be 
allowed  to  fall  on  an  excised  muscle  b.  so  that  two 
points  of  the  nerve  are  in  contact  with  the  cut  end 
and  with  the  surface  of  the  second  muscle  b,  the 
muscle  a  will  contract  each  time  the  nerve  touches  b 
so  as  to  complete  the  circuit. 

Whatever  be  the  explanation  of  this  current  of 
resting  muscle,  there  is  no  doubt  that  a  very  definite 
electrical  change  occurs  in  a  muscle  when  it  contracts 
To  show  this  change,  we  may  lead  off  two  points,  one 
on  the  cut  end  and  one  on  the  surface  of  the  muscle  of  a  muscle-nerve  pre- 
paration,to  a  galvanometer,  We  shall  then  obtain  a  deflection  of  the  mirror  of 


Fio.  70. 

Rheoscopic  frog. 


225 


15 


226 


PHYSIOLOGY 


the  magnet,  due  to  the  current  of  rest  or  demarcation  current.  If  now  the 
nerve  be  stimulated  with  an  interrupted  current  so  as  to  throw  the  muscle 
into  a  tetanus,  the  ray  of  light  from  the  galvanometer  mirror  swings  back 
towards  the  zero  of  the  scale,  showing  that  the  current  which  was  present 
before  is  diminished.  When  the  excitation  of  the  nerve  is  discontinued,  the 
galvanometer  indicates  once  more  the  original  current  of  rest.  This 
diminution  of  the  current  of  rest  during  activity  of  a  muscle  is  spoken  of  as 
the  '  negative  variation.' 

In  carrying  out  this  experiment  it  is  usual  to  compensate  the  demarcation  current 
by  sending  in  a  small  fraction  of  the  current  from  a  constant  cell.  The  arrangement 
of  the  apparatus  is  represented  in  the  accompanying  diagram.     Two  non-polarisable 

D 


Fig.  80. 

electrodes  wp  are  applied  to  the  surface  and  cross-section  of  a  muscle  m.  These  are 
connected  with  the  shunt  of  the  galvanometer,  one  of  the  wires  however  being  con- 
nected with  a  Pohl's  reverser  P,  and  this  in  its  turn  with  the  shunts.  The  two  end- 
terminals  of  the  reverser  are  connected  with  a  rheochord,  through  the  wire  of  which 
ab  a  constant  current  is  passing  from  the  Daniell  cell  D.  By  means  of  the  rider  c  the 
fraction  of  current  passing  through  the  reverser  can  be  modified  to  any  extent.  The 
key  k  being  open,  the  muscle  is  connected  with  the  shunt  and  galvanometer,  and  the 
direction  and  extent  of  the  swing  noticed.  The  key  k  is  then  closed,  and  by  means 
of  the  reverser  the  current  is  sent  through  the  galvanometer  in  the  opposite  direction  to 
the  demarcation  current,  and  the  rider  c  shifted  until  the  two  currents  exactly  balance 
one  another,  and  the  needle  of  the  galvanometer  returns  to  zero  of  the  scale.  This 
adjustment  is  first  made,  using  only  ir}Tli^  of  the  total  current,  and  then  by  means  of 
the  shunt,  t± rn,  fo,  and  finally  the  whole  current  is  thrown  into  the  galvanometer. 
If  this  precaution  be  not  taken,  much  too  large  a  current  may  in  the  first  case  be  sent 
through  the  galvanometer,  to  the  detriment  of  the  instrument.    If  we  know  the  difference 

of  potential  between  the  two  ends  of  the  wire,  the  proportion—-  will  give  us  the  E.M.F.  of 

ab 

the  demarcation  current.     The  galvanometer  needle  having  by  compensation  been 

brought  to  zero,  stimulation  of  the  nerve  at  e  by  interrupted  currents  causes  the  needle 

to  swing  at  once  in  the  opposite  direction  to  the  first  variation.     This  swing  is  the 

measure  of  the  negative  variation  or  current  of  action. 

In  order  to  study  the  electrical  changes  accompanying  a  single  muscle  twitch, 

it  is  necessary  to  employ  some  instrument  which  can  react  much  more  rap  idly  than  the 


ELECTRICAL  CHANGES   IN   MUSCLE 


227 


ordinary  galvanometer.     For  this  purpose  we  may  employ  either  the  capillary  electro- 
meter or  the  string  galvanometer  of  Einthoven. 

The  capillary  electrometer  is  an  instrument  for  recording  and  measuring  difference 
of  potential.  That  is  to  say,  if  connected  with  two 
points,  it  measures  the  force  which  would  make  a 
current  flow  between  these  two  points  if  they  were 
connected  by  a  wire.  Its  structure  is  very  simple.  It 
consists  of  a  glass  tube  drawn  out  to  a  fine  capillary 
point.  This  tube  with  the  capillary  is  filled  with 
mercury.  The  point  dips  into  a  wide  tube  containing 
dilute  sulphuric  acid,  at  the  bottom  of  which  is  a 
little  mercury.  Two  platinum  wires  fused  into  the 
glass  and  dipping  into  the  mercury  serve  as  terminals. 
When  the  instrument  is  used,  the  meniscus  of  the 
mercury  in  the  capillary  at  its  junction  with  the  acid 
is  observed  under  the  microscope,  or  a  magnified 
image  of  it  is  thrown  on  a  screen  with  the  aid  of  the 
electric  light.  If  now  the  capillary  and  acid  be  con- 
nected with  two  points,  it  will  be  observed  that  any 
difference  in  the  potential  of  these  two  points  causes 
a  movement  of  the  meniscus.  If  the  point  connected 
to  acid  be  negative  as  compared  with  the  point 
connected  to  mercury  in  capillary,  the  meniscus 
moves  towards  the  point  of  the  capillary.  If  the 
acid  be  positive  as  compared  with  the  capillary,  the 
meniscus  moves  away  from  the  point.  The  extent 
of  the  excursion  is  proportional  to  the  difference  of 
potential.  Since  the  capillary  electrometer  appears 
to  have  no  latent  period,  and  is  free  from  instru- 
mental vibrations,  it  is  extremely  useful  in  recording 
the  quick  changes    in  potential    occurring    in  the  y       8] 

diphasic  electrical  changes    that  accompany  every   Capillary  electrometer, 
contraction-wave  in  the  body.     The  excursions  lend 

themselves   well  to   photography,  so  that  we   may   obtain  a  graphic  record 
electrical  variation,  and  thus  determine  its  extent  and  its  time-relations. 

It  must  be  remembered  that  this  instrument  is  an  electrometer  (measurer  of  differ- 


(Burch.) 
of  every 


Fig.  82.  Fig.  83. 

ence  of  potential),  and  not  a  galvanometer  (current  measurer).     When  the  electrometer 
is  connected  with  two  points  at  different  potential,  current  passes  into  it  for  a  fraction 


228 


PHYSIOLOGY 


ol  a  second,  and  polarises  the  surface  of  the  mercury,  so  that,  it  takes  up  a  new  position 
in  the  capillary.  This  polarisation  causes  an  electromotive  force  which  exactly  balances 
the  E.M.F.,  setting  up  the  polarisation  so  that  no  current  passes  the  surface.  Hence 
the  use  of  non-polarisable  electrodes  is  not  so  essential  in  experiments  with  this  instru- 
ment as  when   we  make  use  of  the  galvanometer. 

In  the  D,Arsonval  galvanometer  (Fig.  82)  the  current  is  sent  through  a  coil  of  fine 
wire  hung  between  the  pules  of  »  permanent  magnet.  The  same  principle  is  made  use 
of  in  the  string  galvanometer  of  Einthovcn  (Fig.  83).  In  this  a  very  delicate  thread 
of  silvered  quartz  or  of  platinum  is  stretched  between  the  poles  of  a  strong  magnet. 
The  poles  of  the.  magnet  are  pierced  by  holes  so  that,  the  thread  may  be  illumined  by 
an  electric,  light:  from  one  side,  and  from  the  other  may  be  observed  by  means  of  a 
microscope  :  or  a  magnified  image  of  the  thread  may  he  thrown  upon  a  screen.  When- 
ever a  current  passes  through  the  thread  it  moves  laterally,  and  the  lateral  movement 
miiv  be  photographed  on  a  moving  photographic  screen.  Owing  to  the  minute  dimen- 
sions of  the  thread  the  instrument  is  one  of  extreme  delicacy.  It  will  detect  very  minute 
currents  and  will  respond  accurately  to  very  rapid  changes  in  potential. 


If  a  perfectly 


uninjured  regular  muscle  (Fig.  84),  surh  as  the  sartorius 
he  stimulated  with  a  single  in- 
duction shock  at  one  end,  x, 
and  two  points,  o  and  b,  be 
led  off  to  a  capillary  electro- 
meter, each  stimulus  applied 
at  a;  gives  rise  to  an  excursion 
of  the  meniscus  of  the  electro- 
meter, known  as  a'  spike,'  and 


Diagram  showing  diphasic  variation 
of  uninjured  muscle. 


shown  in  Fig.  85.  Knowing  the  constants  of  the  instrument  used,  we 
can  analyse  this  spike,  and  we  find  that  it  represents  a  diphasic  change. 
Our  study  of  the  mechanical 
changes  in  muscle  has  shown 
that,  when  the  muscle  is  stimu- 
lated at  x,  a  contraction  wave 
commences  which  travels  down 
the  muscle  through  a  and  b. 
The  electrical  investigation  of 
the  muscle  shows  that  excita- 
tion of  x  arouses  an  electrical 
change  which  also  passes  down 
the  muscle  at  the  same  rate  as 
the  mechanical  change  which 
it  precedes.  If  we  are  leading 
off  from  x  and  a,  the  electrical 
change  ensues  immediately 
upon  stimulus,  i.e.  there  is  no 
latent  period  to  the  electrical 
change.  On  leading  off  from  a 
and  b  there  is  a  latent  period 
between  the  stimulus  and  the 
first   change,   representing    the 


Fig.  85.  A  typical  electrometer  record  from  a  sar- 
torius muscle  excited  by  a  single  induction  shock. 
Time-marking =200  D.V.     (Keith  Lucas.) 

time    taken    for1  the    change    to    travel 


ELECTRICAL  CHANGES  IN  MUSCLE 


229 


from  x  to  a.  When  the  change  reaches  a  this  becomes  the  seat  of  an 
electromotive  force  of  such  a  direction  that  the  current  would  pass  in 
the  outer  circuit  from  b  to  a.  We  may  say  therefore  that  a  is  negative  to  b. 
A  fraction  of  a  second  later  the  excitatory  change  has  passed  on  to  b  and  has 
died  away  at  a.  -Now  b  is  negative  to  «,*  and  the  current  therefore  passes 
in  the  opposite  direction.  Between  a  and  b  therefore,  there  is  a  diphasic 
current,  the  first  phase  representing  negativity  of  a  to  b,  and  the'second  phase 
A  B 


FlQ.  80.     Diphasic  response  of  uninjured  sartorius  (obtained  by  analysis  of  curves  such  as 
Fig.  85).     a,  at  8°C.  ;   B,  at  18°C.        (Keith  Lucas.) 

representing  negativity  of  b  to  a.     A  diphasic  change  is  thus  also  a  sign  of  a 
propagated  change.     Every  excitation  of  a  normal  muscle  gives  rise  to  a 

*  The  statement  that  the  excited  portion  of  the  muscle  becomes  '  negative,'  though 
sanctioned  by  long  usage,  is  not  very  exact  and  may  give  rise  to  misconception.  When 
we  lead  off  the  terminals  of  a  copper-zinc  couple  or  cell  to  a  galvanometer,  a  current 
flows  outside  the  cell  from  copper  to  zinc  and  inside  the  cell  from  zinc  to  copper.  In 
this  case  the  zinc  is  said  to  be  electropositive  to  the  copper,  and  in  the  same  way  we 
must  assume  that  the  excited  portion  of  a  muscle  is  electropositive  to  the  unexcited 
portions.  When  therefore  we  speak  of  any  part  of  a  tissue  being  negative,  we  are 
using  a  conventional  expression  to  indicate  the  direction  of  the  current  in  the  outer 
circuit,  and  not  the  electrical  condition  of  the  tissue  itself.  In  order  to  avoid  the  con- 
fusion which  might  result  from  an  attempt  to  replace  the  loose  expression  '  negative  ' 
by  the  more  correct  expression  '  electropositive,'  Waller  has  suggested  the  employ- 
ment of  the  term  '  zincative  '  to  indicate  the  electrical  condition  accompanying  excita- 
tion. This  term  would  also  serve  to  emphasise  the  fact  that  the  excited  portion,  like 
the  zinc  in  a  zinc-copper  cell,  is  the  chief  seat  of  chemical  change. 


230  PHYSIOLOGY 

diphasic  variation  of  such  a  direction  that  the  point  stimulated  first  becomes 
negative  to  all  other  points  of  the  muscle,  and  this  '  negativity,'  to  use  a  loose 
but  convenient  expression,  passes  as  a  wave  down  the  muscle,  preceding  the 
wave  of  contraction  and  travelling  at  the  same  rate. 

If  one  leading-off  point  be  injured,  e.g.  at  b,  the  change  accompanying 
excitation  is  absent  at  that  rjoint.  A  single  stimulus  applied  at  x  will  in 
this  case  give  only  a  monophasic  variation  in  which  a  is  relatively  negative 
to  b. 

When  we  study  the  time  relation  of  the  electrical  variation  ensuing  on  a 
single  stimulus,  we  find  that  the  electrical  change  under  the  electrodes 
begins  at  the  moment  that  the  stimulus  is  applied.  It  takes  about  -C025 
sec.  to  attain  its  culminating  point.  At  this  point  the  mechanical  change 
or  contraction  of  the  muscle  begins.  These  time-relations  vary  with  the 
temperature  of  the  muscle.  We  have  already  seen  that  the  effect  of  lowering 
the  temperature  is  to  increase  that  latent  period  of  the  contraction.  In  the 
same  way  it  slows  the  rise  of  the  electrical  change  and  the  rate  of  propagation 
of  the  wave  of  electrical  change.  This  is  shown  in  Fig.  86,  in  which  are 
given  the  diphasic  response  of  the  sartorius  first  at  8°C.  and  secondly  at 
18°C.  We  are  therefore  justified  in  regarding  the  electrical  change  as  an 
index  to  the  chemical  changes  evoked  in  the  muscle  as  the  direct  result  of  the 
stimulus.  The  flow  of  material,  which  is  responsible  for  the  change  in  form 
of  each  contracting  unit,  is  secondary  to  these  changes.  As  the  result  of 
stimulation,  a  chemical  change  is  aroused  at  the  point  of  excitation  and 
travels  thence  along  the  muscle  fibres  at  a  rate  of  about  three  metres  per 
second,  i.e.  the  same  rate  as  that  of  the  following  wave  of  mechanical  change 
and,  like  this,  varying  with  the  temperature. 

Under  certain  conditions  an  excitatory  condition  may  be  propagated  without  the 
presence  of  a  visible  contraction.  Thus,  if  the  middle  third  of  the  sartorius  be  soaked 
for  a  time  in  water,  it  passes  into  a  condition  known  as  '  water  rigor,'  in  which  it  is 
incapable  of  contracting,  although  capable  of  transmitting  an  excitation  from  one  end 
of  the  muscle  to  the  other. 

The  connection  of  a  diphasic  current  of  action  with  an  excited  condition 
of  the  tissues  passing  as  a  wave  from  one  end  to  the  other  is  shown  still  more 
clearly  on  a  slowly  contracting  tissue,  such  as  the  ventricle  of  the  frog  or 
tortoise.  Fig.  87,  a,  is  a  photographic  record  of  the  variation  obtained  from 
the  tortoise  ventricle,  which  is  led  off  to  a  capillary  electrometer,  one  (acid) 
terminal  being  connected  with  the  base  of  the  ventricle,  the  other  (mercury) 
with  the  apex.  Each  part  of  the  ventricle  remains  contracted  for  a  period  of 
1  \  to  2  seconds,  and  then  the  contraction  passes  off,  first  at  the  base  and  later 
at  the  apex.  The  electrical  events  are  an  exact  replica  of  tie  mechanical. 
Directly  after  the  stimulus  has  been  applied,  the  base  becomes  negative  and 
the  column  of  mercury  moves  up.  A  moment  later  the  excitatory  condition 
extends  to  the  apex.  There  is  thus  a  sudden  equalisation  of  potential 
between  the  two  terminals,  and  the  mercury  comes  back  quickly  to  the  base 
line.  Here  it  stays  for  1  \  to  2  seconds.  During  this  time  the  whole  heart  is 
in  an  excited  condition.     Both  base  and  apex  are  equally  excited,  and  there 


ELECTRICAL  CHANGES   IN  MUSCLE 


231 


can  be  no  difference  of  potential  between  them.  The  excitatory  condition 
then  passes  off,  first  at  the  base  and  then  at  the  apex.  There  is  thus  a  small 
period  of  time  in  which  the  apex  is  still  contracted  or  excited  while  the  base 
is  relaxed,  and  the  apex  is  therefore  negative  to  the  base.  This  terminal 
negativity  of  the  apex  is  shown  on  the  photograph  by  the  excursion  of  the 
column  of  mercury  away  from  the  point  of  the  capillary.  If  one  terminal, 
e.y.  the  apex,  be  injured,  we  obtain  quite  a  different  variation,  which  is  shown 
in  Fig.  87,  b.     It  is  evident  from  this  figure  that  the  electrical  sign  lasts  practi- 


Fio.  87.     Electrometer  records  of  the  electrical  variations  in  a  tortoise  ventricle, 
excited  to  beat  rhythmically  by  single  shocks. 
a,   Ventricle  uninjured.     B,  One  leading  off  spot  injured.     (B.  Sanderson.) 

cally  as  long  as  the  mechanical  sign  of  the  excited  state,  and  that  we  are  not 
justified  in  regarding  the  first  spike  of  the  diphasic  variation  as  indicative 
of  an  excitatory  wave  attended  by  an  electrical  change  which  is  independent 
of  the  succeeding  mechanical  change. 

The  only  difference  between  the  electrical  changes  in  this  case  and  in  that 
of  voluntary  muscle  is  that  in  the  latter  all  processes  are  very  much  quicker, 
so  that  as  a  rule  the  point  a  (Fig.  84)  has  ceased  to  be  negative  before  the 
negativity  of  b  has  attained  its  full  height,  and  there  is  thus  no  prolonged 
equipotential  stage. 

Although  in  the  case  of  the  slowly  contracting  ventricle  of  the  tortoise,  the  record 
obtained  of  the  electrical  changes  accompanying  its  contraction  by  means  of  the  capillary 
electrometer  shows  with  great  clearness  the  diphasic  nature  of  the  variation,  and  there- 
fore the  wave  character  of  the  electrical  change,  considerable  difficulty  is  experienced 
sometimes  in  recognising  that  the  '  spike  '  record  of  the  electrical  change  in  voluntary 


232 


PHYSIOLOGY 


muscle  or  in  nerve  is  also  due  to  a  diphasic  variation.     In  this  rase  the  electrical  change 

at  any  spot  lasts  only  about  s ,',  „   second,  and  there  is  not  a   prolonged  oquipotential 
period,  as  in  the  case  of  ( In-  heart.        The  nature  of  the  variation  is  however  obvious,  if 
we  compare  Hie  electrometer  record  of  an  intact  and  therefore  (  uncut  less  muscle  with 
that  of  a  muscle  in  which  one  of  the  leading-off  points  has  been  injured,  so  as  to  give 
rise  to  a  demarcation  current.     The  two  curves  are  given  in  Pig.  MS,  the  upper  shadowy 
tracing   being  that    obtained    from    (lie   injured    muscle.      It  will   be  seen   that  the  dis- 
tinguishing   character    of 
an  electrometer  record  of 
a    diphasic    variation    in 
the    rapidly     contracting 
striated    muscle    consists 
in  the  fact  that  the  down- 
stroke   of    the    image   of 
the  meniscus  is    as  rapid 
as  the  upstroke,  whereas 
Fig.   88.  ■  Superimposed  photographs  of  the  electrical  varia-  the  monophasic  variation 
tion  of    the    sartorius   in     response   to    a   single    stimulus,  of    the    injured     muscle 
(Bitrdon  Sanderson.)  presents  a  slow  fall  pro- 

duced by  the  gradual 
leakage  of  the  charge  imparted  to  the  instrument  back  through  the  electrodes  and  muscle. 
When  such  a  record  is  analysed,  we  obtain  a  curve  similar  to  those  in  Fig.  89, which  repre- 
sent monophasic  variations  of  a  sartorius  injured  at  one  end,  under  different  conditions  of 
temperature.  A  similar  curve  to  the  diphasic  variation  can  be  obtained  by  putting 
in  a  current  of  similar  E.M.F.  from  a  battery,  first  in  one  direction  for  jl,-,  second,  and 
then  in  a  reverse  direction 
for  another  ., ',  ,j  second.  It 
must  be  remembered  that  a 
diphasic  variation  does  not 
mean  that  one  part  of  a 
muscle  changes  from  normal 
in  one  direction,  and  then 
swings  back  past  the  normal 
in  another  direction,  but 
that  a  change  in  one  direc- 
tion at  one  electrode  dies 
away  and  is  succeeded  by  a 
similar  change  in  the  same 
direction,  which  also  dies 
away,  at  the  second  electrode: 
that  is  to  say,  a  diphasic 
variation  implies  the  pro- 
gression of  a  wave  of  electri- 
cal change  between  the  lead- 
ing-off points.  Using  a  string 
galvanometer,  which  reacts 
much  more  rapidly,  the 
diphasic  nature  of  the  varia- 
tion is  immediately  apparent 
from  the  photographic  record  j-IQ  89  Monophasic  variations  of  an  injured  sartorius. 
even  with  voluntary  muscle,  a,  at  18°C.  ;  B,  at  8°C.     (Keith  Lucas.) 

or  nerve. 

The  electrical  variation  obtained  by  leading  of!  a  heart  beating  normally 
is  a  much  more  complex  affair.  The  question  will  be  discussed  more  fully 
in  chapter  xiii. 


ELECTRICAL  CHANGES   IN  MUSCLE  233 

THE  DEMARCATION  CURRENT  OR  CURRENT  OF  INJURY 

Muscle  or  nerve  may  become  negative  under  two  conditions  :  (1)  During 
activity  ;  (2)  when  dying  as  the  result  of  injury.  It  is  doubtful  however 
whether  these  two  conditions  are  really  distinct.  Section  or  injury  of  a  muscle 
causes  a  prolonged  stimulation  of  the  adjacent  parts  of  the  muscle  fibres. 
These  parts  therefore  being  excited,  must  be  negative  to  the  unexcited  parts 
which  are  further  away  from  the  seat  of  injury  so  that  a  demarcation  current 
is  really  an  excitatory  current.  We  thus  come  to  the  conclusion,  para- 
doxical only  in  terms. that  the  so-called  currents  of  rest  are  really  currents  of 
action  and  are  due  to  excitation  around  the  injured  spot.* 

SECONDARY  CONTRACTION.      RHEOSCOPIC  FROG 
The  negative  variation  of  one  muscle  may  be  used  to  make  another 

contract. 

If  the  nerve  of  the  preparation  a  (in  Fig.  90)  be  laid  so  as  to  touch  at  two 

points  the  cut  end  and  surface  of  the  muscle  b,  and  the 

nerve    of  b    then  stimulated  with    single    induction 

shocks,  every  contraction  of  b  will  be  attended  by  a 

contraction    of   a,  excited    by  the  negative   variation 

of  the  current  passing  through  its    nerve    from  the 

point  touching  the  cut  end  to  that  in  contact  with  rf 

the  equator  of  b. 

If  the  nerve  of  b  is  tetanised,  a  as  well  as  b  enters        _.   FlG-  ?°- 

•  Rheoscopic  frog, 

into  a  continued  contraction.    This  'secondary  tetanus  ' 

is  of  interest  as  showing  that,  although  the  contractions  of  b  are  fused,  the 

excitatory  process  and  negative  variations  are  still  quite  distinct. 

*  If  the  demarcation  current  is  really  clue  only  to  excitation,  we  should  expect 
to  find  it  weaker  than  the  action  current  obtained  by  exciting  the  whole  muscle  to 
contract.  And  this  is  the  case.  The  E.M.F.  of  the  demarcation  current  of  a  sar- 
torius  equals  about  0'05  of  a  Daniell  cell.  The  action  current  of  the  same  muscle  may 
attain   to  an    E.M.F.  =  0"08  of  a  Daniell  cell  (Gotoh). 


SECTION  VIII 

THE    INTIMATE    NATURE    OF   MUSCULAR 
CONTRACTION 

Experiments  on  the  metabolism  of  the  body  as  a  whole  show  that  the 
energy  of  muscular  work  is  derived  from  the  oxidation  of  the  food-stuffs. 
In  man  the  performance  of  work  involves  an  increase  of  the  oxidative 
processes  of  the  body  with  a  corresponding  evolution  of  energy,  of  which 
four-fifths  will  appear  as  heat  while  one-fifth  may  be  transformed  into 
mechanical  work.  In  this  respect  the  physiological  mechanisms  for  the 
production  of  mechanical  energy  resemble  the  greater  number  of  the  machines 
employed  by  man  for  the  same  purpose.  In  nearly  all  these  the  prime 
source  of  energy  is  the  oxidation  of  carbon  and  hydrogen  in  the  form  of 
coal  or  oil.  In  the  steam-engine  and  internal-combustion  engine  the  whole 
energy  set  free  by  the  process  of  oxidatio%  appears  first  as  heat,  and  then  a 
certain  portion  of  the  heat  is  converted  into  mechanical  work.  There 
is  a  limit  to  the  efficiency  of  such  heat  engines,  depending  on  the  maximum 
differences  of  temperature  available  between  the  two  sides  of  the  working 
part  of  the  machine.     The  efficiency  of  any  heat  engine  is  expressed  by 

T [pi 

the  formula  E  = ,  where  T  is  the  highest  temperature  (in  absolute 

measurement)  obtained  by  the  working  substance  and  T1  is  the  lowest 
temperature  of  the  same  substance.  Ordinary  engines  rarely  attain  more 
than  half  this  ideal  efficiency,  but  it  is  evident  that  the  greater  the  difference 
of  temperature  available  the  greater  will  be  the  efficiency  of  the  machine. 
Internal-combustion  engines,  such  as  the  gas  engine  or  the  oil-engine, 
therefore  give  a  greater  percentage  of  the  total  energy  of  the  fuel  out  as 
mechanical  energy  than  is  the  case  with  the  steam-engine. 

Engelmann  has  maintained  that  in  muscle  there  is  a  similar  transforma- 
tion of  heat  into  mechanical  energy.  He  has  found  that  non-living  sub- 
stances, which  contain  doubly  refractive  particles  and  possess  the  property 
of  imbibition  (e.g.  catgut)  when  soaked  with  water,  will  contract  on  heating 
and  relax  again  on  cooling.  He  has  constructed  a  model  in  which  a  thread 
of  catgut  in  water,  surrounded  by  a  platinum  coil,  can  be  made  to  simulate 
muscular  contractions  and  relaxations  by  passing  a  heating  current  through 
the  platinum  coil.  He  imagined  that  the  chemical  changes  in  the  muscle 
liberate  heat  and  that  the  effect  of  this  heat  upon  the  doubly  refractive 
particles  is  to  make  them  imbibe  the  surrounding  water  so  that  they  change 

234 


THE   INTIMATE  NATURE   OF  MUSCULAR  CONTRACTION    235 

from  an  oval  to  a  spherical  shape.  It  would  be  impossible  however  for 
any  large  changes  of  temperature  to  take  place  in  the  muscle  without  entirely 
destroying  its  chemical  character,  and  with  small  differences  of  tempera- 
ture it  would  be  impossible  to  attain  the  efficiency  of  50  to  100  per  cent, 
which  characterises  muscle. 

Under  certain  conditions  we  may  obtain  by  a  machine  almost  the  entire 
energy  of  a  chemical  change.  The  condition  is  that  the  chemical  change 
shall  be  susceptible  of  taking  place  in  a  galvanic  battery.  We  may  use, 
for  instance,  a  series  of  Daniell  cells  to  drive  an  electric  motor  and  allow 
the  motor  to  perform  mechanical  work.  Under  these  circumstances  we 
could  theoretically  obtain  ICO  per  cent,  of  the  total  chemical  energy  avail- 
able, and  in  conditions  of  practice  the  efficiency  of  the  machine  may  attain 
to  70  or  80  per  cent.  A  similar  arrangement  might  be  present  in  the  ultimate 
contracting  elements  of  the  muscle  fibre.  The  mechanism  in  the  fibre  must 
be  one  which  will  provide  for  a  more  or  less  direct  transformation  of  chemical 
energy  into  mechanical  energy  without  a  previous  conversion  of  the  chemical 
into  heat  energy.  In  the  living  body,  where  everything  is  in  solution,  all 
the  energies  may  be  reduced  to  one  of  two  kinds,  osmotic  energy  and  surface 
energy.  The  contractile  machine  must  therefore  be  one  which  employs 
one  or  other,  or  both,  of  these  forms  of  energy.  We  might  with  Macdougall, 
regard  the  contractile  element  as  a  cylindrical  structure  differing  in  its 
contents  from  the  surrounding  sarcoplasm.  When  the  muscle  is  at  rest 
the  contents  of  the  muscle  prism  will  be  in  equilibrium  with  the  surrounding 
sarcoplasm.  We  might  imagine  the  excitatory  process  to  consist  in  a  sudden 
chemical  change  occurring  in  the  contents  of  the  muscle  prism.  The 
production  of  a  number  of  new  molecules  within  the  muscle  prism  (e.g.  of 
lactic  acid)  would  raise  the  osmotic  pressure  within  the  prism  and  occasion 
a  rapid  flow  of  water  from  the  sarcoplasm.  As  a  result  the  pressure  in  the 
muscle  prism  would  rise  and  cause  a  bulging  of  its  lateral  wall  and  a  shorten- 
ing of  the  whole  element.  The  subsequent  phase  of  relaxation  may  be  due 
either  to  a  secondary  change,  e.g.  oxidation,  leading  to  the  formation  of  a 
substance  to  which  the  walls  of  the  prism  are  freely  permeable,  or  to  the 
gradual  leak  of  the  primary  products  of  oxidation  or  disintegration  into  the 
sarcoplasm.  The  substance  or  substances  giving  rise  to  the  osmotic  differ- 
ences which  determine  contraction  may  be  either  products  such  as  lactic 
acid  and  carbon  dioxide,  which  are  formed  during  contraction,  or  may 
possibly  be  of  the  nature  of  neutral  salts  set  free  from  some  condition  of 
combination  with  the  proteins  of  the  sarcous  element.  Macdonald  has 
brought  forward  micro-chemical  evidence  of  the  appearance  of  potassium 
salts  in  the  sarcous  element  during  the  state  of  activity  of  the  muscle. 

On  the  other  hand,  Bernstein  has  suggested  that  the  changes  during 
muscular  contraction  are  determined  by  alterations  in  surface  tension. 
If  a  little  mercury  be  spilt  on  a  plate  the  particles  form  globules.  They  are 
kept  from  spreading  themselves  out  in  a  thin  film  under  the  influence  of 
gravity  in  consequence  of  the  surface  tension  of  the  mercury.  Any  modifica- 
tion of  the  surface  will  alter  the  tension,  and  therefore  state  of  expansion,  of 


236  PHYSIOLOGY 

i  be  globule.  Thus,  if  the  globule  be  in  sulphuric  acid  it  undergoes  a  certaia 
amount  of  polarisation,  and  becomes  positively  charged.  By  altering  the 
charge  of  such  a  globule  we  can  change  its  shape,  as  is  shown  diagram- 
matically  in  Fig.  91.  It  b  represents  the  shape  of  the  globule  lying  on  the 
plate  in  some  weak  sulphuric  acid,  a  will  represent  the  shape  of  the  globule 
when  it  is  connected  with  the  negative  pole  of  a  battery,  while  c  will  repre- 
sent its  shape  when  it  is  connected 
"  &  C  with  the  positive  pole  of  a  battery, 

the  other  pole  in  each    case    being 

connected  with  the  acid.      If     we 

Pja   ,M  consider  muscle  as  made  up  of  a 

series  of  chains  of  oval  particles,  a 

chemical  change  in  the  surface  of  these  particles,  causing  an  increase  of 

surface  tension,  will  tend   to   make   them  assume  the  globular  shape,  and 

will  therefore  cause  a  shortening  and  thickening  of  the  whole  fibre. 

According  to  Schafer,  contraction  is  associated  with  a  flow  of  the  outer  hyaline 
contents  of  the  sarcous  element  into  the  tubular  structure  forming  the  middle  portion. 
Such  a  flow  may  be  determined  either  by  osmotic  differences  between  the  centre  and 
periphery  of  the  sarcous  element,  or  by  a  change  in  the  surface  tension  obtaining  between 
the  isotropic  fluid  at  the  ends  and  the  anisotropic  structures  in  the  centre  of  the  muscle 
prism. 

The  tendency  of  recent  investigation  is  all  in  favour  of  the  second  hypo- 
thesis, namely,  that  the  essential  factor  in  the  processes  of  excitation  and 
contraction  is  an  alteration  of  surface.  In  the  first  place  the  electrical 
changes  accompanying  the  excitatory  process  denote  a  polarisation  or 
accumulation  of  ions  on  the  surfaces  situated  in  the  excited  area.  The 
chemical  change  which  is  responsible  for  the  current  of  action,  or  the  negative 
charge  at  the  excited  spot,  takes  place  almost  instantaneously  and  disappears 
somewhat  more  slowly.  It  would  seem  that  the  excitatory  process  consists 
essentially  in  the  setting  free  of  certain  ions  on  the  surface  or  surfaces  in 
the  contractile  tissue,  and  that  the  passing  away  of  the  excitatory  state 
is  due  to  the  disappearance  of  these  ions,  either  by  diffusion  away  into  the 
surrounding  fluid  or  by  further  chemical  changes,  such  as  oxidation.  A 
study  of  the  development  of  tension  and  of  heat  production  in  a  muscle  on 
excitation  has  shown  that  in  both  cases  the  yield  of  energy  on  excitation 
is  increased  by  lengthening  and  diminished  by  shortening  the  muscle.  Now 
alteration  in  length  of  the  muscle  will  not  alter  its  volume,  but  will  alter 
the  extent  of  its  longitudinal  surfaces,  and  it  appears  therefore  that  the 
production  of  heat  as  well  as  of  mechanical  energy  is  not  a  volume,  but  a 
surface  effect.  Finally  the  work  of  A.  V.  Hill  on  the  heat  production  in 
muscle  seems  to  show  that  the  rise  of  tension  in  a  muscle  on  excitation  is 
due  to  the  liberation  of  chemical  bodies,  of  which  lactic  acid  is  certainly  one, 
in  the  neighbourhood  of  certain  longitudinal  surfaces  or  membranes,  and 
that  the  presence  of  these  bodies  changes  the  tension  at  such  surfaces  and 
thereby  the  longitudinal  tension  of  the  fibre.  The  extent  and  intensity  of 
the  production  of  these  bodies  must  depend  on  the  area  of  the  chemically 


THE   INTIMATE   NATURE   OF  MUSCULAR  CONTRACTION    237 

active  surfaces  and  therefore  on  the  length  of  the  muscle  fibres.  The 
muscle  reacts  at  the  end  of  the  excitatory  stage,  not  by  any  active  process 
of  lengthening,  but  by  neutralisation,  or  simply  physical  diffusion  of  the 
active  chemical  bodies  away  from  the  interfaces  or  membranes.  Later  on, 
lactic  acid  is  removed  or  replaced  by  its  previously  unstable  precursor  under 
the  influence  of  oxygen  with  the  production  of  some  carbon  dioxide  and  a 
certain  amount  of  heat.  We  have  seen  already  that  the  efficiency  of  the 
initial  chemical  change  in  which  lactic  acid  is  set  free  may  approximate  ICO 
per  cent. 

It  must  be  noted  that,  although  the  oxidative  processes  are  responsible 
ultimately  for  all  the  energies  of  the  higher  animal,  no  oxidative  change 
is  involved  in  the  production  of  lactic  acid  from  e.g.  glucose,  nor  is  the 
presence  of  oxygen  necessary  for  the  contraction  of  muscle  to  take  place. 
On  the  other  hand,  if  we  wish  to  obtain  the  maximum  amount  of  work 
from  a  muscle,  we  must  supply  it  richly  with  oxygen,  the  presence  of  which 
seems  essential  not  to  the  contractile  process  but  to  the  stage  of  recovery. 
I  n  this  stage  a  certain  amount  of  heat  is  evolved,  set  free  by  the  oxidation 
of  the  lactic  acid,  and  we  must  assume  that  part  of  the  energy  so  available 
is  utilised  for  building  up  the  precursor  from  which  the  lactic  acid  is  derived. 
It  is  as  if  the  process  of  oxidation  furnished  the  energy  for  winding  up  a 
spring,  whereas  excitation  removed  a  catch  and  allowed  the  spring  to  run 
down,  setting  free  this  energy  for  the  performance  of  work  or  for  conversion 
into  heat* 

For  many  years  it  was  imagined,  as  a  result  of  experiments  by  Hermann,  Pfliiger, 
and  others,  that  the  oxygen  supplied  to  a  muscle  was  built  up  with  its  other  constituents, 
especially  carbohydrates,  into  a  complex  '  inogen  '  molecule.  On  stimulation  this  mole- 
cule underwent  an  explosive  rearrangement,  the  carbohydrate  and  oxygen  parts  of 
the  molecule  combining  to  form  carbonic  acid,  another  product  of  the  decomposition 
being  lactic  acid.  The  careful  experiments  of  Fletcher  have  shown  however  that 
in  the  absence  of  oxygen  there  is  no  evidence  of  the  formation  of  carbonic  acid  during 
contraction,  and  therefore  no  reason  to  assume  the  presence  of  oxygen  in  the  muscle 
in  an  intramolecular  form.  Everything  points  to  oxygen  being  taken  in  and  applied 
forthwith  to  the  purposes  of]  oxidation,  so  that  the  output  of  carbon  dioxide  and  water 
keeps  pace  with  the  intake  of  oxygen. 

It  is  at  present  quite  impossible  to  come  to  any  conclusion  as  to  the  nature  of  the 

*  Peters  has  shown  that,  if  a  muscle  be  stimulated  to  exhaustion  under  anaerobic 
conditions,  about  0'2  per  cent.  lactic  acid  is  formed  with  the  evolution  of  '9  calories 
per  gramme  of  muscle  substance.  The  production  of  1  gm.  of  lactic  acid  is  therefore 
accompanied  by  the  evolution  of  450  calories.  According  to  A.  V.  Hill  the  '  recovery 
heat  production '  in  oxygen  is  of  about  the  same  order  as  the  initial  heat  production, 
so  that  in  the  oxidative  removal  of  1  gm.  of  lactic  acid  there  would  also  be  an  evolution 
of  about  450  calories.  The  oxidation  of  1  gm.  of  lactic  acid  produces  3700  calories, 
about  eight  times  as  much  as  the  quantity  observed.  Hill  considers  this  amount 
far  too  large  to  have  escaped  detection  in  his  experiments,  and  therefore  concludes 
that  the  lactic  acid  is  not  oxidised  but  replaced  in  its  previous  position  under  the 
influence  and  with  the  energy  of  the  oxidation  either  :  (a)  of  a  small  part  of  the  lactic 
acid  itself,  or  (b)  some  other  body.  He  regards  the  latter  alternative  as  the  more 
probable,  and  concludes  therefore  that  the  lactic  acid  is  part  of  the  machine  and  not, 
part  of  the  fuel  of  the  muscle, 


238  PHYSIOLOGY 

precursor  from  which  the  lactic  acid  is  derived.  The  immediate  precursor  cannot  be 
glucose  or  glycogen  since  the  heat  evolved  in  the  imtial  stage  of  contraction  is  two  or 
three  times  as  great  as  could  be  derived  from  the  mere  conversion  of  either  of  these 
substances  into  lactic  acid.  We  must  therefore  conclude  that  the  oxidation  of  lactic 
acid  which  goes  on  during  the  process  of  recovery  is  used  to  yield  the  energy  necessary 
for  building  up  the  active  molecules,  which  are  the  precursors  of  lactic  acid  and  which 
have  a  higher  potential  energy  than  glucose  itself,  so  that  when  it  rapidly  decomposes 
sufficient  energy  is  set  free  to  account  for  the  observed  heat  production.  Some  such 
utilisation  of  the  energy  of  oxidation  of  the  lactic  acid  is  indicated  by  the  results  of 
Parnas,  who  found  that  the  heat  evolved  during  this  recovery  process  corresponded  to 
only  about  one  half  the  beat  which  would  be  evolved  by  the  formation  of  the  carbon 
dioxide  output  of  the  muscle  during  the  same  time  as  a  result  of  the  oxidation  of  lactic 
acid. 


SECTION    IX 
VOLUNTARY  CONTRACTION 

The  whole  of  our  analysis  of  the  processes  accompanying  the  contraction 
of  a  skeletal  muscle  has  so  far  had  reference  merely  to  the  contractions 
evoked  by  artificial  stimuli,  mainly  electric.  These  contractions  have 
either  been  the  simple  twitch,  with  a  duration  of  about  one- tenth  of  a  second, 
evoked  by  a  momentary  stimulus,  or  the  tetanus,  a  continued  contraction 
composed  of  a  number  of  single  twitches,  summated  and  fused  together. 
Under  normal  circumstances  the  contraction  of  skeletal  muscles  is  brought 
about  either  reflexly,  or  in  response  to  some  stimulus  descending  from  the 
cerebral  cortex,  the  so-called  '  voluntary  contraction.'  These  contractions 
may  have  a  duration  of  almost  any  extent.  The  quickest  contractions 
carried  out  by  man  have  a  duration  of  about  0-1  sec.  Considerable  effort, 
and  training  are  required  to  reduce  a  muscular  movement  to  this  degree, 
and  nearly  all  contractions,  even  the  rapid  ones,  last  considerably  over 
0-1  sec.  Since  we  have  no  certain  means  of  producing  contractions  of  any 
given  length,  except  by  means  of  repeated  stimuli,  it  is  natural  that  physiolo- 
gists have  regarded  voluntary  contractions  as  similar  to  the  artificial  tetanus, 
and  as  like  this  composed  of  fused  single  contractions,  and  have  endeavoured 
to  determine  the  number  of  con  tractions  per  second,  i.e.  the  natural  rhythm 
of  the  tetanus.  If  however  every  muscular  contraction  in  the  body  is  to 
be  regarded  as  of  the  nature  of  a  tetanus,  effected  by  rapidly  repeating 
stimuli  sent  down  the  motor  nerve  from  the  central  nervous  system,  we 
must  assume  a  similar  discontinuity  for  the  process  underlying  the  normal 
tone  of  muscles,  and  for  the  continued  contraction  of  unstriated  muscles, 
e.g.  of  the  arteries.  Is  this  discontinuity  of  muscles  really  essential  for  the 
production  of  a  prolonged  contraction  ?  So  far  as  our  present  knowledge 
of  the  intimate  nature  of  muscular  contraction  goes,  it  would  seem  quite 
possible  that  the  continuous  state  of  contraction  is  dependent  on  a  continuous 
evolution  of  energy  in  the  muscle.  We  have  seen  reason  to  regard  the 
chemical  processes  in  a  contracting  muscle  as  presenting  two  phases,  namely, 
(1)  the  production  of  a  substance  which  increases  the  osmotic  pressure 
within  the  sarcous  elements,  or  raises  the  surface  tension  of  the  ultimate 
contractile  elements  of  the  muscle,  thus  causing  a  shortening  and  thickening 
of  those  elements  ;  and  (2)  the  further  change  of  this  substance  into  one 
which  can  escape  by  diffusion,  or  into  a  substance  with  a  low  surface  tension. 
so  that  now  the  muscle  relaxes  and  can  be  stretched  by  any   extending 

239 


240  PHYSIOLOGY 

force.  If  these  two  phases  went  on  continuously,  but  the  first  phase  kept 
ahead  of  the  second  one,  a  continuous  state  of  contraction  would  be  produced 
in  the  muscle.  Since  the  contraction  of  the  muscle  occurs  only  in  response 
to  impulses  from  the  central  nervous  system,  we  should  have  to  imagine 
also  a  continuous  stream,  e.g.  of  negatively  charged  ions,  descending  the 
nerve  and  evoking  an  excitatory  change  in  the  muscle  fibres  as  they  impinge 
on  the  neuro-muscular  junction.  We  have  evidence  that  a  state  of  excita- 
tion of  a  nerve,  which  is  apparently  continuous,  may  excite  a  correspondingly 
continuous  state  of  excitation  in  the  muscle  attached.  During  the  passage 
of  a  constant  current  through  muscle  there  is  a  continuous  contraction  in 


/vWvJlw^_ 


Fig.  92.     Continued  contraction  followed  by  rhythmic  contractions  of  a  muscle 
in  response  to  a  constant  stimulus.     (Biedermann.) 
The  muscle  was  excited  by  the  passage  of  a  constant  current,  the  cathoda 
end  having  been  moistened  with  a  weak  solution  of  NaC03. 

the  neighbourhood  of  the  cathode.  If  the  irritability  of  the  muscle  at  this 
point  be  increased  by  the  application  of  a  solution  of  sodium  carbonate, 
Biedermann  has  shown  that  this  excitation  is  propagated  to  the  rest  of  the 
muscle,  and  on  closure  of  the  current  we  obtain  a  prolonged  contraction 
followed  by  rhythmic  contractions  (Fig.  92).  Moreover  in  frogs,  the  ex- 
citability of  which  has  been  heightened  by  keeping  them  at  2°  to  3°  C.  for 
some  days,  the  closure  of  a  descending  current  through  the  sciatic  nerve 
causes  a  prolonged  contraction  of  the  gastrocnemius  ;  and  in  the  same  way 
there  may  be  a  prolonged  contraction  produced  by  the  opening  of  an  ascend- 
ing current  through  the  nerve. 

The  question  however  can  only  be  decided  by  experiment.  If  a  volun- 
tary or  reflex  contraction  is  of  the  nature  of  a  tetanus,  we  should  be  able, 
by  a  study  of  the  mechanical  and  electrical  phenomena  combining  the 
contraction,  to  obtain  distinct  evidence  of  this  causation.  It  was  shown 
by  Wollaston  that,  on  listening  to  a  contracting  muscle,  a  low  sound  was 
heard  which,  according  to  him,  corresponded  to  a  vibration  frequency  of 
36  to  40  per  second.  The  same  observation  was  made  by  Helmholtz,  and 
can  be  repeated  by  any  one  who  will  place  the  end  of  a  stethoscope  on  a 
muscle,  e.g.  the  biceps,  and  listen  to  the  sound  produced  when  it  contracts. 
Helmholtz  pointed  out  however  that  the  tone  heard  corresponded  to  the 
resonance  tone  of  the  external  ear,  and  was  the  same  as  that  noted  when 
listening  to  any  irregular  sound  of  low  intensity.  Thus  the  roar  of  London 
that  we  hear  in  the  middle  of  Hyde  Park  has  the  same  pitch  as  the  muscle 
sound  of  the  contracting  biceps.  The  muscle  sound  therefore  teaches  us 
nothing  as  to  the  pitch  or  number  of  contractions  per  second  making  up  I  he 


VOLUNTARY  CONTRACTION  241 

voluntary  tetanus.  It  merely  points  to  an  irregularity  or  discontinuity  in 
this  contraction.  By  bringing  vibrating  reeds  of  different  frequency  in 
contact  with  the  contracting  muscles  of  the  frog,  Helmholtz  came  to  the 
conclusion  that  the  chief  element  in  the  muscle  sound  was  the  first  over-tone 
of  a  sound  with  a  vibration  frequency  of  18  to  20  per  second,  which,  according 
to  him,  was  to  be  taken  as  representing  the  number  of  single  contractions 
in  every  voluntary  muscular  contraction. 

Nearly  all  voluntary  contractions  present  a  certain  degree  of  irregularity,  and  the 
same  irregularities  are  observed  \\  hen  a  tetanic  spasm  in  the  muscle  of  the  body  is 
caused  by  strong  excitation  of  the  cerebral  cortex,  as  in  epilepsy.  On  taking  a  record 
of  such  contractions,  Schafer  and  Horsley  showed  that  in  nearly  all  cases  the  tracing 
presents  superposed  undulations  repeated  at  the  rate  of  eight  to  twelve  per  second. 
These  observers  concluded  that  this  was  the  normal  rate  at  which  the  impulses  descend 
the  nerve  to  arouse  a  voluntary  contraction.  One  difficulty  in  this  conclusion  is  that 
when  human  muscle  is  excited  by  eight  to  twelve  stimuli  per  second,  we  obtain,  not  a 
tetanic  contraction  with  a  few  irregularities  superposed  on  it,  but  a  series  of  single 
contractions,  the  so-called  clonus.  In  order  to  produce  a  nearly  continuous  contraction 
we  must  employ  a  vibration  frequency  of  about  30  per  second.  It  has  been  suggested 
to  get  over  this  difficulty  that  under  normal  circumstances  the  discharge  does  not  travel 
along  all  the  nerve  fibres  at  the  same  time,  so  that  the  different  muscle  fibres  composing 
the  muscle  will  be  in  different  phases  of  contraction,  and  there  will  be  never  any  large 
degree  of  relaxation  between  the  individual  contractions  of  the  whole  muscle.  Von 
Kries  has  found  that  the  duration  of  a  muscle  twitch  may  be  lengthened  by  increasing 
the  duration  of  the  electrical  change  used  to  excite  the  nerve,  and  has  suggested  that 
the  normal  excitatory  process  may  resemble  the  prolonged  electrical  change  which 
can  be  produced  electro-magnetically,  rather  than  the  short  sudden  shock  represented 
by  the  induced  current  of  an  induction-coil.  Attempts  have  been  made  to  decide  the 
question  by  recording  the  electrical  changes  accompanying  the  natural  contractions 
of  a  muscle,  i.e.  those  excited  reflexly  from  the  central  nervous  system.  It  was  long  ago 
shown  by  Loven  that  a  certain  discontinuity  could  be  seen  in  records  of  the  electrical 
changes  obtained  from  a  frog's  muscle  in  the  tetanic  spasms  produced  by  an  injection 
of  strychnine,  but  according  to  Burdon  Sanderson  this  discontinuity  represents  a  series 
of  spasms  discharged  from  the  central  nervous  system.  Each  discharge  produces,  not 
a  twitch,  but  a,  continued  contraction  of  short  duration.  On  photographing  the  electrical 
changes  of  strychnine  spasm  as  obtained  by  a  capillary  electrometer,  he  found  that 
each  individual  spasm  could  be  compared  only  to  a  short  tetanus. 

The  most  recent  investigations  of  the  question  we  owe  to  Piper,  who 
made  use  of  the  string  galvanometer,  an  instrument  much  more  delicate  in 
the  reproduction  of  rapid  changes  than  is  the  capillary  electrometer.  Piper 
led  off  two  points  in  the  fore-arm,  one  electrode  being  placed  about  two 
inches  below  the  bend  of  the  elbow,  and  the  other  about  four  inches  above 
the  wrist.  A  single  stimulus  of  the  median  nerve  was  found  by  him  to 
give  a  typical  diphasic  variation  in  the  muscles.  When  the  muscles  were 
contracted  voluntarily,  well-marked  oscillations  of  the  galvanometer  wire 
were  obtained,  indicating  the  existence  in  the  muscle  of  forty-eight  to 
fifty  complete  diphasic  variations  in  the  second  (Fig.  93).  Piper  obtained 
similar  records  on  leading  off  other  muscles  of  the  body  when  these  were 
placed  voluntarily  in  a  state  of  contraction,  and  he  concludes  therefore 
that  each  voluntary  contraction,  short  or  long,  is  a  tetanus  composed  of 
about  fifty  fused  twitches  per  second.      These  results  would  indicate  that 

16 


242 


PHYSIOLOGY 


the  impulse,  which  normally  travels  down  the  motor  nerve  from  the  anterior 
cornual  cell  to  the  muscle,  is  discontinuous,  and  therefore  that  on  leading 
off  a  motor  nerve  to  a  galvanometer  we  ought  to  obtain  electrical  oscillations 
of  fifty  distinct  stimuli  per  second.  Dittler  has  investigated  by  means  of 
the  string  galvanometer  the  electrical  changes  accompanying  the  ordinary 
contractions  of  the  diaphragm,  and  also  those  occurring  in  the  phrenic 


Fig.  93.     Electrical  variations  produced  by  voluntary  contractions  of 
human  muscle.     (Piper.) 

nerve.  He  finds  that  both  in  the  muscle  and  in  the  nerve  there  is  evidence 
that  each  contraction  is  a  fused  series  of  single  contractions,  evoked  by 
the  discharge  along  the  nerve  of  between  fifty  and  seventy  excitations  per 
second.  So  far  therefore  the  evidence  is  in  favour  of  the  view  that  volun- 
tary contraction  and,  one  must  add,  the  tonic  contractions  of  all  skeletal 
muscles,  are  discontinuous  in  nature  and  analogous  to  the  tetanus  which 
we  may  evoke  artificially  by  rapid  stimulation  either  of  muscle  or  of  its 
motor  nerve. 


SECTION  X 
OTHER   FORMS   OF  CONTRACTILE   TISSUE 

SMOOTH  OR  UNSTRIATED  MUSCLE 

The  little  we  know  about  the  physiology  of  unstriated  muscle  is  derived 
chiefly  from  experiments  on  the  intestine,  ureter,  bladder,  and  retractor 
penis.*  This  tissue  differs  from  voluntary  muscle  in  containing  numerous 
plexuses  of  nerve  fibres  (non-medullated)  and  ganglion  cells,  so  that  in  all 
our  researches  it  is  difficult  to  be  certain  whether  the  results  are  due  to  the 
muscle  fibres  themselves,  or  to  the  nerves  and  nerve  cells  which  are  so  inti- 
mately connected  with  them  ;  especially  as  we  have  as  yet  no  convenient 
drug  like  curare,  by  aid  of  which  we  might  discriminate  between  action  on 
muscle  and  action  on  nerve. 

The  differences  between  unstriated  and  voluntary  muscle,  although  at 
first  sight  very  pronounced,  on  further  investigation  prove  to  be  in  most 
cases  differences  of  degree  only,  qualities  and  reactions  which  are  marked 
in  involuntary  muscle  being  also  present  in  a  minor  degree  in  the  more 
highly  differentiated  tissue. 

The  contraction  of  smooth  muscle  is  so  sluggish  that  the  various  stages 
of  latent  period,  shortening,  and  relaxation  can  be  easily  followed  with  the 
eye.  The  latent  period  may  be  from  0-2  to  0-8  second,  and  the  contraction 
may  last  from  three  seconds  to  three  minutes. 

Smooth  muscle  preserves  many  of  the  properties  of  undifferentiated 
protoplasm,  especially  an  automatic  power  of  contraction,  which  is  regulated 
by  the  condition  of  the  muscle.  Thus  whereas  the  voluntary  muscle  is 
intimately  dependent  on  its  connection  with  the  central  nervous  system, 
and  in  the  absence  of  this  is  reduced  to  a  flabby  inert  tissue,  the  smooth 
muscle,  isolated  from  all  its  nervous  connections,  presents  in  many  cases 
rhythmic  contractions,  and  can  carry  out  a  peripheral  adaptation  to  its 
environment.  These  rhythmic  contractions  are  almost  invariably  observed 
if  the  muscular  tissue  be  subjected  to  a  certain  amount  of  tension,  after 

*  The  retractor  penis,  which  is  found  in  the  dog,  cat,  horse,  hedgehog  (but  not  in 
rabbit  or  man),  is  a  thin  band  of  longitudinally  arranged  unstriated  muscle,  which 
is  inserted  at  the  attachment  of  the  prepuce,  and  is  continued  backwards  in  a  sheath  of 
connective  tissue  to  the  bulb,  where  it  di\  ides  into  two  slips,  which  pass  on  either  side 
of  the  anus.  It  is  innervated  from  two  sources,'  the  motor  fibres  being  derived  from 
the  Lumbal  sympathetic  and  running  to  the  muscle  in  the  internal  pudic  nerve,  while 
the  inhibitory  fibres  rim  in  the  pelvic  visceral  nerves  (nervi  erigentes)  and  are  derived 
from  the  second  and  third  sacral  nerve-roots. 

243 


244 


PHYSIOLOGY 


separation  from  the  central  nervous  system.  The  rhythm  of  the  contrac- 
tions may  vary  from  one  (spleen)  to  twelve  (small  intestine)  contractions 
in  the  minute. 

The  stimuli  for  smooth  muscle  are  essentially  the  same  as  for  striated. 
As  we  should  expect  however  from  the  sluggish  response  of  this  kind  of 
contractile  tissue,  the  optimum  rate  of  change  of  current  which  excites  is 
very  much  slower  than  in  the  case  of  striated  muscle.  Thus  in  many  in- 
stances a  single  induction  shock,  even  if  very  strong,  is  powerless  to  excite 
contraction,  and  the  make-induction  shock  of  long  duration  and  low  intensity 
is  always  more  efficacious  than  the  short  sharp  break-induction  current. 
A  still  better  stimulus  is  the  make  or  break  of  a  constant  current.  When 
the  latter  form  of  stimulation  is  used,  response  occurs  at  the  make  sooner 
than  at  the  break,  and,  just  as  in  the  voluntary  muscle,  the  make  excitation 
starts  from  the  cathode  and  the  break  excitation  from  the  anode. 

An  apparent  exception  to  this  statement  is  afforded  by  the  behaviour  of  certain 
forms  of  involuntary  muscle.     In  the  intestine,  in  the  skin  of  worms,  and  in  many 

other    muscular     tubes     the     smooth 
muscle-fibres    are    arranged     in     two 
different  sheets,  one  consisting  of  longi- 
tudinal,  the  other  of    circular    fibres. 
If  non-polarisable  electrodes,  connected 
with  a  constant    source  of  current,  be 
applied   to   the   surface   of   the    small 
intestine,  when  the  current    is   made 
there  will  be  apparently  a  strong  eon- 
Fig.  94.    At  the  cathode  k  there'is  a  small  line   traction  of  the    circular    coat   at    the 
of   constriction,    surrounded    by   an   area   of   anode,  which  spreads  up  and  down  the 
relaxation      At  the  anode  itself  the  muscle   intestine  and  a  1^^   contraction  of 
is  relaxed.  Imt  is  stronelv  contracted  <>n  each    ,,,..,.,  ,   „  ^,     , 

side  of  the  anode,  so  that  on  rough  observation  the  longitudinal  coat  at  the  cathode, 
it  would  be  thought  that  contraction  occurred  The  same  result  is  observed  in  the 
at  the  anode  itself.  earthworm   and   leech.       But   careful 

observation  shows  in  each  case  that  the 
irregularity  is  really  only  apparent,  and  that  in  the  immediate  neighbourhood  of  the 
anode  there  is  relaxation  of  both  coats,  with  a  contraction  of  the  circular  coat  on  each 
side,  and  that  at  the  cathode  there  is  a  contraction  of  both  coats.  The  accompanying 
diagram  (Fig.  94)  will  serve  to  show  the  condition  of  the  circular  coat  at  each  electrode. 

As  a  matter  of  fact,  in  con- 
sequence of  the  arrangement  of 
the  fibres,  we  have  in  the  neigh- 
bourhood of  the  anode  a  num- 
ber of  places  (virtual  cathodes) 
where  the  current  is  leaving  the 
muscle-cells  to  enter  inert  con- 
ducting tissues,  and  in  the  same 
way  there  will  be  in  the  neigh- 
bourhood of  the  cathode  a  num- 
ber of  virtual  anodes  (Fig.  95). 
Thus  if  we  take  the  ureter  and 
lead  a  current  through  it  while 
it  is  slung  up  in  thread  loops 
serving  as  electrodes,  there  is  contraction  of  both  coats  at  the  cathode  and  relaxation 
of  both  at  the  anode.       If  however  the  ureter  be  packed  in  a  pulp  of  blotting-paper 


Fia.  95.  Diagram  to  show  the  spread  of  current  which 
occurs  when  a  current  is  led  tlirough  a  tube  such  as  the 
ureter  by  means  of  two  electrodes  applied  to  its  surface. 
It  will  be  noticed  that  while  +  E  is  the  anode,  there  are 
immediately  below  and  around  it  a  number  of  cathodes, 
E,,  E„,  E,„,  E„„  due  to  the  current  leaving  the  muscle  to 
flow  through  indifferent  tissues.     (BiEDERMAira.) 


OTHER  FORMS  OF  CONTRACTILE  TISSUE  245 

moistened  willi  normal  saline,  thus  allowing  the  current  to  leave  the  contractile  tissues 
anywhere  along  the  ureter,  we  get  the  same  aberrant  results  of  stimulation  as  are 
obtained  with  the  intestine. 

In  voluntary  muscle,  if  one  stimulus  follows  another  at  an  interval 
which  is  not  too  large,  a  summated  contraction  is  produced  which  is  greater 
in  amplitude  than  that  due  to  a  single  stimulus.  This  summation  may 
be  mechanical  or  physiological,  the  former  being  observed  when  the  stimulus 
is  repeated  during  the  decline  of  the  excitatory  process  and  being  due 
simply  to  the  after-loading  of  a  muscle  by  the  first  contraction.  It  is 
best  marked  when  the  muscle  is  heavily  loaded.  If  however  the  stimuli 
be  sent  in  at  sufficiently  short  intervals  so  that  two  stimuli  fall  within 
the  period  of  rise  of  contractile  stress,  an  increased  height  of  contraction 
is  obtained  under  all  conditions,  and  under  isometric  conditions  the  tension 
developed  is  greater  than  that  with  a  single  stimulus.  If  the  interval  between 
two  stimuli  be  so  short  that  the  second  falls  within  what  we  have  called 
the  refractory  period  due  to  the  first  stimulus,  no  summation  is  obtained, 
the  second  stimulus  being  ineffective. 

In  the  slow  contraction  of  involuntary  muscle  we  could  hardly  expect 
mechanical  summation  to  come  into  play.  Most  types  of  this  tissue  show 
however  the  true  summation,  i.e.  the  increased  liberation  of  energy  due 
to  repetition  of  the  stimulus  during  the  rise  of  the  excitatory  condition. 
As  might  be  expected  the  refractory  period  is  also  longer  in  involuntary 
muscle,  since  all  the  processes  of  this  muscle  are  slowed  in  comparison  with 
those  of  voluntary  muscle.  In  certain  types  of  tissue,  and  especially  in 
heart  muscle,  the  refractory  period  lasts  during  the  whole  of  the  period 
of  contraction.  During  this  time  therefore  a  second  shock  will  be  ineffective. 
As  the  contraction  dies  away  the  muscle  fibre  gradually  recovers  its  sus- 
ceptibility to  stimulation,  but  it  does  not  recover  its  full  irritability  until 
it  has  entirely  relaxed.  On  this  account  it  is  impossible  to  obtain  summa- 
tion in  or  to  tetanise  heart  muscle,  the  application  of  interrupted  currents 
to  this  tissue  producing  only  a  series  of  rhythmic  contractions. 

In  all  involuntary  muscle  we  may  observe  summation  of  the  effects  of 
stimuli  even  when  the  individual  stimuli  are  insufficient  to  produce  any 
excitation.  Thus  in  a  muscle  such  as  the  retractor  penis,  we  may  find  a 
strength  of  induction  shock  which,  applied  singly,  is  just  insufficient  to  evoke 
any  response.  If  however  the  shocks  are  repeated  at  intervals  of  a  second, 
it  will  be  found  that  the  first  three  or  four  stimuli  are  ineffective  and  then 
the  muscle  enters  into  a  contraction  which  increases  with  each  succeeding 
stimulus  until  it  has  attained  its  maximum.  There  is  thus  summation 
before  any  contraction  has  occurred,  a  summation  of  stimuli.  Each  stimulus, 
in  fact,  alters  the  state  of  the  contractile  tissue  and  makes  it  more  ready 
to  respond  to  the  next  stimulus,  so  that  the  stimuli  become  more  and  more 
effective.  If  time  is  allowed  for  the  muscle  to  relax  between  successive 
stimuli,  this  summation  is  evidenced  by  a  continually  increasing  height 
of   contraction,    the   so-called   '  staircase.'     The   same   initial   increase   of 


246  PHYSIOLOGY 

effect  is  observed  when  voluntary  muscle  is  excited  by  continually  recurring 
stimuli  {v.  Fig.  70,  p.  209). 

We  shall  meet  with  other  examples  of  this  summation  of  stimuli  when 
dealing  with  the  physiology  of  the  central  nervous  system.  It  is  indeed  a 
fundamental  phenomenon  in  the  physiology  of  excitation. 

CHEMICAL  STIMULATION.  Strong  salt  solution  excites  contractions 
just  as  in  the  case  of  skeletal  muscle.  Many  drugs,  such  as  physostigmine, 
ergot,  salts  of  lead  and  barium,  digitalis,  may  act  directly  on  smooth  muscle 
and  cause  contraction.  As  one  would  expect  however  from  the  greater 
independence  of  the  smooth  muscle,  the  action  of  these  drugs  varies  from 
organ  to  organ,  muscle-fibres,  which  apparently  are  histologically  identical, 
reacting  diversely  according  to  their  origin. 

MECHANICAL  STIMULATION.  Smooth  muscle  may  react  to  a  local 
pinch  or  blow  with  a  local  or  a  general  (propagated)  contraction.  The  most 
important  form  of  mechanical  stimulation  is  that  produced  by  tension. 
The  effect  of  increasing  the  tension  on  smooth  muscle  may  be  twofold  : 
causing  in  the  first  place  relaxation  and  in  the  second  excitation  with  in- 
creased contraction.  These  two  effects  may  be  illustrated  by  taking  the 
case  of  the  bladder.  If  this  viscus  (which  is  surrounded  by  a  complete 
coat  of  smooth  muscle)  has  all  its  connections  with  the  central  nervous 
system  severed,  it  is  when  empty  in  a  state  of  tonic  contraction.  If  fluid 
be  injected  into  it  rapidly  there  is  a  great  rise  of  pressure  in  its  cavity,  due 
to  the  forcible  distension.  If  however  the  fluid  be  injected  slowly,  the 
bladder  muscle  relaxes  to  make  room  for  it,  so  that  a  considerable  amount 
of  fluid  may  be  accommodated  in  the  bladder  without  any  great  rise  of 
pressure.  This  process  of  relaxation  has  its  limit.  If  the  injection  of  fluid 
be  continued,  the  walls  begin  to  be  stretched  passively,  and  this  increased 
tension  acts  as  a  stimulus  causing  marked  rhythmic  contractions  of  the 
whole  bladder. 

In  the  same  way  the  response  of  a  smooth  muscle  to  an  electrical  stimulus 
is  much  increased  by  previous  increase  of  the  tension  on  the  muscle  fibres. 

PROPAGATION  OF  THE  EXCITATORY  STATE,  OR  WAVE  OF 
CONTRACTION.  On  stimulating  any  part  of  a  voluntary  muscle  fibre, 
a  wave  of  contraction  is  started  which  travels  to  each  end  of  the  fibre,  but 
no  further.  There  is  no  propagation  from  muscle  fibre  to  muscle  fibre, 
the  synchronous  contraction  of  the  whole  muscle  being  brought  about  by 
simultaneous  excitation  of  all  its  fibres.  It  is  doubtful  whether  this  isolation 
of  the  excitatory  state  is  found  in  smooth  muscle.  As  a  rule  a  stimulus 
applied  to  any  part  of  a  sheet  of  smooth  fibres  may  travel  all  over  the  sheet 
just  as  if  it  were  a  single  fibre.  It  seems  probable  indeed  that  there  is 
protoplasmic  continuity  by  means  of  fine  bridge-like  processes  between 
adjacent  muscle  cells.  And  even  in  the  absence  of  such  bridges  the  jjropaga- 
tion  of  the  contraction  could  be  easily  accounted  for.  Although  in  the  case 
of  voluntary  muscle  the  rule  is  isolated  contraction,  yet  a  very  small  change 
in  the  muscle,  such  as  that  produced  by  partial  drying  or  by  pressure,  is 
sufficient  to  cause  the  contraction  to  spread   from  one  fibre  to  another. 


OTHER  FORMS   OF  CONTRACTILE  TISSUE  247 

Indeed  by  cla'mping  two  curarised  sartorius  muscles  together,  as  in  the 
diagram  (Fig.  96),  it  is  found  that  stimulation  of  the  muscle  a  causes  con- 
traction of  the  muscle  b.  The  current  of  action  of  a  in  this  case 
has  served  to  excite  a  contraction  in  B. 

It  must  be  remembered  that  in  all  unstriated  muscle  the  fibres  are  sur- 
rounded by  a  network  of  non-medullated  nerve  fibres.  Some  physiologists  are 
inclined  to  ascribe  to  these  fibres  an  important  part  in  the  propagation  of  the 
contraction  wave.  In  the  case  of  the  heart  muscle  however,  it  can  be  shown 
almost  conclusively  that  the  propagation  takes  place  independently  of  nerve  Fig.  96. 
fibres,  and  probably  the  same  is  true  for  many  kinds  of  involuntary  muscle. 

INFLUENCE  OF  TEMPERATURE.  Smooth  muscle  is  extremely  sus- 
ceptible to  changes  of  temperature  ;  as  a  ride  warming  causes  relaxation, 
while  application  of  cold  causes  a  tonic  contraction.  The  condition  of  the 
muscle  at  any  given. time  depends  not  only  on  its  actual  temperature, 
but  also  on  the  rapidity  with  which  this  temperature  has  been  reached. 
Thus  a  rapid  cooling  of  the  retractor  penis  muscle  of  a  dog  from  35°  to  25° 
may  cause  a  contraction  as  extensive  as  would  be  produced  by  a  slow  cooling 
to  5°C.  On  warming  a  muscle  from  30°  to  E0°C.  it  lengthens  gradually  up 
to  about  40°,  and  it  may  then  undergo  a  marked  heat  contraction  (varying 
in  degree  in  different  muscles)  at  about  50°O,  which  may  pass  off  at  a 
somewhat  higher  temperature.  It  is  killed  somewhere  between  40°  and 
50CC.  It  seems  very  doubtful  whether  any  true  rigor  mortis  occurs  in 
smooth  muscle.  The  hard  contracted  appearance  of  the  smooth  muscle 
in  a  recently  dead  animal  is  chiefly  conditioned  by  the  fall  of  temperature. 
On  excising  the  muscle  and  warming  it  up  to  body  temperature  it  may 
again  relax  and  show  signs  of  irritability  two  or  three  days  after  the  death 

of  the  animal.  Different  smooth 
muscles  however  vary  very  much 
in  their  tenacity  of  life. 

DOUBLE  INNERVATION. 
Voluntary  muscle  is  absolutely 
dependent  for  its  activity  on  the 
central  nervous  system.  Cut  off 
froni_this  it  is  flabby  and  motion- 
less. Its  sole  function  is  to  con- 
tract efficiently  and  smartly  on  re- 
ceipt of  impulses  arriving  along  its 
nerve.  It  is  only  necessary  therefore 
Fio.  97.  Tracing  from  the  retractor  pi  nis  muscle  that  these  impulses  should  be  of  one 
of  the  dog,  showing  lengthening  (inhibition)      i  .  n       ,  ,, 

on  stimulation  of  the  nervus  erigens,  and  a  character — motor,andweknowthat 
smart  contraction  on  stimulating  the  pudic  each  fibre  of  a  muscle,  such  as  the 
(motor)   nerve.     (Movements   of    muscle   re-  ,  .  ~ 

duced  $.)  sar tonus,  receives  one  efferent  nerve 

fibre  terminating  in  an  end-plate. 

In  the  case  of  smooth  muscle  we  have  a  tissue  which  has  an  activity 

and  reactive  power  of  its  own,  and  apart  from  its  innervation  may  be  at 

one  time  in  a  state  of  relaxation,  at  another  in  a  state  of  tonic  contraction. 


m 


248  PHYSIOLOGY 

In  order  that  the  central  nervous  system  should  have  efficient  control  over 
such  a  tissue,  it  must  be  able  to  influence  it  in  two  directions  :  it  must  be 
able  to  induce  a  contraction  or  increase  a  contraction  already  present,  and 
it  must  also  be  able  to  put  an  end  to  a  spontaneous  contraction,  i.e.  to  induce 
relaxation.  In  order  to  carry  out  these  two  effects,  smooth  muscle  receives 
nerve  fibres  of  two  kinds  from  the  central  nervous  system,  one  kind  motor, 
analogous  to  the  motor  nerves  of  skeletal  muscle,  the  other  land  inhibitory, 
causing  relaxation  or  cessation  of  a  previous  contraction.  All  these  fibres 
belong  to  the  visceral  or  '  autonomic '  system.  They  are  connected  with 
ganglion-cells  in  their  course  outside  the  central  nervous  system,  and  their 
ultimate  ramifications  in  the  muscle  are  always  non-medullated.  A  typical 
tracing  of  the  opposite  effects  of  these  two  sets  of  nerves  is  given  in  Fig.  97. 

In  the  invertebrata  many  '  voluntary  '  striated 
muscles  probably  possess  a  double  innervation. 
Thus  in  the  crayfish  the  adductor  muscle  of  the  claw 
consists  of  striated  muscular  fibres,  every  fibre  of 
which  is  supplied  with  two  kinds  of  nerve  fibres. 
By  exciting  these  fibres  one  may  get,  according  to 
the  conditions  of  the  experiment,  either  contraction 
of  a  relaxed  muscle  or  relaxation  of  a  tonically  con- 
tracted muscle  (Fig.  98). 

Fig.  98.    Tracing  of  contraction  AMCEBOID    MOVEMENT 

of  adductor  muscle  of  claw  of 
crayfish,  showing  inhibition  re-        Amoeboid  movement  is  seen  in  the  uni- 

^rtVtTby^tfof^con!  cellular  organisms  such  as  the   amoeba  and 
stant  current.    The  break  of  the  m  the  white  blood  corpuscles.     It  can  occur 

current  causes  a  second  smaller        .  ...  ,    •        !•_•*  t    +,.„,.-,„„„j-,,..« 

inhibition.    (Biedekmank.)        only   within  certain    hmits    of   temperature 
(about  0°C.  to  40°) ;    within  these  limits  it  is 
the  more  active  the  higher  the  temperature.     At  about  45°  the  cell  goes 
into  a  condition  resembling  heat  rigor. 

The  fluid  in  which  the  corpuscles  are  suspended  is  of  great  importance. 
Distilled  water,  almost  all  salts,  acids  and  alkalies,  if  strong  enough,  stop  the 
action  and  kill  the  cell. 

The  movements  are  also  stopped  by  C02  or  by  absence  of  oxygen. 
Artificial  excitation,  whether  electrical,  chemical,  or  thermal,  causes 
universal  contraction  of  the  corpuscle,  which  therefore  assumes  the  spherical 
form. 

CILIARY  MOVEMENT 
Cilia  are  met  with  in  man  in  nearly  the  whole  of  the  respiratory 
passages  and  the  cavities  opening  into  them,  in  the  generative  organs,  in  the 
uterus  and  Fallopian  tubes  of  the  female,  and  the  epididymis  of  the  male,  and 
on  the  ependyma  of  the  central  canal  of  the  spinal  cord  and  its  continuation 
into  the  cerebral  ventricles. 

The  cilia  (Fig.  99)  are  delicate  tapering  filaments  which  project  from  the 
hyaline  border  of  the  epithelial  cells.  There  are  about  twenty  or  thirty  to 
each  cell .  The  hyaline  border  is  really  made  up  of  the  enlarged  basal  portions 
of  the  cilia. 


OTHER  FORMS   OF  CONTRACTILE  TISSUE 


249 


In  action  the  cilia  bend  suddenly  down  into  a  hook  or  sickle  form,  and 
then  return  slowly  to  the  erect  position.  This 
movement  is  repeated  many  (twelve  to  twenty) 
times  a  second,  and  thus  serves  to  mova  forward 
mucus,  dust,  or  an  ovum,  as  the  case  may  be. 
The  movement  seems  to  be  entirely  automatic, 
and  it  is  quite  unaffected  by  nerves,  at  any  rate 
in  all  the  higher  animals. 

There  seems  to  be  a  functional  connection 
between  all  the  cells  of  a  ciliated  epithelial 
surface,  so  that  movement  of  the  cilia,  started  in 
one  cell,  spreads  forward  as  a  wave,  just  as, 
when  the  wind  blows,  waves  of  bending  pass 
over  a  field  of  corn. 

The  conditions  of  ciliary  action  are  the  same  Fio.  99.      Ciliated  columnar 

*,,  r  i-T  LfiJii  epithelium  from  the  trachea 

us  those  tor  amoeboid  movement  of  naked  cells.      0j    a     rabbit  ■     m1      m\ 
The  minuteuess  of  the  object  has  up  to  now      m3,    mucus-secreting    cells, 
prevented  us  from  deciding  whether  the  cilium       ('  CHAFEK-> 
is  itself  actively  contractile,  or  whether  it  is  simply  passively  moved  by 
the  action  of  the  basal  part  situated  in  the  hyaline  border  of  the  cell. 


CHAPTER  VI 
NERVE    FIBRES   (CONDUCTING   TISSUES) 


SECTION  I 

THE   STRUCTURE    OF   NERVE   FIBRES 

On  stimulating  the  nerve  of  a  nerve-musele  preparation  at  any  part  by 
electrical,  thermal,  or  mechanical  means,  the  stimulus  is  followed,  after 
a  very  short  interval,  by  a  contraction 
of  the  muscle.  This  observation  illus- 
trates the  two  functions  of  nerve  fibres, 
irritability  and  conductivity — that  is  to  say, 
a  suitable  stimulus  can  set  up  changes  in 
any  part  of  the  nerve,  which  are  trans- 
mitted down  the  nerve  without  any  visible 
effects  occurring  in  it,  and  it  is  not  until 
this  nervous  change  has  reached  the 
muscle  that  a  visible  effect  takes  place  in 
the  shape  of  a  contraction.  In  the  animal 
body  a  direct  excitation  of  the  nerve 
fibre  in  its  course  never  takes  place  under 
normal  circumstances.  The  only  function 
the  nerve  fibre  has  ,  to  perform  is  that 
of  conducting  impulses  from  the  sense 
organs  at  the  periphery  to  the  central 
nervous  system,  and  efferent  impulses 
from  this  to  the  muscles  and  other  of 
its  servants.  Hence  it  is  absolutely  es- 
sential that  there  should  be  vital  continuity 
along  the  whole  length  of  the  fibre.  Dam- 
age to  any  part,  such  as  by  crushing,  heat, 
or  any  other  injurious  condition,  infallibly 
causes  a  block  to  the  passage  of  an 
impulse. 

A  nerve  fibre  is  essentially  a  long  process  or 
arm  of  a  nerve-cell  (Fig.  100).  The  cell  may 
either  be  situated  on  the  surface  of  the  body  or, 
as  in  most  cases  in  the  higher  animals,  may  be 
withdrawn  from  the  surface  into  a  special 
collection  of  cells  such  as  the  posterior  root 
ganglion,  or  may  be  one  of  the  mass  of  cells  and 
250 


Fig.  100.  Diagram  of  a  motor  nerve- 
cell  with  its  nerve-fibre.  (After 
Barker.) 

a.li,  axon  hillock  ;  d,  dendrites ; 
a.x.  axis  cylinder  ;  to,  medullary 
sheath  ;   n.R.  node  of  Ranvier. 


THE  STRUCTURE   OF  NERVE  FIBRES 


251 


interlacing  processes  making  up  a  central  nervous  system.  All  nerves  are  alike  in  possess- 
ing as  their  conducting  part  the  continuous  strand  of  protoplasm  produced  from  the 
nerve-cell  and  known  as  the  axon  or  axis  cylinder.  By  special  methods  the  axon  may  be 
shown  to  be  made  up  of  fibrillar  or  neuro-fibrils,  embedded  in  a  more  fluid  material  (Fig. 
101).    These  neuro-fibrils  are  supposed  to  be  continuous  throughout  the  cell  and  the  axis 


Fio.  101.     Medullated  nerve  fibres,  showing  continuity  of  the  neuro-fibrils  across 
the  node  of  Kanvier.     (Bethe.) 
o,  longitudinal ;    b,  transverse  section. 

cylinder  and  to  represent  the  essential  conducting  constituents  of  the  nerve.  In  the 
course  of  growth  the  nerves  develop  certain  histological  differences,  which  appear  to 
bear  some  relation  to  the  nature  of  the  processes  they  conduct  or  to  the  character  of 
their  parent  cell.  Thus  all  the  fibres  which  are  given  off  from  and  which  enter  the 
central  nervous  system,  i.e.  the  brain  and  spinal  cord,  belong  to  the  class  known  as 
medullated.  In  this  type  the  conducting  core  or  axis  cylinder  is  surrounded  with  a 
layer  of  apparently  insulating  material  known  as  myelin,  forming  the  medullary  sheath, 
or  the  sheath  of  Schwann.  This  sheath  consists  of  a  fatty  material  composed  largely 
of  lecithin,  and  staining  black  with  osmic  acid,  supported  in  the  interstices,  of  a  network 
formed  of  a  horny  substance  known  as  neurokeratin.  The  medullary  sheath  is  sur- 
rounded by  a  structureless  membrane,  the  primitive  sheath  or  neurilemma.  At  regular 
intervals  a  break  occurs  in  the  medullary  sheath,  the  neurilemma  coming  in  close 
contact  with  the  axis  cylinder.  This  break  is  the  node  of  Ranvier,  the  intervening 
portions  of  medullated  nerve  being  the  intemodes.  In  each  internode,  lying  closely 
under  the  neurilemma,  is  an  oval  nucleus  embedded  in  a  little  granular  protoplasm. 
The  medullated  nerve  fibres  vary  considerably  in  diameter,  the  largest  fibres  being 
distributed  to  the  muscles  and  skin,  the  smallest  carrying  impulses  from  the  central 
nervous  system  to  the  viscera.  The  latter  all  come  to  an  end  in  some  collection  of 
ganglion- cells  of  the  sympathetic  chain  or  peripheral  ganglia,  the  impulses  being  carried 
on  to  their  destination  by  a  fresh  relay  of  non -medullated  nerve  fibres. 


252 


PHYSIOLOGY 


The  non-medullated  fibres  (Fig.  102)  differ  from  the  niedullated  simply  in  the 
absence  of  a  medullary  sheath.  They  possess,  in  many  cases  at  any  rate,  a  primitive 
sheath,  under  which  we  find  nuclei  lying  clbsely  on  the  side  of  the  fibre  and  bulging  out 
the  sheath.  In  their  ultimate  ramifications  they  tend  to  form  close  networks  or 
plexuses  and  appear  to  lose  the  last  traces  of  a  sheath. 

The  medullated  nerves  are  bound  together  by  connective  tissue  (endoneurium) 
into  small  bundles,  which  :'re  again  united  by  tougher  connective  tissue  into  larger 
nerve-trunks.  These  fibres  as  a  rule  branch  only  when  in  close  proximity  to  their 
destination,  and  then  the  branching  always  occurs  at  a  node  of  Ranvier. 


Fig.  102.    Non-medullated  nerve  fibres.     (SchAfer.) 

As  to  the  functions  of  the  myelin  sheath  in  the  medullated  nerve  fibre  very  little 
is  known.  It  does  not  make  its  appearance  until  the  axis  cylinder  is  formed,  and  is 
apparently  derived  from  a  series  of  cells  which  grow  out  from  the  spongioblasts  of  the 
central  nervous  system  and  form  a  chain  surrounding  the  out-growing  axons.  .In  the 
regeneration  of  a  nerve  fibre  after  section  the  myelin  sheath  appears  later  than  the 
axon  in  the  peripheral  part  of  the  nerve.  It  has  been  supposed  by  some  to  act  as  a  sort 
of  insulator  ensuring  isolated  conduction  within  any  given  nerve  fibre.  We  have  how- 
ever no  proof  that  equally  isolated  conduction  is  not  possible  in  the  non-medullated 
fibres  of  the  visceral  system,  although  it  is  certainly  true  that  a  finer  ordering  of  move- 
ments is  required  in  the  skeletal  muscles  than  in  the  visceral  mistriated  muscles.  More- 
over in  the  central  nervous  system  the  main  tracts  cannot  be  shown  to  be  functional 
before  the  date  at  which  they  acquire  their  medullary  sheaths,  suggesting  that  pre- 
viously any  impulse  making  its  way  along  the  tract  underwent  dissipation  before  arriving 
at  its  destination.  It  is  possible  too  that  the  myelin  sheath  may  serve  as  a  source 
of  nutrition  to  the  enclosed  axis  cylinder  winch,  in  the  greater  part  of  its  course,  is 
far  removed  from  its  trophic  centre,  namely  the  cell  of  wliich  it  is  an  outgrowth.  This 
trophic  f  imction  of  the  myelin  sheath  has  a  certain  basis  of  fact  in  that  the  myelin  sheath 
is  as  a  rule  larger  in  those  fibres  which  take  the  longer  course. 


SECTION  II 
PROPAGATION   ALONG   NERVE   FIBRES 

The  velocity  of  propagation  along  a  nerve  fibre  may  be  measured,  although 
in  early  times  it  was  thought  to  be  as  instantaneous  as  the  lightning  flash. 
To  measure  the  velocity  of  propagation  in  a  motor  nerve,  a  frog's  gastroc- 
nemius is  prepared,  with  a  long  piece  of  sciatic  nerve  attached.  The  muscle 
is  arranged  (Fig.  103)  so  that  its  contraction  may  be  recorded  on  a  rapidly 
moving  surface,  on  which  are  also  recorded,  by  means  of  electro-magnetic 


Fig.   103.     Diagram  of  arrangement  of  experiment  for  the  determination  of  the 
velocity  of  transmission  of  a  motor  impulse  down  a  nerve. 

The  battery  current  passes  through  the  primary  coil  of  the  inductorium  c, 
and  a  '  kick  over  '  key  k.  By  means  of  the  switch  s,  the  break  shock  in  the 
secondary  circuit  can  be  sent  through  the  nerve  n,  either  at  6  or  at  a.  The 
muscle  m  is  arranged  to  write  on  the  blackened  surface  of  a  trigger  or  pendulum 
myograph,  and  is  excited  during  the  passage  of  the  recording  surface  bj  the 
automatic  opening  of  the  key  k.     (The  time-marker  is  not  shown.) 

signals,  the  moment  at  which  the  stimulus  is  sent  into  the  nerve,  and  also  a 
time-marking  showing  w-t-g-  sec.  Tracings  are  now  taken  of  the  contraction 
of  the  muscle  :  first,  when  the  nerve  is  stimulated  at  its  extreme  upper  end  ; 
secondly,  as  close  as  possible  to  the  muscle.  It  will  be  found  that  the  latent 
period,  which  elapses  between  the  point  at  which  the  stimulus  is  sent  into 
the  nerve  and  the  point  at  which  the  lever  begins  to  rise,  is  rather  longer  in  the 
first  case  than  in  the  second.  The  difference  in  the  two  latent  periods  gives 
the  time  that  the  nervous  impulse  has  taken  to  travel  down  the  length  of 
nerve  between  the  two  stimulated  points.  Calculated  in  this  way,  the 
velocity  of  propagation  in  frog's  nerve  is  about  28  metres  per  second. 

In  man  and  in  warm-blooded  animals  the  velocity  has  been  variously 
estimated  at  from  60  to  120  metres  per  second.  The  higher  of  these  figures 
is  probably  nearer  the  truth. 

253 


254 


PHYSIOLOGY 


On  the  other  hand,  in  invertebrata  the  velocity  of  propagation  along  nerve  fibres 
may  be  quite  slow.  The  following  Table  represents  the  velocity  of  transmission  along 
a  number  of  different  fibres,  as  determined  by  Carlson,  compared  with  the  duration  of 
a  single  muscle  twitch  in  the  same  animal. 


Species 

Muscle 

Nerve 

Contrac- 

Rate of 

Muscle 

tion 
time  in 
seconds 

Nerve 

the  Impulse 
in  metres 
per  second 

Frog 

Gastrocnemius 

010 

Sciatic 

(medullated) 

27-00 

Snake 

Hyoglossus 

0-15 

Hyoglossal 
(medullated) 

14-004 

Lobster    . 

Adductor  of 

0-25 

Ambulacra! 

1200 

(Homarus) 

forceps 

(non -medullated) 

Hag  fish    . 

Retractor  of  jaw  . 

018 

Mandibular 

(non-medullated) 

4-50 

Limulus   . 

Adductor  of 
forceps 

1-00 

Ambulacral 

(non-medullated) 

3-25 

Octopus   . 

Mantle 

0-50 

Pallial 

(non-medullated) 

200 

Slug  (Limax)     . 

Foot 

400 

Pedal 

(non  -medullated ) 

1-25 

Limulus    . 

Heart 

2.25 

Nerve  plexus  in  heart 

0.40 

(non-medullated) 

The  velocity  of  propagation  in  sensory  nerves  is  more  difficult  to  deter- 
mine owing  to  the  fact  that  a  sensory  impulse,  on  arrival  at  the  receiving 
organ — i.e.  some  part  of  the  central  nervous  system — does  not  at  once  give 
rise  to  some  definite  recordable  mechanical  change,  such  as  a  muscular  con- 
traction. There  is  another  method  of  determining  the  velocity  of  conduction 
which  may  be  used  also  with  sensory  fibres.  The  passage  of  a  nerve- 
impulse  down  a  nerve,  just  as  the  passage  of  a  wave  of  contraction  along  a 
muscle  fibre,  is  immediately  preceded  or  accompanied  by  an  electrical  change, 
which  also  travels  along  the  nerve  as  a  wave  of  '  negativity.'  The  velocity 
of  propagation  of  this  wave  may  be  measured,  and  is  found  to  give  the  same 
numbers  as  the  velocity  determined  by  the  preceding  method. 

The  existence  of  this  electrical  change  enables  us  to  show  that  a  nerve- 
impulse,  excited  at  any  point  in  the  course  of  a  nerve  fibre,  travels  in  both 
directions  along  the  fibre.  The  power  of  nerves  to  transmit  impulses  in  either 
direction  is  shown  further  by  the  experiment  known  as  Kuhne's  gracilis 
experiment.  The  gracilis  muscle  of  the  frog  is  separated  into  two  portions 
by  a  tendinous  intersection,  so  that  there  is  no  muscular  continuity  between 
the  two  halves.  The  nerve  to  the  muscle  divides  into  two  branches,  one 
to  each  half,  and  at  the  point  of  junction  there  is  division  of  the  axis  cylinders 
themselves.  If  the  section  a  in  the  diagram  (Fig.  104),  which  is  quite  isolated 
from  the  rest  of  the  muscle,  be  stimulated,  as  by  snipping  it  with  scissors, 


PROPAGATION  ALONG   NERVE   FIBRES 


255 


Fio.  104. 

Kiihne's  gracilis 
experiment. 


the  whole  muscle  contracts.  If  the  portion  of  the  muscle  which  is  free  from 
nerve  fibres  be  stimulated  in  the  same  way,  the  contraction  is  limited  to 
the  fibres  directly  stimulated,  showing  that  in  the  first  case  the  stimulus 
excited  nerve  fibres  which  transmitted  the  impulse  up  the  nerve  to  the  point 
of  division  and  then  down  again  to  the  other  half  of  the  muscle. 

Since  nerves  have  this  power  of  conduction  in  both  directions,  it  might 
be  thought  that  a  single  set  of  nerve  fibres  might  very  well  subserve  both 
afferent  and  efferent  functions,  at  one  time  conducting 
sensory  impulses  from  periphery  to  cord,  at  another  time 
motor  impulses  from  cord  to  muscles.  But  this  is  not  the 
case.  As  a  matter  of  fact  we  find  in  the  body  a  marked 
differentiation  of  function  between  various  nerve  fibres. 
Thus  Bell  and  Majendie  showed  that  the  spinal  roots 
might  be  divided  into  afferent  and  efferent,  the  anterior 
roots  carrying  only  impulses  from  spinal  cord  to  periphery, 
while  the  posterior  roots  carried  impulses  from  periphery 
to  central  nervous  system.  The  law  known  by  the  name 
of  these  observers  states  indeed  that  a  nerve  fibre  cannot 
be  both  motor  and  sensory.  We  may  find  both  kinds  of 
fibres  joined  together  into  a  single  nerve-trunk,  but  the 
fibres  in  each  case  are  isolated  and  conduct  impulses  only 
in  one  or  other  direction.  Under  normal  conditions  the  afferent  fibres 
are  excited  only  at  their  endings  on  the  surface  of  the  body,  while 
the  efferent  fibres  are  excited  only  at  their  origin  from  the  spinal  cord. 
The  difference  in  the  function  of  different  nerve  fibres  depends  there- 
fore not  so  much  on  the  structure  of  the  nerve  fibre  itself  as  on  the 
connections  of  the  fibre.  We  can  show  this  experimentally  by  graft- 
ing one  set  of  nerve  fibres  on  to  another.  If  the  cervical  sympathetic 
be  united  to  the  lingual  nerve,  stimulation  of  the  sympathetic,  instead 
of  causing,  as  usual,  constriction  of  the  vessels  of  the  head  and  neck,  will 
cause  dilatation  of  the  vessels  of  the  tongue  and  secretion  of  watery  saliva. 
In  the  same  way  the  finer  functional  differences  between  the  various  forms  of 
sensory  nerves  seem  to  be  determined  by  their  connections  within  the  central 
nervous  system.  Stimulation  of  the  optic  nerve  by  any  means  whatsoever 
evokes  a  sensation  of  light.  One  and  the  same  stimulus  applied  to  different 
nerves  will  evoke  different  sensations,  e.g.  a  tuning-fork  applied  to  the  skin 
will  give  a  sensation  of  vibration,  to  the  ear  a  sensation  of  sound.  We  shall 
have  occasion  to  return  to  this  question  of  the  restricted  function  of  nerve 
fibres  when  we  deal  with  Midler's  '  law  of  specific  irritability  '  in  the  chapter 
on  Sensations. 


SECTION   III 

EVENTS    ACCOMPANYING   THE   PASSAGE    OF    A 
NERVOUS   IMPULSE 

In  muscle  we  saw  that  the  passage  of  an  excitatory  wave  was  accompanied 
or  followed  by  electrical  changes,  production  of  heat,  and  mechanical  change, 
all  pointing  to  an  evolution  of  energy  from  the  explosive  breaking-down  of 
contractile  material. 

In  nerve  however  which  serves  merely  as  a  conducting  medium,  we 
should  not  expect  so  much  expenditure  of  energy,  or  in  fact  any  expenditure 
at  all.  All  that  is  necessary  is  that  each  section  of  the  nerve  should  transmit 
to  the  next  section  just  so  much  kinetic  energy  as  it  has  received  from 
the  section  above  it.  And  experiment  bears  out  this  conclusion.  The 
most  refined  methods  have  failed  to  detect  the  slightest  development  of 
•  heat  in  a  nerve  during  the  passage  of  an  excitatory  process,  and  we  know 
already  that  there  is  no  mechanical  change  in  the  nerve.  The  only  physical 
change  in  a  nerve  under  these  circumstances  is  the  development  of  a  current 
of  action.  A  nerve  becomes,  when  excited  at  any  point,  negative  at  this 
point  to  all  other  parts  of  the  nerve  and,  just  as  in  muscle,  this  '  negativity  ' 
is  propagated  in  the  form  of  a  wave  in  both  directions  along  the  nerve. 

That  the  excitatory  process  in  nerves  is  probably  accompanied  by  certain 
small  chemical  changes  is  indicated  by  the  facts  that,  in  the  complete 
absence  of  oxygen,  the  nerve  fibres  lose  their  irritability,  and  that  this  loss 
of  irritability  is  hastened  by  repeated  stimulation  of  the  nerve.  When  the 
irritability  has  been  abolished  by  stimulation  in  the  absence  of  oxygen,  it 
may  be  restored  within  a  few  minutes  by  readmission  of  oxygen  to  the  nerve. 

If  we  connect  a  galvanometer  to  two  p.oints  of  an  uninjured  nerve,  no 
current  is  observed,  all  points  of  a  living  nerve  at  rest  being  isoelectric.  On 
making  a  cross-section  of  the  nerve  at  one  leading-off  point,  a  current  is  at 
once  set  up,  which  passes  from  the  surface  through  the  galvanometer  to  the 
cross-section.  This  is  a  demarcation  current,  set  up  at  the  junction  between 
living  and  dying  nerve.  This  current  rapidly  diminishes  in  strength  and 
finally  disappears,  owing  partly  to  the  fact  that  the  dying  process  started 
in  the  nerve  by  the  section  extends  only  as  far  as  the  next  node  of  Ranvier  and 
there  ceases,  so  that  after  a  short  time  the  electrode  applied  to  the  cross- 
section  is  simply  leading  off  an  intact  living  axis  cylinder  through  the  dead 
portion  of  the  nerve,  which  acts  as  an  ordinary  moist  conductor.  On  making 
a  fresh  section  just  above  the  previous  one,  the  process  of  dying  is  again  set 

256 


EVENTS  ACCOMPANYING  A  NERVOUS  IMPULSE         257 

up,  and  the  demarcation  current  is  restored  to  its  original  strength.  If, 
while  the  demarcation  current  is  at  its  height,  we  stimulate  the  other  end  of 
the  nerve  with  an  interrupted  current,  the  needle  of  the  galvanometer  swings  I 
back  towards  zero,  i.e.  there  is  a  negative  variation  of  the  resting  current. 
In  order  to  demonstrate  the  wave-like  progression  of  the  electrical  change 
from  the  excited  spot  along  the  nerve,  it  is  necessary,  as  in  the  case  of  muscle, 
to  make  use  of  a  very  sensitive  capillary  electrometer  or  a  string  galvano- 
meter. It  is  then  found  that  the  change  progresses  along  the  nerve  at  the 
same  rate  as  the  nervous  impulse,  i.e.  28  to  33  metres  per  second  in  the  frog. 
Hut  it  lasts  only  an  extremely  short  interval  of  time  at  each  spot,  viz.  six  to 
eight  ten-thousandths  of  a  second.  Thus  the  length  of  the  excitatory  wave 
in  nerve  is  about  18  mm. 


SECTION  IV 


CONDITIONS    AFFECTING   THE    PASSAGE    OF    A 
NERVOUS    IMPULSE 

TEMPERATURE.      Below   a    certain   temperature   the  propagation  of  the 
exeitatorv  process  in  the  nerve  is  absolutely  abolished.      The  exact  tempera- 
ture at  which  this  occurs  varies  according  as  we  use  a  warm-  or  a  cold-blooded 
i  animal.     In  the  frog  it  is  necessary  to  cool 

the  nerve  below7  0°C.  before  conduction 
is  abolished,  whereas  in  the  mammal  it  is 
sufficient  to  cool  the  nerve  to  somewhere 
between  0°  and  5°C.  Since  cooling  the 
G  nerve  does  not  excite  it.  this  procedure  forms 
a  convenient  method  for  blocking  the  passage 
of  impulses  along  a  nerve  without  using 
the  irritating  procedure  of  section.  On 
warming  the  nerve  again  the  conductivity 
returns.  The  rapidity  with  which  the  excita- 
tory process  is  propagated  along  either  a  nerve 
or  a  muscle  fibre  depends  on  the  temperature. 
Thus  the  mean  rate  of  conduction  in  the 
frog's  nerve  at  8°  to  9°C.  is  about  16  metres 
per  second.  The  temperature  coefficient 
of   the    velocity    of    nerve    propagation,    i.e. 

velocity  at  Tn  +  in        .  .        , ,      T 

-. has  been  found  bv  Lucas 

velocity  at  Tn 

to    be    about     1-79.     The    same    value    was 
found  by  Maxwell  for  conduction  in  molluscan 
H  nerve,  and  in  frog's   striated  muscle  Woolley 

•  10°'  found  the  temperature    coefficient    for    con- 

duction of  the  excitatory  process  to  vary  between  1-8  and  '2. 

An  ingenious  method  (Fig.  105)  has  been  used  by  Keith  Lucas  for  the  determination 
of  the  conduction  rates  in  nerve  at  different  temperatures.  The  glass  vessel  repre- 
sented in  the  figure  is  filled  with  Ringer's  solution,  in  which  the  whole  nerve-muscle 
preparation  is  immersed.  The  muscle  used  was  the  flexor  longus  digitorum,  so  that 
the  whole  length  of  the  sciatic,  tibial,  and  sural  nerves  could  be  used.  The  nerve  is 
passed  up  through  the  constrictions  in  the  inner  glass  vessels  at  c  and  D,  and  is  attached 
to  the  thread  E.     F,  I,  and  G  are  three  non-polarisable  electrodes  composed  of  porous 

258 


CONDITIONS  AFFECTING  A  NERVOUS  IMPULSE 


259 


clay,  containing  saturated  zinc  sulphate,  in  which  a  zinc  rod  is  immersed.  If  the  current 
is  passed  in  at  G  and  out  at  p  the  effective  cathode  is  at  the  lower  end  of  the  constriction 
c,  and  similarly  if  the  current  is  passed  in  at  I  and  out  at  G,  the  effective  cathode  is  at 
D.  The  tendon  of  the  muscle  A  is  attached  by  a  thin  glass  rod  H  to  a  very  light  recording 
lever,  the  movement  of  which  is  magnified  by  jjlacing  it  in  the  focal  plane  of  a  projecting 
eye-piece  and  recording  itsimageon  a  moving  sensitive  plate.  The  whole  apparatus,  with 
the  exception  of  the  glass  rod  at  H,  can  be  immersed  in  a  water  bath  at  any  given  tempera- 
ture. Two  records  are  taken  with  the  whole  apparatus,  first  stimulating  at  c,  and 
secondly  stimulating  at  D.  The  difference  between  the  latent  periods  in  these  two 
cases  is  the  time  taken  for  the  excitatory  wave  to  travel  from  D  to  c.  The  rate  of 
propagation  is  similarly 
recorded  when  the  water 
bath  is  raised  to  18°C. 
or  to  any  desired  tempera- 
ture. Since  we  are  only 
dealing  with  differences 
in  latent  periods  the  effect 
of  die  rise  of  temperature 
on  t  he  latent  period  of  the 
muscle  itself  does  not 
affect  the  determinations. 

THE  INFLUENCE 
OF  FATIGUE.  In  the 
description  of  the 
phenomena  of  mus- 
cular fatigue  given  in 
i  lie  last  chapter,  it  was 
assumed  that  the 
muscle     was       being 

excited  directly.  The  same  phenomena  are  observed  when  the  muscle 
is  excited  through  its  nerve,  though  in  this  case  fatigue  comes  on  much 
more  quickly.  If,  after  the  muscle  has  been  excited  in  this  way  until 
exhausted,  it  be  excited  directly,  it  will  respond  with  a  contraction  nearly  as 
high  as  at  the  beginning  of  the  experiment.  We  see  therefore  that  the 
nervous  structures  are  more  susceptible  to  the  influences  causing  fatigue 
than  the  muscle  itself,  and  it  can  be  shown  that  the  weak  point  in  the  nerve- 
muscle  preparation  is  not  the  nerve,  but  the  end-plates.  In  fact  it  is  not 
possible  to  demonstrate  any  phenomena  of  fatigue  in  the  nerve-trunk.* 
This  fact  can  be  shown  in  mammals  by  poisoning  the  animal  with  curare,  and 
then  stimulating  a  motor  nerve  continuously  while  the  animal  is  kept  alive 
by  means  of  artificial  respiration.  As  the  effect  of  the  curare  on  the  end- 
plates  begins  to  wear  off  in  consequence  of  its  excretion,  the  muscles  supplied 
by  the  stimulated  nerve  enter  into  tetanus.  The  action  of  the  curare  may  be 
cut  short  at  any  time  by  the  injection  of  salicylate  of  physostigmine,  when 
the  muscles  will  at  once  begin  to  react  to  the  excitation. 

The  same  fact  may  be  shown  on  the  excised  nerve-muscle  preparation 
of  the  frog.  The  gastrocnemii  of  the  two  sides  with  the  sciatic  nerves  are 
dissected  out,  and  an  exciting  circuit  is  so  arranged  that  the  interrupted 

*  Unless  it  be  asphyxiated  by  total  deprivation  of  oxygen. 


)6.     Curve    of    muscle-twitch    obtained    by    foregoii 

method.     (Keith  Lucas.) 
moment  of  excitation,     b  =  movement  of  muscle, 
c  =  time-marker. 


2  CO 


PHYSIOLOGY 


secondary  currents  pass  through  the  upper  ends  of  both  nerves  in  series  (Fig. 
L07).  At  the  same  time  a  constant  cell  is  connected  with  two  non-polarisable 
electrodes  (np,  np)  placed  on  the  nerve  of  b,  so  that  a  current  runs  in  the 
nerve  in  an  ascending  direction.  The  effect  of  passing  a  constant  current 
through  a  nerve  is  to  block  the  passage  of  impulses  through  the  part  traversed 

by  the  current.  When  the  con- 
stant polarising  current  is  made, 
the  muscle  may  give  a  single 
luamnitf  1_  twitch,  and  then  remains  quies 
v^^^/  cent.  The  exciting  current  is 
then  sent  through  both  nerves  by 
the  electrodes  ^  and  e2.  The 
muscle  a  enters  into  tetanus, 
which  gradually  subsides  owing 
to  '  fatigue.'  When  a  no  longer 
responds  to  the  stimulation,  the 
constant  current  through  the 
nerve  of  b  is  broken,  b  at  once 
enters  into  tetanus,  which  lasts 
as  long  as  the  contraction  did  in 
the  case  of  a,  and  gradually  sub- 
Fl°f  ^    ^rraT ment  °ff  e(\P.e"meak  ior?TTA  sides  as  fatigue  comes  on.     Since 

strating  the  absence   of  fatigue   in   medullated  6 

nerve  fibres.  both  nerves  have   been   excited 

EC,  exciting  circuit ;  or,  polarising  circuit.         ^0^0^  it  is  evident  that  the 

fatigue  does  not  affect  the  nerve-trunk.  We  have  already  seen  that  a  muscle 
will  respond  to  direct  stimulation  when  stimulation  of  its  nerve  is  without 
effect,  and  must  therefore  conclude  that  the  first  seat  of  fatigue  is  the  junction 
of  nerve  and  muscle,  i.e.  the  end-plates. 

In  the  normal  intact  animal  the  break  in  the  neuro-muscular  chain  which 
is  the  expression  of  fatigue  occurs  still  higher  up,  i.e.  in  the  central  nervous 
system,  and  is  probably  due  to  some 
reflex  inhibition  of  the  central  motor 
apparatus  from  the  muscle  itself.  Thus 
after  complete  fatigue  has  been  produced 
in  a  muscle  so  far  as  regards  voluntary 
efforts,  direct  stimulation  of  the  muscle 
itself  or  its  nerve  will  produce  a  contrac- 
tion as  great  as  would  have  been  the  case 
at  the  beginning  of  the  experiment. 

THE  INFLUENCE  OF  DRUGS.  The 
most  important  drugs  with  an  influence 
on  nerve  fibres  are  those  belonging  to  the 

class  of  anaesthetics.  Of  these  we  may  mention  carbon  dioxide,  ether, 
chloroform,  and  alcohol. 

The  action  of  any  of  these  substances  on  the  excitability  and  conductivity  of  a  nerve 
may  be  studied  by  means  of  the  simple  apparatus  represented  in  Pig.  108.     The  nerve 


CONDITIONS  AFFECTING  A  NERVOUS  IMPULSE       261 

of  a  nerve-muscle  preparation  is  passed  through  a  glass  tube  which  is  made  air-tight  by 
plugs  of  normal  saline  clay  surrounding  the  nerve  at  the  two  ends  of  the  tube.  By  means 
of  two  lateral  tubulures  a  current  of  C02,  or  air  charged  with  vapour  of  ether  or  other 
narcotic,  can  be  passed  through  the  tube.  The  nerve  is  armed  with  two  pahs  of  elec- 
trodes which  are  stimulated  alternately,  the  pair  within  the  tube  serving  to  test  the 
action  of  the  drug  on  the  excitability,  while  the  pair  outside  the  tube  show  the  presence 
or  absence  of  any  effect  on  the  conducting  power  of  the  nerve  below  it. 

Of  the  gases  and  vapours  mentioned  above,  CO.,  and  ether  both  diminish 
and  finally  abolish  the  excitability  and  conductivity  of  the  nerve  fibres. 
The  conductivity  however  persists  after  all  trace  of  excitability,  has  dis- 
appeared, before  in  its  turn  being  also  abolished.     On  removing  the  gas 


1,  -   11  ii 


Fio.  109.  Tracing  to  show  the  effect  of  ether  on  excitability  and  conductivity  of  nerve. 
Nerve  excited  by  single  induction  shocks  alternately  within  and  above  ether  chamber.  The 
vertical  lines  indicate  contractions  of  the  muscle  (gastrocnemius.)  The  lower  line  indicates 
the  periods  during  which  the  nerve  was  exposed  to  the  action  of  ether. 

a.  disappearance  of  excitability:  a,  reappearance  of  excitability;  c,  disappearance  of 
conductivity  ;   i>,  reappearance  of  conductivity.     (From  a  tracing  kindly  lent  by  Prof.  Gotch.) 

or  vapour  by  blowing  air  over  the  nerve,  the  conductivity  and  excitability 
gradually  return  in  the  reverse  order  to  their  disappearance  (Fig.  109). 

Alcohol  is  said  to  increase  the  excitability  or  leave  it  unaffected,  while 
diminishing  the  conductivity  of  the  nerve. 

Chloroform  rapidly  abolishes  both  excitability  and  conductivity.  It 
is  a  much  more  severe  poison  than  the  drugs  just  mentioned,  so  that  in  many 
cases  its  effects  are  permanent,  and  no,  or  only  a  very  partial,  recovery  of  the 
nerve  is  obtained  on  removal  of  the  chloroform  vapour  from  the  apparatus. 


SECTION  V 
THE    EXCITATION   OF   NERVE   FIBRES 

Many  different  forms  of  stimuli  may  be  used  to  arouse  the  activity  of  an 
excitable  tissue  such  as  muscle  or  nerve.  Thus  we  may  use  thermal,  mechani- 
cal, or  chemical  stimuli.  If  the  temperature  of  a  motor  nerve  be  gradually 
raised,  no  effect  is  noticed  till  about  40°C.  is  reached,  when  the  muscle  may 
enter  into  weak  quivering  contractions.  Sudden  warming  of  the  nerve 
always  gives  rise  to  excitation.  At  about  45°C.  the  nerve  loses  its  irritability 
and  dies.  On  the  other  hand,  a  nerve  may  be  rapidly  cooled  without  any 
excitation  taking  place. 

A  nerve  may  be  excited  mechanically  by  crushing  or  cutting.  These 
methods  destroy  the  nerve.  It  is  possible  to  excite  a  nerve  mechanically, 
without  any  serious  injury  to  it,  by  carefully  graduated  taps,  and  this  method 
has  been  used  in  investigating  the  phenomena  of  electrotonus. 

All  chemical  stimuli  applied  to  the  nerve  have  a  speedy  effect  in  destroying 
its  irritability.  The  chemical  stimuli  most  used  are  strong  salt  solutions, 
glycerin,  or  weak  acids.  If  any  one  of  these  be  applied  to  a  motor  nerve,  the 
muscle  enters  into  an  irregular  tetanus,  which  lasts  till  the  irritability  of  the 
nerve  is  destroyed  at  the  part  stimulated. 

None  of  these  forms  of  stimuli  can  be  adequately  controlled  either  as  to 
strength  or  duration.  Moreover,  owing  to  their  destructive  effects,  any 
repetition  of  the  stimulus  will  fall  on  a  nerve  or  muscle  more  or  less  altered 
by  the  first  stimulus.  We  are  therefore  justified  in  the  use  of  electrical 
stimuli  not  only  for  arousing  the  activity  of  excitable  tissues,  but  also  for 
determining  the  conditions  of  excitation  of  muscle  and  nerve.  For  this  pur- 
pose we  may  use  either  the  make  and  break  of  a  constant  current,  the  induced 
current  of  short  duration  produced  in  a  secondary  coil  of  -an  inductorium 
by  the  make  or  break  of  the  primary  circuit,  or  the  discharge  of  a  condenser. 

The  last-named  method  of  stimulation  is  especially  useful  when  we  desire  to  deter- 
mine the  total  amount  of  energy  involved  in  the  electrical  stimulation  of  a  nerve  or 
muscle.  The  arrangement  of  such  an  experiment  is  shown  in  Fig.  110.  By  means 
of  the  switch  S  the  condenser  can  be  put  into  connection  either  with  the  battery  from 
which  it  receives  its  charge  or  with  the  nerve  through  which  it  can  discharge.  By 
knowing  the  capacity  of  the  condenser  and  the  electromotive  force  by  which  it  is 
charged,  we  can  estimate  the  energy  of  the  charge-  sent  through  the  nerve. 
E  (energy  in  ergs)*  =  5PV2 
(P  =  capacity  in  microfarads  ;    V  =  electromotive  force  in  volts). 

*  An  erg  is  the  amount  of  work  produced  or  energy  expended  by  the  action  of 
one  dyne  -through  one  centimetre.  A  dyne  is  the  force  which  will  give  to  a  mass  of 
one  gram  an  acceleration  of  one  centimetre  per  second. 

262 


THE  EXCITATION  OF  NERVE   FIBRES 


263 


In  this  way  it  has  been  found  that  the  energy  of  a  minimal  effective  stimulus  for  frog's 
nerve  is  about  1  ,„',;„  of  an  erg. 

The  amount  of  energy  necessary  to  excite  the  nerve  will  vary  with  the  rate  at  which 
the  condenser  is  allowed  to  discharge  through  the  nerve.  Its  rate  can  be  modified 
by  altering  the  resistance  in  the  discharging  circuit  or  by  altering  the  electromotive 
force  of  the  charge.  This  method  has  been  adopted  by  Waller  in  determining  the  rate  of 
change  at  which  excitation  is  obtained  with  a  minimal  ex- 
penditure of  energy,  which  he  calls  the  "  characteristic  "  of 
the  tissue  in  question.  To  this  point  we  shall  have  occasion 
to  refer  later. 


FlO.  1  Ml.  Arrangement  of  apparatus 
for  the  excitation  of  a  nerve  by 
means  of  condenser  discharges. 

c,  battery  ;  R,  rheoehord  ;  c,  rider 
of  rheoehord  ;  s,  switch  (Pohl's  re- 
verse!-without  cross  wires)  ;  o,  con- 
denser ;  «,  nerve  :  m,  muscle  ;  e.  non- 
polarisable  electrodes. 


When  using  the  make  and  break  of  a  constant 

current  as  a  stimulus,  the  first  fact  of  importance  is 

the   relation  of  the  seat  of  excitation  to  the  rjoles 

I iy  which  the  current  is  led   into   or  out  of  the  ex- 
citable tissue.      We  have  already  seen  that  when  a 

current  is   passed   through   a    muscle   or   nerve  the 

muscle  contracts  only  at  make  or  at  break 

of  the  current,  no   propagated    excitatory 

effect  being  produced  during   the    passage 

of  the  current.     The  excitation    at    make 

is  obtained  with  a  smaller  current  than  the 

excitation  at  break. 

Besides  this  difference  in  intensity,  there 

is   a    difference    in  the  point  from  which 

excitation  starts.     A  make  contraction  starts 

from  the    cathode,  a  break  contraction   from 

the   anode.     This  is  well  shown  by  the  two  following  experiments  : 

(«)  A  curarised  sartorius  muscle  of  the  frog  (Fig.  Ill),  with  its  bony 

insertions  still  attached,  is  fastened  at  the  two  ends  to  two  electrodes,  which 

are  able  to  swing  when  the  muscle  contracts,  and  are  attached  by  threads 

to  levers  which  serve  to  record  the  contraction.     The  middle  of  the  muscle  is 

then  fixed  by  clamping  it  light!)'. 
A  circuit  is  arranged  so  that  a  con- 
stant current  can  be  sent  through  the 
electrodes  and  the  whole  length  of 
the  muscle.  It  is  found,  on  making 
the  current,  that  the  lever  attached 
to  the  cathode- — that  is,  to  the  elec- 
trode by  which  the  current  leaves  the 

muscle — rises  before  the  other  lever.     On  the  other  hand,  on  breaking  the 

current,  the  lever  at  the  anode  rises  first,  showing  that  the  anodic  half  of 

the  muscle  contracts  before  the  cathodic  half. 

(b)  The  irritability  of  a  muscle,  i.e.  its  power  of  responding  to  a  stimulus 

by  contracting,  is  intimately  dependent  on  the  life  of  the  muscle.     If  the 

muscle  be  injured  or  killed  at  any  spot,  its  irritability  at  this  spot  will  be 

therefore  diminished  or  destroyed.     Hence,  if  we  stimulate  a  muscle  at  the 

injured  spot,  no  contraction  will  ensue.     This  fact  maybe  used  to  demon- 


Fici.   111.     Sartorius  clamped  in   middle  and 
attached  to  levers  at  either  end. 


jj} 


264  PHYSIOLOGY 

strate  the  production  of  excitation  at  cathode  on  make,  and  at  anode  on 
break  of  a  constant  current. 

A  muscle  with  parallel  fibres,  such  as  the  sartorius,  is  injured  at  one 
end,  and  a  constant  current  passed,  first  from  the  injured  to  the  uninjured 
end,  and  then  in  the  reverse  direction  (Fig.  112).  It  is  found  in  the  former 
case,  when  the  anode  is  on  the  injured  part  (which  is  therefore  less  excitable), 

that  break  of  the  current  is  ineffec- 
i-L-_^...^_  '  tive,  and    in  the  latter,  when    the 

contraction  at  make      cathode  is  on  the    injured    surface, 

that   the  make   stimulus  is  ineffec- 
tive, showing  that  the  part  excited 

an0dM3fbs8»  kath°d8  <inJUred '  corresponds  to  the  cathode  at  make 

no  contraction  at  make.  aud  to  the  anode  at  break. 

With   a    current    of   very    short 
b  duration  no  excitation  is  produced 

PIO.112.     Diagmmto  show  the  effect  of  local      t   bk      j,  induction     shock 

injury   on   the   excitability   ot   a   muscle,     o,  •' 

battery ;    m.   muscle.     The  arrows  indicate  can    be     therefore    regarded     as     a 
the  direction  of  the  current.  make  8timuluS;  and    wnen     such    a 

shock  is  led  through  a  muscle  the  contraction  in  each  case  will  start  at 
the  cathode,  i.e.  the  point  at  which  the  induction  shock  leaves  the  muscle. 
The  results  of  stimulating  nerve  fibres  are  similar  to  those  obtained  by 
stimulating  muscle  fibres  directly. 

Under  normal  circumstances,  if  a  constant  current  be  passed  through  the 
nerve  of  a  nerve-muscle  preparation  for  a  short  time,  the  muscle  responds 
only  at  the  make  and  the  break  of  the  current,  remaining  perfectly  quiescent 
all  the  time  the  current  is  passing.  If  the  nerve  be  in  a  very  excitable 
condition,  it  is  possible  that  the  muscle  may  be  thrown  into  a  tetanus  or 
continued  contraction  during  the  whole  time  that  the  current  is  passing 
('  closing  tetanus  ').  On  the  other  hand,  if  a  strong  ascending  current  be 
passed  through  the  nerve  for  a  considerable  time,  the  muscle  when  the  current 
is  broken  may  go  into  continued  contraction,  which  may  last  some  time. 
Normally  the  muscle  simply  responds  with  a  single  twitch  at  the  make 
and  break  of  the  current,  although,  on  investigating  the  condition  of  the 
nerve  during  the  passage  of  the  current,  we  find  that  it  is  considerably' 
modified.  This  modification  in  the  condition  of  the  nerve  is  spoken  of  as 
electrotonus,  and  includes  changes  in  its  irritability  and  its  electrical  condition. 

To  investigate  these  changes  the  following  apparatus  is  necessary  :  two  constant 
batteries,  induction-coil,  a  reverser  and  keys,  a  pair  of  non-polarisable  electrodes, 
and  a  pair  of  ordinary  platinum  electrodes.  Fig.  113  represents  roughly  the  arrange- 
ment of  the  experiment.  A  constant  current  from  the  battery  is  led  through  a  part 
of  the  nerve  by  means  of  non-polarisable  electrodes,  which  are  about  one  inch  apart. 
In  this  circuit  we  put  a  reverser,  by  means  of  which  the  direction  of  the  current  of 
the  nerve  may  be  changed  at  will,  and  a  key  to  make  or  break  the  current.  This  is  the 
polarising  circuit.  The  other  battery  is  arranged  in  the  primary  circuit  of  the  coil,  a  key 
being  interposed,  so  that  we  may  use  make  or  break  induction  shocks,  which  are  applied 
to  the  nerve  by  means  of  the  small  platinum  electrodes.  The  tendon  of  the  muscle 
is  connected  by  a  thread  with  a  lever,  which  is  arranged  to  write  on  a  smoked  surface, 
so  that  the  height  of  the  contraction  can  be  recorded. 


till      e     \Pj 


THE  EXCITATION  OF  NERVE  FIBRES  265 

We  first  find  the  position  of  the  secondary  coil,  at  which  the  break  induction  shock 
is  a  submaximal  stimulus,  and  we  employ  this  strength  of  stimulus  throughout  the 
experiment.  The  make  induction  shock  is  prevented  from  acting  on  the  nerve  by  closing 
a  shortcircuiting  key  in  the  circuit  of  the  secondary  coil.  The  nerve  is  now  stimulated 
at  various  points  with  a  single  break  induction  shock,  and  the  contractions  recorded. 
The  heights  of  these  contractions  serve  to  indicate  the  irritability  of  the  nerve  at  the 
point  stimulated.  We  now  throw  the  polarising  current  into  the  nerve.  At  the  make 
of  this  current  the  muscle  will  prob- 
ably respond  with  a  twitch  which  is 
not  recorded.  We  then  test  once  more 
the  irritability  of  different  points  of 
the  nerve,  and  we  find  that,  when 
the  stimulus  is  applied  near  a,  the 
point  where  the  current  enters  the 
nerve  (anode),  the  stimulus,  which 
before  gave  a  moderately  large  con-  c= 
traction  of  the  muscle,  now  has  either 
no  effect  or  else  produces  a  very  weak 
contraction.  On  the  other  hand,  in 
the  region  of  the  cathode  the-  stimulus, 

which    before   was    submaximal,     has  V    c^fjy 

now  become  maximal,  as  is  shown  by 

the  increase  in  the  height  of  the  con-  FlQ-  H3-  Arrangement  of  apparatus  for  showing 
traction      evoked    by    the    induction  electrotonic  changes  in  irritability, 

shock.  e,  exciting  current  ;   p,  polarising  current  ; 

We  now  reverse  the  direction  of  the  r,  Pohl's  reverser. 

polarising  current,so  that  the  current  of  ' 

the  nerve  runs  from  k  to  a.  With  this  reversal  of  current  there  is  also  a  reversal  of  thP 
changes  in  the  nerve  ;  that  is  to  say,  the  normally  submaximal  stimulus  is  maximal 
when  applied  near  as,  and  minimal  when  applied  near  k.  On  break  of  the  polarising 
current  the  condition  of  the  nerve  returns  to  normal,  and  the  submaximal  stimulus 
is  once  more  submaximal  throughout. 

This  return  to  normal  conditions,  is  not  immediate,  since  the  first  effect  of 
breaking  the  current  is  a  swing-back,  so  to  speak,  past  the  normal,  the  diminished 
irritability  at  the  anode  giving  place  to  an  increased  irritability,  which  only  gradually 
subsides.  In  the  same  way,  immediately  after  the  polarising  current  has  ceased  to 
flow,  the  neighbourhood  of  the  cathode  acquires  a  condition  of  diminished  irritability, 
and  this  only  gradually  gives  place  to  a  normal  condition. 

This  experiment  teaches  us  that,  when  a  constant  current  is  passed 
through  a  nerve,  there  is  increase  in  the  irritability  in  the  nerve  near  the 
cathode,  and  a  diminution  in  irritability  near  the  anode.  These  conditions 
of  increased  and  diminished  irritability  are  spoken  of  as  caielectrotonus  and 
anelectrotonus  respectively.  In  muscle  we  have  seen  that  a  make  contraction 
always  starts  from  the  cathode,  and  a  break  contraction  from  the  anode. 
Now  the  event  that  takes  place  at  the  cathode  on  make  and  at  the  anode  on 
break  of  a  constant  current  is,  as  the  last  experiment  shows  us,  a  rise  in 
irritability,  in  the  former  case  from  normal  to  above  normal,  in  the  latter 
from  subnormal  to  normal.  Hence  we  may  say  that  the  excitation  is  caused 
by  a  sudden  rise  of  irritability,  which  may  be  due  either  to  a  sudden  appear- 
ance of  catelectrotonus  or  a  sudden  disappearance  of  anelectrotonus.  I 
have  said  sudden  because  the  steepness  of  the  rise  of  irritability  is  a  necessary 
factor  in  causing  excitation.     If  the   polarising  current  passing  through 


N- 


200 


PHYSIOLOGY 


a  nerve  be  slowly  and  gradually  increased  to  considerable  strength,  it  will 
give  rise  to  no  contraction.  The  degree  of  suddenness  of  the  rise,  which  is 
most  beneficial  in  causing  contraction,  varies  with  the  nature  of  the  tissue 
stimulated.  Thus  it  is  more  rapid  in  nerve  than  in  muscle,  and  in  pale 
muscle  than  in  red  muscle,  and  in  voluntary  muscle  than  in  unstriated 
muscle. 

It  is  evident  that   there  must  be,  somewhere  between   the  anode  and 
cathode,  an  indifferent  poinl     that  is  to  say.  a  region  where  the  irritability 


I'm.  11 1.  Diagram  to  show  the  variations  of  irritability  in  a  nerve  during  the  passage 
of  polarising  currents  of  different  strengths.  The  degree  of  change  is  represented  by  the 
distance  of  the  curves  from  the  base  line  ;  the  part  of  the  curve  below  the  line  signifying 
decrease,  that  above  the  line  increase  of  irritability. 

a, anode;  b,  cathode  ;  y, ,  effect  of  weak  current ;  i/o.  medium  current ;  1/3.  strong  current. 
It  will  be  noticed  that  the  indifferent  point,  x,  where  the  curve  crosses  the  horizontal  line, 
approaches  nearer  and  nearer  the  cathode  as  the  current  is  increased  in  strength.  (From 
Foster,  after  Pfluger.) 

is  neither  increased  nor  diminished.  We  find  experimentally  that  this  in- 
different point  is  nearer  the  anode  when  the  polarising  current  is  weak,  and 
approaches  the  cathode  as  the  current  is  strengthened,  so  that  with  very 
strong  currents  nearly  the  whole  intrapolar  length  is  in  a  condition  of 
anelectrotonus  (Fig.  114).  When  a  strong  polarising  current  is  used,  the 
depression  of  irritability  at  the  anode  is  so  marked  that  no  impulse  can  pass 
ascendinq   current 

make  excitation  blocked 
at  anode. 


break  excitation  at  anode 
blocked  at  kathode. 
kath7 

Fig.  115.     Diagram  to  show  the  blocking  effect  of  a  strong  constant  current 
passed  through  the  nerve  of  a  nerve-muscle  preparation. 

this  region.  Thus  if  we  send  a  very  strong  ascending  current  through  the 
nerve,  there  is  no  contraction  at  make.  This  is  owing  to  the  fact  that  the 
impulse  started  at  the  cathode  on  make  of  the  current  cannot  reach  the 
muscle,  its  passage  down  the  nerve  being  blocked  in  the  region  of  the  anode 
(Fig.   115,  A). 

The  results  of  stimulating  motor  nerves  by  means  of  constant  currents  were  studied 
by  Pttiiger  and,  embodied  in  a  Table,  make  up  what  is  known  as  Pfliiger's  law.  The 
result  of  stimulating  varies  with    tin-  strength  of  a  current. 


THE   EXCITATION   OF   NERVE  FIBRES 


267 


Law  op  Contraction 

Strength  of  current 

Ascending 

Descending 

Make               Break 

Make                  Break 

Weak 

c                    0 

c                          0 

Medium 

c                   c 

C                     c 

Strong 

0               C  or  T 

C  or  T                 0 

contraction. 


strong  contraction.      T  =  tetanus.      O  =  no  effect. 


With  tin-  weakest  currents  excitation  occurs  only  at  make,  since  a  make-stimulus, 
i.e.  the  rise  of  catelectrotonus,  is  always  more  effectual  than  a  break-stimulus,  i.e.  the 
disappearance  of  anelectrotonus.  With  currents  of  moderate  strength  excitation 
occurs  both  at  make  and  break,  being   better  marked  at  make,  especially  in  the  case  of 


7rn:.   116,     Arrangement  of  experiment  to  demonstrate  Pfliiger's  law  of  contraction. 

descending  currents.  With  verj  strong  currents  we  get  a  contraction  at  make  only 
when  the  current  is  descending,  since,  when  the  current  is  ascending,  the  excitation 
started  at  the  cathode  cannot  pass  the  block  at  the  anode.  For  the  same  reason  a 
break  contraction  is  obtained  only  with  an  ascending  current,  since  at  the  break  of 
i  descending  current  there  is  a  swingback  of  the  nerve  at  the  cathode  to  a  condition 
of  diminished  irritability,  which  effectually  blocks  the  excitation  started  higher  up 
the  nerve  at  the  anode. 

The  arrangement  of  the  experiment  for  demonstrating  Pliiiger's  law  is  shown  in 
Fig.  110.  The  strength  of  the  current  is  graduated  by  means  of  the  rheochord,  the 
current  being  led  into  the  nerve  by  means  of  non-polarisable  electrodes.  It  is  extremely 
important  in  these  experiments  to  avoid  any  injury  or  drying  of  the  nerves  at  either  of 
the  two  elect  roi  les,  since  the  excitatory  effect  neither  at  make  or  break  would  be  abolished 
by  local  injury. 

These  results,  worked  out  chiefly  on  motor  nerves,  have  been  con- 
firmed as  far  as  possible  experimentally  on  sensory  nerve,  and  on  muscle 
and  contractile  tissues  generally,  and  probably  hold  good  for  all  irritable 
living  tissues. 

It  is  said  that  an  anelectrotonus  takes  some  time  to  attain  its  full  height, 
and  a  catelectrotonus  reaches  its  maximum  almost  directly  after  the  current 
is  made,  and  that  it  is  on  this  account  that  a  current  of  very  short  duration 
excites  only  at  the  make,  the  break  occurring  before  the  anelectrotonus  is 
developed  enough  for  its  disappearance  to  cause  a  stimulus. 

Other  things  being  equal,  a  current  of  given  strength  causes  a  stronger 


268 


PHYSIOLOGY 


excitation  the  greater  the  length  of  nerve  that  it  flows  through.  It  must 
be  remembered  however  that  the  nerve  offers  considerable  resistance  to  the 
passage  of  the  current  and  so,  to  keep  the  current  constant  while  increasing 
the  length  of  intrapolar  nerve,  we  must  largely  increase  the  electromotive 
force  employed. 

A  very  convenient  method  of  showing  the  effect  of  the  length  of  intrapolar  nerve 
on  excitation  has  been  suggested  by  Ootch.     The  two  sciatic  nerves  of  a  frog  are  dissected 

out,  one  of  them  being  in  connection  with 
the  gastrocnemius.  These  are  first  arranged 
as  in  Fig.  117.  a,  b,  and  c  are  three  non- 
polarisable  electrodes,  the  terminals  of  a 
constant  battery  being  connected  to  a  and 
c.  The  position  of  the  rider  on  the  rheo- 
chord  is  then  ascertained  at  which  make  of 
the  current  just  excites  contraction  in  the 
muscle  of  nerve  2,  the  current  in  this  case 
passing  from  a  to  b  along  nerve  1,  and 
from  b  to  c  along  a  small  piece  of  nerre  2. 
We  will  suppose  that  eleven  units  of 
current  are  necessary  to  produce  excita- 
tion, b  is  then  withdrawn  and  the  nerve 
2  laid  on  a  (Fig.  117,  B),  so  that  the 
current  can  now  pass  from  a  to  c  entirely 
through  a  long  stretch  of  nerve  2.  On 
again  seeking  the  minimal  stimulus,  it 
will  be  found  that  a  smaller  current  is 
sufficient  to  excite,  contraction  being 
obtained  with  seven  units.  Since  the 
length  of  nerve  traversed,  and  therefore  the  resistance  to  the  current,  are  the  same 
in  both  cases,  it  is  evident  that  a  current  is  more  effective  the  greater  the  length  of 
excited  nerve  that  it  traverses. 

A  nerve  cannot  be  excited  by  currents  passed  transversely  across  it,  since 
in  such  cases  the  anode  and  cathode  lie  so  close  to  one  another  in  a  nerve- 
fibril,  as  it  is  traversed  by  a  current,  that  their  effects  counteract  one  another. 

ELECTRICAL  STIMULI  AS  APPLIED  TO  HUMAN  NERVES 
When  we  attempt  to  apply  the  results  gained  on  frog's  nerves  to  man,  we 
are  met  at  once  by  the  difficulty  that  we  cannot  dissect  out  the  nerves  and 
apply  stimuli  to  them  directly.  So  usually  unipolar  excitation  is  used,  one 
electrode,  either  anode  or  cathode,  being  applied  to  the  skin  over  the  nerve  to 
be  stimulated,  and  the  other  to  some  indifferent  point,  such  as  the  back.  It 
is  evident  under  these  circumstances  that  the  current  is  concentrated  as  it 
leaves  the  anode  and  reaches  the  cathode,  and  diffuses  widely  in  the  body, 
seeking  the  lines  of  least  resistance.  Thus  it  is  impossible  to  get  pure  anodic 
or  cathodic  effects.  If  the  anode  be  applied  over  the  nerve,  the  current 
enters  by  a  series  of  points  (the  polar  zone),  and  leaves  by  a  second  series 
(the  peripolar  zone).  The  polar  zone  will  thus  be  in  the  condition  of  anelec- 
trotonus,  and  the  peripolar  zone  in  that  of  catelectrotonus.  The  current 
however  will  be  more  concentrated  at  the  polar  than  at  the  peripolar  zone, 
and  so  the  former  effect  will  predominate.     These  restrictions  in  the  applica- 


Fig.  117. 


THE  EXCITATION  OF  NERVE  FIBRES 


269 


tion  of  the  current  cause  slight  apparent  irregularities  in  the  law  of  contrac- 
tion as  tested  on  man. 

In  stimulating  the  nerves  of  man  for  the  purpose  of  determining  the  conditions 
of  the  different  muscles,  we  may  use  either  induced  currents  (generally  called  faradic 
stimulation)  or  the  make  and  break  of  a  battery  current  (galvanic  stimulation).  The 
electrodes  are  covered  with  chamois  leather  moist- 
ened with  salt  solution  in  order  to  diminish  the 
resistance  of  the  skin.  When  it  is  desired  to 
stimulate  any  given  muscle  the  stimulating  elec- 
trode is  brought  as  nearly  as  possible  over  the 
spot  where  the  muscle  receives  its  motor  nerve. 
These  '  motor  points '  have  been  mapped  out. 
and  reference  is  generally  made  to  a  diagram 
in  determining  the  point  for  any  given  muscle. 
Bj  reversing  the  current  the  stimulating  elec- 
trode may  be  made  either  anode  or  cathode.  It 
is  found  that  stimulation  occurs  most  easily  on 
closure  of  the  current  when  the  stimulating 
electrode  is  the  cathode ;  with  the  greatest  diffi- 
culty when  the  current  is  broken  and  the  stinm- 
lating  electrode  is  the  cathode.  These  different 
contractions  are  generally  represented  by  capital 
letters,  and  the  usual  relationship 
pressed  by  the  statement  that  CCC  is 
most  easily,  then  AOC  and  AOC,  and  finally 
COC. 

CCC  =  cathodal  closing  contraction. 

ACC  =  anodal  closing  contraction. 

AOC  =  anodal  opening  contraction. 

COC  =  cathodal  opening  contraction. 
\\  hen  the  motor  nerve  to  a  muscle  has  under- 
gone degeneration  the  muscle  also  begins  to  de- 
generate, and  we  find  certain  alterations  in  its  response  to  artificial  stimulation. 
In  the  first  place,  the  muscle  may  fail  to  respond  to  induction  shocks,  while  it 
may  show  an  increased  irritability  for  galvanic  shocks.  In  the  second  place,  qualita- 
tive alterations  in  irritability  may  be  present,  so  that  ACC  may  be  obtained  with  a 
smaller  current  than  CCC.  These  alterations  are  spoken  of  as  the  '  reaction  of 
degeneration.' 


obtained  ^IG.  lls-  Electrodes  applied  to 
the  skin  over  a  nerve-trunk.  In 
A  the  polar  area  is  anelectrotonic 
and  the  peripolar  catelectro- 
tonic.  The  former  condition 
therefore  preponderates,  since 
the  current  here  is  more  con- 
centrated. In  B  the  conditions 
are  reversed,  the  polar  zone 
corresponding  in  this  case  to  the 
cathode.     (Waller.) 


SECTION  VI 


THE   CONDITIONS   WHICH    DETERMINE    ELECTRICAL 
STIMULATION 

For  every  tissue  traversed  by  a  current  there  is  a  minimum  rate  of  change 
at  which  the  current  through  the  tissue  must  be  increased  or  diminished 
in  order  to  cause  excitation.  If  instead  of  suddenly 
making  and  breaking  the  current  passing  through  an 
irritable  structure  we  carry  out  the  change  gradually, 
no  excitatory  effect  is  produced,  even  although  the 
current  may  finally  attain  a  considerable  strength. 
This  fact  may  be  demonstrated  by  the  use  of  an  appara- 
tus known  as  the  rheonome. 


Ill 


A  useful  form  of  rheonome  is  that  devised  by  Lucas  (Fig.  119). 
Two  zinc  plates  D  and  E,  immersed  in  a  saturated  solution  of 
zinc  sidphate  contained  in  a  rectangular  cell,  are  separated  from 
one  another  by  a  vulcanite  diaphragm.  In  the  diaphragm  is  a 
hole  G  by  which  the  two  sides  of  the  vessels  are  connected.  This 
hole  can  be  closed  at  any  desired  rate  by  a  shutter  F.  When  the 
hole  is  closed  no  current  can  pass  between  the  plates,  and  the 
amount  which  can  pass  will  depend  on  the  extent  to  which  the 
shutter  has  been  raised.  By  giving  the  hole  the  right  shape  it  is 
possible  to  diminish  the  resistance  of  the  apparatus  regularly.  If 
this  rheonome  be  placed  in  circuit  with  a  battery  and  an  excitable 
tissue,  such  as  the  nerve  of  a  nerve-muscle  preparation,  we  can 
make  a  current  or  break  a  current  through  the  tissue  at  any 
desired  rate.  Thus  the  course  of  the  current  through  the  tissue 
will  be  represented,  not  by  a  vertical  line,  but  by  a  sloping  line 
which  may  be  given  any  desired  degree  of  steepness  (Fig.  120). 

If  the  current  be  slowly  increased  through  the 
nerve  or  be  slowly  cut  off  from  the  nerve,  no  excitatory 
effect  takes  place,  while  quickly  opening  or  closing  the 
shutter  will  cause  excitation.  It  might  be  concluded 
that  the  excitatory  effect   of   a    current    increases    with 

1.  The  intensity  of  the  current. 

2.  The  rate  of  change  of  the  current. 

The  second  of  these  conditions  needs  however  some  correction.  As  we 
increase  the  rate  of  change  of  current,  by  employing  in  the  case  of  induced 
currents  more  and  more  rapid  alterations,  we  find  that  the  excitatory  effect, 

270 


Fio.  119. 
Rheonome  of 
Keith  Lucas. 


ELECTRICAL  STIMULATION 


271 


instead  of  increasing,  begins  to  diminish  and  finally  disappears,  so  that  high- 
frequency  currents  of  enormous  tension  can,  as  in  Tesla's  experiments,  be 
led  through  the  body  without  any  apparent  physiological  effect.  On  the 
other  hand,  by  using  more  sluggish  forms  of  irritable  tissue,  we  may  find  that 
even  induction  shocks  are  too  rapid  for  effective  excitation.  Thus  the  red 
muscles  of  the  slow-moving  tortoise  react  better  to  the  slow  make  than  to  the 
sudden  break  induction  shock,  and  many  forms  of  unstriated  muscle  are 
unaffected  by  either  make  or  break  shock.  There  is  in  fact  for  each  tissue 
an  optimum  rate  of  change  varying  with  the  character  of  the  tissue,  at  which 
the  current  necessary  to  produce  a  response  is  at  a  minimum.  This  optimum 
rate  of  change  is  spoken  of  by  Waller  as  the  '  characteristic  '  of  an  irritable 
tissue. 

A  further  investigation  of  the  time  relations  of  electrical  stimuli  by 
Keith  Lucas  has  thrown  important  light  on  the  character  of  the  excitatory 


Fig.  120.  String  galvanometer  records  of  the  change  of  current  obtained  by 
opening  the  diaphragm  in  the  rheonome  (Fig.  119)  at  different  rates.  (K. 
Lucas.) 

response  itself.  The  difference  between  various  excitable  tissues  is  perhaps 
best  brought  out  by  rinding  the  minimum  strength  of  current  which  will 
excite  at  make  and  then  determining  how  much  this  current  must  be  in- 
creased when  it  is  broken  at  a  very  short  interval  of  time  after  it  has  been 
made.  The  following  Table  represents  the  relation  between  duration  and 
strength  of  current  necessary  to  stimulate  in  the  case  of  the  sciatic  nerve 
of  the  toad  : 


Duration  of  current  (sec.) 
Go 
•0070 
•110.3:, 
■tii)087 
•00043 


Strength  of  current,  (volts) 

•086 
■091 

•119 
■179 
•245 


If  we  slightly  alter  the  use  by  Waller  of  the  word  '  characteristic  '  we 
may  take  as  the  characteristic  of  the  tissue  the  duration  of  the  stimulus 
at  which  the  current  necessary  to  stimulate  was  just  double  the  minimum. 
In  the  above  case  the  minimal  stimulating  current  was  approximately 
doubled  when  the  duration  of  the  current  was  limited  to  about  -001  sec. 
From  a  number  of  experiments  of  this  description,  Lucas  gives  the  following 
as  the  characteristic,  or  what  he  terms  the  '  excitation  times,'  of  muscle 
and  of  nerve : 


272  PHYSIOLOGY 

Muscle     ......      -017       sec. 

Nerve  fibre        .....       '003 

Nerve-ending  (or  intermediary  substance)        '00005     ,-, 

Similar  differences  are  obtained  when  we  attempt  to  determine  by  means  of  the 
rheonome  the  minimal  gradient  of  current  necessary  to  excite  a  nerve.  In  the  case 
of  the  toad's  nerve  the  minimal  gradient  must  be  ten  times  as  steep  as  in  the  case  of 
the  toad's  muscle,  and  is  such  that  in  one  second  the  current  must  reach  a  strength 
forty-five  times  the  minimal  strength  which  is  necessary  to  excite  when  the  current 
is  made  instantaneously.  In  the  frog's  nerve  the  minimal  gradient  is  still  steeper, 
so  that  in  one  second  the  current  must  reach  sixty  times  the  strength  of  the  minimal 
exciting  current.  We  may  interpret  these  results  as  signifying  that  the  excitatory 
state  produced  in  an  irritable  tissue  involves  the  production  of  some  change  which 
passes  away  spontaneously.  The  rate  of  production  of  the  change,  and  still  more  the 
late  of  its  spontaneous  disappearance,  differ  from  tissue  to  tissue.  If  the  gradient 
of  a,  current  which  is  made  through  the  tissue  is  too  slight,  the  spontaneous  disappearance 
of  the  excitatory  change  goes  on  as  rapidly  as  the  production  in  consequence  of  the 
rise  of  current.  No  excitation  therefore  takes  place.  The  '  excitation  time '  of  the 
tissue  will  thus  be  proportional  to  the  duration  of  the  excitatory  change  produced  in 
the  tissue  as  a  result  of  the  stimulus.  We  may  compare  the  excitation  time  of  three 
tissues  with  the  duration  of  the  electrical  change  produced  in  the  same  tissues  by  a 
single  stimulus. 

The  excitation  times  were  : 

Frog's  nerve  fibre         .....       '003  sec. 
Muscle  fibre  of  sartorius       .  .         .         .       '017     .. 

Ventricular  muscle  of  frog    ....     2O00     ., 

In  the  case  of  muscle,  according  to  Burdon  Sanderson,  the  electrical  change  reaches 
its  culminating  point  in  -0025  sec.  and  may  take  perhaps  eight  times  this  interval 
before  it  dies  away.  In  the  cardiac  muscle  of  the  tortoise  Sanderson  found  the  electrical 
change  to  last  between  two  and  three  seconds. 

SUMMATION  OF  STIMULI.  Closely  associated  with,  the  excitation 
time  of  the  tissues  are  the  phenomena  of  '  summation  of  stimuli '  and  '  re- 
fractory period.'  If  two  subminimal  stimuli  are  sent  in  within  a  sufficiently 
short  interval  of  time,  their  effect  is  summated,  so  that  two  stimuli,  each 
of  which  would  be  ineffective,  may  together  produce  an  excitation.  In 
the  case  of  striated  muscles,  in  order  that  mechanical  summation  of  con- 
traction may  take  place,  the  second  stimulus  must  become  effective  before 
the  muscle  has  completely  relaxed  ;  the  second  contraction,  that  is  to  say, 
starts  from  the  height  to  which  the  first  contraction  has  brought  the  muscle. 
A  similar  condition  of  things  appears  to  hold  for  summation  of  stimuli,  if 
we  substitute  for  mechanical  change  in  muscle  the  molecular  change  which 
accompanies  the  excitatory  state.  For  summation  of  two  stimuli  to  take 
place,  the  second  stimulus  must  occur  at  a  time  before  the  condition  excited 
by  the  first  stimulus  has  passed  away.  The  maximum  time  at  which  summa- 
tion of  two  stimuli  can  take  place  will  therefore  vary  from  tissue  to  tissue 
and  will  bear  a  relation  to  what  we.  have  designated  the  '  excitation  time ' 
of  the  tissue  and  also  to  the  rapidity  of  current  gradient  necessary  to  excite 
the  tissue.  This  will  be  evident  if  we  compare  the  maximum  summation 
intervals  for  different  tissues  with  the  excitation  time  of  the  same  tissues. 


ELECTRICAL  STIMULATION  273 

Stimulating  current  5%  above  minimal  stimulus 


Summation  interval 

•  Excitation  time 

sec. 

sec. 

•0005 

•003 

•0015 

•017 

•0080 

.     2-000 

Frog's  nerve 
,,        sartorius 
,,        heart 

REFRACTORY  PERIOD.  The  phenomenon  of  a  refractory  period 
has  long  been  known  in  connection  with  the  heart  muscle  and  has  often 
been  regarded  as  characteristic  of  this  muscle.  If,  in  the  isolated  ventricle, 
a  beat  be  evoked  by  a  single  minimal  stimulus,  subsequent  repetition  of 
the  stimulus  during  the  course  of  the  contraction  is  ineffective,  and  becomes 
effective  only  when  the  contraction  has  passed  away.  The  heart  is  said  to 
be  refractory  to  stimuli  during  this  period.  The  duration  of  the  refractory 
period  is  a  question  of  the  strength  of  the  stimulus  used.  With  strong 
stimuli  the  heart  may  be  made  to  contract  when  the  relaxation  has  only 
progressed  half  way,  and  with  very  strong  stimuli  one  contraction  may 
be  made  to  follow  the  last  at  such  a  short  interval  that  hardly  any  trace 
of  relaxation  is  observable  between  the  beats.  The  phenomenon  seems  to 
be  common  to  all  excitable  tissues.  Thus  if  two  stimuli  are  applied  to  a 
nerve  within  a  sufficiently  brief  interval,  the  second  stimulus  is  ineffective, 
so  far  as  can  be  determined  by  the  response  of  an  attached  muscle  or  by 
means  of  a  capillary  electrometer.  The  period  is  longer  the  lower  the 
temperature  and  varies  Irom  -0006  sec.  at  40°C.  to  -002  sec.  at  12°C.  This 
critical  interval  is  lengthened  if  the  irritability  of  the  nerve  is  depressed 
by  narcotics.  We  may  ascribe  it  'to  the  second  stimulus  being  applied 
before  the  excitatory  change  due  to  the  first  stimulus  has  reached  its 
culminating  point. 

THE  EFFECT  OF  TEMPERATURE  ON  EXCITABILITY.  It  was 
found  by  Gotch  that  the  excitability  of  a  nerve  within  certain  limits  was 
increased  by  cooling  the  nerve  and  diminished  by  raising  its  temperature 
(Fig.  121).  Thus,  if  a  frog  be  cooled  to  2°C.  or  3°C.  for  a  day,  it  will  be 
found  that  simple  section  of  the  sciatic  nerve  may  suffice  to  send  the  gastroc- 
nemius into  continued  contraction,  and  under  these  circumstances  '  closing 
tetanus '  va&y  be  obtained  with  the  greatest  ease.  This  increase  of  excita- 
bility does  not  apply  to  all  kinds  of  stimuli.  In  the  case  of  nerve  its  irri- 
tability was  found  to  be  increased  by  warming,  and  diminished  by  cooling 
for  induction  shocks  and  for  all  galvanic  currents  of  less  duration  than 
•005  sec.  In  skeletal  muscle  Gotch  found  the  excitability  for  all  forms  of 
stimuli  increased  by  cooling.  Lucas  has  shown  that  these  paradoxical 
effects  in  nerve,  namely,  increase  of  excitability  towards  currents  of  long 
duration  and  the  simultaneous  decrease  towards  currents  of  short  duration, 
are  conditioned  by  two  opposed  changes  in  the  tissue.  The  fall  of  tempera- 
ture (1)  delays  the  subsidence  of  the  excitatory  process,  (2)  renders  more 
difficult  the  initiation  of  a  propagated  disturbance.  The  first  of  these 
effects  reduces  the  current  required  for  excitation  in  a  ratio  which  varies 
with  the  duration  of    the  current.      The    second  increases  the  current 

18 


274  PHYSIOLOGY 

required  in  the  same  ratio  for  all  durations.  If  the  change  of  tempera- 
ture is  such  that  the  two  opposite  effects  are  exactly  balanced  at  a 
certain  medium  duration  of  current,  it  follows  that  for  currents  of  longer 
duration  the  net  result  will  be  to  reduce  the  current  required  for  excitation, 
while  for  currents  of  shorter  duration  the  net  result  will  be  to  increase  the 
current  required.  The  effect  of  temperature  therefore  on  the  minimum 
exciting  current  will  vary  from  tissue  to  tissue  according  as  the  two  factors, 
rate  of  subsidence  of  excitatory  change  and  the  initiation  of  a  propagated 


Fig.  121.  Tracing  of  muscle  contractions  to  show  effect  of  cooling  a  nerve  on  its 
excitability.  Thelower  line  indicates  the  changes  in  temperature  of  the  excited 
part  of  the  nerve.  The  muscle  responded  only  when  the  nerve  was  cooled,  the 
stimulus  becoming  ineffectual  when  the  nerve  was  warmed.      (Gotch.) 

disturbance  as  a  result  of  the  excitatory  change,  are  relatively  affected  by 
change  of  temperature. 

THE  EFFECT  OF  INJURY.  The  irritability  of  the  nerve  of  a  muscle- 
nerve  preparation  is  not  equal  in  all  parts  of  its  course,  but  is  greater  at  the 
upper  end,  probably  in  consequence  of  the  proximity  of  the  cross-section. 

Some  time  after  a  motor  nerve  is  divided  the  increased  irritability  at 
the  upper  end  gives  way  to  a  decreased  irritability,  and  this  decrease  goes  on 
till  the  nerve  is  no  longer  excitable.  The  diminution  in  excitability  gradually 
extends  down  the  nerve  fibre,  so  that  the  part  of  the  nerve  nearest  the  muscle 
remains  excitable  the  longest.  This  progressive  change  in  the  irritability 
of  a  nerve  after  section  is  spoken  of  as  the  Ritter-Valli  law.  It  is  soon' 
followed  by  definite  histological  changes  in  the  nerve,  which  we  shall  describe 
later. 


SECTION    VII 


THE    NEURO-MUSCULAR   JUNCTION 

The  excitatory  process  travelling  down  a  motor  nerve  has  to  be  transmitted 
to  the.  muscle  by  the  intermediation  of  the  nerve-ending  or  end-plate.  We 
have  learnt  to  regard  the  axis  cylinder  as  the  seat  of  the  propagated  ex- 
citatory process.  In  the  end-plate  however  the  axis  cylinder  comes  to 
an  end.  When  stained  by  methylene  blue  or  by  impregnation  with  chromate 
of  silver  or  mercury,  the  axis  cylinder,  after  passing  through  the  sarcolemma 
of  the  muscle  fibre,  is  seen  to  break  up  into  a  number 
of  branches  (in  some  cases  forming  a  typical  end- 
arborisation),  which  lie  on  or  are  embedded  in  a 
small  amount  of  undifferentiated  protoplasm  con- 
taining nuclei  (the  *  sole  plate  ').  A  similar  break 
in  structural  continuity  seems  to  occur  in  the  central 
nervous  system  wherever  an  impulse  is  propagated 
from  the  axon  process  of  one  nerve-cell  to  the  body 
or  dendrites  of  another  nerve-cell.  The  end-pro- 
cesses of  the  axon  come  in  contact  with  the  next 
member  in  the  chain  of  neurons,  but  no  anatomical 
continuity  is  to  be  made  out,  at  any  rate  in  the 
higher  animals.  In  the  central  nervous  system 
the  area  of  contiguity,  where  an  impulse  passes 
from  one  neuron  to  another,  is  spoken  of  as  a  synapse. 
The  presence  of  the  synapse,  or  end-plate,  between 
muscle  and  nerve  imposes  certain  new  conditions 
on   the   conduction  of  the  excitatory  impulse.     One 

of  the  most  important  of  these  lies  in  the  fact  that  the  conduction  across 
the  end-plate,  and  probably  across  the  synapse  of  the  central  nervous 
system,  is  irreciprocal.  An  excitatory  process  started  in  the  nerve 
travels  easily  across  the  end-plate  to  the  muscle.  On  the  other  hand,  an 
excitatory  process  started  in  the  muscle  does  not  extend  through  the  end- 
plate  to  the  nerve  fibre.  This  fact  may  be  shown  on  the  frog's  sartorius.  If 
the  lower  tibial  end  of  the  muscle  be  split,  as  in  Fig.  122,  a  mechanical 
stimulus,  such  as  a  snip  with  the  scissors,  applied  to  the  lower  nerve-free  end 
of  one  of  the  limbs,  e.g.  at  a,  causes  a  contraction  of  the  corresponding  half  of 
the  muscle,  which  does  not  extend  to  the  other  half.  On  snipping  the 
muscle  a  little  higher  up  at  b.  where  nerve-endings  are  present,  the  resulting 

275 


276  PHYSIOLOGY 

contraction  involves  the  whole  of  the  muscle,  owing  to  the  fact  that  the 
excitation  started  in  the  nerve-endings  spreads  in  both  directions  through 
the  branching  nerve  fibres. 

It  is  possible  that  thisirreciprocity  of  conduct  ion  may  be  of  comparatively  late  appear- 
ance in  evolution.  So  far  as  we  know,  an  excitatory  process  in  a  sheet  of  muscle  and 
nerve  fibres,  such  as  we  find  in  lower  invertebrata,  e.g.  in  medusa,  may  travel  with  equal 
facility  in  all  directions.  We  are  probably  not  warranted  from  our  experiments  on 
skeletal  muscle  in  concluding  that  the  contraction  of  a  cardiac  muscle-cell  may  not  set 
up  an  excitatory  process  in  the  surrounding  network  of  nerve  fibres.  It  is  impossible 
however  to  put  such  a  suggestion  to  experimental  test,  since  in  the  heart  there  is  no 
portion  of  muscle  fibre  sufficiently  removed  from  nerves  to  allow  of  an  excitation  being 
applied  which  might  not  at  the  same  time  affect  the  nerve  fibres. 

There  is  evidence  that  the  transmission  of  the  excitatory  condition 
across  the  end-plate,  from  nerve  to  muscle,  involves  a  special  excitatory 
process  and  the  expenditure  of  energy.  Thus  there  is  a  period  of  delay 
between  the  arrival  of  an  excitatory  impulse  at  the  terminations  of  the 
motor  nerve  and  the  beginning  of  the  electrical  change  which  marks  the 
moment  of  stimulation  of  the  muscle  fibre.  If  we  compare  the  latent  period 
of  a  muscle  stimulated  directly  with  its  latent  period  when  excited  through 
the  nerve,  we  find  that  there  is  an  increased  period  of  delay  in  the  latter 
which  is  not  wholly  accounted  for  by  the  time  taken  for  the  impulse  to 
travel  from  the  stimulated  spot  down  the  nerve  fibres  to  the  muscle.  The 
extra  delay  is  due  to  the  processes  occurring  in  the  end-plate.  This  end- 
plate  delay  amounts  to  -0013  sec.  We  may  take  it  roughly  at  a  thousandth 
of  a  second.  The  end-plate  seems  to  be  the  weakest  point  in  the  neuro- 
muscular chain.  We  have  already  seen  that,  when  a  nerve  of  a  nerve- 
muscle  preparation  is  stimulated  repeatedly,  the  muscle  very  soon  shows 
signs  of  fatigue,  and  that  the  seat  of  this  fatigue  is  not  in  the  nerve,  nor 
in  the  muscle,  but  in  the  end -plate. 

It  has  been  suggested  that  the  excitation  of  muscle  through  nerve 
depends  on  an  electrical  change  or  discharge  at  the  nerve-ending.  This 
discharge  must  originate  in  the  terminations  of  the  axon  and  must  influence, 
in  the  first  instance,  the  substance  which  forms  the  intermediary  between 
the  axon  and  the  contractile  material  of  the  muscle.  We  have  indeed 
direct  evidence  of  the  existence  of  a  third  substance,  neither  nerve  nor 
muscle,  at  the  point  of  junction  of  these  two  tissues.  Thus,  curare  is 
generally  said  to  paralyse  the  end-plates.  Evidence  for  this  statement 
has  been  given  in  the  previous  chapter.  Kiihne  has  shown  that  when  the 
irritability  of  the  frog's  sartorius  is  tested  at  different  points  it  is  greater  in 
the  situation  of  the  end-plates.  This  might  be  ascribed  to  the  presence 
of  the  more  irritable  nerve-fibres  passing  into  the  muscle-fibres  at  these 
points.  The  unequal  distribution  of  irritability  is  not  however  changed 
when  the  muscle  is  fully  poisoned  with  curare,  so  as  to  block  entirely  the 
passage  of  any  impulse  from  the  nerve  to  the  muscle.  We  must  therefore 
regard  curare  as  acting,  not  on  the  axon  terminations,  but  on  the  substance 
intervening  between  these  terminations  and  the  contractile  substance  of 


THE  NEURO-MUSCULAR  JUNCTION  277 

the  muscle.  Additional  evidence  of  the  existence  of  such  a  '  receptor  ' 
substance,  as  he  calls  it,  has  been  furnished  by  Langley.  Nicotine  resembles 
curare  in  blocking  the  passage  of  impulses  from  the  motor  nerve  to  skeletal 
muscle,  though  inferior  to  curare  in  this  respect.  If  4  mg.  of  nicotine  be 
injected  into  the  vein  of  an  anaesthetised  fowl,  the  hind  limbs  become 
gradually  stiff  and  extended  in  consequence  of  a  tonic  contraction  of  all  their 
muscles.  The  effect  slowly  passes  off,  but  can  be  reinduced  by  a  second 
dose  of  nicotine.  It  is  worthy  of  note  that  the  stimulating  effect  of  nicotine 
occurs  even  when  sufficient  is  given  entirely  to  paralyse  the  motor  nerves. 
It  might  be  thought  that  the  stimulating  effect  of  nicotine  was  a  direct 
one  upon  the  muscle  fibre,  but  experiment  shows  that  curare  has  a  marked 
antagonising  action  on  the  contraction  produced  by  nicotine.  A  sufficient 
dose  of  curare  annuls  the  contraction  produced  by  a  small  amount  of  nicotine 
and  diminishes  that  caused  by  a  large  amount.  The  point  of  action  of  the 
nicotine  must  therefore  be  the  same  as  that  of  the  curare.  After  a  muscle 
has  been  relaxed  by  curare  it  can  be  still  made  to  contract  by  direct  stimula- 
tion. On  the  other  hand,  nicotine  will  produce  its  stimulating  effect  when 
injected  into  a  bird  in  which  degeneration  of  all  the  nerve  fibres  of  the 
muscle  has  been  produced  by  previous  section  of  the  nerve-trunks.  It  is 
evident  therefore  that  nicotine,  like  curare,  acts,  not  on  the  axon  termina- 
tions, but  on  a  receptor  substance,  an  intermediary  substance  intervening 
between  the  axon  terminations  and  the  contractile  substance  of  the  muscle. 

Evidence  in  favour  of  such  an  intermediary  substance  has  been  brought 
by  Keith  Lucas  from  an  entirely  different  standpoint.  In  determining 
the  optimal  electrical  stimuli  or  the  '  characteristic  '  of  muscle  and  nerve 
by  the  condenser  method  (v.  p.  271),  Lucas  finds  that,  even  after  moderate 
doses  of  curare  sufficient  to  abolish  the  possibility  of  excitation  through 
the  nerve-trunk,  the  muscles  show  two  optimal  stimuli,  pointing  to  the 
existence  in  them  of  two  excitatory  substances,  one  of  which  is  not  paralysed 
by  moderate  doses  of  curare.  This  result  was  confirmed  when  the  tissue 
was  investigated  by  determining  the  relation  of  current  duration  to  the 
liminal  eurrent  strength  necessary  to  excite.  In  a  normal  sartorius  he  finds 
three  substances,  each  distinguished  by  its  own  '  excitation  time.'  In  the 
pelvic  nerve-free  end  of  the  sartorius  there  is  only  one  substance  with  an 
excitation  time  of  -017  sec.  This  may  be  regarded  as  the  muscle  substance 
proper.  In  the  sciatic  nerve-trunk  there  is  a  second  substance  with  a  much 
steeper  characteristic  and  with  an  excitation  time  of  -C03  sec.  On  experi- 
menting on  the  middle  region  of  the  sartorius  we  find  not  only  these  two 
substances  but  a  third  substance,  which  Lucas  calls  the  substance  /3,  with 
an  extremely  rapid  excitatory  process.  Its  excitation  time  is  -CCC05  sec. 
The:  presence  of  these  three  substances  in  the  middle  part  of  the  toad's 
sartorius  is  shown  in  the  diagrams  (Fig.  123),  which  represent  the  relation  of 
strength  to  duration  of  the  currents  necessary  to  evoke  a  contraction.  In 
this  curve  «  represents  the  muscle  material,  y  the  nerve  material,  and  /?  the 
curve  of  the  intermediary  substance. 

Similar  conditions  are  found  in  the    visceral  neuro-muscular  svstem. 


278 


PHYSIOLOGY 


Here  the  nerve  fibres  leaving  the  central  nervous  system  do  not  pass  direct 
to  the  muscle  fibres,  but  end  in  arborisations  round  ganglion-cells,  which 
are  collected  to  form  the  ganglia  of  the  sympathetic  chain  or  ganglia  situated 
more  peripherally  and  nearer  the  reacting  tissue.  Relays  of  fibres,  for  the 
most  part  non-medullated,  arise  from  these  ganglion-cells  and  pass  to  the 
unstriated  muscles  of  the  blood-vessels  and  viscera,  where  they  end  in 
plexuses  or  networks  among  the  muscle  fibres,  possibly  connected  by  short 
branches   with    the    fusiform    muscle    fibres    themselves.     No   structure   is 


t1 

-  \l 

-t — r 

N^ 

0 

• 

present  at  the  periphery  exactly  analogous  to  the  end-plate,  and  it  is  possible 
that,  as  Elliott  suggests,  the  end-plate  is  really  homologous  with  the  whole 
of  the  sympathetic  ganglion  with  its  post-ganglionic  fibres  passing  to  the 
visceral  muscles.  At  any  rate,  the  action  of  curare  and  of  nicotine  on  these 
peripheral  ganglia  is  very  similar  to  their  action  on  the  skeletal  end-plates, 
nicotine  however  having  a  relatively  stronger  action  than  curare.  In- 
jection of  nicotine  stimulates  and  then  paralyses  the  peripheral  nerve-cells 
of  the  visceral  system  ;  curare  in  sufficiently  large  doses  paralyses  them. 
More  instructive  in  relation  to  the  presence  of  receptor  substances  is  the 
action  of  adrenalin.  This  substance,  which  is  produced  by  the  medulla 
of  the  suprarenal  glands,  has  a  specific  action  on  all  tissues  innervated  by 
the  sympathetic  system.  It  causes  almost  universal  constriction  of  the 
blood-vessels,  dilatation  of  the  pupil,  acceleration  of  the  heart,  and  inhibition 
of  the  intestinal  muscles,  with  the  exception  of  the  ileo-colic  sphincter 
(which  it  causes  to  contract),  all  of  which  effects  can  also  be  produced  by 
stimulation  of  branches  of  the  sympathetic  nerve.  The  opposite  effects  of 
adrenalin  on  different  unstriated  muscles  show  that  its  action  cannot  be  a 
direct  one  on  muscle-fibre.  It  presents  a  marked  contrast,  for  instance,  to 
barium  salts,  which  produce  a  contraction  of  every  unstriated  muscle-fibre 
in  the  body.  On  the  other  hand,  we  cannot  ascribe  this  action  to  a  stimula- 
tion of  the  sympathetic  nerve-endings,  since  adrenalin  is  equally  effective  if 
applied  after  the  whole  of  these  nerve-endings  have  been  made  to  degenerate 


THE  NFAJRO-MUSCULAR  JUNCTION  279 

by  section  of  the  post-ganglionic  sympathetic  nerve-trunks.  Its  action 
therefore  must  lie  at  the  junction  between  nerve  and  muscle,  and  must  be  on 
some  intermediate  or  receptor  substance  developed  at  the  myoneural  junc- 
tion, and  having  for  its  function  the  transference  of  the  excitatory  process 
from  the  nerve  fibre  to  the  contractile  substance  of  the  muscle  fibre.  Similar 
receptor  substances  may  act  as  intermediaries  in  every  case  of  propagation  of 
an  impulse  across  a  synapse  of  whatever  description,  and  may  by  their  pro- 
perties determine  the  peculiar  qualities  of  the  synapse.  We  may  compare 
them  to  the  fulminating  cap  which  in  a  shell  is  used  to  transfer  the  process  of 
combustion  from  the  slow-match  to  the  bursting  charge.  Their  existence  is  of 
especial  importance  when  we  endeavour  to  investigate  the  mode  of  action  of 
drugs.  It  is  probable  that  they  will  be  found  to  play  a  great  part  in  deter- 
mining the  differential  action  of  drugs  on  various  tissues  in  the  body. 


SECTION   VIII 
POLARISATION   PHENOMENA   IN   NERVE 


ELECTROTONIC  CURRENT.  If  a  constant  current  be  passed  through 
a  nerve  fibre  through  the  electrodes  x  and  y, — x  being  the  anode  and  y  the 
cathode — and  the  extrapolar  portions  of  the  nerve  ab,  cd  be  connected  with 
galvanometers,  the  needles  of  both  are  deflected,  and  the  direction  of  the 
deflection  shows  the  existence  of  a  current  in  the  extrapolar  portions  of 
the  nerve  a  to  b,  and  from  c  to  d. 

We  thus  see  that  a  passage  of  a  current  through  a  part  of  a  nerve  gives 


K 


k 


t  i 


t  i 


G'  G2 

Fig.    124.     Diagram   showing   electrotonic   currents,     p,    polarising   circuit ; 
a1,  o2,  galvanometers. 

The  galvanometers  will  indicate,  before  the  passage  of  the  polarising  current, 
the  ordinary  demarcation  current  of  the  nerve  resulting  from  the  cross-section  at 
the  upper  end.  This  current  flows,  in  the  outer  circuit,  from  equator  to  cut  end, 
and  therefore  in  the  nerve  fibre  from  a  to  6,  and  from  d  to  c.  The  effect  of  closing 
the  polarising  current  will  be  to  increase  the  current  of  rest  between  a  and  b, 
and  to  diminish  that  between  c  and  d. 

rise  to  a  current  flowing  through  a  considerable  portion  of  the  nerve  fibre 
on  each  side  of  the  polarising  current  and  in  the  same  direction.  This 
current  is  called  the  electrotonic  current.  It  must  not  be  confounded  with 
the  current  of  action,  which  originates  at  one  of  the  poles,  only  at  make  or 
break  of  the  current,  and  is  transmitted  thence  in  the  form  of  a  wave  with 
a  measurable  velocity  (in  the  frog)  of  about  30  metres  per  second.  The 
electrotonic  current  is  developed  instantaneously,  and  lasts  the  whole  time 
that  the  current  is  flowing  through  the  nerve.     Its  production  is  dependent 

280 


POLARISATION  PHENOMENA  IN  NERVE  281 

on  the  occurrence  of  polarisation  between  the  sheath  and  the  conducting 
part  of  the  nerve  fibre  and  may  be  exactly  reproduced  on  a  model  consisting 
of  a  core  of  zinc  or  platinum  wire  in  a  casing  of  cotton  soaked  with  ordinary 
salt  solution.  Although  thus  physical  in  origin,  its  production  is  dependent 
on  the  vitality  of  the  nerve,  and  so  is  not  to  be  confounded  with  the  simple 
spread  of  current. 

The  polarisation  phenomena  resulting  from  the  passage  of  a  constant 
current  through  a  medullated  nerve  can  be  studied  on  a  model  made  up  of 
a  glass  tube  filled  with  normal  salt  solution,  containing  a  platinum  or  zinc 
wire  stretched  through  it  (Fig.  125).     On  leading  a  current  through  a  and  b, 


Glass  tube 

containing  0-6%  Na  CI., 


b  e  f 

Fio.    125.     Apparatus   for   imitating   the   polarisation   phenomena   in    medullated 
nerve  ('  Kernleiter  '  model). 

and  connecting  o  and  d  with  a  galvanometer,  a  current  will  be  observed  in 
the  extrapolar  portion  of  the  model  in  the  same  direction  as  in  the  intrapolar. 
That  this  spread  of  current  is  due  to  polarisation  is  shown  by  the  fact  that, 
if  the  model  be  made  of  zinc  wire  immersed  in  saturated  zinc  sulphate  solu- 
tion, so  that  no  polarisation  can  occur,  the  spread  of  current  to  the  extra- 
polar  area  is  also  wanting.  If  we  examine  the  phenomena  taking  place  at 
the  anode,  we  see  that  a  current  passes  here  through  an  electrolyte  to  the 
conducting  core.  Every  passage  of  a  current  through  an  electrolyte  must 
be  accompanied  by  dissociation,  the  current  being  carried  by  the  ions. 
We  get  therefore  a  movement  of  negative  ions  up  into  the  electrode,  and 
a  deposition  of  electropositive  ions  on  the  core  (Fig.  127,  a).  In  the  same 
way  at  the  cathode  there 
will  be  a  deposit  of  electro 
negative  ions  on  the  core 
(Fig.  126,  d),  so  we  may 
say  that  the  core   is  posi-     **-'**-  t 

tively     polarised     at    the     ''        ""\      b""a  ._~*.^—.~—--.— 

anode  and  negatively  polar- 

i«prl  nt  +hp  ™tWlp        Tlii«FlQ-   126'     Mag™™  to  show  polarisation  at  the  surface 
lsea  at  une  cainoae.       lms      b(tel|  conducting  core  and  electrolyte  sheath  in  a 
polarisation,  while  opposing     '  Kernleiter.' 
the  primary  current,  will 

set  up  currents  in  the  surrounding  electrolytic  sheath,  as  shown  by  the 
arrows  in  Fig.  127,  the  current  passing  from  a  to  b  and  from  b  to  c  in  the 
electrolyte,  returning  towards  a  in  the  core.  Hence  if  we  lead  off  from 
the  sheath  in  the  neighbourhood  of  the  anode  from  a  and  c,  a  current 
will  pass  in  the  galvanometer  from  a  toe,  that  is  along  the  core  in  the 
same  direction  as  the  intrapolar  current.  The  same  factors  will  cause  an 
extrapolar  current  in  the  cathodic  area,  the  catelectrotonic  current. 


282  PHYSIOLOGY 

This  polarisation  will  not  disappear  at  once  on  breaking  the  polarising 
current.  The  nerve  or  nerve-model  will  still  he  positively  polarised  at  the 
anode  and  negatively  polarised  at  the  cathode.  On  connecting  therefore 
these  two  points  with  the  galvanometer,  we  shall  get  a  current  in  the  direction 
opposite  to  the  previous  polarising  current,  viz.  from  anode  to  cathode 
(Fig.  128).  This  is  the  so-called  negative  polarisation  of  nerve.  Similarly 
in  the  extrapolar  regions  of  the  nerve  we  shall  have  currents  in  the  same 


Polarising 
Ik 


\V 


*'~-(Ty'        Positive  polarisation 


Flo.     Il'7.      Diagram    to    show    polarisation 
currenta  in  a  '  Kernkiter.'  or  in  a  medul,    FlG;     V2K     DmZ™m    to   th"w   direction    of 
lated  nerve  megative  polarisation  current. 

direction  as  the  previous  polarising  current,  as  shown  by  the  arrows.  So 
far  then  the  nerve  behaves  exactly  like  the  mechanical  model.  If  how  ever 
we  pass  a  very  strong  current  through  a  nerve,  and  then  quickly  switch 
the  nerve  on  to  a  galvanometer,  we  find  a  momentary  current  through  the 
galvanometer  in  the  same  direction  as  the  previous  polarising  current.  This 
is  known  as  positive  polarisation  of  nerve.  It  is  absolutely  dejtendent  on 
the  living  condition  of  the  nerve,  and  is  in  fact  an  excitatory  phenomenon 
due  to  the  strong  excitation  which  occurs  at  break  of  the  current  at  the 
anode.  Thus  in  the  diagram  (Fig.  129)  a  strong  current  is  passing  through 
the  nerve  from  a  to  k.  When  this  current  is  broken,  excitation  occurs, 
as  we  have  already  learnt,  at  the  anode,  and  this  excitatory  state  may, 
if  the  previous  currents  were  strong,  last  two  or  three  seconds.     An  excited 


/^K     Polarising 
» + 1  +  -  -L  _  => 


Fro.   129.     Diagram  to  show  direction  of  the  Fig.  130.     Diagram  of  arrange- 

positive  polarisation  current,  clue  to  a  break  ment  for: showing' paradoxical 

excitation  at  the  anode.  contraction. 

tissue  is  however  always  negative  towards  adjacent  unexcited  tissue, 
and  therefore  if  we  connect  a  to  k,  there  must  be  a  current  outside  the 
nerve  from  k  to  a,  and  in  the  nerve  from  a  to  k,  viz.  in  the  same  direction 
as  the  polarising  current.  We  see  therefore  that  negative  polarisation  is 
due  to  polarisation  occurring  between  an  electrolytic  sheath  and  a  con- 
ducting core,  whereas  positive  polarisation  is  hardly  a  polarisation  effect  at 
all,  but  is  a  current  of  action. 

PARADOXICAL  CONTRACTION.     If   the   sciatic  nerve   of  a   frog  be 


POLARISATION  PHENOMENA  IN  NERVE  283 

dissected  out,  and  one  of  the  two  branches  into  which  it  divides  be  cut, 
and  the  central  end  of  this  branch  stimulated,  the  muscles  applied  by  the 
other  half  of  the  nerve  contract  to  each  stimulus.  Ligature  or  crushing 
of  the  nerve  x  (Fig.  130)  between  the  points  stimulated  and  the  point 
which  joins  the  main  trunk  puts  a  stop  to  this  effect,  showing  that  it  is 
not  due  to  a  mere  spread  of  current..  The  fibres  passing  down  n  are  in 
fact  stimulated  by  the  electrotonic  current  developed  in  x  during  the  passage 
of  the  exciting  current. 


SECTION  IX 
THE   NATURE    OF   THE    EXCITATORY   PROCESS 

Under  this  heading  we  have  really  two  questions  to  discuss,  namely,  (a)  the 
nature  of  the  change  excited  at  the  stimulated  spot  in  an  excitable  tissue, 
and  (b)  the  propagation  of  the  .excitatory  change  away  from  the  excited  spot, 
e.g.  down  a  nerve  fibre.  That  these  two  phenomena  are  more  or  less  in- 
dependent and  may  be  dealt  with  separately  is  shown  by  the  result  of  passing 
a  constant  current  through  a  parallel-fibred  muscle,  such  as  the  sartorius. 
In  this  case,  as  we  have  seen  (p.  192),  at  make  of  the  current  an  excitatory 
change  occurs  at  the  cathode  and  is  transmitted  throughout  the  whole 
length  of  the  muscle,  giving  rise  to  a  twitch  of  the  muscle.  During  the 
passage  of  the  current  there  is  still  an  excitatory  change  at  the  cathode, 
but  limited  to  a  region  within  one  or  two  millimetres  of  the  cathode. 

An  attempt  has  been  made  by  Boruttau  and  other  physiologists  to 
explain  the  nerve  process,  not  as  a  wave  of  electrical  change  affecting  the 
substance  of  the  axis  cylinder  itself,  but  as  a  propagated  catelectrotonic 
current.  This  observer  found  that,  by  working  with  a  '  platinum  core 
model '  ('  Kemleiter ')  (Fig.  125)  of  considerable  length,  the  catelectrotonic 
current  was  developed  at  one  end  of  the  model  some  appreciable  time  after 
a  current  had  been  sent  in  at  the  other  end,  thus  resembling  a  current  of 
action.  It  is  however  impossible  to  explain  all  the  electrical  phenomena 
of  nerve  as  due  simply  to  polarisation.  We  might  go  so  far  as  to  assume 
that  the  excitatory  effect  at  the  cathode  is  due  to  negative  polarisation, 
and  that  excitation  at  break,  i.e.  at  the  anode,  is  caused  by  the  sudden 
coming  into  existence  of  a  negative  polarisation  current ;  but  then  it  would 
be  difficult  to  imderstand  how  the  excitation,  so  produced  at  the  anode,  should 
give  rise  to  a  current  so  much  exceeding  the  current  which  produced  it  that 
it  would  appear  in  our  external  circuit  as  a  current  of  positive  polarisation. 

The  same  objection  would  hold  to  the  comparison  of  a  nerve-fibre  with 
a  submarine  cable.  An  electric  disturbance  produced  at  any  part  of  a  cable 
(i.e.  a  conducting  wire  in  an  insulating  sheath)  is  propagated  along  the 
cable  at  a  certain  finite  velocity  which  can  be  calculated  when  we  know 
the  conductivity  of  the  core,  the  capacity  of  the  cable,  and  the  di-electric 
constant  of  the  sheath.  In  all  these  cases  there  must  be  a  decrement  of 
the  change  as  it  is  transmitted  away  from  its  seat  of  origin,  a  decrement  for 
the  existence  of  which  there  is  no  evidence  in  a  nerve  fibre  or  other  excitable 
tissue*     Moreover  the  phenomenon  of  propagation  of  an  excitatory  process 

*  It  might  be  urged,  on  the  other  hand,  that  one  would  not  expect  to  find  any 
appreciable  decrement  in  a  cable  only  1  to  3  inches  long. 

284 


THE  NATURE   OF  THE  EXCITATORY  PROCESS  285 

is  equally  well  marked  in  tissues,  such  as  muscle  and  non-medullated  nerve 
fibres,  which  show  very  little  of  the  electrotonic  effects  described  in  the  last 
section.  The  absence  of  decrement  in  the  excitatory  process  has  been 
taken  as  an  indication  that  the  axis  cylinder  of  the  nerve  is  the  seat  of  energy 
changes  which  may  be  let  loose  under  the  influence  of  chemical  or  electrical 
changes,  just  as  the  energy  of  a  contracting  muscle  is  set  free  by  the  exertion 
of  an  infinitesimal  force  applied  as  a  stimulus.  The  nerve  on  this  view 
does  not  simply  transmit  the  energy  which  is  imparled  to  it,  like  a  telegraph 
wire,  but  itself  furnishes  the  energy  of  the  descending  nerve-process. 

Against  this  view  might  be  urged  the  absence  of  phenomena  of  fatigue 
in  nerve',  as  showing  that  nervous  activity  is  not  accompanied  by  any  ex- 
penditure of  energy  or  using  up  of  material.  But  it  must  be  remembered 
that  this  absence  of  fatigue  holds  good  only  for  medtdlated  nerve  fibres  and 
is  not  found  in  non-medullated  nerves,*  and  even  in  medullated  nerves  the 
persistence  of  irritability  is  dependent  on  the  continual  supply  of  a  certain 
small  amount  of  oxygen.  It  may  therefore  possibly  be  explained  by  a 
continual  process  of  restitution  taking  place  at  the  expense  of  the  sheath. 
Fatigue  is  absent,  not  because  nothing  is  used  up,  but  because  the  assimilative 
changes  exactly  balance  and  make  good  the  dissimilation  involved  in  the 
propagation  of  a  nervous  impulse. 

There  is  thus  a  certain  amount  of  justification  in  the  comparison  of  a 
nerve  fibre  to  a  chain  of  gunpowder,  though  in  the  nerve  fibre  the  impetus 
to  disintegration,  imparted  from  each  particle  to  the  next  in  order,  consists, 
not  in  a  rise  of  temperature  at  the  point  of  ignition,  but  in  all  probability 
in  an  electrical  change  ;  and  the  total  evolution  of  energy  is  so  small  that 
it  cannot  be  measured  as  heat  by  the  most  sensitive  methods  at  our  disposal. 
The  excited  condition  at  any  segment  of  a  nerve  is  associated  with  a  develop- 
ment of  electromotive  forces  at  the  junction  of  the  segment  with  the  adjacent 
resting  segments.  The  current  of  action  thereby  produced  can  pass  by  the 
sheath  of  the  nerve,  so  that  it  must  enter  the  axon  at  the  excited  spot,  and 
leave  it  at  the  adjacent  unexcited  segment.  Hermann  has  suggested  that  in 
this  way  the  current  of  action  at  any  excited  spot  may  excite  the  adjacent 
segments  or  molecules,  causing  them  to  become  negative  and  thus  setting  up 
a  current  of  action  which  in  its  turn  excites  the  succeeding  segments.  In  this 
way  the  excitatory  process  may  travel  the  whole  length  of  the  nerve.  Propa- 
gation would  thus  involve  the  successive  setting  up  of  an  excitatory  process 
all  along  the  nerve  or  excitable  tissue,  though  it  is  difficult  to  see  why  on  this 
theory  every  excitatory  state  should  not  give  rise  to  a  propagated  change. 

We  are  as  yet  a  long  way  from  a  comprehension  of  the  changes  involved 
in  the  process  of  excitation,  though  we  are  able  to  form  some  idea  of  many  of 
the  factors  which  must  be  involved.  Any  theory  of  the  excitatory  process 
must  take  into  account  the  following  phenomena  : 

(1)  The  excitatory  state  is  attended  with  an  electrical   change  of  such 

*  This  statement  is  based  chiefly  on  experiments  on  the  olfactory  nerve  of  the  pike. 
Halliburton  and  Brodie  found  no  signs  of  fatigue  in  the  non-medullated  fibres  of  the 
sympathetic  supply  to  the  spleen,  even  after  several  hours'  stimulation. 


286  PHYSIOLOGY 

a  nature  that  the  excited  spot,  is  negative  to  adjacent  unexcited  spots.  Tliis 
electrical  change  rises  rapidly  to  a  maximum  and  dies  away  more  slowly, 
the  rate  of  its  rise,  and  still  more  of  its  subsidence,  varying  largely  according 
to  the  nature  of  the  tissue  under  investigation. 

(2)  The  excitatory  change  is  aroused  only  at  the  poles  of  a  current 
passing  through  the  tissue,  i.e.  at  those  places  where  polarisation  can  occur 
in  consequence  of  the  electrical  movement  of  ions. 

(3)  Excitation  only  occurs  at  the  cathode  at  make  of  the  current, 
and  only  occurs  if  the  current  attains  a  sufficient  strength  within  a  certain 
period  of  time,  the  relation  of  strength  of  current  to  rate  of  change  varying 
in  different  tissues. 

(4)  All  living  tissues  are  made  up  of  colloids,  divided  into  compartments 
by  membranes  of  various  permeabilities  and  permeated  with  salts  and  other 
electrolytes  in  solution. 

Disregarding  for  the  moment  all  considerations  of  structure,  it  is  possible 
to  form  a  hypothesis  of  the  nature  of  electrical  excitation  which  takes  into 
account  the  facts  just  mentioned  and  enables  us  to  give  a  quantitative  or 
mathematical  expression  to  the  factors  involved.  An  electrical  current 
passing  through  a  tissue  containing  membranes,  impermeable  to  the  dis- 
solved ions,  will  set  up  differences  of  concentrations  at  and  near  the  mem- 
branes. Nernst,  on  the  supposition  that  these  differences  of  concentrations, 
when  sufficiently  large,  would  cause  an  excitation,  arrived  at  a  formula 
connecting  the  lowest  current  required  to  excite  with  its  duration,  and 
another  formula  connecting  the  lowest  amplitude  of  an  electrical  current 
with  its  frequency.  The  mathematical  investigation  of  the  question  has  been 
continued  by  A.  V.-Hill  in  conjunction  with  Keith  Lucas.  For  this  purpose 
we  may  suppose  that  the  excitable  unit  is  represented  by  a  cylindrical  space 

closed  at  its  two  ends  by  the  mem- 
branes A  and  B  (Fig.  131)  and 
filled  with  a  solution  of  electro- 
lytes. If  a  current  be  passed 
from  b  to  A,  the  positively  charged 
ions  will  move  towards  a  and 
FlG-  13L  tend  to  accumulate  there.     The 

accumulation  of  the  ions  near  the  membranes  will  be  limited  by  the  tendency 
of  the  ions  to  equalise  their  concentration  in  all  parts  of  the  cell  by  diffusion. 
If  we  suppose  that  a  necessary  condition  for  excitation  is  that  the  concentra- 
tion of  the  ions  in  the  neighbourhood  of  one  of  the  membranes  shall  reach  a 
certain  definite  value,  it  becomes  possible  to  calculate  under  what  conditions 
of  strength,  duration,  &c,  an  electrical  current  will  just  produce  excitation. 
The  rise  of  the  excitatory  state  would  here  be  determined  by  the  rate  at 
which  the  ions  accumulate,  the  subsidence  of  the  excitatory  state  by  the  rate 
of  dispersal  of  the  ions  by  diffusion.  The  formula  arrived  at  by  these 
observers  has  this  form  : 

X 


THE   NATURE   OF  THE  EXCITATORY  PROCESS  287 

where  i  is  the  smallest  current  which  will  excite, 

I   is  duration  of  the  current; 
while  y,  //,  0  are  constants  which  depend  on  : 

(1)  The  distance  between  the  membranes. 

(2)  The  distance  from  the  membrane  at  which  the  concentration 

changes  are  being  considered. 

(3)  The  diffusion  constant  of  the  ion. 

(4)  The  number  of  ions  by  which  a  given  quantity  of  electricity  is 

carried. 
(•">)   A  constant  expressing  in  general  terms  the  ease  with  which  a 

propagated  disturbance  is  set-  lip. 
Investigation  on  these  linos  may  give  us  in  future  sufficient  infor- 
mation to  form  a  material  conception  of  the  factors  involved  in  excitation, 
factors  which  in  the  above  formula  have  only  a  symbolic  existence.  Thus 
a  determination  of  the  distance  between  the  membranes  would  give  us  some 
clue  to  the  size  of  the  ultimate  excitatory  units  in  the  tissue  involved.*  The 
constant  it.  has  reference  only  to  the  position  relative  to  the  membranes  at 
which  the  changes  of  concentration  are  effective.  From  Lucas's  experiments 
it  would  seem  that  the  changes  of  concentration  occur  in  the  immediate 
neighbourhood  of  one  of  the  membranes.  Macdonald  has  brought  forward 
evidence  that  the  passage  of  a  currenl  through  a  nerve  involves  the  setting 
free  of  certain  inorganic,  ions.  The  subsidence  of  the  excitatory  state 
depends  on  the  rate  of  diffusion  of  ions.  If  however  we  compare  the  rates 
of  subsidence  of  the  excitatory  state  in  different  tissues,  we  find  much  greater 
divergence  than  would  be  possible  on  the  assumption  that  the  diffusion  is  one 
affecting  inorganic  ions.  Thus  between  the  substance  /?  (the  intermediate 
substance)  of  the  frog's  sartorius  and  the  ventricular  muscle  fibre  of  the 
same  animal,  the  rate  of  subsidence  of  the  excitatory  state  changes  in  the 
ratio  H'U)  :  1.  If  the  ions  concerned  were  simple  ions,  such  as  H-,  Ca--,  Na-, 
CI',  Sec,  it  would  be  impossible  to  account  for  this  wide  variation,  since  their 
velocities  differ  in  the  ratio  of  10  :  1  at  most.  Moreover  the  effect, of  rise  of 
temperature  on  the  rate  of  subsidence  is  greater  than  the  effect  of  a  similar 
rise  on  ionic  velocities.  It  is  evident  therefore  that  the  theory  is  one  for  use 
as  a  working  hypothesis  only.  That  excitation  is  associated  with  accumu- 
lation of  ions  in  the  region  of  the  exciting  electrode,  that  the  subsidence  of 
the  excitatory  state  is  due  to  disappearance  by  diffusion  or  otherwise  of 
t  hese  ions,  there  can  be  little  doubt.  But  the  questions  as  to  the  nature  of 
these  ions,  and  their  relation  to  the  colloidal  constituents  of  the  excitatory 
tissue,  or  to  other  possible  substances,  changes  in  which  may  form  an  integral 
part   in  the  excitatory  state,  must  be  left-  for  future  investigation. 

*  It  would  bo  premature  at  present  to  give  any  histological  significance  to  Hill 
and  Luoas's  diagrammatic  cylinder.  As  Hardy  has  pointed  out,  the  nerve  cannot 
consist  of  a  row  of  such  cylinders,  otherwise  excitation  would  occur  throughout  the 
whole  intrapolar  region,  and  not  be  confined  to  the  cathode  at  make  and  the  anode 
at  break.  It  may  be  that  we  are  dealing  here  again  with  the  polarisable  sheath  of  the 
'  Kernh/trr,'  and  that  the  membrane  A  corresponds  to  the  surface  of  the  axis  cylinder 
or  of  its  neuro-fibrils. 


CHAPTER  VII 
THE    CENTRAL   NERVOUS   SYSTEM 

SECTION  I 

THE    EVOLUTION    AND   SIGNIFICANCE    OF   THE 
NERVOUS   SYSTEM 

Every  vital  phenomenon  may  be  regarded  as  a  reaction  conditioned  by  some 
change  in  the  environment  of  the  animal  and  adapted  to  its  preservation.  In 
the  community  of  cells  forming  the  whole  organism,  the  defence  of  any  one 
part  must  involve  the  co-operation  of  the  whole  community  ;  no  change 
in  a  cell  of  the  body  can  be  regarded  as  a  matter  of  indifference  to  any  of  the 
other  cells.  For  this  subordination  of  the  activities  of  each  part  to  the 
welfare  of  the  whole,  as  for  the  co-operation  of  all  parts  in  maintaining  the 
welfare  of  each,  a  means  of  communication  is  necessary  between  the  various 
cells.  For  some  of  the  lower  functions  the  channel  of  communication  is  the 
blood,  which  serves  as  a  medium  for  carrying  food  material  from  one  part  of 
the  body  to  another,  or  for  the  transmission  of  chemical  messengers  which, 
elaborated  by  one  set  of  cells,  may  affect  the  metabolism  of  cells  in  distant 
parts  of  the  body.  *  This  method  of  correlating  different  activities  would 
however  be  too  slow  and  clumsy  for  the  quick  adaptation  of  the  organism 
to  sudden  changes  of  environment.  Such  a  rapid  correlation  can  be  effected 
only  by  a  propagation  of  some  molecular  change  from  the  seat  of  incidence  of 
the  stimulus,  either  to  all  parts  of  the  body  or  to  some  mechanism  controlling 
all  parts  of  the  body.  The  medium  for  the  propagation  of  a  state  of  excitation 
is  furnished  by  the  nervous  system.  We  have  seen  that  stimuli  of  various 
kinds,  involving  such  various  forces  as  thermal,  chemical,  and  electrical 
energy,  are  transformed  by  a  muscle  or  nerve  fibre  into  what  we  call  a  state 
of  excitation,  which  is  propagated  along  the  fibres,  whether  nerve  or  muscle, 
at  a  certain  definite  rate,  its  passage  in  the  case  of  the  muscle  being  followed 
by  a  wave  of  contraction. 

In  unicellular  animals,  such  as  the  amoeba  and  vorticella,  there  is  no 
differentiation  of  any  structure  which  can  be  regarded  as  peculiarly  nervous. 
A  stimulus  applied  to  any  part  of  the  amoeba  may  evoke  responsive  activity 
in  all  other  parts.  A  slight  touch  applied  to  any  point  on  a  vorticella  will 
cause  an  excitation  which  is  rapidly  propagated  to  the  stalk,  causing  this  to 

288 


EVOLUTION  OF  THE   NERVOUS  SYSTEM 


289 


contract  and  so  withdraw  the  organism  from  any  possible  injury.  In  the 
lowest  metazoa,  such  as  the  sponges,  we  find  no  special  nervous  structures. 
The  cells  forming  the  sponge  may  react  to  changes  in  their  environment  by 
contraction  or  by  alteration  of  their  relative  positions.  Many  of  the  cells  can 
move  from  one  part  of  the  sponge  to  the  other  in  response  to  chemical 
changes  occurring  in  the  body  of  the  sponge.  So  far  however  no  cells  have 
been  distinguished  as  endowed  above  their  fellows  with  the  property  of 
irritability  or  the  power  of  reaction  to  stimulus.  It  is  in  the  next  class,  that 
of  the  Coelenterata,  where  we  first  find  a  definite  nervous  system.     The  object 


B 


FlG.  132,     Diagrammatic  representation  of  evolution  of  a  nervous  system. 
(Modified  from  Foster.) 

ec,  epithelial  cell ;  mp,  muscular  process  j  sc,  sensory  cell ;  np,  nerve  process 
or  fibre  :  mc,  muscle  cell ;  sn/p,  sensory  nerve  process  ;  mnp,  motor  nerve  process  ; 
cc,  central  cell. 

of  a  nervous  system  is  to  ensure  the  co-operation  of  the  whole  organism  in  any 
reaction  to  changes  in  its  surroundings.  At  its  first  appearance  therefore  we 
should  expect  a  nervous  system  to  be  developed  in  connection  with  that  layer 
of  the  animal  which  is  in  immediate  relation  to  the  environment,  namely, 
the  epiblast  or  external  layer.  In  some  species  of  hydra,  though  no  typical 
nervous  tissues  have  been  detected,  many  of  the  epithelial  cells  lying  on  the 
surface  are  prolonged  at  their  inner  ends  into  a  long  contractile  process  (Fig. 
132,  a),  so  that  stimuli  applied  to  the  surface  and  acting  on  the  epithelial 
cells  can  cause,  as  an  immediate  response,  a  contraction  of  the  underlying 
muscular  processes.  We  may  easily  conceive  that  in  such  an  animal,  among 
the  cells  forming  the  epiblast,  certain  cells  might  become  endowed  with  a 
special  sensitiveness  to  external  changes,  other  cells  being  developed,  like 
those  of  the  hydra  just  mentioned,  into  special  contractile  structures.  If  in 
the  course  of  development  the  protoplasmic  continuity  between  these  two 
sets  of  cells  had  not  become  interrupted  (and  we  have  no  ground  for  assuming 
that  such  an  interruption  occurs  under  normal  circumstances),  it  is  evident 
f  hat  we  should  have  so  produced  the  simplest  form  of  a  reflex  arc  (Fig.  132,  B), 
namely,  a  sensory  cell,  which  is  stimulated  by  slight  physical  changes  in  its 
surroundings  and  is  thereby  thrown  into  a  state  of  activity  similar  to  that 
which  we  have  already  studied  in  muscle  and  nerve.  This  state  of  activity 
would  be  propagated  bv  the  protoplasmic  channels  to  the  muscular  cell  and 

19 


290 


PHYSIOLOGY 


arouse  there  the  specific  function  of  the  muscle,  namely,  contraction.  In  such 
a  simple  reactive  tissue,  lines  of  less  resistance  would  be  rapidly  laid  down 
through  the  protoplasmic  continuum,  and  these  lines,  acquiring  a  specific 
structure  or  composition,  would  form  a  network  uniting  sensory  and  muscular 
cells.  Thus  a  stimulus  applied  to  any  sensory  cell  would  spread  to  the  ad- 
jacent sensory  and  muscular  cells,  and  the  response  of  the  muscle  cells  would 
be  greatest  near  the  stimulated  spot,  gradually  dying  away  as  the  area  of  the 
excitation  widened.  A  further  step  in  the  development  of  such  a  hypotheti- 
cal elementary  nervous  system  would  occur  when  certain  of  the  sensory  cells 
(Fig.  132,  c)  developed  a  special  sensitiveness,  not  to  mechanical  changes  in 
the  environment,  but  to  the  protoplasmic  excitatory  process  arriving  at  them 
along  the  nerve  network.     These  cells  would  act  as  relays  of  force,  picking 

up  the  excitations  arriving    from 
the  undifferentiated  sensory  cells, 
V  and  sending  them  on  with  increased 

-<:^--_rs^>^.  vigour  along  the   nerve  network. 

In  such  a  manner  a  stimulus 
applied  at  one  point  could  be  sent 
on  in  successive  relays  from  cell  to 
cell  throughout  the  whole  reactive 
tissue  on  the  surface  of  the  body. 
We  cannot  point  to  any  par- 
ticular animal  as  presenting  in- 
stances of  either  of  the  two  types 
of  elementary  nervous  system 
just  described.  If  such  exist,  t hex- 
have  not  yet  been  investigated, 
or  the  undifferentiated  character 
of  their  nervous  tissues  has 
thwarted  the  efforts  of  zoologists 
to  display  their  specific  characters 
by  staining  reagents.  In  the 
lowest  definite  nervous  system 
with  which  we  are  acquainted, 
namely,  that  of  the  jelly-fish, 
all  three  types  of  cell,  the  sensory  cell,  the  reactive  or  central  cell,  and 
the  motor  cell,  are  already  developed  and  have  undergone  among 
themselves  a  considerable  degree  of  differentiation.  In  a  jelly-fish  or  medusa, 
such  as  aurelia  or  sarsia  (Fig.  133),  the  reactive  tissue  of  the  body  is  confined 
to  the  under-surface  of  the  so-called  umbrella  with  the  tentacles  and  manu- 
brium. A  section  through  the  umbrella  shows  a  layer  of  epithelium  contain- 
ing differentiated  sense  cells,  below  which  is  a  plexus  or  rather  network 
of  fine  nerve  fibres  with  a  certain  number  of  nerve  cells  at  the  nodes  of  the 
network.  From  this  network  fibres  pass  more  deeply  to  end  in  a  finer  net- 
work situated  among  a  layer  of  muscle  fibres  formed,  like  the  sensory  cells,  by 
a  differentiation  of  the  primitive  epithelium  or  epiblast  (Fig.  134).      Besides 


:g.   133.     Diagrammatic   view    of  a  jelly-fish. 

(Hem  wig.) 
umbrella  ;   M,  manubrium  ;   t,.  t2,  tentacles  ; 
T,  velum  ;   s,  nerve  ring  ;   it.  '  marginal  body.' 


EVOLUTION  OF  THE  NERVOUS  SYSTK.M 


291 


this  diffuse  aervous  system,  there  is  a  continuous  ring  of  nerve  fibres  round 
the  margin  of  the  umbrella,  thickened  at  intervals  by  the  accumulation  of 
nerve  cells,  which  are  in  close  relation  to  special  collections  of  sensory  cells  in 
the  '  marginal  bodies.'  These  sensory  cells  present  a  differentiation  among 
themselves,  some  being  apparently  determined  for  the  reception  of  mechani- 


Fio.  134.  Diagram  of  subepithelial  plexus  of  nerve  fibres  and  nerve  cells,  communicat- 
ing on  the  one  side  with  the  sensory  epithelium,  and  on  the  other  side  with  the  sub- 
umbrellar  sheet  of  muscle  fibres.     (After  Bethe.) 

cal  stimuli,  others  for  the  reception  of  light  stimuli,  while  others  again  are 
found  in  close  relation  with  little  masses  of  calcium  carbonate  crystals,  by  the 
direction  of  the  weight  of  which  the  cells  are  able  to  react  to  changes  in  the 
position  of  the  animal  in  space.  In  the  jelly-fish  therefore  the  nervous  or 
reactive  system  has  already  acquired  a  considerable  degree  of  differentiation. 


I'lc.  1  :!5.  Figure  of  a  jelly-fish  in  which  all  the  marginal  bodies  except  one  have 
been  removed,  and  which  has  been  incised  in  various  diie<ti<  ns  so  as  to  divide 
tlic  nerve  ring  anil  all  the  '  long  |iatlis.'  so  that  only  the  diffuse  nerve  network 
remains  functional.     (Romanes.) 

We  may  study  the  behaviour  of  a  more  primitive  system  if  we  remove 
the  special  sense-organs  of  the  medusa  by  cutting  off  the  whole  of  the  marginal 
ring  with  its  contained  marginal  bodies  (Fig.  135).     We  have  then  a  layer 


2D2 


PHYSIOLOGY 


dt  contractile  tissue,  innervated  by  a  nerve  network,  and  covered  by  a  layer 
of  epithelium  containing  sense  cells.  To  this  network  is  attached  the 
manubrium,  which  represents  the  mouth  and  stomach  of  the  animal.  In 
such  a  mutilated  jelly-fish  it  is  easy  to  show  that  a  stimulus  applied  to  one 
spot  on  the  surface  travels  outwards  from  the  excited  spot  to  all  parts  of  the 
bell.  The  stimulus  is  propagated  also  to  the  manubrium,  which  in  some 
species  bends  in  the  direction  of  the  excited  spot — that  is  to  say,  in  the  direc- 
tion which  represents  the  shortest  possible  path  from  the  excited  spot  to  the 
manubrium.  This  preparation  rarely  presents  any  automatic  activity.  It 
may  react  to  a  constant  stimulus  by  a  rhythmic  series  of  contractions,  but 
remains  perfectly  motionless  in  the  absence  of  stimulus.     The  unmutilated 


i  showing  the  utility  of  the  multiplication  of  neurons  and  their 

grouping  in  central  ganglia.     (Cajal.) 
a,  an  ideal  invertebrate  with  only  cutaneous  'sensory  '  neurons. 
B,  invertebrate,  such  as  a  medusa,  with   sensory  and   motor  neurons,  but 
no  central  nervous  system. 

c,  invertebrate  (e.g.  Annelid)  in  which  the  motor  neurons  are  concentrated 
n  central  ganglia. 

u.  sensory  neuron  ;    b,  muscle  ;    c,  motor  neuron. 

jelly-fish  presents  rhythmic  contractions  of  its  sub-umbrella  tissue  which  are 
inaugurated  in  any  or  all  of  the  marginal  bodies  and  serve  to  drive  the 
animal  onwards  through  the  water  in  which  it,  is  immersed.  The  rhythmic 
contractions  may  be  initiated,  augmented,  or  diminished,  in  response  to 
stimidi  of  light,  mechanical  irritation,  or  changes  in  the  position  of  the  whole 
animal  acting  on  the  marginal  bodies.  In  the  reaction  of  an  animal  to  ex- 
ternal stimuli  it  must  be  an  advantage  if  the  energies  of  the  whole  can  be 
concentrated  in  defence  of  any  one  part  and  be  evoked  by  a  stimulus  applied 
at  one  point.  Such  a  co-operation  of  the  whole  for  the  benefit  of  the  part 
involves  the  existence  of  direct  paths  from  the  stimulated  point  to  all  parts 
of  the  animal  if  the  reaction  is  to  take  place  with  any  promptitude.  In  the 
medusa  we  find  a  beginning  of  such  '  long  paths.'  The  general  direction  of 
the  fibres  of  the  network  is  radial,  and  there  is  a  concentration  of  such  fibres 
in  the  neighbourhood  of  the  marginal  bodies,  so  that  an  excitation  can  pass 
more  readily  from  a  sense  organ  to  the  manubrium  than  it  can  laterally  along 
the  circumference  of  the  animal.  Moreover  a  stimulus  which  is  too  slight 
to  excite  a  reflex  contraction  of  the  muscular  tissue  may  travel  along  the 
nerve  tissue  to  each  of  the  marginal  ganglia  and  arouse  these  to  a  discharge  of 
motor  impulses.  We  have  therefore  in  the  medusa  sensory  cells  of  different 
sensibilities  :    central  cells  specially  adapted  to  reacting  to  and  reinforcing  a 


EVOLUTION  OF   THE  NERVOUS  SYSTEM 


293 


nerve  stimulus  started  by  a  small  change  in  the  environment  ;  a  general 
nerve  network  propagating  the  excitatory  changes  in  all  directions,  but  with 
special  ease  in  certain  directions  ;  and  a  reactive  muscular  tissue  which 
carries  out  movements  at  the  end  of  the  chain  of  excitation,  all  the  elements 
forming  the  chain  being  derived  from  epiblastic  cells. 

A  further  differentiation  of  a  nervous  system,  such  as  that  just  described, 
must  in  the  first  place  involve  the,  laying  down 
of  more  '  long  paths  '  and  the  collection  of  the 
special  '  central :  cells  into  closely  connected 
masses  (ganglia),  so  as  to  concentrate  the  control 
of  the  reactions  of  the  body,  and  to  permit  of  the 
ready  subordination  of  every  part  to  the  needs  of 
the  whole.  A  special  direction  is  given  to  this 
development  by  the  evolution  of  animals,  such  as 
worms  and  crustaceans,  which  are  segmented  and 
capable  of  locomotion.  The  fact  that  these  animals 
are  segmented  determines  the  collection  of  the 
central  cells  into  a  chain  of  ganglia,  one  ganglion 
or  pair  of  ganglia  being  provided  for  each  segment. 
In  the  act  of  locomotion  it  is  of  advantage  to  the 
animal  that  those  sense-organs  or  sensory  cells 
which  are  projicient,  i.e.  which  are  stimulated  by 
changes  in  the  environment  originating  at  a  dis- 
tance from  the  animal,  should  be  collected  together 
near  that  part  which  goes  first,  namely,  the  head 
end.  Thus  the  projected  sensations  of  sight, 
those  which  are  excited  by  chemical  changes  in 
the  surrounding  medium  and  represent  the  sense 
of  smell,  and  those  which  are  specially  aroused 
by  vibrations  in  the  surrounding  medium  and 
correspond  to  those  which  we  call  the  sense  of 
sound,  are  in  the  majority  of  these  animals  sub- 
served by  organs  situated  near  the  head  end. 

The  wisdom  of  a  man  is  measured  by  his  fore- 
sight. The  chances  of  an  animal  in  the  struggle 
for  existence  are  determined  by  the  degree  to  which 
the  reactions  of  the  animal  to  its  immediate  en- 
vironment are  held  in  check  in  response  to  stimuli 
arising  from  approaching  events.  An  animal  with- 
out power  to  see,  smell,  or  hear  its  enemy  will  re- 
ceive no  impulse  to  flee  until  it  is  already  within 
its  enemy's  jaws.  It  must  therefore  be  of  ad- 
vantage to  a  segmented  animal  that  the  activities  of  the  whole  chain  of 
s  sgmented  ganglia  should  be  subservient  to  those  central  nerve-cells  which 
are  in  direci  connection  with  the  projicient  sense-organs  at  the  head.  The 
influence  exerted  by  the  head  ganglia  will  be  in  the  first  place  inhibitory  of 


Fig.  137.  View  of  central 
nervous  system  of  cray- 
fish. (After  Yung  and 
Vogt.) 

a,  cerebral  ganglion. 

b,  commissure. 
c,suboesophageal  ganglion. 
rj.  first  abdominal  ganglion 
1,  oesophagus. 

tn,  optic  nerve. 

p,  antennary  nerve. 

s,  stomato-gastric  nerve. 


294 


PHYSIOLOGY 


the  direct  reaction  excited  in  each  segment  by  stimulation  of  its  surface,  and, 
tor  this  influence  to  be  propagated,  long  tracks  must  be  laid  down,  joining 
up  ganglion  to  ganglion  and  propagating  impulses  from  the  head  ganglia 
to  Hi"  most  distant  part  of  the  chain.  As  a  type  of  such  a  system  we  may 
refer  to  the  crayfish. 

In  this  animal  the  rent  nil  nervous  system  (Fig.  137)  consists  of  a  chain  of  thirteen 

«anglia,  namelv,  six  abdominal  ganglia,  six  thoracic  ganglia,  anil  ■  supraoesophageal 

or  cerebral  ganglion.  In  the  abdomen  and  thorax  the  ganglia  form  a  longitudinal 
series  situated  in  the  middle  line  of  the  ventral  aspect  of  the  body  close  to  the  integu- 


GangliON  -  C 


Fig.  138.     Diagram  of  nervous  system  of  a  segmented  invertebrate  (earthworm 

or  crayfish).     (From  Schafer,  after  Retziis.  ) 

s\  sensory  cells  ;    •*,  afferent  nerve  fibres;    in,  motor  neuron  :    i,  central 

or  intermediate  cell. 

meiit.  All  give  origin  to  a  valuable  number  of  nerves,  which  are  distributed  partly 
to  the  muscles,  partly  to  the  skin  and  sense-organs.  They  are  connected  by  longitu- 
dinal bands  of  nerve  til  ires  or  commissures,  which  are  double,  each  ganglion  being  bilobed. 
The  most  anterior  of  the  thoracic  ganglia,  which  is  the  largest,  is  marked  at  the  side 
by  notches,  as  if  it  were  made  up  of  several  pairs  of  ganglia  fused  together.  From  this 
ganglion  two  commissures  pass  forward  round  the  gullet  to  unite  in  front  of  this  tube, 
behind  the  eyes,  with  the  transversely  elongated  mass  of  ganglion  cells  and  fibres 
called  the  supraoesophageal  ganglion.  This  ganglion  consists  of  three  fused  pairs  of 
ganglia,  which  have  been  termed  the  protocerebron,  the  deuterocerebron,  and  the  trilo- 
cerebron.  The  most  anterior  gives  origin  to  the  optic  nerves,  which  run  by  the  optic 
stalks  to  the  eyes.  From  the  middle  ganglion  on  each  side  a  tegumentary  nerve  passes 
to  ramify  in  the  integument  and  from  the  inferior  surface  the  antennulary  nerves 
pass  to  the  internal  antenna?.  From  these  small  branches  are  distributed  to  the  organ 
of  hearing.  The  posterior  protuberance  of  the  brain  gives  origin  to  the  antennary 
nerves  which  pass  to  the  large  external  antennae  of  the  animal.      The  first  thoracic. 


EVOLUTION   OF  THE  NERVOUS  SYSTEM 


295 


01  Bubcesophageal,  ganglion  gives  origin  to  ten  pairs  of  nerves  which  are  distributed 
to  the  mandibles,  to  the  jaws  or  maxillae,  to  the  maxillipedes,  and  to  the  branchial 
appendages  of  the  latter. 

When  we  investigate  the  structural  basis  of  such  a  nervous  system  we 
find  that,  as  in  medusa,  the  starting-point  of  the  reflex  arc  is  in  certain 
neuro-epithelial  cells  (Fig.  138)  lying  on  the  surface  of  the  body.  These  cells 
are  spindle-shaped,  and  have  one  short  process  passing  to  the  surface,  and  a 
long  process  which  runs  in  a  nerve  fibre  or  collection  of  fibres  towards  the 
ganglion  of  the  segment.  Arrived  at  the  ganglion  it  divides  into  two 
branches,  which  pass  towards  the  two  ends  of  the  body  and  become  lost  in 


Nerve  CelL__ 


£xtensor    M. 


NerveGII 


Fig.  Kin.     Diagram  "i  a  ceflea  arc  in  a  (neuro-fibrillar)  invertebrate  nervous  system. 
(Bethe.)    The  efferent  paths  are  coloured  red.  the  afferent  black. 

the  granular  material  forming  the  inner  part  of  each  ganglion.  The  ganglia 
themselves  consist  internally  of  this  'punctuated  substance'  or  granular 
material,  and  externally  of  a  capsule  of  ganglion-cells.  Each  of  the  ganglion- 
cells  sends  (jne  thick  process  towards  the  centre,  which  rapidly  divides, 
some  of  the  branches  passing  into  the  granular  material,  while  one  branch 
passes  outwards  in  a  nerve  to  end  in  a  network  of  fine  fibrils  within  the 
muscles  on  the  surface  of  the  body.  The  nervous  impulse  excited  in  the 
sensory  cell  on  the  periphery  travels  therefore  up  a  nerve  fibre  into  the  granu- 
lar substance  of  the  ganglion.  From  this  granular  substance  it  is  collected 
by  the  fine  branches  of  the  ganglion-cells  and  is  transmitted  by  them  along 
the  motor  nerve  fibre  to  the  muscles.  The  central  granular  material  consists 
entirely  of  a  close  felt>work  of  fibres,  which  may  be  regarded  as  processes 
either  of  the  sensory  nerve  fibres  or  of  the  nerve  cells.  The  typical  reflex 
arc  in  this  case  therefore  is  formed  by  two  nerve  cells  with  their  processes. 
Such  a  nerve  cell  with  its  processes  is  spoken  of  as  a  neuron.  The  first  neuron, 
the  recipient  neuron,  or  receptor,  is  represented  by  the  sensory  cell  with  its 


296  PHYSIOLOGY 

two  processes  in  the  granular  material.  The  second  neuron  is  formed  by  t  lnj 
ganglion-cell  with  its  finely  branched  dendritic  processes  in  the  granular 
matter  and  its  motor  axon,  which  passes  into  the  muscle  fibres. 

As  to  the  manner  in  which  the  impulse  passes  from  the  branches  of  one 
cell  into  those  of  the  other,  opinions  are  still  divided.  The  question  will 
have  to  be  more  fully  considered  when  we  come  to  deal  with  the  vertebrate 
nervous  system.  Many  believe  that  there  is  no  anatomical  continuity  1  letween 
the  two  neurons,  and  that  the  excitatory  change  is  transmitted  by  a  mere 
contiguity,  a  change  in  one  set  of  nerve-endings  exciting  a  corresponding 
change  in  another  set  of  nerve-endings  in  immediate  contact  with  them. 
By  certain  methods  however  it  is  possible  to  show  the  existence  of  an  anato- 
mical continuum  throughout  the  whole  nervous  system  in  these  inverte- 
brate animals.  Apathy  and  Bethe  have  demonstrated  the  presence  of  a 
continuous  system  of  neurofibrils  (much  smaller  than  an  individual  nerve 
fibre),  which,  starting  in  a  sensory  cell,  pass  into  a  network  of  fibrils  forming 
the  greater  part  of  the  central  granular  matter.  From  this  network  neuro- 
fibrils run  along  the  dendrites  into  the  ganglion  cells,  forming  there  a  small 
network  through  the  centre  of  which  a  neurofibril  is  continued  down  the  nerve 
processes  again,  and  passes  out  along  the  motor  nerve  to  end  in  a  network 
of  fibrils  among  the  muscle  fibres.  In  a  system  so  constituted  it  is  evident 
that,  although  an  excitatory  process  passing  along  a  given  fibril  may  find 
certain  paths  easier  than  others,  and  so  maintain  a  constant  prescribed 
path  through  the  nerve  system,  yet  it  will  be  possible,  by  sufficiently  increas- 
ing the  strength  of  the  excitatory  process,  to  cause  it  to  travel  in  all  direc- 
tions in  the  central  nervous  system  and  to  evoke  in  this  way  a  general 
activity  of  all  parts  of  the  body,  a  condition  in  fact  found  to  obtain  in  the 
normal  animal.  It  is  significant  that,  although  a  great  number  of  fibrils 
pass  into  the  bodies  of  the  ganglion  cells,  yet  in  many  cases,  especially  in 
crustaceans,  fibrils  are  to  be  found  sweeping  from  the  neuropilem  or  nerve 
network  of  the  granular  substance  into  a  nerve  process,  and  thence  into 
its  motor  axon  without  at  any  time  entering  the  body  of  the  cell  (Fig.  139). 


SECTION  II 
THE   NERVOUS   SYSTEM   OF   VERTEBRATES 

In  these,  as  in  the  invertebrata,  the  central  nervous  system  is  developed 
by  an  involution  of  the  epiblast,  revealing  thereby  its  primitive  relations 
to  the  surface  of  the  body.  At  an  early  period  in  foetal  life,  shortly  after  the 
formation  of  the  two  layers  of  epiblast  and  hypoblast,  a  thickening  is  ob- 
served in  the  epiblast.  Tliis  thickening  soon  gives  place  to  a  groove,  the 
neural  groove  (Fig.  140),  and  the  walls  of  the  groove  folding  over  form  a 


Fig.  ]40.     Transverse  section  of  human  embryo  of  2"4  mm.  to  show  developing 
neural  canal.     (T.  H.  Bryce.) 
lie,  neural  canal;    me,  museleplate  :   my,  outer  wall  of  somite; 
sc,  sclerotome. 

(anal,  the  neural  canal,  which  is  dilated  at  the  head  end  of  the  embryo  to 
form  three  enlargements  known  as  the  cerebral  vesicles. 

When  first  formed  the  canal  is  oval  in  cross-section,  its  wall  being  made 
up  of  a  layer  of  columnar  cells  between  the  outer  extremities  of  which 
an-  seen  smaller  rounded  cells.  The  internal  layer  of  columnar  cells  sends 
a  process  peripherally  which  branches  at  the  end  so  as  to  form  a  close 
nu'shwork  of  fibres.  These  fibres  branch  more  and  more  as  development 
progresses,  and  eventually  form  the  supporting  tissue  of  the  adult  central 
nervous  tissue,  known  as  the  neuroglia.  As  the  wall  of  the  canal  grows  in 
thickness,  some  of  the  cells  may  wander  outwards  and  form  neuroglia-cells 
with  numerous  radiating  branches.  In  the  adult  nervous  system  little  is 
left  of  these  cells  except  their  nuclei,  so  that  the  neuroglia  appears  as  a  close 
felt-work  of  fibres,  to  which  here  and  there  nuclei  are  attached.    These  cells 

297 


298 


PHYSIOLOGY 


B 


are  formed  from  the  most  superficial  layer  of  the  invaginated  epiblast,  and 
are  spoken  <>f  as  spongioblasts.  The  deeper  layer  of  cells,  which  are  to  give 
rise  to  the  permanent  nerve-cells,  and  are  therefore  known  as  neuroblasts, 
rapidly  divide  and  form  a  thick  layer  surrounding  the  internal  layer  of 
spongioblasts,  through  which  pass  the  peripheral  processes  of  the  latter. 
When  first  formed  these  cells  have  no  processes.  Later  on  each  neuroblast 
acquires  a  pear  shape,  the  stalk  of  the  pear  having  a  somewhat  bulbous 
extremity  (Fig.  142).  The  stalk  continually  elongates,  and  the  elongated 
process  may  leave  the  spinal  cord  altogether  and  grow  outwards  to  any  part 

of  the  body  of  the  embryo,  or  may  pass 
to  other  parts  of  the  central  nervous  sys- 
tem. This  long  process  of  the  developing 
nerve  cell  is  known  as  the  axon.  Some 
time  after  its  formation  other  processes 
grow  out  from  the  cell,  which  soon  branch 
and  end  in  the  immediate  neighbourhood 
of  the  cell.  The  axons  of  the  cells  near  the 
ventral  part  of  the  neural  tube  grow  out 
to  the  different  muscles  of  the  body, 
where  they  end  in  close  connection  with 
the  muscular  fibres  by  an  arborisation 
1  which  forms  the  end-plate.  They  provide 
an  efferent  path  for  impulses  running 
from  the  central  nervous  system  to  the 
musculature  of  the  body.  The  afferent 
channel  is  formed  in  a  somewhat  different 
manner.  Even  before  the  neural  groove 
has  closed  in,  a  thickening  of  the  epiblast 
is  seen  immediately  external  to  the 
groove  on  each  side.  This  thickening 
becomes  divided  into  a  series  of  collections  of  cells  lying  immediately 
under  the  epiblast  on  the  lateral  and  dorsal  surface  of  the  neural 
canal.  The  cells,  which  are  at  first  round  or  oval,  send  off  two  pro- 
cesses in  opposite  directions  so  that  they  become  bi-polar  (Fig.  142). 
One  process  passes  into  the  central  nervous  system,  where  it  divides,  some 
of  its  branches  being  distributed  in  the  nervous  system  at  the  same  level, 
while  others  run  a  considerable  distance  towards  the  head  immediately  out- 
side the  tube  of  nerve  cells.  The  other  process  grows  downwards,  along 
with  the  processes  from  the  ventral  cells  of  the  tube,  towards  the  periphery 
of  the  body,  where  it  ends  in  close  connection  with  the  surface  in  the  various 
sense  organs  of  the  skin  and  muscles.  These  collections  of  bi-polar  cells  form 
the  posterior  root  ganglia.  In  fishes  they  retain  their  primitive  character 
throughout  life,  but  in  mammals  the  bi-polar  cell  is  to  be  found  only  in  the 
spiral  and  vestibular  ganglia  which  give  origin  to  the  fibres  of  the  eighth 
nerve.  In  all  the  other  ganglia  the  shape  of  the  cell  becomes  modified 
by  an  approximation  of  the  points  of  attachment  of  the  two  processes  until 


Fig.  141.      Neuroblast*  from  the  spinal 
cord  of  a  chick  embryo.     (Cajal.) 
a.  three  neuroblasts  stained  to  show 

neurofibrils  :    o.  a  bi-polar  cell. 
1!.  a  neuroblast  showing  the  '  incre- 
mental cone     c. 


THE  NERVOUS  SYSTEM  OF  VERTEBRATES 


299 


finally  the  cell  becomes  uni-polar.  giving  off  one  process  which  divides  by 
a  T-shaped  junction  into  two,  one  of  which  runs  towards  the  spinal  cord, 
while  the  other  takes  a  peripheral  course  as  the  afferent  nerve  fibre.  The 
central  nervous  system  thus  becomes  provided  with  a  '  way  in  :  and  a  '*way 
out '  for  the  chain  of  impulses  concerned  in  a  nervous  reaction  or  reflex  action. 
The  further  development  of  the  spinal  cord  is  mainly  determined  by  the  exten- 


Fig.   14i'.     Section   through  developing   spinal  cord   and  nerve  roots  from  chick 
embryo  of  fifth  day.     (Cajal.) 

a.  ventral  root  :  n.  dorsal  root  ;  c,  motor  nerve  cells  ;  d,  sympathetic  ganglion 
cells  ;  E.  spinal  ganglion  cells  still  bi-polar  :  F.  mixed  nerve  ;  b,  c,  d,  motor  nerve 
tilires  to  /.  developing  spinal  muscles  ;    i.  a  sensory  nerve-trunk. 

sion  of  the  axons  of  the  cells  outside  the  tube  of  cells  themselves,  and  by 
the  provision  of  the  '  long  paths  '  which  are  a  necessary  condition  of  increased 
efficiency  of  the  reacting  organ.  Some  time  after  the  outgrowth  of  the  axon 
.!  medullary  sheath  is  formed,  apparently  by  the  agency  of  the  axon  itself, 
so  that  each  group  of  axons  leaving  or  entering  the  cord  forms  a  bundle  of 
medullated  nerve  fibres.  The  long  branches  of  the  posterior  or  dorsal  roots 
running  up  towards  the  head  form  a  mass  of  fibres  behind  the  tube  of  cells 
known  as  the  posterior  columns.  Fibres  starting  in  the  spinal  cord  itself 
run  upwards  and  downwards  to  end  in  other  parts  of  the  cord,  or  in  the  more 
anterior  divisions  of  the  central  nervous  system  forming  the  brain,  and 
-ui  round  the  neural  tube  on  its  ventral  and  lateral  aspects  with  a  sheath 
oi  white  matter.  To  these  white  fibres  are  added  others,  which  take  origin 
in  the  brain  and  pass  all  the  way  down  the  cord.     Meanwhile  the  cells 


300 


I'HYSHH.OCY 


themselves  become  separated  by  the  ramifications  between  them  of  the 
branches  of  axons  entering  the  cord,  as  well  as  of  the  dendrites  of  the  cells 
themselves.  Thus,  in  its  adult  form,  the  spinal  cord  ((insists  of  a  central 
mass"  of  nerve  cells  and  fibres,  known  as  the  grey  matter,  which  is  encased 
in  a  sheath  of  white  matter  formed  of  medulla  ted  nerve  fibres.  The  cord 
itself  is  cylindrical  in  shape,  and  is  divided  into  two  symmetrical  halves  by 
the  anterior  and  posterior  fissures.  In  each  half  of  the  cord  the  grey  matter 
on  cross-section  is  crescentic  in  shape,  presenting  an  anterior  or  ventral 
horn  and  a  posterior  or  dorsal  horn,  and  is  connected  with  the  corresponding 
mass  in  the  other  half  of  the  cord  by  grey  matter  known  as  the  anterior 
and  posterior  grey  commissures.  Between  the  two  grey  commissures  is 
the  central  canal,  relatively  very  minute  when  compared  with  the  condition 
in  the  foetus  and  lined  by  a  single  layer  of  columnar  ciliated  epithelium, 
the  cells  of  which  are  directly  descended  from  the  neural  epithelium  lining 
the  medullary  canal. 

THE  STRUCTURE  OF  NERVE  CELLS 
In  the  adult  animal  a  typical  nerve  cell,  such  as  those  forming  a  prominent 
feature  in  the  anterior  horn  of  the  spinal  cord,  is  a  large  cell  with  many 
branches.     It   lias   a   large   vesicular  nucleus  with   very   little   chromatin, 


Fir.,  14.'!.  Nerve  cell  from  the  spinal  cord, 
stained  by  Nissl's  method. 
a,  axis-cylinder  process  or  axon  ;  b,  proto- 
plasm of  cell,  consisting  of  c,  fibrillated 
ground  substance,  and  e,  the  grannies  of 
Nissl ;   d,  nucleus.     (Lenhossek.) 


Fig.  144.  The  point  of  origin 
of  the  axon,  the  '  nerve- 
hillock,  highly  magnified, 
to  show  absence  of  Nissl's 
granules  from  the  origin  of 
the  process.     (Held.) 

which  may  be  collected  into  one  or  two  nucleoli.  The  body  of  the  cell 
presents  different  appearances  according  to  the  manner  in  which  it  has 
been  treated  for  histological  examination.  When  separated  from  the  sur- 
rounding tissues  by  means  of  dissociating  fluids  it  may  present  traces  of 
striation.  the  individual  stihe  running  from  one  process  to  another  of  the 
cell.     "When  treated  fresh  with  methvlene  blue,  or  hardened  by  alcohol 


THE   NERVOUS   SYSTEM   OF   VERTEBRATES 


301 


or  corrosive  sublimate  and  stained  with  methylene  blue  or  toluidine  blue, 
the  protoplasm  is  seen  to  contain  angular  masses  which  are  deeply  coloured 
with  the  dve  (Fig.  143).  These  masses  are  known  as  the  Nissl  granules  or 
bodies.  By  other  methods  it  is  possible  to  demonstrate  that  the  whole 
protoplasm  of  the  cell  between  the  Nissl  bodies  is  pervaded  by  fine  fibrils, 
which  enter  the  cell  from  the  processes  and  may  run  out  of  the  cell  by  the 
axon  or  may  run  into  some  of  the  other  shorter  processes  (Fig.  146).  The 
processes  of  the  cell,  as  is  evident  from  their  development,  are  of  two  kinds. 
The  axon  which  becomes  continuous  with  the  axis  cylinder  of  the  medullated 


Figs.  145  and  140.     Nerve  cells  from  spinal  cord.     (Bethe.) 
14.").  showing  Golgi  network,  and  neurofibrils  :   </.  e,  /,  junctions  of  axons 
w  'i  h  <  tolgi  network.     Fig.  140,  showing  neurofibrils  and  Xissl  bodies. 

nerve  fibre  arises  from  a  part  of  the  cell  body  known  as  the  axon  hillock, 
which  is  the  only  part  of  the  celi  free  from  Nissl  bodies  (Fig.  144).  The 
other  processes,  which  may  be  very  numerous,  are  known  as  the  dendrites. 
They  are  generally  thicker  than  the  axon  at  their  origin  from  the  cell,  but 
rapidly  diminish  in  size  as  they  give  off  branches,  the  branches  apparently 
terminating  freely  in  the  grey  matter  in  the  immediate  neighbourhood  of 
the  cell.  In  specimens  stained  by  the  Golgi  method  the  dendrites  may 
sometimes  present  a  somewhat  serrated  outline.  The  Nissl  bodies  of  the 
cell  extend  some  way  into  the  dendrites 

A  nerve  cell  with  all  its  processes,  axon,  and  dendrites  is  spoken  of  as  a 
neuron .  From  the  development  of  the  central  nervous  system  in  vertebrates, 
it  is  evident  that  the  nervous  path  of  every  reaction  must  be  made  up  of 
two  or  more  neurons,  if  we  take,  for  example,  the  simplest  possible  reaction 
which  might  be  effected  through  a  single  segment  of  the  spinal  cord,  we  see 
that  the  afferent  impulse  might  be  started  by  some  stimulus  applied  to  the 
ramifications  in  the  sldn  of  the  distal  processes  of  the  posterior  root  ganglion 
cell  (cf.  Fig.  132).    The  nerve  impulse  so  started  is  carried  by  the  nerve  fibre 


302  PHYSIOLOGY 

past  the  T-shaped  junction  in  the  posterior  root  ganglion  into  thecord, 
and  along  a  branch  of  the  entering  nerve  fibre  which  runs  right  across  the 
cord  to  terminate  in  the  neighbourhood  of  the  anterior  horn  cells.  Here 
the  impulse  must  be  transmitted  in  some  way  to  the  dendrites  or  body  of 
one  of  the  large  motor  nerve  cells  in  the  anterior  horn,  whence  it  is  can  nil 
along  the  axon  of  the  cell,  leaving  the  cord  by  the  anterior  root  and  passing 
down  a  peripheral  nerve  to  the  end-plate'  on  a  muscle  fibre.  Here  again 
by  some  means  the  arrival  of  the  impulse  excites  the  muscle  to  contract. 
This  reaction  never  takes  place  in  the  contrary  sense,  i.e.  no  impulse  started 
in  the  motor  nerve  can  travel  back  through  the  spinal  cord  and  along  the 
sensory  nerve.  Although  an  impulse  excited  in  the  nerve  passes  easily 
to  the  muscle,  an  excitatory  process  started  in  the  muscle  itself  is  confined 
to  this  tissue  and  never  extends  to  the  nerve  fibre.  Apparently  the  same 
rule  holds  good  within  the  grey  matter  of  the  central  nervous  system,  where 
two  neurons  come  into  relation  with  one  another.  An  impulse  passes  easily 
from  the  axon  of  one  into  the  dendrites  and  cell  of  the  other  neuron,  but, 
so  far  as  we  are  aware,  it  is  impossible  by  exciting  an  axon  to  cause  a 
retrograde  wave  of  excitation  to  pass  through  its  corresponding  cell  and 
into  the  terminations  of  the  axons  in  immediate  contact  with  the  cell. 
This  statement  has  been  called  by  Sherrington  the  '  Law  of  Forward  Direc- 
tion.' It  might  be  also  spoken  of  as  the  irreciprocal  conduction  of  the  nerve 
arc.  The  character  of  a  reaction  to  any  stimulus,  applied  to  the  surface 
of  the  body,  is  determined  by  the  course  which  the  impulse,  excited  in 
the  afferent  nerves,  takes  on  entrance  into  the  central  nervous  system. 
This  course  is  laid  down  by  the  connections  of  the  neurons  through  which 
the  nerve  impulse  passes.  In  the  central  nervous  system  therefore,  more 
than  in  any  other  part  of  the  body,  function  is  directly  dependent  on  struc- 
ture. Theoretically  if  we  had  a  perfect  knowledge  of  the  connections  of 
the  neurons  in  the  central  nervous  system  and  knew  the  nerve  fibres  affected 
by  any  given  stimulus,  we  should  be  able  to  prophesy  exactly  the  result 
of  such  stimulus.  In  the  case  of  the  simpler  reactions  this  is  already  possible, 
but  in  the  higher  parts  of  the  nervous  system  the  enormous  complexity  of 
the  systems  of  neurons  excludes  any  possibility  of  our  forming  more  than 
a  general  idea  as  to  the  nerve  paths  traversed  in  any  given  reaction  ;  and 
the  variations  which  exist  from  individual  to  individual  must  always  prevent 
in  the  intact  animal  an  absolute  prediction  of  the  results  of  any  stimulus. 


SECTION  III 

GENERAL   CHARACTERISTICS   OF    REFLEX 
ACTIONS 

There  are  certain  features  common  to  all  reactions,  carried  out  through 
the  intervention  of  the  central  nervous  system,  which  must  be  regarded 
as  determined  by  the  properties  of  the  neurons,  i.e.  the  conducting  links 
in  the  chain  of  excitatory  tissues  intervening  between  the  stimulated  spot 
on  the  exterior  and  the  reacting  tissue,  muscle  or  gland.  These  charac- 
teristics may  be  roughly  classified  as  follows  : 

(1)  LOCALISATION.  In  a  simple  system  of  neurons  a  given  stimulus 
will  nearly  always  produce  the  same  reaction.  In  a  frog  possessing  only  a 
spinal  cord,  the  upper  parts  of  the  central  nervous  system  having  been 
destroyed,  any  harmful  stimulus  applied  to  a  toe  will  cause  a  lifting  of  the 
leg.  If  the  motor  nerve  to  the  gastrocnemius  be  excited,  the  whole  muscle 
contracts.  If  one  of  the  nerve  roots  entering  into  the  formation  of  the 
sciatic  nerve  be  excited,  only  certain  fibres  of  the  gastrocnemius  contract, 
the  locality  of  the  reacting  fibres  being  determined  by  their  connection  with 
the  excited  nerve  fibres.  In  the  same  way  the  contraction  of  certain  muscles 
of  the  leg,  in  response  to  a  stimulus  applied  to  the  skin  of  the  foot,  is  deter-- 
mined  by  the  fact  that  the  nerve  fibres,  which  carry  the  impulses  from  the 
toe  into  the  spinal  cord,  divide  there  and  make  connections  with  the  motor 
neurons,  whose  axons  are  distributed  to  the  several  muscles  involved  in  the 
reaction.  The  connection  of  the  sensory  with  the  motor  neuron  may  be 
direct,  but  in  most  cases  the  impulse  has  to  pass  through  intermediate 
neurons  before  arriving  at  the  motor  neurons.  The  path  of  the  impulse 
however,  in  spite  ol  it<  enormous  extension,  is  as  definite  as  is  the  path  from 
an  excited  motor  nerve  root  to  a  muscle  fibre. 

(2)  DELAY.  Instead  of  one  nerve-ending  intervening  between  the 
stimulated  nerve  and  the  reacting  tissue,  there  will  be,  in  the  case  of  the 
reflex  action,  two.  three,  or  more  nerve-endings  interpolated  in  the  path  of 
the  impulse.  These  nerve-endings  are  the  fields  of  conjunction, the  synapses, 
between  the  axon  of  one  neuron  and  the  dendrites  and  cell  body  of  the  neuron 
next  in  the  chain. 

We  have  seen  that  there  is  a  distinct  difference  between  the  latent  period 
of  a  muscle  excited  through  its  nerve  as  compared  with  the  latent  period 
when  excited  directly,  and  we  ascribed  this  latent  period  to  a  delay  in  the 
motor  end-plate.     We  should  expect  therefore  to  find  that  the  delay  or 

303 


304  PHYSIOLOGY 

latenl  period  in  the  case  of  a  reflex  action,  i.e.  the  lost  time  in  the  conversion 

of  an  afferent  into  an  efferent  impulse  in  the  central  nervous  system,  would  be 
appreciable  and  would  increase  with  the  complexity  of  the  response — that  is, 
with  the  number  of  neurons  involved  in  the  reaction.     Such  is  indeed  the  case. 

In  determining  the  actual  '  lost  time  '  in  the  central  nervous  system 
for  any  given  reflex,  it  is  necessary  to  subtract  from  the  total  delay,  inter- 
in  ised  between  the  application  of  the  stimulus  and  the  resultant  movement, 
the  time  taken  by  the  impulse  in  travelling  to  and  from  the  central  nervous 
system,  as  well  as  the  latent  period  of  the  muscles  themselves.  The  re- 
mainder is  known  as  the  '  reduced  reflex  time.'  Wundt  found  in  the  frog, 
when  a  reflex  contraction  of  the  gastrocnemius  was  excited  by  a  stimulation 
of  a  posterior  root  of  the  same  side  that  the  reduced  reflex  time  was  -COS  sec. 
For  a  crossed  reflex  the  delay  was  increased  by  -C04  sec.  If  we  assume  that 
one  additional  neuron  is  involved  in  the  crossed  reflex,  the  lost  time  at  a 
synapse  would  be  -C04  sec.  ;  if  two  cells  are  intercalated,  the  synapse  delay 
would  be  only  -002  sec.  Since  the  uncrossed  reflex  has  a  delay  of  *C08  sec.,. 
at  least  two,  and  possibly  four,  synapses  are  involved  in  the  path  of  this 
simple  reflex. 

The  blinking  excited  by  stimulation  of  the  eyelid  has  a  reduced  reflex 
time  of  -047  sec. 

(3)  SUMMATION.  When  contractile  tissues,  such  as  striated  or  un- 
striated  muscle,  are  excited  by  single  shocks,  a  certain  minimal  strength 
of  stimulus  is  necessary  in  order  to  produce  a  contraction.  Weaker  stimuli 
are  spoken  of  as  sub-minimal,  and  when  applied  singly  have  apparently 
no  effect  on  the  muscle.  In  dealing  with  the  properth^  ot  involuntary 
muscle  we  saw  that  a  sub-minimal  stimulus  is  not  necessarily  devoid  of 
effect  because  it  fails  to  evoke  a  contraction,  since,  if  repeated  at  sufficiently 

•  frequent  intervals,  a  summation  of  stimulus  occurs,  so  that  at  the  fifth  or 
sixth  application  a  stimulus,  which  was  previously  ineffective,  becomes 
effective  and  a  contraction  results.  The  muscle  will  now  continue  to  respond 
to  each  stimulus,  but,  if  the  excitations  be  discontinued  for  a  time,  reapplica- 
tion  of  a  stimulus  of  the  same  strength  becomes  once  more  ineffective.  This 
summation  of  stimulus  is  a  prominent  feature  in  all  reflex  actions,  so  much 
so  that  it  may  be  often  impossible  to  evoke  a  reaction  to  a  very  strong 
single  induction  shock,  whereas  the  application  of  a  tetanising  current  too 
weak  to  be  felt  on  the  tongue  may  produce  a  marked  reaction.  We  shall 
have  occasion  later  on  to  deal  with  special  examples  of  this  summation  of 
stimulus. 

(4)  FATIGUE.  In  the  muscle-nerve  preparation  the  weakest  point 
and  that  which  soonest  suffers  from  fatigue  is  the  end-plate,  or  rather  the 
field  of  conjunction  of  nerve  fibre  and  muscle  fibre.  In  the  central  nervous 
system  the  synapses  of  the  different  neurons  are  equally  susceptible,  and 
since  several  of  such  synapses  are  involved  in  every  reflex  action,  we  should 
expect  to  find  that  the  central  nervous  system  would  show  signs  of  fatigue 
before  the  peripheral  structures.  If  a  given  reaction  be  repeatedly  elicited 
by  applying  a  stimulus  to  a  certain  area  of  the  surface,  the  reaction  becomes 


CHARACTERISTICS   OF  REFLEX   ACTIONS  305 

feebler  and  finally  disappears  altogether  long  before  any  signs  of  fatigue 
in  the  motor  apparatus  can  be  detected  by  stimulation  of  the  motor  nerve 
itself.  The  fatigue  is  produced  equally  well  if  the  reaction  be  excited  by 
stimulating  a  sensory  nerve  directly,  and  since  we  know  that  it  is  practically 
impossible  to  fatigue  nerve  fibres,  we  must  conclude  that  the  seat  of  fatigue 
is  in  the  grey  matter  of  the  spinal  cord  itself. 

(5)  '  BLOCK  '  OR  RESISTANCE.  In  the  central  nervous  system 
there  is  an  absolute  block  to  the  passage  of  an  impulse  backwards  through 
a  synapse,  i.e.  from  a  nerve-cell  or  its  dendrites  into  the  end  ramifications 
of  an  axon.  The  phenomena  of  fatigue  show  that  there  is  a  certain  degree 
of  resistance  at  the  synapse,  to  the  passage  of  an  impulse  in  the  normal 
direction,  and  that  this  resistance  is  rapidly  increased  under  the  conditions 
which  produce  fatigue.  When  we  study  the  structure  of  the  central  nervous 
system  more  fully,  we  find  that  although  there  are  certain  shortest  possible 
paths,  i.e.  ones  involving  few  neurons,  for  every  impulse  arriving  at  the 
central  nervous  system,  yet  so  extensive  is  the  branching  of  the  entering 
nerve  fibres  and  so  complex  are  the  neuron  systems  with  which  they  come 
in  connection  that  an  impulse  entering  along  one  given  fibre  could  spread 
to  practically  every  neuron  in  the.  spinal  cord  and  brain.  Such  a  result  is 
indeed  observed  in  animals  poisoned  by  strychnine.  In  such  animals  the 
slightest  stimulus  applied  to  any  part  of  the  skin  excites  strong  tonic  spasms 
in  the  whole  musculature  of  the  body.  Every  single  nerve  fibre,  that  is  to 
say,  can  discharge  into  every  motor  neuron  of  the  cord.  That  this  result 
does  not  ensue  on  localised  stimulation  in  a  normal  animal  is  dependent  on 
the  varying  resistance  to  the  passage  of  an  impulse  into  the  several  neurons 
with  which  the  entrant  fibre  comes  in  relation.  A  small  stimulus  will  dis- 
charge only  along  the  few  neurons  where  the  resistance  is  lowest.  Increase 
of  the  stimulus,  either  by  increase  of  its  strength  or  by  summation  of  weak 
stimuli,  will  enable  the  impulse  to  spread  along  more  neurons  and  therefore 
will  elicit  a  more  widespread  response.  Only  when  the  '  blocks '  are  entirely 
removed  by  the  administration  of  strychnine,  or  when  the  stimuli  are 
abnormally  powerful  and  long  continued,  will  the  impulse  spread  to  all 
regions  of  the  central  nervous  system,  so  that  response  becomes  general 
and  inco-ordinate  instead  of  local  and  adapted  to  the  stimulus. 

(6)  FACILITATION  OR  •  BAHNUNG.'  The  passage  of  a  nervous 
impulse  across  a  synapse  or  series  of  synapses  in  the  central  nervous  system 
has  a  twofold  effect.  If  the  passage  be  too  often  repeated,  phenomena  of 
fatigue  are  produced  and  there  is  an  increase  of  the  block  at  each  synapse. 
If  however  the  stimulus  be  not  excessive  and  the  reaction  not  too  frequently 
evoked,  the  effect  of  passage  of  an  impulse  once  is  to  diminish  the  resistance, 
so  that  a  second  application  of  the  stimulus  evokes  the  reaction  more  easily. 
The  process  of  summation  in  fact  is  chiefly  in  the  direction  of  removal  of 
block.  We  have  a  close  analogy  to  this  process  of  facilitation  in  the  '  stair- 
case phenomenon '  observed  in  cardiac  and  unstriated  muscle.  In  these 
tissues  the  repetition  of  a  sub-minimal  stimulus  renders  it  in  time  effective, 
and  then  repetition  of  the    now  effective    stimulus    causes  a  gradually 

20 


306  PHYSIOLOGY 

increasing  height  of  contraction, which  depends  on  the  state  of  the  contracting 
tissue  itself  and  cannot  be  evoked  by  changes  in  the  strength  of  the  stimulus. 
This  process  of  facilitation  or  '  Bahnung  '  is  of  great  interest  in  connection 
with  the  development  of  '  long  paths  '  in  the  central  nervous  system,  and 
more  especially  with  the  acquirement  of  new  reactions  by  the  higher  animals. 
The  Law  of  Facilitation  is  really  the  Law  of  Habit.  When  an  impulse  has 
passed  once  through  a  certain  set  of  neurons  to  the  exclusion  of  others  it 
will  tend,  other  things  being  equal,  to  take  the  same  course  on  a  future 
occasion,  and  each  time  that  it  traverses  this  path  the  resistances  in  the 
path  will  be  smaller.  Education  is  the  laying  down  of  nerve  channels  in 
the  central  nervous  system,  while  still  plastic,  by  this  process  of  'facilitation' 
along  fit  paths,  combined  with  inhibition  (by  pain)  in  the  other  unfit  paths. 
Memory  itself  has  the  process  of  facilitation  as  its  neural  basis. 

(7)  INHIBITION.  The  constant  occurrence,  of  a  reaction  in  response 
to  a  given  stimulus  is  obtained  only  if  care  be  taken  to  isolate  the  segment 
of  the  central  nervous  system  involved  from  the  entry  of  other  afferent 
stimuli.  As  a  rule,  if  two  stimuli  be  applied  simultaneously  at  different 
points,  the  reaction  which  ensues  will  not  be  a  combined  one,  the  resultant 
of  the  reactions  which  would  be  normally  conditioned  by  each  single  stimulus, 
but  will  be  a  response  to  one  of  the  stimuli,  which  we  must  therefore  regard 
as  the  more  effective.  The  reaction  to  the  other  stimulus  is  either  abolished 
altogether  or  comes  on  after  a  considerable  period  of  delay.  The  central 
nervous  system  can  apparently  attend  to  only  one  thing  at  a  time.  In 
physiological  terms  we  should  say  that  every  effective  reaction  inhibits 
every  other  reaction.  In  the  spinal  cord  of  the  frog  the  normal  withdrawal 
of  the  foot  in  response  to  stimulation  of  the  toe  of  the  same  side  can  be 
inhibited  by  strong  stimulation  of  the  other  sciatic  nerve,  by  stimulation 
of  the  spinal  cord  at  a  higher  level,  or  by  stimulation  of  the  optic  lobes. 
Immediately  after  pithing  the  brain  of  the  frog,  the  whole  animal  becomes 
flaccid  and  motionless,  and  for  the  next  few  minutes  it  is  impossible  to  elicit 
any  reaction  by  stimulation,  however  strong,  applied  to  the  skin  of  the 
body.  In  the  production  of  this  condition  of  '  shock  '  the  inhibition  of  all 
the  spinal  centres,  produced  by  the  strong  stimulation  of  the  injury  to  the 
brain  and  medulla,  plays  at  any  rate  an  important  part.  We  may  say  that 
the  passage  of  an  impulse  through  a  chain  of  neurons  diminishes  the  block 
for  subsequent  impulses  at  each  synapse  that  it  traverses,  but  increases 
during  its  passage  the  block  in  all  the  adjacent  synapses. 

In  dealing  with  the  special  reactions  of  the  spinal  cord  we  shall  have 
occasion  to  refer  more  fully  and  in  greater  detail  to  many  of  these  pro- 
perties which  are  characteristic  of  all  reflexes.  Before  treating  of  the 
functions  of  the  separate  parts  of  the  central  nervous  system  in  the  higher 
mammals,  it  may  be  of  interest  to  consider  the  exact  nature  of  the  structure 
intervening  between  neuron  and  neuron  at  each  field  of  conjunction  or 
synapse,  as  well  as  the  significance  of  the  two  chief  elements  of  the  central 
nervous  system,  nerve  cell  and  nerve  fibre,  in  the  production  of  co-ordinated 
purposive  reactions. 


SECTION  IV 

NATURE    OF   THE   CONNECTION   BETWEEN 
NEURONS 

The  study  of  the  development  of  the  central  nervous  system  in  higher 
animals  has  shown  that  this  system  is  made  up  of  neurons,  the  connections 
of  which  determine  the  possible  paths  of  impulses  in  the  adult  cord.  The 
first  stage  in  the  development  of  the  neuron  is  a  single  cell  without  processes,, 
and  it  is  only  by  the  growth  of  these  processes  out  from  the  cell  that  the 
spinal  cord  becomes  capable  of  serving  as  an  aggregate  of  conducting  paths. 
Moreover  the  deferred  acquisition  of  an  influence  of  one  neuron  on  the  next 
neuron  in  the  line  of  impulse,  or  at  any  rate  on  the  peripheral  tissue  which 
receives  the  end  arborisation  of  its  axon,  is  shown  by  the  fact  that  entire 
destruction  of  the  spinal  cord  in  the  embryo  at  an  early  stage  in  its  develop- 
ment does  not  prevent  in  any  way  the  development  of  the  voluntary  muscles 
(Harrison)  ;  although,  after  birth,  a  severance  of  the  connection  between 
spinal  cord  and  skeletal  muscle  leads  to  a  rapid  degeneration  and  atrophy 
of  the  latter.  In  the  muscle-nerve  preparation  there  is  an  apparent  break 
of  structure  at  the  termination  of  the  nerve  in  the  muscle  fibre,  any  con- 
tinuity between  nerve-ending  and  contractile  substance  being  subserved 
by  undifferentiated  protoplasm.  There  is  therefore  no  difficulty  in  con- 
ceiving a  propagation  across  a  similar  nerve-ending  or  synapse,  between 
the  axon  of  one  neuron  and  the  cell  body  or  dendrites  of  another  neuron. 
If  however  the  conception  we  have  formed  above  of  the  evolution  of  a 
nervous  system  from  a  continuous  conducting  protoplasmic  network,  by 
a  process  of  '  facilitation  '  attended  by  histological  differentiation,  be 
correct,  we  should  expect  to  find  in  the  fully  developed  brain  and  spinal 
cord  some  traces  at  any  rate  of  continuity  throughout  the  whole  system  of 
neurons.  The  question  as  to  the  existence  of  anatomical  continuity  from 
neuron  to  neuron  has  been  hotly  discussed  both  for  vertebrates  and  in- 
vertebrates. In  the  case  of  the  latter,  evidence  in  favour  of  the  continuity 
of  neuro-fibrillae  from  sensory  surface  to  reacting  tissue  is  very  strong. 
Many  observers,  especially  Apathy,  Bethe,  and  Held,  have  described  a 
similar  continuity  in  the  nervous  system  of  mammals.  The  last-named 
observer  regards  this  continuity  as  a  product  of  later  development  and  as  due 
to  a  process  of  concrescence  occurring  between  the  axon  terminations  and 
the  bodies  of  the  nerve  cells  with  which  they  come  in  contact.  It  is  easy 
to  show  the  existence  of  a  fibrillar  structure  both  in  the  nerve  cell  and  in  the 

307 


308 


PHYSIOLOGY 


nerve  fibre  (Fig.  147).  The  axis  cylinder  of  the  nerve  fibre  can  be  regarded 
as  made  up  of  fine  fibrillse  embedded  in  an  interfibrillar  substance.  At  the 
nodes  of  Ranvier  the  interfibrillar  substance  is  interrupted,  the  fibrillse  alone 
extending  into  the  next  internode  and  representing  the  continuous  structure 
which  determines  the  conducting  power  of  the  nerve  fibre.  In  the  nerve 
cell  the  fibrillse  occupy  all  the  space  between  the  Nissl  bodies,  passing  from 
dendrite  to  dendrite,  and  many  of  them  from  all  the  dendrites  and  all  parts 
of  the  cell  sweeping  through  the  axon  hillock  to  form  the  fibrillse  of  the  nerve 
fibre.     The  existence,  of  these  fibrillar  structures  in  nerve  cell  and  nerve 


...»:';" 


Fig.  147.  Part  of  an  anterior  cornual 
cell  from  the  calf's  spinal  cord, 
stained  to  show  neurofibrils. 
(Bethe.) 

ix,  axon  ;  a,  b.  r.  dendrites. 


Fni.  148.  Arborisation  of 
collaterals  from  the  pos- 
terior root-fibres  round 
the  cells  of  the  posterior 
horn.   (Ram6v  y  Ca.ul.) 


fibre  is  accepted  by  most  histologists.  The  question  however  of  the  con- 
nection between  the  fibrillse  of  one  axon  and  those  of  the  next  neuron,  i.e. 
the  histology  of  the  synapse,  presents  much  greater  difficulties  and  has 
excited  much  difference  of  opinion.  If  we  examine  a  nerve  cell  such  as  a 
cell  of  Purkinje  of  the  cerebellum,  or  a  cell  of  Clarke's  column  in  the  cord, 
we  find  that  it  is  surrounded  by  a  thick  basket-work  of  fibres  which  are  the 
arborisations  or  end  terminations  of  the  axons  which  pass  to  the  cell  to 
enter  into  functional  relationships  with  it  (Figs.  148  and  149).  This  peri- 
cellular network  is  of  great  extent  and  may  equal  in  total  diameter  the 
diameter  of  the  cell  itself,    Whether  the  basket-work  is  really  a  network, 


Nature  of  connection  between  neurons      309 

or  merely  a  felt-work  in  which  the  fine  fibres  intertwine  among  each  other 
without  becoming  actually  continuous  at  any  points,  is  difficult  to  make 
out.  On  the  periphery  of  the  cell  itself  another  network  has  been  described 
and  is  known  as  the  Golgi  network  (Fig.  150).  This  has  been  displayed 
both  by  the  process  of  impregnation  with  silver  chromate  (Golgi  method), 
as  well  as  by  staining  with  methylene  blue.  Some  authors  have  regarded 
this  network  as  an  artefact  due  to  precipitation  of  albuminous  fluids  on  the 
surface  of  the  cell.  According  to  Bethe  however,  the  Golgi  network  on  the 
one  hand  receives  fibres  from  the  encircling  pericellular  basket-work  of  axons, 


Fig.  140.  Basket-work  of  fibres 
around  two  cells  of  Purkinje. 
(Cajal.  ) 

a,  axis-cylinder  or  nerve-fibre 
pnn  ess  of  one  of  the  corpuscles 
of  Purkinje  ;  6,  fibres  prolonged 
over  the  beginning  of  the  axis- 
cylinder  process  ;  c,  branches  of 
the  nerve-fibre  processes  of  cells 
of  the  molecular  layer,  felted 
together  around  the  bodies  of 
the  corpuscles  of  Purkinje. 


Fig.   150.      Superficial    network  of  Golgi   surrounding 
two  cells  from  the  cerebral  cortex  of  the  cat ;  Erlich's 
method.     (Cajal.) 
A,  large  cell ;   B.  small  cell  ;  a,  a.  folds  in  the  network  ; 

').  a  ring-like  condensation  of  the  network  at  the  poles 

of   the   larger   cell ;     c,    spinous    projections   from   the 

surface. 


and  on  the  other  hand  gives  off  towards  the  interior  of  the  cell  fine  fibrils, 
which  are  continuous  with  the  neurofibrillas  of  the  cell  and  pass  out  in  its 
axon.  The  diagrammatic  course  of  a  nerve  impulse  according  to  Bethe  is 
represented  in  the  accompanying  diagram  (Fig.  151).  An  impulse  starting 
from  the  periphery  of  the  body  travels  up  the  distal  process  of  the  posterior 
root  ganglion-cell,  passes  either  through  the  cell  or  directly  to  the  central 
process,  and  travels  along  this  to  the  terminations  of  the  posterior  root 
fibres  round  a  posterior  horn-cell.  Here  it  passes  into  the  peri-cellular 
basket-work  or  axon  network,  thence  into  the  Golgi  network  and  along 
the  fibrillar  of  the  cell  out  by  the  fibrilla?  of  the  axon  and  so  to  a  fresh  synapse 
with  a  cell  of  the  anterior  horn. 

There  are  certain    physiological  difficulties  in  the  acceptance  of    this 


310 


PHYSIOLOGY 


doctrine  of  continuity  through  the  central  nervous  system.  Even  if  it  be 
true,  it  would  not  in  any  way  upset  the  importance  of  the  neuron  theory. 
Every  plant  or  animal  individual  must  be  regarded  as  a  protoplasmic  con- 
tinuum. With  growth  of  the  living  matter,  its  metabolic  functions  demand 
the  dispersion . of  nuclear  material  through  the  protoplasm,  and  this  is 
effected  by  division  of  the  nucleus.  Considerations  of  strength  and  rigidity 
demand  the  division  of  the  protoplasm  into  compartments  or  cells  which, 
at  first  at  any. rate,  remain  in  protoplasmic  continuity.  This  division  has 
probably  a  further  advantage  in  that  lesions  of  parts  of  the  individual  entail 
merely  the  death  of  the  cells  immediatelj  affected  and  do  no1  necessarily 


¥10.  151.     Schema  of  the  neurofibrillar  continuum,  involved  in  an  ordinary  reflex 
act,  in  a  yertebrate  nervous  system.     (Bethe.) 

spread  to  the  whole  organism.  Thus  in  the  central  nervous  system  injury 
to  one  axon  causes  degeneration  of  the  axon  below  the  point  of  section,  but 
the  degeneration  stops  short  at  the  end  arborisation  and  does  not  spread 
into  the  next  neuron.  If  we  assume  that,  in  consequence  of  the  straitness 
of  the  path,  the  propagation  through  the  fibrillas  is  especially  difficult  in  the 
synapse,  most  of  the  phenomena  described  above  as  characteristic. of  the 
reactions  which  take  place  in  the  central  nervous  system  can  be  easily  ex- 
plained on  the  theory  of  continuity  of  the  fibrillse.  The  serious  difficulty 
in  the  acceptance  of  this  theory  is  however  the  '  Law  of  Forward  Direction.' 
i.e.  the  fact  that  an  impulse  will  pass  from  an  axon  to  the  next  neuron, 
but  will  not  pass  backwards  across  the  synapse  from  the  cell  body  to  the 
contiguous  axon. 

Bethe  suggests  that  this  rule  of  Forward  Direction,  which  is  possibly  present  only 
in  the  more  highly  developed  nervous  systems,  may  be  due  to  a  species  of  '  polarity  ' 
of  the  nerve  fibril,  of  such  a  nature  that  an  impulse  is  strengthened  and  so  assisted  on 
its  passage  in  the  normal  direction,  but  is  diminished  and  finally  abolished  when  if 
passes  in  the  opposite  direction.  Such  an  explanation  is  unsatisfactory,  since  there  is 
absolutely  no  experimental  evidence  of  the  existence  of  such  polarity  in  a  nerve  fibre; 
all  the  evidence  that  we  have  at  present  points  to  a  nerve  fibre  having  (he  power  of 


NATURE  OF  CONNECTION  BETWEEN  NEURONS        311 

propagating  equally  well  in  either  direction.  It  is  certainly  more  useful  to  regard  a 
synapse  as  of  the  nature  of  a  motor  nerve-ending,  in  which  an  impulse  arriving  along 
the  branches  of  an  axon  excites  a  fresh  impulse  in  the  excitable  tissue,  i.e.  the  nerve- 
cill.  with  which  the  branches  of  the  axon  come  in  contact.  Moreover  the  neurons  are 
formed  without  any  structural  connection  with  the  future  destination  of  their  axons. 
These  grow  out  as  processes  with  thickened  amoeboid  extremities.  Harrison  has  shown 
that  the  growth  of  the  axon  from  the  cell  may  be  observed  under  the  microscope  in  a 
neuroblast  separated  altogether  from  the  body,  and  kept  on  a  warm  stage  in  a  thin 
layer  of  coagulated  lymph. 

It  is  possible  that  we  may  have  to  distinguish  two  types  of  nervous 
systems,  viz.  : 

(a)  A  neurofibrillar  type,  peculiar  to  invertebrata,  with  conduction  in 
all  directions. 

(6)  A  synaptic  type,  in  which  the  Law  of  Forward  Direction  holds,  of 
later  evolution,  and  forming  the  greater  part  of  the  nervous  system  of 
vertebra  ta. 


SECTION  V 

FUNCTIONS   OF   THE   NERVE    CELL 

When  a  unicellular  organism,  containing  a  single  nucleus,  is  cut  into  two 
parts,  both  continue  to  live  for  some  time,  each  performing  active  move- 
ments and  evincing  all  the  phenomena  which  we  associate  with  activity 
and  therefore  with  destructive  katabolism.  For  the  continued  existence 
of  a  cell  the  processes  of  constructive  metabolism,  or  anabolism,  must  take 
place  pari  passu  with  those  of  disintegration,  and  for  this  the  presence  of 
the  nucleus  is  necessary.  Hence,  in  a  few  days,  the  half  cell  with  the  nucleus 
has  repaired  its  loss  and  become  once  again  a  normal  individual,  whereas 
the  half  without  a  nucleus  undergoes  degeneration  and  death.  The  axon 
of  a  nerve  cell  can  be  regarded  as  analogous  to  a  long  pseudopodium  of  an 
amoeba.  Like  this,  if  cut  away  from  that  part  of  the  cell  containing  the 
nucleus,  though  capable  for  a  time  of  discharging  its  active  function  of 
propagation  of  excitatory  impulses,  yet  it  finally  dies,  death  of  the  nerve 
fibre  occurring  in  the  mammal  within  three  to  five  days  after  separation 
of  the  axon  from  the  oell.  Every  nerve  cell  therefore  may  be  looked  upon 
as  a  trophic  centre  of  the  nerve  fibre  rjroceeding  from  it  as  well  as  of  the 
medullary  sheath,  which  is  practically  a  product  or  secretion  of  the  axis 
cylinder.  But  has  the  nerve  cell  any  more  important  functions  to  dis- 
charge ?  It  has  long  been  customary  to  endow  the  nerve  cell  with  all 
the  properties  which  are  distinctive  of  a  nervous  system,  and  to  ascribe 
to  it  the  active  part  in  the  origination  of  automatic  actions,  in  the  reflection 
of  afferent  impulses,  and  in  the  supply  of  energy  to  all  nervous  processes. 
That  the  passage  of  impulses  through  the  nerve  centres  requires  the  ex- 
penditure of  energy  by  these  centres  can  be  proved  in  various  ways.  In 
the  first  place,  we  have  the  fact  that  in  all  nervous  systems,  at  any  rate  of 
the  higher  animals,  arrangements  are  made  for  their  free  supply  with  oxygen. 
Very  short  deprivation  of  oxygen  causes  a  complete  block  throughout  the 
system,  in  many  cases  preceded  by  a  short  period  of  increased  excitability 
or  ease  of  transmission.  If,  in  the  rabbit,  the  thoracic  aorta  be  clamped 
for  a  few  minutes,  the  hind  limbs  become  paralysed,  and  if  the  obstruction 
be  continued  for  half  an  hour,  there  is  widespread  degeneration  and  death 
of  the  cells  with  their  fibres  in  the  grey  matter  of  the  lumbar  and  sacral 
cord.  In  the  second  place,  the  ready  production  of  fatigue  of  the  nervous 
system  points  to  a  considerable  using  up  of  material  as  a  condition  of  the 
passage  of  nerve  impulses.  In  many  instances  moreover,  an  infinitesimal 
stimulus  travelling  up  a  few  nerve  fibres  may  excite  widespread  activity 
of  the  whole  central  nervous  system  with  the  discharge  of  impulses  along 

312 


FUNCTIONS  OF  THE  NERVE  CELL  313 

practically  every  nerve  of  the  body.  Tims  the  presence  of  a  crumb  on  the 
larynx  will  excite  impulses  travelling  up  the  superior  laryngeal  nerve,  which 
in  themselves  can  involve  but  little  expenditure  of  energy.  The  result 
however  of  their  arrival  at  the  central  nervous  system  is  the  discharge  of 
impulses  along  the  motor  nerves  causing  spasmodic  contractions  of  almost 
every  muscle  in  the  body.  It  seems  beyond  doubt  then  that  energy  is 
evolved  in  the  central  nervous  system  as  a  result  of  metabolic  changes,  and 
that  energy  may  be  added  to  impulses  passing  through  the  central  nervous 


Flo.  152.  Diagrammatic  representation  of  the  brain  of  Carcinus  to  show  the  parts 
involved  in  Bethe's  experiment.  The  dotted  line  x  shows  the  incision  employed 
to  isolate  the  neuropilem  of  the  ganglion  of  the  second  tentacle. 

system,  which  therefore  acts  as  a  relay  of  force.  But  this  activity  does  not 
necessarily  require  the  presence  or  co-operation  of  nucleated  cells.  In 
dealing  with  the  nature  of  a  nerve  impulse  we  had  reason  to  conclude  that 
there  may  be  an  actual,  though  minimal,  liberation  of  energy  in  the  axis 
cylinder  with  the  passage  of  each  nerve  impulse.  The  non-nucleated  parts 
of  a  cell,  whether  the  axon  or  the  cell  body,  are  equally  capable  of  this 
evolution  of  energy,  and  we  might  conceive  therefore  of  a  nervous  system 
which,  existing  for  a  few  days,  might  act  as  a  normal  reflex  centre  in  the 
entire  absence  of  the  nucleated  cell  bodies. 

This  conception  has  been  realised  by  Bethe  in  an  experiment  in  the  crab  (Carcinus 
menas).  In  this  animal  the  reflex  movements  of  the  tentacle  are  carried  out  by  a  gang- 
lion situated  at  its  base.  As  in  the  other  Crustacea,  the  cell  bodies  in  this  ganglion  lie 
outside  the  mass  of  neurofibrils  in  the  centre,  forming  a  sort  of  capsule  (Fig.  152). 
Bethe  was  able,  under  the  dissecting  microscope,  to  remove  the  cell  bodies  without 
interfering  with  the  nerves  entering  or  leaving  the  central  mass  of  fibrils.  All  the 
nerve  processes  with  their  connections  were  therefore  h  ft  intact.  In  animals,  operated 
in  this  way,  Bethe  found  that  for  two  or  three  days  the  tentacle  reacted  normally  to 
stimuli  applied  to  its  surface.  The  reflex  functions  of  the  ganglion  were  not  in  any 
way  affected  by  the  removal  of  the  nucleated  bodies  of  the  cells.     A  similar    experi- 


314  PHYSIOLOGY 

ment  would  be  impossible  in  the  central  nervous  system  of  vertebrates,  since  hnpult  es 
must  of  necessity  pass  through  the  cell  body  on  their  way  from  the  termination  of  one 
axon  to  the  beginning  of  the  next.  '  In  the  spinal  root  ganglion  however,  most  of  the 
cells  lie  on  the  surface.  In  the  rabbit  Steinach  exposed  a  posterior  root  ganglion, 
separating  it  from  all  its  vascular  supply,  but  leaving  its  nervous  attachments  intact. 
Tin-  wound  was  opened  every  day  for  the  next  few  days  and  an  instrument  passed 
under  the  ganglion  so  as  to  divide  any  newly  forming  vessels.  As  a  result  of  the 
deprivation  of  blood-supply  the  ganglion-cells  died.  But  Steinach  found  that  nerve 
impulses  were  still  conducted  perfectly  well  through  the  ganglion  at  a  time  when 
microscopic  examination  showed  a  complete  atrophy  of  all  cells.  It  is  therefore  only 
in  virtue  (if  tin-  fact  that  the  nerve  cell  is  the  scat  of  the  nucleus,  and  therefore  of  the 
assimilative  functions  of  the  neuron,  that  any  pre-eminent  importance  can  be  ascribed 
to  it  in  the  building  up  of  a  reactive  nervous  system. 

Prominent  among  the  functions  with  which  the  nerve  cell  has  been 
endowed  is  that  of  automaticity  of  action  in  the  absence  of  stimulus  other 
than  that  supplied  by  its  own  metabolism  or  by  the  fluids  which  bathe  it. 
A  priori  there  is  no  reason  to  deny  to  the  neuron  a  property  which  is  pos- 
sessed by  other  cells  of  the  body,  such  as  the  muscular  cells  of  the  heart,  and 
is  a  fundamental  quality  of  undifferentiated  protoplasm.  The  purpose 
however  for  which  these  cells  have  been  evolved  and  differentiated  is 
that  of  reaction,  of  adapting  the  organism  to  changes  in  its  environment, 
and  it  is  doubtful  whether,  in  this  differentiation,  it  has  retained  any  auto- 
matic properties  whatsoever.  In  the  absence  of  any  afferent  impulse  the 
whole  central  nervous  system  would  probably.be  inert.  In  a  frog  retaining 
only  the  spinal  cord  Hering  divided  all  the  posterior  roots.  The-  frog 
remained  flaccid  and  motionless.  Injection  of  strychnine  was  powerless 
to  evoke  the  usual  tetanic  spasms.  In  such  a  strychninised  frog  however, 
it  was  necessary  only  to  open  the  wound  and  touch  one  of  the  divided 
posterior  roots  to  throw  the  whole  body  into  convulsions.  As  shown  by 
Sherrington  and  Mott.  division  of  all  the  afferent  nerves  coming  from  the 
upper  limb  in  monkey  or  man  entirely  abolishes  all  such  contractions  of  the 
limb,  as  are  usually  affected  through  the  intermediation  of  the  cerebral 
cortex.  Cutting  off  the  major  portion  of  the  afferent  impulses  to  the  respira- 
tory centre  does  not,  it  is  true,  abolish  all  respiratory  discharges,  but  converts 
the  rhythmic  respirations  into  a  series  of  inspiratory  spasms  which  are 
repeated  at  long  intervals  and  are  entirely  inadequate  for  the  proper  aeration 
of  the  blood.  According  to  Sherrington  a  repetition  on  the  mammal  of 
Hering's  experiment  does  not  lead  to  the  same  results,  since  a  spasmodic 
discharge  is  produced  from  the  isolated  spinal  cord  as  a  result  of  asphyxia. 
But  it  is  doubtful  whether  in  this  case  there  was  not  some  continuous  excita- 
tion of  the  cord  going  on,  as  a  result  of  the  closure  of  the  demarcation  current 
in  the  cut  ends  of  the  posterior  roots  by  the  body  fluids.  It  is  possible  that 
the  neurons  possess  some  automatic  power,  i.e.  some  power  of  initiating 
nervous  processes,  as  a  result  of  changes  in  the  fluids  surrounding  them. 
This  automaticity  however  is  not.  a  prominent  feature  of  the  nervous  system, 
which  has  been  evolved  as  a  purely  reactive  mechanism  to  the  afferent 
impulses  resulting  from  the  material  changes  continually  taking  place  in  the 
environment  of  the  animal. 


SECTION  VI 
STRUCTURE    OF   THE   SPINAL   CORD 

In  the  higher  representatives  of  the  invertebrate  class,  the  central  nervous 
system  consists,  as  we  have  seen,  of  a  chain  of  ganglia,  each  ganglion  or  pair 
of  ganglia  presiding  over  the  reactions  of  its  own  segment,  but  connected  by 
long  paths  with  the  other  ganglia  and  with  the  head  ganglia.  The  latter,  being 
especially  developed  in  connection  with  the  organs  of  special  sense  which  are 
projicient  in  function,  acquire  a  control  over  the  rest  of  the  ganglia  (Fig.  153). 
The  vertebrate  spinal  cord  may  be  looked  upon  as  a  chain  of  ganglia  which 


Neufeattric  canal 


N'u^utum       VENTRAL 


Pig.    153.     Vertebrate  central   nervous    system    compared    with   that   of  the  arthropod. 

(i  '•  iskkj.l.)     (Note  that  according  to  Gaskell  the  ventricles  of  the  brain  and  the  primitive 
neural  canal  correspond  to  the  invertebrate  stomach  and  intestine.) 

have  become  fused  concurrently  with  a  diminution  in  the  importance  of  the 
local  segmental  reactions  and  with  a  growth  in  the  solidarity  of  the  whole 
system  ;  so  that  in  the  higher  vertebrates,  at  any  rate,  little  trace  of  the 
primitive  segmental  arrangement  is  evident  in  the  internal  structure  of  the 
cord.  Some  remains  of  this  arrangement  still  persist  however  in  the  origin 
from  the  cord  of  nerve  roots,  which  are  distributed  roughly  within  the  area  of 
the  corresponding  segment  of  the  body. 

In  man  the  spinal  cord  is  an  elongated  cylindrical  structure  slightly 
flattened  from  before  backwards  and  about  eighteen  inches  long.  It 
gives  nil  a  series  of  nerve  roots,  which  are  arranged  in  thirty-one  pairs 
and  are  distributed  symmetrically  to  the  two  sides  of  the  body.     Each 

315 


316  PHYSIOLOGY 

nerve  arises  by  two  roots,  an  anterior  and  a  posterior,  the  anterior  being 
composed  of  a  series  of  rootlets  spread  over  a  considerable  area  of  the  cord, 
while  the  posterior  roots  arise  as  a  compact  bundle  from  a  groove  on  the 
postero-lateral  aspect  of  the  cord.  The  posterior  nerve-roots  pass  through  a 
garjglion  and  join  the  anterior  roots  in  the  intervertebral  foramina  to  form  the 
mixed  nerve.  On  section  the  cord  is  seen  to  consist  of  a  core  of  grey  matter 
surrounded  on  all  sides  by  white  matter.  The  white  matter  is  made  up  of 
medullated  nerve  fibres  which  are  devoid  of  a  neurilemma,  and  run  within 
tunnels  or  tubes  in  the  supporting  neuroglia.  The  grey  matter  has  roughly 
the  form  of  a  letter  H,  and  consists,  in  cross-section,  of  a  comma-shaped 
mass  on  each  side  of  the  cord,  joined  across  the  middle  line  by  a  band  of  grey 
matter.  On  the  anterior  aspect  of  the  cord  is  a  furrow,  the  anterior  fissure, 
which  contains  a  process  of  the  enveloping  membrane  of  the  cord,  the  pia 
mater,  and  is  limited  at  its  bottom  by  a  band  of  white  matter,  the  anterior 
white  commissure,  which  unites  the  anterior  columns  of  white  matter. 

On  the  hinder  aspect  of  the  cord  is  another  fissure,  the  posterior  fissure, 
which  is  very  narrow  and  is  built  up  chiefly  by  neuroglia.  A  third  fissure  at 
the  point  of  origin  of  the  posterior  nerve-roots  serves  to  divide  the  white 
matter  of  the  cord  into  an  antero-lateral  column  and  a  posterior  column,  and 
the  former  is  imperfectly  separated  by  the  spread-out  anterior  rootlets 
into  anterior  and  lateral  columns.  The  cord  in  cross-section  (Fig.  154) 
is  circular  in  the  dorsal  region  and  oval  in  the  cervical  and  lumbar  regions. 
It  presents  two  marked  enlargements,  namely,  the  cervical  enlargement, 
corresponding  to  the  outflow  of  the  nerves  going  to  the  upper  limb,  and 
the  lumbo-sacral  enlargement,  which  gives  off  the  nerves  to  the  lower  limb. 
In  the  sacral  region  it  rapidly  tapers  off  to  a  blunt  point.  In  the  centre  of 
the  band  of  grey  matter.,  connecting  the  two  masses  on  each  side  of  the  middle 
line,  is  the  central  canal  of  the  cord,  the  remains  of  the  primitive  neural  canal 
of  the  embryo.  The  grey  matter  in  front  of  it  is  called  the  anterior  grey 
commissure,  that  behind  the  posterior  grey  commissure.  The  comma- 
shaped  mass  of  grey  matter  on  each  side  of  the  cord  presents  in  front  the 
broad  anterior  cornu,  and  behind  the  narrower  posterior  cornu,  which 
extends  up  to  the  postero-lateral  groove  in  the  line  of  emergence  of  the 
posterior  roots.  In  the  dorsal  region  of  the  cord  the  grey  matter  projects 
into  the  lateral  column  of  white  matter  to  form  the  lateral  horn.  The  grey 
matter  consists  of  a  supporting  tissue  of  neuroglia  in  which  are  embedded 
nerve  cells  and  their  processes  and  the  endings  of  nerve  fibres.  The  neuroglia 
is  formed  of  a  thick  felt-work  of  fibres  with  here  and  there  nuclei  applied  to 
the  fibres.  Occasionally  we  may  meet  cells  provided  with  a  very  large 
number  of  branches  and  representing  the  cells  from  which  all  the  fibres  of 
the  neuroglia  have  been  derived.  The  neuroglia  is  present  in  specially  large 
amount  in  two  situations,  namely,  immediately  around  the  central  canal 
and  as  a  capsule  to  the  enlargement  of  the  posterior  cornu,  known  as  the 
head  or  caput  cornu  posterioris.  In  this  latter  situation  the  neuroglia  con- 
tains a  large  number  of  small  richly-branched  nerve  cells  and  is  spoken  of  as 
the  substantia  gelatinosa   of  Rolando.     The  nerve  cells  are  arranged  in 


STRUCTURE   OF  THE  SPINAL  CORD 


317 


distinct  groups.  In  the  anterior  horn  we  may  distinguish  three  groups,  a 
median  group  of  cells  near  the  middle  line,  many  of  which  send  their  processes 
across  to  the  other  side  in  the  anterior  white  commissure,  and  an  external 


Fig.  154.     Sections  of  human  spinal  cord  from  the  lower  cervical,  mid-dorsal,  and 
mid-lumbar  regions,  showing  the  principal  groups  of  nerve  cells,  and  on  the 
right  side  of  each  section  the  conducting  tracts  as  they  occur  in  the  several 
regions  (magnified  about  7  diameters).     (E.  A.  Schafer.) 
a,  b,'c,  groups  of  cells  of  the  anterior  hom  ;  d,  cells  of  the  lateral  horn  ;  e.  middle 

group  of  cells  ;   /,  cells,  of  Clarke's  column  ;  q,  cells  of  posterior  horn;   cc,  central 

canal ;   ac,  anterior  commissure. 


318 


PHYSIOLOGY 


group  often  subdivided  into  a  postero-extemal  and  an  antero-external.      The 

latter  group  is  especially  developed  in  the  regions  of  the  cervical  and  lumbal 
enlargements  and  consists  of  very  large  multipolar  cells  with  many  dendrites 
which  send  their  axons  into  the  anterior  roots  and  by  these  to  the  muscles  of 
the  limbs.  Another  group  of  rather  smaller  cells  is  found  in  the  lateral 
horn,  in  that  region  of  the  cord  where  this  is  marked.  A  very  definite  group 
of  cells  may  be  seen  in  the  dorsal  region  of  the  cord  in  the  inner  aspect  of 
the  root  of  the  posterior  horn.  This,  which  is  known  as  Clarke's  column, 
is  formed  by  large  cells  elongated  in  the  longitudinal  direction  of  the  cord. 
Besides  these  definite  columns  a  number  of  nerve  cells  are  distributed  irregu- 
larly through  the  grey  matter,  especially  of  the  posterior  horn. 


meetpt/mnticfat 


Pig.  J-V>.  Spinal  cord,  [After  Lenhossek.)  (In  left  side  of  ti»\irc  arc  shown 
the  nerve  cells  with  their  axis-cylinder  processes.  On  the  right  side  the  dis- 
tribution of  the  chief  collaterals. 


I,  motor  cells  ;   2,  cells  of  the  columns  ; 
processes  across  into  direct  cerebellar  tract  : 


2a,  cells  of  Clarke's  column,  sending 
3,  4.  and  5,  commissural  cells. 


According  to  the  destiny  of  their  axons  these  nerve  cells  may  be  divided  into  four 
groups  (Fig.   155). 

(1)  THE  MOTOR  CELLS,  the  largest  of  all.  which  send  their  axons  into  the  anterior 
roots,  where  they  run  to  supply  skeletal  muscle  fibres.  As  a  sub-group  of  these  cells  we 
may  class  the  somewhat  smaller  cells  of  the  lateral  horn,  which  in  all  probability  send 
their  axons  by  the  anterior  roots  to  supply  visceral  muscles.  Their  axons  can  be 
distinguished  from  the  motor  axons  by  the  smaller  diameter  of  the  nerve  fibres  they 
form.  They  pass  later  from  the  mixed  nerve  along  a  white  ramus  communicans  into 
the  sympathetic  system,  in  the  ganglia  of  which  they  end. 

(2)  CELLS  OF  THE  COLUMNS.  As  typical  of  these  cells  we  may  take  those 
which  form  Clarke's  column.  Their  axons  do  not  leave  the  central  nervous  system, 
but  pass  out  into  the  white  matter  to  some  other  part  of  the  central  nervous  system, 
contributing  thus  to  form  the  white  columns  of  the  cord. 

(3)  COMMISSURAL  CELLS.  These  cells  send  their  axon  across  the  middle 
line  to  the  opposite  side  of  the  cord,  making  up  a  great  part  of  the  anterior  white 
commissure. 

(4)  CELLS  OF  GOLGI.  These  cells  are  found  chiefly  in  the  posterior  horn.  They 
are  multipolar  and  are  distinguished  from  all  the  other  cells  by  the  fact  that  their 


STRUCTURE   OF  THE  SPINAL  CORD 


319 


axon  does  not  pass  far  from  the  cell,  but  rapidly  breaks  up  into  a  number  of  blanches 
which  terminate  in  the  near  neighbourhood  of  the  cell  giving  off  the  axon.  They  may 
be  regarded  as  association  cells,  i.e.  as  serving  to  establish  a  functional  connection 
between  many  different  cells  at  any  given  level  of  the  grey  matter. 

The  white  matter  of  the  cord  is  divided  by  the  fissures  already  described 
into  anterior,  lateral,  and  posterior  columris.  The  nerve  fibres  of  which 
it  is  composed  are  all  of  them  axons  of  nerve  cells  situated  at  different  levels 
of  the  central  nervous  system  or  outside  the  cord.  Since  the  whole  object  of 
the  study  of  the  anatomy  of  the  cord  is  the  tracing  out  of  the  systems  of 
neurons  of  which  it  is  made  up,  and  therefore  of  the  possible  paths  of  any 
reflexes  or  nerve  impulses  through  the  cord,  a  mere  anatomical  differentiation 
of  different  columns  is  quite  useless  unless  we  can  determine  in  each  column 
the  origin  and  destination  of  the  fibres  of  which  it  is  composed. 


IN      II,  i 


ratral  nervous 


For  tracing  out  the'  course  of  the  different  axon  system 
system  several  methods  are  available. 

(a)  HISTOLOGICAL.  Two  methods  may  be  employed  for  staining  a  nerve  cell 
with  all  its  processes,  namely,  the  intravitum  staining  with  methylene  blue  and  the 
impregnation  method  invented  by  Golgi.  In  the  latter  method,  of  which  there  are 
many  modifications,  the  nervous  tissue  is  hardened  in  some  chromate  or  bichromate, 
and  is  then  soaked  in  a  solution  of  silver  nitrate  or  mercuric  chloride.  In  this  way 
a  precipitate  of  silver  or  mercuric  chromate  is  formed  within  the  nerve  cells  and  their 
processes  ;  but  for  some  unexplained  reason  the  impregnation  is  not  general,  and  is 
confined    to   a   small   percentage   of   the   neurons.     If 

the  precipitate  were  diffuse,  even  a  thin  section 
would  be  absolutely  opaque  :  since  it  is  partial, 
thick  sections  maybe  cut  and.  after  clearing,  allow 
the  tracing  of  the  processes  of  the  few  impregnated 
nerve  cells  through  the  whole  thickness  of  the  section. 
We  may  in  this  way  get  sections  01  mm.  thick  at 
the  point  of  entrance  of  a  posterior  nerve  root,  and 
trace  out  the  course  and  ending  of  a  large  number  of 
the  fibres  composing  the  nerve  root,  or  we  may  in  a  r/i 
section  involving  the  anterior  nerve  root  trace  the 
course  of  an  axon  of  an  anterior  cornual  cell  out  of 
the  cord  into  the  root.  This  method  is  of  no  use  in 
tracing  any  given  nerve  fibre  through  the  whole 
length  of  the  cord.  For  this  purpose  however 
several   methods  are  available. 

(b)  MYELINATION  METHOD  OF  FLECHSIG. 
Nerve  fibres  at  their  first  formation  as  axons  of  a 
nerve  cell  are  non-medullated,  the  medullary  sheath 
being  formed  later  with  the  beginning  of  function  of 
the  nerve.  It  has  been  shown  by  Flechsig  that  I  he 
mvclination  docs  not  occur  simultaneously  through 
all  parts  of  the  central  nervous  system,  but  that  it 
is  later  in    proportion    as   the    nerve  fibre    is    more 


Fig.  156.  Section  through  the  cer- 
vical spinal  cord  of  a  new-bora 
child,  stained  by  Weigert's 
method,  to  show  absence  of 
medullation  in  pyramidal  tract. 
,".    anterior   commissure  ;     Fp. 

crossed  pyramidal  tract ;  Fe,  direct 


cerebellar    tract  :     Zrp.    posterior 
recent     in     the   phylogenetic    history    of    the    animal.    root    zone  ;      rp\    posterior    root 
The  cord  in  its  most  primitive  form  can  be  regarded    fibres.     (Bechterew.) 
as   a    scries   of   ganglia    presiding  over   the   different 

segments  of  the  body.  The  most  primitive  fibres  therefore  would  be  those  which  run 
from  the  periphery  of  the  body  to  each  segment  and  from  each  segment  out  to  the 
muscles,  and  so  a  medullary  sheath  is  first  formed  in  a  number  of  the  fibres  entering 
and   leaving    the  cord  in  the  nerve-roots.     Next  in  order  of  myelination   are   those 


320 


PHYSIOLOGY 


fibres  which  connect  different  segments  of  the  cord,  the  internuncial  or  intra -spina  I 
fibres.  Next  come  those  fibres  which  connect  the  spinal  cord  with  the  cerebellum. 
Last  of  all  to  receive  a  medullary  sheath  are  the  fibres  which  take  a  direct  course  from 
the  cerebral  cortex  to  the  spinal  cord.  These  are  called  the  pyramidal  tracts,  and  in 
man  arc  not  medullated  until  flic  first   month  after  birth  (Fig.  156). 

(c)  THE  WALLERIAN  METHOD.  A  nerve  fibre,  when  cut  off  from  the  nerve 
cell  of  which  it  is  a  process,  degenerates.  This  degeneration  is  marked  by  a  breaking 
up  of  the  medullary  sheath  and  a  conversion  of  the  phosphorised  fat,  myelin, of  which 
it  is  composed,  into  ordinary  fat.  Later  on  the  fat  is  absorbed  and  the  nerve  becomes 
replaced  by  a  strand  of  fibrous  tissue  in  the  case  of  peripheral  nerves,  of  neuroglia 
in  the  central  nervous  system.  If  the  white  matter  of  one  half  of  the  spinal  cord  be 
divided  in  the  dorsal  region,  and  the  animal  be  killed  about  three  weeks  after  the  opera- 
tion, sections  of  the  cord  both  above  and  below  the  lesion  will  show  the  presence  of 
degenerated  fibres.  In  order  to  display  these  fibres  pieces  of  the  cord  are  hardened 
in  a  solution  containing  bichromates  and  are  then  immersed  in  a    mixture  of  osmic 


FlG.   157.     Cells  from  the  oculo-motor  nuclei  thirteen  days  after  section  of  the 

nerve  on  one  side. 

a,  cell  from  healthy  side  ;    6.  cell  from  side  on  which  nerve  was 

divided.     (Flatait.) 

acid  and  bichromate.  By  this  method  ordinary  fat  is  stained,  but  myelin  is  left  un- 
stained (Marehi's  method).  Degenerated  fibres  are  therefore  stained  black  in  virtue 
of  their  content  in  fat.  The  black  staining  has  different  distribution  according  as  we 
take  a  section  of  the  cord  above  or  below  the  lesion.  The  existence  of  the  degeneration 
shows  that  those  fibres  which  are  degenerated  in  the  cervical  region  are  axons  of  nerve 
cells  situated  below  the  lesion,  while  the  fibres  in  the  lumbar  cord  which  are  degenerated 
must  have  their  nerve  cells  in  some  part  of  the  nervous  system  which  is  above  the 
lesion.  If  the  animal  be  kept  alive  for  a  considerable  time,  six  months  or  more,  before 
being  killed,  the  occurrence  of  degeneration  in  any  given  area  of  the  cord  will  be  shown 
by  the  absence  of  normal  nerve  fibres  in  this  area.  In  such  a  case  some  method  of 
staining  the  medullary  sheath,  such  as  that  of  Weigert  or  Heller,  is  employed,  when  the 
degenerated  area  will  be  evident  owing  to  its  inability  to  take  the  stain.  This  method 
however  is  not  so  satisfactory  as  the  Marchi  method,  since  it  is  impossible  in  this  way 
to  detect  in  a  section  the  presence  of  one  or  two  degenerated  nerve  fibres,  whereas 
by  the  use  of  the  Marchi  method  they  would  appear  as  black  dots  in  the  unstained 
section  (cp.  Fig.  164). 

(d)  METHOD  OF  RETROGRADE  DEGENERATION.  When  a  nerve  fibre  is 
divided  there  is  no  degeneration  as  a  rule  in  the  part  of  the  nerve  fibre  central  to  the 
lesion.      The  nerve  cell  is  however  affected,  and  the  extent  to  which  this  occurs  is 


STRUCTURE  OF  THE  SPINAL  CORD  321 

more  pronounced  according  as  the  lesion  is  nearer  to  the  cell  (Fig.  157.)  If,  for  instance, 
an  anterior  root  be  divided  and  three  weeks  later  the  animal  be  killed  and  sections  made 
of  the  corresponding  segment  of  the  cord  and  stained  with  toluidine  blue  or  methylene 
blue,  a  striking  difference  will  be  observed  between  the  cells  of  the  anterior  horn  of 
the  two  sides  of  the  cord.  On  the  side  of  the  lesion  the  nucleus  of  the  cells  will  be 
somewhat  swollen,  and  may  be  displaced  towards  the  periphery  of  the  cell.  The  Nissl 
granules  are  no  longer  distinct,  but  the  whole  cell  is  diffusely  stained  blue.  In  some 
r;isrs  this  change  may  go  on  to  complete  atrophy  of  the  cell  and  consequent  degenera- 
tion of  the  whole  of  its  axon.  Generally  however  the  cell  gradually  recovers,  so  that 
six  months  after  the  lesion  no  difference  will  be  observable  between  the  cells  on  the 
two  sides  of  the  cord.  This  method  must  be  used  with  some  caution  as  a  means  of 
tracing  out  the  connections  of  any  given  neurons  in  the  central  nervous  system,  since 
it  has  been  shown  by  Warrington  that  somewhat  similar  changes  may  be  produced 
in  the  anterior  horn-cells  by  division  of  the  posterior  roots,  thus  cutting  off  those  im- 
pulses by  which  their  activity  is  normally  excited.  Here  we  have  a  lesion  applied  to 
one  neuron  causing  a  histological  change  in  the  cell  body  of  another  neuron  which 
is  next  in  the  chain  of  the  nervous  arc. 

0 
The  structure  of  the  cord  is  closely  connected  with  and  determines  its  two- 
fold function,  namely,  as  a  series  of  reflex  centres  for  the  different  segments 
of  the  body,  and  as  a  means  of  communication  between  the  trunk  and  limbs 
and  the  higher  parts  of  the  central  nervous  system.  An  examination  of  the 
relative  area  of  the  white  matter  at  different  levels  of  the  cord  shows  a 
steady  increase  from  the  lower  to  the  upper  end.  The  increase  is  not  how- 
ever proportional  to  the  number  of  fibres  which  enter  or  leave  the  cord  in  the 
various  spinal  nerve  roots.  Of  these  fibres  therefore  a  certain  proportion  are 
destined  to  serve  merely  the  local  segmental  reflexes,  while  others  are  con- 
tinued directly  upwards  to  the  brain  or  are  connected  with  cells  which  them- 
selves send  their  axons  up  to  the  brain  (cells  of  the  columns).  All  the  motor 
fibres  in  the  nerve  roots  arise  from  cells  in  the  spinal  cord  near  the  point  of 
origin  of  the  root.  Any  direct  influence  of  the  brain  on  the  motor  mechan- 
isms of  the  body  is  therefore  effected  through  the  intermediation  of  the 
segmental  neural  mechanisms  of  the  grey  matter  of  the  cord.  We  will 
consider  the  function  and  related  structure  of  the  cord  in  these  two  aspects  : 
first,  as  a  reflex  centre,  and  secondly,  as  a  conductor  of  impulses  to  the 
higher  parts  of  the  central  nervous  system. 


■21 


SECTION  VII 

THE    SPINAL   CORD    AS    A    REFLEX   CENTRE 

In  the  evolution  of  the  cord  the  primitive  segmental  arrangement  has  been 
especially  interfered  with  by  the  development  of  the  four  limbs.  Since 
the  reactions  of  the  limbs  transcend  in  importance  and  complexity  those  of 
the  rest  of  the  body,  a  great  enlargement  of  the  cord  has  occurred  in  the  region 
of  the  nerve  roots  which  supply  the  limbs.  Each  limb  must  be  considered 
as  produced  by  the  fusion  of  a  number  of  body  segments,  in  which  the 
morphological  segmental  arrangement  has  entirely  given  place  to  a  physio- 
logical one.  Thus  no  single  muscle  of  the  limbs  is  innervated  from  one 
nerve  root,  every  muscle  being  formed  from  elements  belonging  to  several 
segments  and  innervated  from  several  nerve  roots.  The  segmental  arrange- 
ment of  the  cord  is  hidden  moreover  by  the  increasing  complexity  of  the  spinal 
reflexes  and  the  consequent  involvement  of  many  segments  in  even  the 
simplest  reactions.  As  we  shall  see  later,  practically  no  reflex  can  be 
evoked,  even  by  stimulation  of  one  nerve  fibre  or  nerve  root  in  any  of  the 
vertebrata,  which  does  not  involve  in  its  response  elements  belonging  to  many 
segments. 

Since  the  reactions,  which  can  be  carried  out  by  any  part  of  the  nervous 
system,  depend  on  the  neurons  of  which  the  part  is  composed,  it  is  necessary, 
before  treating  of  the  reactions  of  the  spinal  animal,  to  consider  the  '  way  in  ' 
to  and  the  '  way  out '  of  the  centre,  as  well  as  the  connections  between  the 
entering  and  issuing  paths.  (Each  segment  of  the  cord  gives  off  a  pair  of 
nerve  roots,  subdivided  into  an  anterior  and  a  posterior  root  (Fig.  158).  In 
mammals  it  is  easy  to  show  that  the  posterior  root  is  exclusively  afferent  in 
function.  Section  of  the  root,  either  distal  or  proximal  to  the  ganglion,  pro- 
duces no  paralysis  of  any  description.  It  may  cause  diminished  sensation  in 
the  area,  supplied  by  it,  andif  two  or  three  adjacent  posterior  roots  be  divided, 
complete  ana?sthesia  results  in  the  central  part  of  the  skin  area  supplied  from 
these  roots.  (.^Stimulation  of  the  central  end  of  a  divided  posterior  rcot 
evokes  in  a  conscious  animal  signs  of  pain.  In  an  animal  possessing  only 
spinal  cord  and  bulb,  reflex  effects  are  produced,  i.e.  movements  of  skeletal 
muscles  as  well  as  effects  on  visceral  muscles,  such  as  constriction  of  blood- 
vessels, relaxation  of  intestinal  muscle,  and  so  on.  '  On  the  other  hand, 
section  of  an  anterior  root  causes  paralysis  of  muscles  or  parts  of  muscles. 
Sestion  of  all  the  anterior  roots  going  to  a  limb  will  produce  complete 
motor  paralysis  of  the  limb.     Stimulation  of  the  central  end  of  a  divided 

322 


THE  SPINAL  CORD  AS  A  REFLEX  CENTRE 


323 


anterior  root  has  no  effect.  Stimulation  of  the  peripheral  end  evokes  con- 
traction of  muscles,  and  if  the  root  experimented  on  be  in  the  upper  dorsal 
region  of  the  cord,  certain  visceral  effects,  e.g.  dilatation  of  the  pupil  or 
augmentation  of  the  heart  beat,  may  result. 

To  this  general  law,  the  law  of  Bell  and  Magendie;  which  affirms  the  purely  afferent 
function  of  the  posterior  roots  and  the  purely  efferent  function  of  the  anterior  roots, 
certain  exceptions  must  be  noted.  In  the  first  place,  in  the  lower  vertebrata  the 
separation  of  afferent  from  efferent  fibres  seems  to  be  not  so  complete  as  in  the  higher 
vertebrates.  Thus  in  the  chick  Oajal  and  others  have  described  fibres  given  off  as 
axons  from  the  cells  of  the  grey  matter  and  leaving  the  cord  by  the  posterior  root. 
The  function  of  these  fibres  is  unknown.     In  the  frog  Steinach  lias  stated  that  visceral 


Flo.  158.     Figures  (from  Yeo)  to  illustrate  the  degree  and  direction  of  degenera- 
tion as  a  result  of  section  of  the  spinal  roots. 
I,   division  of    whole    nerve    below    ganglion.     IT,   division   of    anterior  root. 
Ill,  division  of  posterior  root  above  ganglion.     IV,  division  of  posterior  root  above 
and  below  ganglion. 

effects  may  ensue  on  stimulation  of  the  lower  posterior  roots.  This  statement  is 
controverted  by  Horton-Smith.  who  however  has  noticed  contractions  of  fibres  of 
voluntary  muscles  as  the  result  of  stimulating  these  roots. 

In  a  class  by  themselves  we  must  place  the  vasodilator  effects  observed  by  Strieker, 
Dastre  and  Morat,  and  Bayliss  to  follow  excitation  of  the  peripheral  ends  of  the  posterior 
roots.  Bayliss  has  shown  that  the  fibres,  through  which  the  vasodilatation  is  produced, 
must  have  their  cell-station  in  the  posterior  root  ganglia.  It  seems  therefore  that 
the  same  fibres  provide  for  carrying  both  afferent  impulses  from  skin  to  cord,  and  vaso- 
dilator impulses  from  the  cord  to  the  vessels  of  the  skin.  Bayliss  has  designated  the 
impulses  which  effect  the  vasodilatation  as  antidromic,  since  they  are  opposed  in  direc- 
tion to  the  normal  impulses  of  the  nerve  fibre.  Of  the  same  nature  are  the  curious 
trophic  impulses  which  extend  along  the  posterior  roots  and  which  must  come  into  play 
when  eruptions  of  erythema  or  herpes  occur  as  the  result  of  inflammation  or  haemorrhages 
in  the  substance  of  the  posterior  root  ganglia.  Both  these  phenomena  are  at  present 
but  imperfectly  understood  ;  and  their  anomalous  character  is  only  intensified  by  the 
further  fact  elicited  by  Bayliss,  viz.  that  it  is  possible,  by  stimulation  of  afferent  nerves, 
to  excite  reflexly  vasodilatation  through  the  intermediation  of  the  posterior  roots. 
Unless  this  reflex  dilatation  is  simply  an  example  of  an  '  axon  reflex '  (v.  p.  275)  it 
would  furnish  an  exception  to  the  otherwise  universal  law  of  forward  direction^in  the 
mammalian  nervous  system. 

A  third  exception  to  the  law  of  Bell  and  Magendie  is  only  apparent.  It  is  sometimes 
found  that  excitation  of  the  peripheral  end  of  a  divided  anterior  root  gives  rise  to  mani- 
festations of  pain  or  to  reflex  movement.  This  has  been  shown  by  Schiff  to  be  due 
to  the  presence,  in  the  sheaths  of  the  anterior  roots,  of  fine  fibres  derived  from  the 
posterior  roots  and  taking  a  recurrent  course  to  end  probably  in  the  membranes  of  the 
cord.  This  recurrent  sensibility  is  at  once  abolished  by  section  of  two  or  three  adjacent 
posterior  roots. 


524 


PHYSIOLOGY 


THE  WAY  IN 
We  may  now  consider  the  possible  ways  open  to  a  nerve  impulse  entering 

the  cord.     Each  posterior  root  on  entering  the  cord  divides  into  two  bundles. 

The  smaller  bundle  passes  t<>  the  outer  side  of  the  tip  of  the  posterior  horn 
where  its  fibres  bifurcate  (Fig.  159),  giving 
rise  to  fibres  which  pass  up  and  down  the 
cords  in  a.  small  longitudinal  band  of  fibres 
known  as  Lissauer's  tract.  The  fibres  run 
only  a  short  distance  before  turning  into  the 
grey  matter,  and  terminate  in  arborisations 
round  the  cells  of  the  substantia  gelatinosa 
in  the  head  of  the  posterior  horn.  By  far 
the  greater  number  of  the  posterior  root- 
fibres  pass  to  the  inner  side  of  the  posterior 
horn  into  Burdach's  or  the  postero-external 
column.  Here  they  also  divide  into  two 
main  branches,  one  running  up  and  the 
other  down  in  the  white  matter.  The 
descending  branch  passes  through  two  or 
three  segments  before  turning  into  the  grey 
matter  of  the  posterior  horn  of  a  lower 
segment.  Of  the  ascending  branches,  some 
end  at  different  levels  of  the  cord,  but  a  cer- 
tain proportion  of  the  fibres  from  every 
root  traverse  the  whole  length  of  the  cord 
in  the  posterior  columns  to  terminate  in  the 
posterior  column  nuclei  (nuclei  gracilis  and 
cuneatus)  in  the  medulla  oblongata.  As  we 
proceed  up  the  cord  the  entering  posterior 
root-fibres  displace  the  long  fibres  of  those 
below  towards  the  middle  line,  so  that  in  a 
section  through  the  cord  in  the  upper  cervical 
region  the  posterior  median  column,  or 
column  of  Goll,  is  made  up  almost  exclu- 
sively of  fibres  from  the  hind  limb,  while 
the  postero-external  column  consists  of  fibres 
from  the  fore  limb. 

Besides  these  distant  connections,  every 
entering  nerve   fibre   makes  connection   with 

all  parts  of  the  grey  matter  in  and  about  its  level  of  entrance  by  means 

of  collaterals  (Fig.  160).     Five  groups  of  these  collateral  branches  can  be 

distinguished,  i.t., 

(1)  Fibres  which  arborise  round  cells  in  the  posterior  horn  of  the  same 
side. 

(2)  Fibres  which  pass  through  the  dorsal  grey  commissure  to  the  grey 
matter  of  the  opposite  side  of  the  cord, 


FlO.  159.  Longitudinal  section 
of  spinal  cord  of  chick,  showing 
bifurcation  of  dorsal  root- 
fibres,  and  the  passage  of  their 
collaterals  into  the  grey  matter. 
Three  cells  of  the  dorsal  horn 
are  also  seen  sending  their 
axons  into  the  dorsal  columns. 
(Cajal.) 


THE  SPINAL   CORD  AS  A  REFLEX  CENTRE 


325 


(3)  Fibres  terminating  round  the  median  group  of  cells  of  the  anterior 
horn. 

(4)  Fibres  which  end  in  a  rich  basket-work  round  the  cells  of  Clarke's 
column. 

(5)  The  sensori-motor  bundle,  which  passes  forwards  through  the 
grey  matter  to  end  round  the  cells  in  the  anterior  horn  of  the  same  side 
of  the  cord. 


Each  entering  posterior  root  fibre, 
of  its  entrance,  gives  but  few  to 
higher  segments  of  the  cord  before 
it  terminates  in  the  posterior  column 
nuclei.  Sherrington  suggests  that 
the  cells  of  Clarke's  column  receive 
fibres  mainly  from  the  ascending 
branches  of  the  nerve  roots  from  the 
posterior  linib,  a  corresponding  sta- 
tion for  the  nerve  fibres  of  the  ante- 
rior limb  being  represented  by  the 
cells  of  the  nucleus  cuneatus. 

That  several  different  systems  of 
fibres  are  included  in  these  roots  is 
shown  by  the  different  periods  at 
which  they  acquire  their  myelin 
^sheath.  Among  the  earliest  to  ac- 
quire a  sheath  are  the  fibres  which 
end  in  the  posterior  horn  and  those 
which  pass  to  the  anterior  horn,  wliile 
the  long  fibres  in  the  dorsal  columns 
do  not  become  medullated  until  much 
later  in  foetal  life.  Since  the  nerve 
fibres  of  the  central  nervous  system 
do  not  become  functional  until  they 
have  acquired  a  medullary  sheath, 
we  must  conclude  that  the  reflex 
responses  affecting  the  segment  in 
which  the  fibres  enter  are  developed 
earlier  than  those  which  involve 
also  the  activity  of  the  cerebellum 
and  medulla. 


besides  these  collaterals  in  the  neighbourhood 


M«|V     gj 


Fig.    160.     Chief    collaterals   of    dorsal    column 
fibres  from  new-bom  mouse.     (Cajax.) 
a,    intermediate    nucleus ;    b,    anterior    (ven- 
tral)   cornu ;     c,    dorsal    or    posterior    cornu  ; 
c.  substance  of  Rolando. 


The  primitive  segmental  character  of  the  central  nervous  system  is 
retained  in  its  pure  form  only  in  the  segmentation  of  the  dorsal  spinal  root 
ganglia.  Each  of  these  ganglia  or  afferent  roots  consists  of  the  fibres  from 
the  sense-organs  in  a  segmental  area  of  the  body  surface  as  well  as  from 
the  muscular  and  visceral  apparatus  in  the  same  segment.  Section  of  one 
dorsal  posterior  nerve  root  will  cause  a  diminution  of  sensibility  over  a 
band-like  area  corresponding  to  the  distribution  of  the  fibres  of  the  root, 
though  to  produce  a  complete  insensibility  the  two  adjacent  nerve  roots  must 
be  divided,  in  consequence  of  the  overlap  of  fibres  at  the  periphery.  In  the 
limbs  the  segmental  distribution  of  the  sensory  fibres  is  distinguished  with 
more  difficulty.     Each  limb  must  be  regarded  as  made  up  from  a  series  of 


32  (i 


PHYSIOLOGY 


fused  segments,  from  five  to  seven  in  number.    The  accompanying  diagram 
(Fig.   162)  from  Sherrington  shows  the  manner  in  which  the  skin  fields  of 


FlO.  161.  Transverse  section  of  spinal  cord,  showing  collaterals  terminating  in  a 
rich  arborisation  round  the  cells  of  Clarke's  column  (a,  b),  as  well  as  others 
passing  to  the  anterior  cornua,  and  through  the  commissures.     (Cajal.) 

these  segments  are  combined  to  make  up  the  total  skin  area  in  the  hind  limb 
of  the  monkey. 


dorsal  or  uercO-oU  rneditfi   Uii£-  of  trunk' 


LetieL  jf  !Ae  omUUi 


THE  SPINAL  CORD  AS  A  REFLEX   CENTRE 


327 


THE  WAY  OUT 

Primitively  the  motor  nerves  also  represent  fibres  passing  from  a  col- 
lection of  ganglion-cells  to  the  muscles  of  the  corresponding  bod)'  segment. 
In  the  dorsal  region  this  segmental  arrangement  of  motor  nerve  fibres  is 
still  traceable  in  the  adult  anirr.al.  In  all  other  parts  the  morphological 
has  become  subservient  to  a  physiological  arrangement.  Every  muscle  of 
the  limbs  contains  elements  from  several  segments,  and  is  innervated  there- 
fore from  several  anterior  spinal  roots.  Hence  it  follows  that  stimulation 
of  one  anterior  root  produces  no  definite  movement  of  a  group  of  muscles, 
but  partial  contraction  of  a  number  of  muscles  which  do  not  normally  con- 
tract simultaneously.  Thus  stimulation  of  a  sensory  nerve  may  evoke 
either  flexion  or  extension  of  a  limb,  but  not  both  simultaneously.  Stimula- 
tion of  the  motor  roots  will  cause  simultaneous  contraction  of  both  flexor  and 
extensor  muscles.  It  is  this  subordination  of  morphological  to  physiological 
arrangement  in  the  limbs -which  has  necessitated  the  formation  of  limb 
plexuses.  The  nerve  root  is  a  mor- 
phological collection  of  fibres  ;  the 
nerve  issuing  from  a  limb  plexus 
and  passing  to  a  group  of  muscles  is 
a  physiological  collection.  When  it 
is  stimulated  it  evokes  a  contrac- 
tion of  a  group  of  muscles  which 
are  normally  synergic,  i.e.  co- 
operate in  various  movements 

The  fibres  passing  to  the  skeleta 
muscles  are  large,  about  14  ^  to  19  p 
in  diameter,  and  their  axis  cylinder; 
represent  the  axons  of  large  nerve 
cells  in  the  anterior  horn.  In  the 
dorsal  region  of  the  cord  in  man, 
from  the  second  dorsal  to  the  second 
lumbar  nerve  roots,  the  anterior 
loots  contain,  besides  these  coarse 
fibres,  a  number  of  fine  fibres  about  CIS  ^  to  3'6  ft  in  diameter  (Fig. 
163).  These  fine  fibres  were  shown  by  Gaskell  to  leave  the  nerve  shortly 
after  the  junction  of  the  two  roots,  to  pass  as  a  white  ram/us  communiccms 
to  the  sympathetic.  Excitation  of  the  white  rami  evokes  various  visceral 
effects,  such  as  dilatation  of  the  pupils,  augmentation  of  the  heart, 
contraction  of  blood-vessels,  inhibition  of  the  gut,  erection  of  hairs,  &c. 
Gaskell  pointed  out  that  the  outflow  of  these  fine  fibres  coincided  with 
the  existence  of  a  prominent  lateral  horn  in  the  grey  matter,  and  sug- 
gested that  cells  of  the  lateral  horn  might  be  regarded  as  the  origin  of  the 
visceral  nerve  fibres.  This  suggestion  has  been  confirmed  by  Anderson, 
who  has  shown  that  section  of  the  white  rami  communicantes  brings  about  an 
alteration  in  the  cells  of  the  lateral  horn  as  a  result  of  retrograde  degeneration. 


<5§S^ 


Fio.  163.  Section  across  the  second  thoracic 
ventral  nerve  root  of  the  dog  (stained  with 
osmic  acid)  to  show  varying  sizes  of  the  con- 
stituent fibres.     (Gaskell.) 


328 


PHYSIOLOGY 


CENTRAL  PATHS  OF  SPINAL  REFLEXES 

The  impulse  entering  the  cord  is  thus  able  to  affect  immediately  a  number 
of  systems  of  neurons,  namely,  cells  in  the  anterior  horn,  in  the  posterior 
horn,  in  Clarke's  column,  in  the  substantia  gelatinosa,  in  the  lateral  column  of 
the  same  side  of  the  cord,  and  the  corresponding  groups  of  cells  on  the  oppo- 
site side  of  the  cord  either  directly  by  crossing  collaterals  or  indirectly  through 


III  -T 


ILL 


V.S. 


Fig.  164.  Cross-sections  of  spinal  cord  of  a  dog,  showing  the  descending  nerve- 
tracts  originating  in  the  first  three  thoracic  segments  (method  of  '  successive 
degeneration').  The  eighth  cervical  segment  had  been  excised  and  568  days 
later  a  cross-cut  was  made  at  level  of  the  tliird  thoracic  nerve.  The  extent  of  the 
lesion  is  shown  in  the  first  figure  (III.  T).  The  other  sections  show  the  degenera- 
tions as  revealed  tliree  weeks  later  by  Marchi's  method.     (Sherrington.) 

cells  which  send  their  axons  across  the  middle  line.  Through  the  ascending 
and  descending  fibres  of  the  posterior  columns  it  can  also  set  into  action  the 
reflex  mechanisms  of  adjacent  segments  of  the  cord.  In  addition  to  this 
direct  spread  of  afferent  impulses  up  and  down  the  cord  there  is  an  anatomical 
basis  for  a  co-ordination  between  the  grey  matter  of  different  levels.  This 
co-ordination  is  effected  through  the  intermediation  of  the  internuncial  or 
intra-spinal  fibres  which  pass  up  and  down  the  cord  from  segment  to  segment. 

The  course  of  the  descending  fibres  may  be  studied  by  carrying  out  a  total  tran- 
section of  the  spinal  cord  at  the  sixth  cervical  vertebra,  and  six  months  later,  when  all 
the  fibres  degenerating  as  a  result  of  the  section  have  disappeared,  carrying  out  a  further 
transection  or  hemisection  a  few  segments  below  the  first  transection.  If  the  animal 
be  killed  two  or  three  weeks  after  the  second  operation  it  will  be  found  that  a  number 
of  fibres  in  the  white  matter  are  degenerated  below  the  second  section  (Fig.  164).  These 
fibres  therefore  must  be  derived  from  cells  of  the  grey  matter  situated  between  the 
levels  of  the  first  and  second  sections,  and  the}-  can  be  traced  down  the  cord  through  a 


THE  SPINAL  CORD  AS  A  REFLEX  CENTRE  '  329 

large  number  of  segments.     Analogous  methods  may  be  used  for  tracing  the  course  of 
the   ascending  intra-spinal   fibres. 

These  intra-spinal  fibres  occur  in  the  following  situations  : 

(1)  In  the  lateral  columns  immediately  outside  the  grey  matter,  in  the  bay  between 
the  anterior  and  posterior  horns. 

(2)  Close  to  the  grey  matter  in  the  anterior  basis  bundle. 

(3)  In  the  posterior  columns,  united  with  the  descending  branches  of  the  entering 
posterior  roots  in  the  comma  tract,  and  also  in  the  immediate  periphery  of  the  cord  and 
abutting  on  the  posterior  fissure  in  the  septomarginal  tract. 

(4)  Mingled  with  the  fibres  of  the  pyramidal  tract. 

All  these  tracts  are  mixed,  i.e.  contain  both  ascending  and  descending  fibres.  As  a 
rule,  the  longer  the  course  of  a  fibre  the  more  peripherally  does  it  lie  in  the  cord.  The 
shortest  of  the  fibres  may  only  unite  segment  to  segment,  while  the  longest  fibres  may 
run  through  the  greater  part  of  the  cord. 

THE  SPINAL  ANIMAL 
An  animal  possessing  only  a  spinal  cord  contains  a  reflex  neural  apparatus 
which  can  be  excited  to  activity  by  impulses  of  various  qualities  and  from  any 
part  of  the  skin.  Thus  the  afferent  impulse  may  correspond  to  what  in 
ourselves  we  call  tactile  and  be  provoked  by  mechanical  stimulation,  or  may 
result  from  changes  of  temperature  and  correspond  to  those  producing 
sensations  of  heat  and  cold.  Strong  stimuli  of  any  kind  may  give  rise  also  to 
afferent  impulses  which  in  the  intact  animal  would  have  the  quality  of  pain. 
Since  these  stimidi  are  such  as  to  produce  injury  if  continued,  they  may  be 
named,  when  applied  to  the  spinal  animal,  pathic  or  nocuous.  The  spatial 
distribution  of  the  stimulus  will  determine  the  situation  and  number  of  nerve 
fibres  set  into  action,  so  that  there  will  be  a  great  variation  in  the  distribution 
of  the  excited  neurons  of  the  central  grey  matter  according  to  the  quality, 
distribution,  and  intensity  of  the  stimulus.  The  efferent  part  of  the  reflex 
is  provided  for  by  the  connection  of  the  anterior  cornual  cells  to  the  whole 
skeletal  musculature  of  the  body,  as  well  as  by  the  distribution  of  the  axons 
of  the  lateral  horn-cells  to  the  sympathetic  system  and  through  this  to. the 
viscera.  On  the  other  hand,  if  the  spinal  cord  be  separated  from  the  medulla 
oblongata  and  higher  parts  of  the  brain,  it  is  deprived  of  all  connection  with 
the  most  highly  elaborated  sense-organs  of  smell,  sight,  hearing,  and  equili- 
bration, and  also  of  the  important  afferent  and  efferent  impulses  which  pass 
between  brain  and  viscera  through  the  vagus  nerves.  In  studying  the 
reaction  of  the  isolated  spinal  cord  we  are  studying  a  nervous  system  cut  off 
from  its  most  complex  components,  but  at  the  same  tune  deprived  of  the 
initiation  and  guidance  which  it  must  normally  be  continually  receiving  from 
the  higher  sense-organs  through  the  brain.  A  study  of  the  spinal  animal 
will  therefore  be  instructive  as  a  study  of  the  mammalian  nervous  system  in 
its  simplest  possible  aspect.  It  will  in  all  cases  be  the  study  of  an  incom- 
plete and  maimed  system,  the  incompleteness  becoming  more  evident 
as  we  ascend  the  scale  of  animals  in  our  experimentation,  owing  to  the 
increasing  subordination  of  the  lower  to  the  higher  centres,  and  of  the 
immediate  reflexes  to  the  educated  reactions  of  the  anterior  part  of  the 
brain. 


330  PHYSIOLOGY 


SPINAL  SHOCK 


If  the  spinal  cord  of  the  frog  be  divided  just  below  the  medulla,  for  some 
minutes  after  the  section  all  four  limbs  are  perfectly  flaccid,  and  it  is  impos- 
sible to  evoke  any  reaction  by  the  application  of  the  strongest  stimuli. 
If  the  animal  be  left  to  itself  for  half  an  hour  there  is  a  gradual  return  of 
reflex  tone  ;  the  animal  draws  up  its  legs  and  assumes  a  position  not  far 
removed  from  that  of  the  normal  frog,  the  head  being  lower  than  under 
normal  conditions.  We  may  say  that  the  phenomena  of  shock  in  the  frog 
last  only  a  short  time.  With  increasing  complexity  of  the  nervous  system 
the  phenomena  of  shock  become  more  lasting,  so  that  among  laboratory 
animals  it  is  in  the  monkey  that  spinal  shock  is  most  apparent.  It  is  in- 
teresting to  note,  as  pointed  out  by  Sherrington,  that  shock  appears  to  take 
effect  only  in  the  aboral  direction.  Thus,  even  in  the  monkey,  section 
through  the  lower  cervical  region,  though  causing  profound  paralysis  of  the 
lower  limbs  and  part  of  the  trunk,  apparently  has  no  influence  at  all  on 
the  reactions  of  the  nervous  system  above  the  section.  '  The  animal  imme- 
diately after  the  section  will  contentedly  direct  its  gaze  to  sights  seen  through 
the  window  or,  if  the  section  has  been  below  the  brachial  region,  may 
amuse  itself  by  catching  flies  on  the  pane.  This  is  the  more  remarkable  since 
the  profound  depression  of  the  nerve-centres  below  the  point  of  section 
extends  also  to  the  blood-vessels  and  viscera,  so  that  there  is  a  great  fall  of 
blood  pressure  and  diminished  production  with  increased  loss  of  heat.  The 
sphincters  are  flaccid  or  patulous,  the  skeletal  muscles  are  toneless,  and  no 
reaction  is  evoked  by  the  strongest  stimulus  to  the  skin  or  to  a  sensory 
nerve.' 

Much  discussion  has  arisen  as  to  the  duration  of  shock.  Goltz  and  others 
Imagined  that  the  phenomena  of  shock  may  persist  for  months  or  even  years. 
According  to  Sherrington,  in  the  higher  animals  the  phenomena  of  shock  are 
complicated  by  the  onset  of  an  '  isolation  dystrophy  '  which  may  occur 
before  the  condition  of  shock  has  entirely  disappeared.  In  order  therefore  to 
examine  the  capabilities  of  the  isolated  spinal  cord  at  their  best,  a  time  must 
be  chosenrwhen  the  sum  of  shock  and  isolation  dystrophy  together  is  at  its 
minimum. 

The  occurrence  of  shock  after  complete  transection  of  the  cord  in  the 
cervical  region  cannot  be  ascribed  to  the  fall  of  blood  pressure  which  ensues 
as  a  result  of  the  severance  of  the  efferent  vaso-motor  tracts  from  the 
vaso-motor  centre  in  the  medulla.  The  centres  above  as  well  as  those  below 
the  transection  are  equally  exposed  to  the  effects  of  the  lowered  blood  pres- 
sure, but  it  is  oidy  those  below  the  section  which  show  signs  of  shock.  Nor 
can  it  be  regarded  as  operative  shock  due  to  the  severity  of  the  lesion  ;  such 
an  operative  shock  would  be  effective  in  either  direction,  and  we  do  not 
find  that  the  method  of  transection,  whether  by  tearing  across  the  cord  or 
cutting  it  with  a  minimum  disturbance,  alters  appreciably  the  amount  of 
shock  displayed  by  the  segment  of  the  cord  situated  below  the  lesion.  On 
the  other  hand,  if  in  a  dog,  which  has  undergone  transection  of  the  cord  in  the 


THE  SPINAL  CORD  AS  A  REFLEX  CENTRE  331 

lower  cervical  region  and  has  been  allowed  sufficient  time  to  recover  from  the 
shock,  a  second  transection  be  carried  out  two  or  three  segments  below  the 
site  of  the  first  operation,  the  influence  of  the  second  section  is  hardly  notice- 
able on  the  lower  segment  of  the  cord.  Apparently  then  the  chief  factor  in 
determining  shock  in  all  those  centres  situated  aborally  of  the  lesion  is  the 
cutting  off  of  the  impulses  which  are  continually  streaming  down  from  the 
higher  centres  and  from  the  great  sense-organs  connected  with  the  anterior 
portions  of  the  nervous  system.  With  every  rise  in  the  animal  scale  the  im- 
pressions received  by  the  special  senses  take  an  increasing  part  in  the  deter- 
mining of  all  the  reactions  of  the  body,  so  that  we  might  expect  the  effect  of 
cutting  off  the  impulses  from  the  higher  centres  to  be  greater,  the  higher  in  the 
scale  of  life  is  the  animal  on  which  the  experiment  is  carried  out. 

The  state  of  profound  shock  produced  in  the  spinal  cord  by  the  operation 
passes  off  gradually.  The  blood  pressure,  which  may  have  fallen  to  40  or 
50  mm.  Hg.,  rises  within  two  or  three  days  to  its  normal  height,  i.e.  80  to 
I  1(1  mm.  Hg.  The  sphincter  muscles  of  the  anus  gradually  recover  their 
tone,  and  within  a  short  time  the  reflex  evacuation  of  the  bladder  and  rectum 
may  occur  as  in  a  normal  animal.  The  skeletal  muscles  recover  their  tone 
within  a  few  days,  and  after  a  short  time  co-ordinated  movements  can  be 
brought  about  in  the  trunk  and  limbs  by  appropriate  stimulation  of  sensory 
surfaces.  At  first  the  reactions  thus  produced  are  feeble  and  the  reflex  is 
rapidly  fatigued.  Of  these  reflexes  those  excited  by  nocuous  or  painful 
stimuli  are  the  first  to  make  their  appearance  ;  a  little  later  are  seen  those 
due  to  stimuli  affecting  the  tactile  organs  in  the  skin,  or  the  sense-organs  of 
deep  sensibility  situated  round  the  bones  and  joints  and  excited  by  deep 
pressure  or  changes  in  posture  of  the  limbs. 

In  a  dog  which  has  undergone  complete  cervical  transection  two  or  three 
months  previously,  the  tone  of  the  muscles  is  somewhat  increased.  Although 
the  dog  is  unable  to  walk,  if  it  be  raised  and  given  a  little  push  forward,  so 
as  to  stretch  the  extensor  muscles  of  its  hind  limbs,  it  may  take  two  or  three 
steps  forward  before  its  legs  collapse.  Although  the  locomotor  apparatus 
is  present,  the  nexus  is  lacking  which  determines  the  regulation  of  these  move- 
ments through  the  organs  of  static  sense,  so  that  the  spinal  movements  are 
insufficient  to  maintain  the  animal  in  such  a  position  that  a  line  drawn  verti- 
cally from  its  centre  of  gravity  shall  fall  between  its  points  of  support.  On 
the  other  hand,  swimming  movements  may  be  carried  out  regularly.  The 
frog  deprived  of  its  brain  can  swim  like  a  normal  animal,  but  in  consequence 
of  the  depression  of  its  head  tends  to  swim  ever  deeper  in  the  water.  If  a 
'  spinal '  dog  be  held  up  by  the  fore  lhnbs,  the  hind  limbs  nearly  always  enter 
into  alternating  movements  of  flexion  and  extension  ('  mark  time  '  move- 
ments), the  two  limbs  acting  alternately  as  in  normal  progression.  The 
stimuli  in  this  case  seem  to  be  started  by  the  stretching  of  the  skin  and  other 
structures  at  the  front  of  the  thighs.  In  such  animals  three  reflexes, 
amongst  others,  can  be  excited  almost  invariably,  viz.  : 

(1)  Scratch  reflex.  Gentle  stimulation,  mechanical  or  electrical,  of  any 
point  over  a  saddle-shaped  area  on   the  dorsum  behind  the  shoulders  (Fig. 


332 


PHYSIOLOGY 


THE   SIMPLE    REFLEX 


105)  causes  rhythmic  movements  of  flexion  and  extension  of  the  hind  limb  of 
the  same  side,  the  effect  of  which  would  be  to  scratch  away  the  irritant 
object.  These  movements  are  repeated  at  the  rate  of  about  four  per  second. 
(2)  Flexor  reflex.  Nocuous  stimuli,  such  as  the  prick  of  a  needle  applied 
to  any  part  of  the  foot,  causes  flexion  of  the  leg  and  thigh,  often  accompanied 

by  extension   of   the  op- 
posite hind  limb. 

(3)  Extensor  or  '  stej>- 
ping  '  reflex.  Gentle  pres- 
sure applied  to  the  plan- 
tar surface  of  the  hind 
foot,  especially  if  the 
limb  is  somewhat  flexed, 
causes  a  movement  of 
extension  of  the  limb, 
accompanied  sometimes 
by  a  flexion  of  the  oppo- 
site hind  limb. 

In  such  an  animal  the 
carrying  out  of  the  vis- 
ceral reflexes  may  be  very 
efficient.  The  blood  pres- 
sure has  attained  its 
normal  height  and  may 
be  altered  reflexly  in  very 
much  the  same  way  as  in 
Fig.  165.  A.  The  receptive  field,  whence  the  scratch  a  normal  animal,  although 
reflex  of  the  left  hind  limb  can  be  evoked.  , ,  ,    i, 

_   _.  .    ,  ,     ,  „  the  medullary  vaso-motor 

B.  Diagram   of  spinal  arcs  involved.     L,  afferent  path 
from  left  foot ;    B.  afferent  path  from  right  foot ;    bo,   b/3,    centre    Can   no    longer    be 
receptive  paths  from  hairs  on  '  scratch  area ' ;    fc,  final   concerned        Thus   in  the 
common  path  (motor  neuron) ;   pa,  pS,  proprio-spinal  neu-    ..  "  .        ,  ,»„.    • 

rons.    (Sherrington.)  diagram  (Fig.   Ib6)  is  re- 

presented the  effect  on  the 
blood  pressure  of  exciting  the  central  end  of  the  digital  nerve  in  a  spinal 
dog.  The  pressure  rises  from  90  to  208-  mm.  Hg. — a  pressor  effect  as 
great  as  any  which  can  be  obtained  in  an  animal  still  possessing  all  the  con- 
nections of  the  vascular  system  with  the  vaso-motor  centre.  The  height 
of  the  rise  shows  that  as  regards  the  influence  on  the  blood  pressure  the 
spinal  cord  must  be  acting  as  a  whole.  No  effect  on  the  blood-vessels  confined 
to  the  segment,  or  segments,  adjacent  to  that  of  the  nerve  stimulated  would 
suffice  to  cause  a  rise  of  more  than  a  few  mm.  Hg. 

The  reflex  apparatus  for  other  visceral  functions  seems  to  be  equally 
perfect.  The  urinary  bladder,  when  sufficient  urine  'is  accumulated,  con-' 
tracts  forcibly,  the  contraction  being  accompanied  by  relaxation  of  the 
sphincter  and  followed  by  rhythmic  contractions  of  the  urethral  muscles ; 
accumulation  of  faeces  in  the  rectum  leads  to  their  normal  evacuation.  With 
a  little  assistance  impregnation  may  be  effected  in  or  by  such  a  maimed 


THE  SPINAL  COED  AS  A  EEFLEX  CENTEE  333 

animal,  and  in  the  female  may  result  in  normal  parturition  which  goes  on  to 
full  term.  Pregnane}-  is  accompanied  by  hypertrophy  of  the  mammary 
glands  and  is  followed  by  secretion  of  milk,  so  that  the  young  may  be  suckled 


Fig.   166.     Blood  pressure  tracing  from  a  spinal  dog.    The  signal  indicates  the 
time  during  which  the  afferent  nerve  was  stimulated.     (Sherrington.) 

as  in  a  normal  animal.    Similar  phenomena  have  been  observed  in  the  human 
subject. 

Such  an  animal  furnishes  us  with  an  opportunity  of  analysing  the  factors 
which  are  involved  in  the  maintenance  of  muscle  tone,  as  well  as  in  the  carry- 
ing out  of  the  simplest  reflexes  involving  contractions  of  the  skeletal  muscles. 

MUSCULAR  TONE 

Every  muscle  in  the  body  is  in  a  condition  of  slightly  continued  contrac- 
tion which  keeps  it  tense,  so  that  when  it  contracts  in  response  to  a  stimulus 
there  is,  so  to  speak,  no  '  slack  '  to  be  taken  up  before  the  muscle  begins  to 
pull  on  its  attachments.  This  tone  is  seen  in  the  retraction  undergone  by 
muscles  or  tendons  when  they  are  divided  in  the  living  animal. 

If  a  frog  possessing  only  spinal  cord  be  hung  up  by  its  jaw,  the  limbs  will 
be  observed  to  occupy  a  position  which  is  short  of  complete  extension.  The 
tone  of  the  muscles  which  is  concerned  in  the  maintenance  of  this  attitude  is 
at  once  abolished  by  the  destruction  of  the  spinal  cord.  It  may  be  abolished 
on  one  side  by  section  either  of  the  anterior  roots  going  to  the  muscles,  or  of 
the  posterior  roots  coming  from  the  muscles  (Fig.  167).  In  the  intact 
animal  muscle  tone  is  diminished  by  disease  and  may  be  abolished  during 
profound  anaesthesia,  as  it  is  indeed  in  the  condition  of  shock. 

Much  light  has  been  thrown  on  the  factors  which  determine  muscular 
tone  by  a  study  of  the  '  tendon  phenomena  '  of  which  the  knee-jerk  is  the 
most  familiar  example.  If  the  leg  is  allowed  to  hang  loosely  in  a  position 
of  slight  flexion  at  hip  and  knee  and  the  patellar  tendon  be  struck,  the 
extensor  muscles  of  the  thigh  contract  and  raise  the  leg.  This  phenomenon 
is  known  as  the  knee-jerk.     Similar  '  tendon  reflexes  '  can  be  obtained  in 


334 


I'llYSloLOCY 


other  muscles,  such  as  the  fcendo  Achillis,  the  triceps,  and  the  extensor 
muscles  of  the  wrist,  but  with  not  so  great  ease  as  is  the  rase  with  the  knee. 
The  knee-jerk  is  not  altered  by  rendering  the  tendon  anaesthetic  by  section 
of  all  its  nerves.      The  essential  feature  is  a  slight  passive  increase  of  the 
tension  to  which  the  muscle   is  already  subjected.      Mere  tension  of  the 
muscle    is  not   however  the  only   factor.       The    tone    which    is    reflexly 
maintained  in  the  muscle  is  necessary  for  this  response  to  direct  stimulation 
In  take  place.     The  knee-jerk  is  therefore  of  special  im- 
portance as  an   index  to  the    tonic    condition  of    the 
muscles  concerned,  being  brisk  and  easily  elicited  when  ~ 
1  j         the  tonus  is  pronounced,  and  slight  or  absent  when  the 

\  j    y         tone  ill  the  muscle  is  depressed. 

The  tone  of  the  muscles,  as  well  as  the  consequent 
tendon  phenomena,  is  dependent  on  the  integrity  of 
the  reflex  arc  governing  the  muscles  in  question.  It 
has  been  shown  by  Sherrington  that  the  afferent  part 
of  the  arc  is  represented  by  the  afferent  nerves  from  the 
muscle  itself,  and  that  these  nerves  receive  their  sense 
impressions  from  the  special  nerve-endings  characteristic 
of  muscle — the  '  muscle-spindles."  Even  in  the  purely 
i Muscular  nerves  a  large  proportion  of  the  fibres  are 
afferent  in  function  and,  after  section  of  the  appro- 
priate posterior  roots  distal  to  the  ganglia,  as  many  as 
10  per  cent,  of  the  fibres  going  to  a  muscle  may  be 
found  degenerated.  Though  most  of  these  have  the 
muscle-spindles  as  their  destination,  a  certain  number 
pass  to  the  tendon  and  aponeuroses  connected  with  the 
muscle,  where  they  end  in  the  end-organs  known  as  the 
organs  of  Golgi  and  the  organs  of  Ruffini.  After  sec- 
tion of  the  motor  nerves  the  muscle  fibres  degenerate, 
Fig.  L67.  Hind  part,  wJth  the  exception  of  the  modified  fibres  which,  enclosed 
hung  upma|iy  The  in  a  connected  tissue  sheath,  are  concerned  in  the  forma- 
jaw.    The  posterior  f[on  0f  the  muscle-spindles.     Muscle  tone  and   tendon 

roots  of  the  nerves       ,  ,,         r  ,  ,     ,.  ,      ,   ,        ,     •  ,■ 

to    the    left    hind  phenomena   may  therefore    be    abolished  by  lesions  ot 
limb     have     been  afferent   nerves,    which   leave    a   considerable   part    of 
(Bechterew.)      the  cutaneous  sensibility  of  the  limb   intact.     In   man 
the  spinal  reflex  mechanism  connected  with  the  knee- 
jerk  is  situated  in  the  third  and  fourth  lumbar  segments.     The  jerk  may  be 
abolished  by  section  of  the  third  and  fourth  posterior  nerve-roots,  although 
tu  render  the  whole  hind  limb  anaesthetic  it  would  be  necessary  to  divide  all 
the  roots  from  the  second  lumbar  to  the  fourth  sacral  inclusive. 

The  extremely  short  period  which  elapses  between  the  moment  of  striking 
the  tendon  and  the  contraction  of  the  muscle,  which  was  found  by  Gotch 
to  be  only  about  "005  second,  has  been  thought  to  prove  that  the  tendon 
reflex  must  be  due  to  direct  stimulation  of  the  muscle  and  could  not  be 
of  the  nature  of  a  true  reflex.     It  was  therefore  suggested  that  the  func- 


THE  SPINAL  CORD   AS  A  REFLEX  CENTRE  335 

tic  hi  of  the  reflex  arc  was  to  keep  the  muscle  in  a  state  of  wakefulness, 
ready  to  respond  to  the  slightest  local  stimulation..  No  one  has  however 
succeeded  in  imitating,  by  a  slight  continuous  stimulation  of  the  motor 
nerve  or  otherwise,  this  reputed  action  of  the  reflex  arc,  and  recent  re- 
searches by  Snyder  and  by  Jolly  indicate  that,  in  spite  of  the  rapidity  of 
the  response,  the  knee-jerk  may  nevertheless  ho  a  true  reflex  action,  and 
in  fact  the  most  rapid  reflex  known. 

Jolly,  using  the  string  galvanometer,  has  taken  the  current  of  action  in  the  vastus 
interims  muscle  as  an  index  of  the  commencing  contraction  of  this  muscle  in  the  knee- 
jerk.  He  has  also  by  the  same  method,  by  leading  off  the  afferent  and  efferent  nerves 
respectively,  measured  the  lost  time  in  the  sense-organs  and  in  the  motor  end-plates 
of  flic  muscle.  In  the  spinal  cord  lie  obtained  the  following  electrical  latencies  in  one 
case  : 

Latency  of  knee-jerk      .....  5-3<r  * 

Afferent  endings     .....         0-4<r 
Nerve  conduction  .  .  .  .  .  1-4 

Motor  endings  and  action  current  .  .  1-8 

Synapse  time        ....  2-2cr 

In  this  case  the  shortest  latency  determined  fur  nerve-endings  has  been  deducted 
from  the  shortest  latent  period  obtained  from  the  knee-jerk  in  the  spinal  cat.  On 
the  other  hand,  some  decapitated  preparations  have  been  found  to  present  considerably 
longer  latent  periods,  e.g.  11  and  12ir.  This  variation  in  the  latent  period  supports 
the  view  that  the  knee-jerk  is  a  reflex  of  which  the  synapse  time  is  very  short,  about  2<r, 
and  that  in  certain  cases  there  may  be  increased  delay  in  the  spinal  cord.  When  the 
latencies  of  the  knee-jerk  and  the  homonymous  flexor  reflex  are  compared  by  the 
electrical  method,  it  is  found  that  the  latter  is  roughly  double  the  former,  the  average 
latency  of  the  knee-jerk  in  the  spinal  cat  being  6-0ir,  and  of  the  homonymous  flexor 
reflex  13  2. r.  Jolly  suggests  that  this  difference  may  be  due  to  the  fact  that  the  knee- 
jerk  mechanism  involves  only  one  spinal  synapse  or  set  of  synapses,  while  the  flexor 
reflex  may  involve  two.  In  these  estimates  the  rati'  of  conduction  in  mammalian  nerve 
has  been   taken  at  120  metres  per  second. 

Especially  interesting  is  the  relation  shown  by  Sherrington  to  exist 
hetween  the  tonic  condition  of  antagonistic  muscles,  e.g.  between  the  ham- 
strings and  the  vastus  internus  of  the  quadriceps  extensor  muscle.  Section 
of  the  hamstring  muscles  (so  as  to  relax  them)  or  even  section  of  their  nerve 
causes  at  once  great  increase  in  the  jerk  elicited  by  tapping  the  patellar 
tendon.  On  the  other  hand,  the  knee-jerk  is  abolished  by  stretching  the  ham- 
string muscles,  or  by  weak  stimulation  of  the  central  end  of  the  cut  nerve  to 
the  hamstrings  (Fig.   168). 

In  this  way  a  voluntary  flexion  of  the  knee  by  contraction  of  the  ham- 
strings automatically  abolishes  the  resistance  which  would  be  offered  by 
the  tonic  contraction  of  the  extensor  muscles.  In  the  absence  of  such  an 
arrangement  every  movement  of  a  joint,  by  stretching  the  antagonistic 
muscles,  would  automatically  increase  their  tone,  and  thus  set  up  a  resistance 
to  itself.  The  subject  would  thus  be  muscle-bound. 
*  ,r  =  -001  sec. 


336 


PHYSIOLOGY 


Very  great  exaggeration  of  the  tendon  phenomenon  is  observed  in  eases  where  the 
pyramidal  tracts  are  degenerated,  and  indicates  a  heightened  reflex  excitability  of  the 
lower  spinal  centres,  perhaps  reinforced  by  impulses  from  the  cerebellum.  The  impor- 
tance of  the  latter  impulses  in  determining  the  myotatic  irritability  of  the" muscles  is 
especially  marked  in  man,  where  total  transverse  lesion  of  the  upper  part  of  the  spinal  cord 
often  abolishes  permanently  the  time  of  the  mnseles  innervated  from  the  lower  portion 
of  the  cord,  and  especially  the  knee-jerk.  Jtew  far  this  absence  of  tone  is  due  to  col- 
lateral changes  in  the  cord  has  nut 
yet  I neii  determined.  In  animals 
complete  transverse  seotion  of  the 
cord  of  the  cervical  region  is  followed 
by  increase  of  the  knee-jerk,  which 
in  the  rabbit  may  lie  elicited  within 
a  quarter  of ,  an  hour  after  the  Bection 
has  been  carried  out.  In  the  increased 
myotatic  irritability  observed  after 
removal  of  the  cerebral  cortex,  or 
after  degeneration  of  the  pyramidal 
tracts  coming  from  the  motor  cortex, 
a  single  tap  on  the  patellar  tendon 
may  evoke  a  series  of  contractions  of 
the  extensor  muscles  of  the  thigh, 
giving  rise  to  what  is  known  as  knee 
clonus.  In  the  same  way  forcible 
flexion  of  the  ankle  causes  a  series  of 
rhythmic  contractions  of  the  calf 
muscles  (ankle  clonus),  varying  in 
Fig.  168.  Diagram  to  show  muscles  and  nerves  rhythni  from  six  to  ten  per  second, 
concerned    in    Sherrington's    experiment  on  the       ^    heightened  tone   0f   the  muscles 

rppinrnca.l  innprvflTinn    nt   nntacrnnisrie    muscles  ° 

under  these  conditions,  and  the  ease 
with  which  any  slight  increase  in 
their  tension  gives  rise  to  clonic 
contractions,  cause  such  patients  to  have  a  peculiar  dancing  gait,  characteristic  of 
pyramidal  degeneration  and  known  as  the  '  spastic '  gait ;  it  is  generally  associated 
with  a  certain  loss  of  voluntary  control  of  the  movements  of  the  limbs,  so  that  the 
whole  complex  of  symptoms  is  called  '  spastic  paraplegia.' 

The  value  of  the  tendon  phenomena  as  a  means  of  diagnosis  has  tended 
to  obscure  their  great  importance  in  the  normal  individual.  Every  joint 
is  protected  by  inextensible  ligaments  and  by  muscles.  A  sudden  strain  on  a 
ligament  either  will  have  no  effect,  or  will  ruptu're  some  of  its  fibres  and  per- 
haps injure  the  adjacent  joint  surfaces.  An  ordinary  reflex  contraction 
would  be  powerless  to  prevent  this,  since  the  mischief  would  be  done  before 
the  reaction  could  take  place.  But  by  means  of  the  enormously  rapid 
mechanism  of  the  '  tendon  reflex  '  the  muscles  are  able  to  react  to  any 
sudden  increase  in  their  tension  by  an  equally  sudden  contraction,  which 
saves  the  joint  before  the  individual  has  even  become  aware  of  the  strain. 


reciprocalinnervation  of  antagonistic  muscles 
l3,  l4,  l5,  third,  fourth,  and  fifth  lumbar  roots 
si,  s2,  first  anil  second  sacral  roots. 


THE  SPINAL  MAN 

During  the  last  few  years  opportunity  has  been  given  for  the  study  in  man  of 
the  effects  of  complete  isolation  of  the  spinal  cord.  The  results  differ  from  those 
observed  in  the  monkey,  much  in  the  same  way  as  these  differ  from  those  in  the  dog 
or  cat. 


THE  SPINAL  CORD   AS   A   REFLEX   CENTRE  337 

The  results  may  be  briefly  summarised  as  follows  : — 

1.  The  period  of  shook  lasts  from  one  to  three  weeks;  during  this  time,  in  addi- 
tion to  the  complete  abolition  of  voluntary  movement  and  sensation  in  the  parts 
below  the  lesion,  the  muscles  are  flaccid  and  toneless,  and  all  reflexes  are  absent, 
except  those  affecting  the  sphincters  of  the  bladder  and  rectum.  These  are  found 
strongly  contracted  as  early  as  the  third  day  after  the  injury.  There  is  in  consequence 
retention  of  urine  and  fasces  ;  the  former,  if  not  relieved,  gives  rise  to  distension  of 
the  bladder  and  a  dribbling  incontinence  due  to  overflow. 

2.  As  the  shock  passes  away,  certain  reflex  functions  of  tin-  cord  return.  The  first 
reflex  which  appears  is  the  ordinary  flexor  reflex  ensuing  on  painful  stimulation  of  the  sole 
of  the  foot.  At  its  earliest  appearance  the  first  effect  is  adduction  and  flexion  of  the 
toes:  but.  with  increased  recovery  of  excitability,  such  a  stimulus  gives  rise  to  a 
flexor  reflex  consisting  of  flexion  at  the  hip,  adduction  of  the  thigh,  flexion  of  the  knee 
and  the  ankle,  and  extension  of  the  toes. 

In  some  cases  this  flexor  reflex  affects  also  the  opposite  limb,  but  there  is  little  or 
no  trace  of  the  crossed  *xtensor  reflex  observed  in  the  spinal  dog.  Later  on  there 
is  some  return  of  reflexes  also  in  the  extensor  muscles,  specially  marked  as  regards  the 
deep  reflexes,  so  that  the  knee-jerk  may  be  obtained. 

The  visceral  reflexes  return  shortly  after  the  flexor  reflex  has  made  its  appearance. 
Thus,  if  the  bladder  has  been  kept  from  over-distension,  it  begins  to  void  itself  naturally 
at  a  certain  degree  of  distension,  varying  from  300  to  500  c.c.  In  this  act  of  micturition, 
the  contraction  of  the  detrusor  is  associated  with  relaxation  of  the  sphincter,  so  that  the 
emptying  of  the  bladder  is  complete.  In  the  same  way  the  rectum  may  empty 
itx  II  when  its  distension  attains  a  certain  degree,  and  defscation  can  always  be  elicited 
bv  the  injection  of  8  ozs.  of  fluid  into  the  rectum. 

Stimulation  of  the  neighbourhood  of  the  genitals,  but  especially  of  the  glans  penis, 
causes  erection,  which  may  be  followed  by  emission  of  semen.  This  reflex  of  coitus  is 
generally  associated  with  strong  movement  of  flexion  of  the  lower  limbs  and  contraction 
of  the  rectus  muscles  of  the  abdomen. 

The  main  points  in  which  the  spinal  man  differs  from  the  spinal  dog  are  in  the  dimin- 
ished localisation  of  response  and  in  the  almost  complete  suppression  of  the  extensor 
reflexes.  On  account  of  the  absence  of  local  sign,  almost  any  stimulus,  if  sufficiently 
intense,  tends  to  evoke  what  has  been  termed  a  '  mass  reflex.'  in  which  there  is  flexion 
of  both  Legs,  and  contraction  of  the  abdominal  muscles  as  well  as  of  the  bladder  and 
rectum,  and  frequently  profuse  sweating  over  all  parts  of  the  body  betow  the  injury. 

The  diminution  of  the  extensor  reflex  as  compared  with  the  spinal  dog  points  to  the 
gradual  shifting  of  the  postural  reflexes  towards  the  upper  part  of  the  central  nervous 
system  which  accompanies  the  rise  in  the  complexity  of  this  system. 

It  should  be  noted  thai  these  reflex  activities  of  the  cord  in  man  arc  only  seen  in 
their  full  development  provided  that  means  are  taken  to  ward  off  septic  disorder,  either 
from  bed-sores  or  infection  of  the  urinary  passages.  Without  extreme  care  general 
infection  is  apt  to  occur  by  one  or  other  of  these  channels,  and  then  the  separated  spinal 
cord  very  rapidly  loses  the  whole  of  its  reflex  powers. 


22 


SECTION  VIII 

THE    MECHANISM   OF   CO-ORDINATED 
MOVEMENTS 

The  detailed  study  of  the  chief  reflexes  obtainable  from  a  spinal  animal  has, 
in  Sherrington's  hands,  yielded  much  information  as  to  the  linking  of  the 
various  events  which  are  concerned  in  the  carrying  out  of  every  co-ordinated 
movement,  and  as  to  the  conditions  which  determine  the  sequence  and 
extent  of  the  activities  involved. 

We  may  take,  as  the  type  of  such  a  reflex,  the  flexion  of  the  leg  and 
thigh  which  ensues  on  the  application  of  a  painful  stimulus  to  the  ball 
of  the  foot,  such  as  pricking  with  a  needle  or  the  application  of  the  faradic 
current.  Of  course,  in  the  spinal  animal  no  pain  can  result  from  stimulation 
of  any  part  below  the  level  of  section  of  the  cord,  and  it  is  better  therefore 
under  such  circumstances  to  speak  of  nocuous  or  pathic  stimuli,  since  all 
stimuli  which  cause  pain  are  such  that,  if  their  operation  continued,  they 
would  result  in  damage  to  the  material  structure  of  the  animal.  This  flexor 
reflex  is  also  easily  obtainable  in  the  frog  as  a  result  of  stimulating  one  of  its 
toes  by  mechanical  or  chemical  stimuli,  but  it  is  easier  to  analyse  the  different 
events  involved  in  the  reaction  in  the  case  of  the  larger  animal. 

The  effect  varies  with  the  strength  of  the  stimulus.  The  minimal  effec- 
tive stimulus  causes  simply  movement  of  the  foot.  As  its  strength  is  in- 
creased this  movement  is  attended  by  flexion  of  the  leg  on  the  thigh,  and 
finally  by  flexion  of  the  thigh  on  the  body.  With  still  further  increase  there  is 
a  spread  to  the  opposite  hind  limb,  which  however  performs  the  opposite 
movement  of  extension.  Increase  in  the  strength  of  stimulus  causes  not 
only  an  increase  in  the  strength  of  contraction  of  the  reacting  muscles,  but 
also  an  extension  of  the  reaction  to  more  and  more  muscles,  or  groups  of 
muscles.  The  spread  occurs  always  in  definite  order.  The  stimulus  when 
represented  by  the  prick  of  a  needle  can  affect  only  one  or  two  nerve  fibres. 
The  impulse  carried  along  these  fibres  through  a  posterior  root  to  the  cord 
spreads  in  the  cord,  affects  the  motor  neurons  of  the  anterior  horns,  and 
causes  these  to  discharge.  The  first  discharge  is  as  a  rule  limited  to  those  in 
the  immediate  proximity  of  the  entering  impulses,  but  even  when  minimal, 
involves  the  simultaneous  action  of  more  than  one  anterior  root.  We  may 
say  that  the  motor  response  is  determined  to  a  certain  extent  by  the  spatial 
proximity  of  the  afferent  to  the  efferent  tracts,  but  that  it  is  always  pluri- 

338 


THE  MECHANISM   OF  CO-OKDINATED   MOVEMENTS      339 

segmental,  the  most  important  determining  factor  being  the  adaptation  of 
the  movement  to  the  stimulus  which  is  applied. 

The  gradual  spread  of  the  response  with  increasing  strength  of  stimulus 
is  spoken  of  as  '  irradiation.'  The  nature  of  the  response  is  determined  by 
the  locus  or  place  of  application  of  the  stimulus  and  by  the  quality  of  the 
latter.  While  a  painful  stimulus  causes  flexion  of  the  leg,  deep  pressure  on 
the  plantar  surface  of  the  paw  causes  extension — the  '  stepping  '  reflex. 
However  extensive  the  irradiation,  the  muscles  which  are  set  into  action  are 
always  such  that  their  actions  co-operate  towards  a  given  end.  Thus, 
when  the  impulse  spreads  to  the  opposite  limb  and  produces  an  extension, 
the  reaction  is  such  as  would  ensue  when  the  dog  steps  on  a  sharp  point  and 
immediately  retracts  the  irritated  limb  away  from  the  injurious  agent  while 
it  extends  the  other  limb  in  the  first  act  of  progression  or  movement  away 
from  the  dangerous  spot. 

A  superficial  study  of  this  reflex  would  therefore  lead  us  to  the  conclu- 
sion that,  by  the  varying  resistance  in  the  different  synapses  on  the  course 
of  the  connections  of  the  stimulated  afferent  nerves,  the  impulses  are  directed 
so  as  to  affect  solely  and  exclusively  the  muscles  whose  activity  will  co- 
operate and  aid  the  primary  reflex.  Such  a  description  would  however  re- 
present only  one  half  of  the  process.  Every  muscle  in  the  body  is  in  a  state  of 
tone  varying  with  its  extension.  If  this  tone  is  not  to  interfere  with  the 
carrying  out  of  a  reflex  movement,  there  must  be  some  means  by  which  it 
can  be  inhibited.  Such  an  inhibition  we  have  seen  occur  as  the  result  of  con- 
traction of  antagonistic  muscles  ;  but  the  remarkable  fact  has  been  brought 
out  by  Sherrington  that  the  impulses,  which  start  on  the  surface  of  the 
body  and  set  loose  a  chain  of  motor  impulses  resulting  in  the  co-ordinated 
contraction  of  certain  muscles,  spread  at  the  same  time  to  the  motor 
mechanisms  governing  the  muscles  antagonistic  to  the  movement,  and  exer- 
cise on  these  an  inhibitory  effect. 

This  inhibition  can  be  easily  shown  in  a  spinal  animal  in  the  following 
way.  The  anterior  thigh  muscles  are  cut  away  from  their  attachments  to 
the  tibia  and  the  patellar  tendon  is  connected  by  a  thread  with  a  recording 
lever.  On  then  exciting  the  flexor  reflex  by  nocuous  stimulation  of  the  foot, 
the  lever  attached  to  the  patellar  tendon  falls  (Fig.  1C9b),  showing  that  the 
extensor  muscles  have  undergone  actual  elongation.  The  same  effect  is 
observed  even  when  the  hamstrings,  the  flexors  of  the  knee,  have  been  divided. 
The  inhibition  of  the  extensor  tone  is  thus  not  only  determined  by  the  in- 
creased tension  of  the  flexors,  but  is  a  direct  result  of  the  primary  cutaneous 
stimulus. 

From  a  broad  standpoint  the  function  of  the  nervous  system  is  the 
co-ordination  of  all  the  activities  of  the  body  so  that  these  may  be  com- 
bined to  one  common  end,  viz.  the  preservation  of  the  organism.  For 
this  purpose  there  must  be  no  clashing  between  opposing  activities  of 
different  parts.  If  one  part  is  engaged  in  any  action  this  action  must  be 
the  policy  of  the  body  as  a  whole.  Yet  the  surface  of  the  body  is  being 
continually  played  upon  by  ever-changing  stimuli,  tending   to  excite  first. 


340 


PHYSIOLOGY 


one  reflex  and  then  another,  and  the  activities  so  excited  would  produce 
confusion  in  the  conduct  of  the  animal,  if  there  were  not  some  means  by 
which  at  any  one  time  only  one  reaction  should  be  in  the  act  of  being  carried 
out.     The  imperative  stimulus  should  dominate  the  actions  of  the  body  as  a 


Fio.  1G9,  a  and  b.     (Sherrington.) 

The  flexion  reflex  observed  as  reflex  contraction  (excitation)  of  the  flexor  muscles 
of  the  knee  (a),  and  as  reflex  relaxation  (inhibition)  of  the  extensor  muscle  (b). 
The  stimulus  was  a  series  of  weak  break  induction  shocks  applied  to  a  twig  of  the 
internal  saphenous  nerve  below  the  knee.  Observation  B  was  made  four  minutes 
after  A.  Note  the  summation  of  stimuli,  in  each  case  six  stimuli  being  required  before 
the  reaction   was  evoked. 

whole.  Just  as,  in  the  mental  world,  attention  must  be  undivided  if  we 
are  to  avoid  confusion  of  judgment,  so  in  the  lower  nervous  activities  there 
must  always  be  concentration4  on  one  act  or  another.  There  may  be  a 
struggle  of  different  stimuli,  but  'one  must  finally  be  prepotent  and  annul 
altogether  the  influence  of  the  others.     The  study  of  the  spinal  animal 


THE  MECHANISM   OF  CO-ORDINATED  MOVEMENTS      341 


Bhows  that  this  concentration  of  energy  is  obtained  by  the  process  of  inhibi- 
tion. Every  successful  reflex,  i.e.  one  which  actually  occurs,  inhibits  all 
other  reflexes  which  are  not  co-operative  with  the  onejwhich  is  taking  place. 
We  may,  for  instance,  stimulate  the  area  of  skin  which  gives  rise  to  the 
scratch  reflex,  and  at  the  same  time  apply  a  painful  stimulus  to  the  foot. 
The  result  is  not  a  movement  compounded  of  the  two  reflexes,  but  as  a  rule 
the  flexor  reflex  preponderates.  If,  for  instance,  the  scratch  reflex  be 
proceeding  and  then  the  foot  be  pricked,  the  scratch  reflex  immediately 
comes  to  an  end,  and  the  flexor  reflex  occurs. 
When  this  in  its  turn  has  come  to  an  end, 
the  scratch  reflex  may  be  once  more  re- 
sumed (Fig.  170). 

One  stimulus  may  reinforce  another  if 
the  reactions  ensuing  on  the  two  stimuli  are 
allied — i.e.  tend  to  co-operate  one  with 
another.  In  every  other  case  however  an 
afferent  impulse  entering  the  cord  and 
spreading  to  a  motor  mechanism,  so  as  to 
produce  a  co-ordinate  contraction  of 
various  muscles,  causes  at  the  same  time 
inhibition  of  the  muscles  antagonistic  to 
the  movement,  and  a  block  or  inhibition 
in  all  other  reflex  arcs  of  the  cord. 

The  anatomical  basis  of  the  various 
events  involved  in  the  carrying  out  of  such 
a  reflex  as  that  just  studied  is  shown  in  the 
diagram  (Fig.  171).  In  this  diagram  the 
nerve  fibre  a  represents  the  pain-receiving  or 
nociceptive  nerve  from  the  skin  of  the 
foot.  This  passes  by  a  posterior  root  into 
the  spinal  cord,  where  it  divides  and  gives 
off  a  number  of  collaterals.  These  collaterals, 
as  we  have  already  seen,  pass  in  various 
directions  ;  some  to  the  neighbouring  grey 
matter,  some  to  the  centres  in  the  higher 
parts  of  the  nervous  system.  Neglecting 
the  latter  and  any  intermediate  neuron 
which  may  be  intercalated  between  the  afferent  fibre  and  the  motor  cell, 
we  see  that  those  collaterals  which  affect  the  motor  cells  of  the  muscles 
of  the  two  hind  limbs  can  be  divided  into  two  sets,  one  of  which  always 
produces  during  activity  excitation  in  certain  efferent  neurons,  whilst  the 
other  produces  inhibition  of  the  efferent  neurons  of  the  antagonistic  muscles. 
The  single  afferent  nerve  fibre  is  therefore,  with  regard  to  one  set  of  its 
central  terminal  branches,  specifically  excitor  and,  in  regard  to  another 
set  of  its  central  endings,  specifically  inhibitor.  In  the  case  in  point  the 
central  terminal  branches  of'  the  nerve  a  are  excitor  for  the  flexor  muscles 


Fig.    170.     Scratch   reflex  tempo- 
rarily inhibited   by  application 
of  a  pathic  stimulus  to  foot. 
Signal  a,  stimulation  of  scratch 
area.     Signal  b.  stimulation  of  paw 
by  strong  induction  shock. 


342 


PHYSIOLOGY 


of  the  same  side  and  inhibitor  for  the  extensor  muscles  of  the  same  side  and 
for  the  flexor  muscles  of  the  opposite  side. 

The  ascending  branches  of  the  nerve  fibre  in  the  same  way  will  have 
endings  which,  while  inhibitor  for  the  greater  number  of  other  possible 
reflex  changes,  will  be  excitor  in  a  slight  degree  for  certain  efferent  neurons 
whose  action  is  allied  to  that  of  the  primary  reflex.  The  diagram  shows 
also  that  the  contraction  of  the  flexor  muscle,  set  up  as  the  result  of  stimu 


Pig.  171.  Diagram  indicating  connections  and  actions  of  two  afferent  spinal 
root  cells  a  and  a'  in  regard  to  their  reflex  influence  on  the  extensor  and  flexor 
muscles  of  the  two  knees.  The  sign  +  indicates  an  excitatory  effect,  the 
sign  ■ —  an  inhibitory  effect.     (Sherrington.) 

lating  a,  itself  initiates  a  secondary  reflex  process  from  muscle  up  the  nerve 
fibre  «'  and  back  again  to  the  muscle  by  the  efferent  neuron.  This  muscular 
afferent  nerve  also  has  central  terminations  of  two  signs- — excitor  to  itself 
and  inhibitor  to  the  antagonistic  muscles.  For  the  sake  of  clearness  the 
diagram  omits  a  number  of  other  channels  coming  from  other  regions  of 
the  cord,  or  from  other  efferent  nerves,  the  sign  of  which  would  be  negative, 
i.e.  which  would  tend  to  inhibit  the  activity  of  the  whole  reflex  arc. 

We  see  therefore  that  from  every  sensitive  point  on  the  surface  of  the  body 
impulses  can  be  initiated  which  will  set  into  action  whole  chains  of  neurons, 
and  will  have  a  widespread  influence  throughout  the  central  nervous  system. 
It  is  important  to  note  that  the  efferent  path  innervating,  say,  the  flexor 
muscles  of  one  side  is  common  to  many  reflexes.  It  is  used,  for  instance,  by 
mutually  antagonistic  reflexes  such  as  the  scratch  reflex  and  the  flexor  or 


THE  MECHANISM  OF  CO-ORDINATED  MOVEMENTS      343 

pain  reflex.  We  must  assume  therefore  that  the  mutual  inhibition  of  differ- 
ent reflexes  occurs,  not  in  the  '  final  common  path ' — i.e.  in  the  motor  neurons 
which  must  always  remain  open — but  further  back  in  the  arc  probably  near 
its  afferent  side. 

We  have  reason  to  believe  that  the  propagation  of  impulses  through  the 
central  nervous  system  involves  expenditure  of  energy,  and  that  the  seat  of 
this  expenditure  may  be  located  in  all  probability  at  the  synapses.  It  follows 
that  the  result  of  any  particular  sensory  stimulation  will  not  be  absolutely 
invariable,  but  that  the  spread  of  the  nerve  process  in  the  nervous  system, 


Fig.  172.  '  Mark  -time  '  reflex  in  spinal  dog,  inhibited  by  slight  stimulation  of 
the  tail  (duration  of  stimulation  shown  by  signal).  Note  the  augmentation  of 
the  mark-time  reflex  following  the  inhibition  (successive  spinal  induction). 
(Sherrington.  ) 

and  the  degree  of  block  presented  by  the  various  synapses  and  determining 
the  potency  of  any  given  reaction,  will  depend  on  the  condition  of  the 
various  synapses  at  the  time  of  the  stimulation. 

This  condition  may  be  altered  in  various  ways.  Repeated  excitation 
causes  in  the  synapses,  just  as  in  the  nerve  endings  of  the  skeletal  muscle,  a 
condition  of  fatigue.  Stimulation  confined  to  a  single  point  in  the  '  scratch 
area  '  of  the  spinal  dog  excites  a  scratch  reflex  which  rapidly  dies  away.  On 
shifting  the  exciting  electrodes  a  little  to  one  side  the  reflex  act  begins  again, 
often  with  greater  force  than  at  first,  and  a  very  prolonged  reaction  can  be 
induced  by  gradually  moving  the  electrodes  along  the  surface  of  the  skin.  A 
reflex  arc  therefore  rapidly  shows  signs  of  fatigue,  and  the  minute  change 
in  locus  of  stimulus  which  is  required  to  reinduce  a  practically  identical 
action,  shows  that  the  seat  of  fatigue  must  lie  chiefly  on  the  afferent  side  of 
the  arc  ;  perhaps  iu  the  first  synapses  through  which  the  impulse  has  to 
pass.  This  easy  incidence  of  fatigue  tends  to  cut  short  any  given  reaction 
and  to  render  it  easier  for  other  reactions  to  take  its  place. 


:;ll  PHYSIOLOGY 

Just  as  excitation  causes  fatigue  and  therefore  furnishes  a  hindrance  to 
repetition  of  the  same  act,  so  the  reverse  process  of  inhibition,  which  is  a 
large  component  of  every  reaction,  is  followed  by  a  condition  of  increased 
excitability,  or  diminished  resistance  to  the  passage  of  impulses.  Jn  each 
case  there  is  a  tendency  for  a  '  swing-back  '  to  take  place  from  inexcitability 
to  over-excitability,  from  excitation  to  inexcitability.  This  '  successive 
spinal  induction,"  as  it  has  beer  termed,  may  be  seen  on  inhibiting  some 
movement  by  the  excitation  of  an  independent  reflex.  Thus  the  scratch 
reflex  is  excited,  and  then  while  the  excitation  is  still  continued  the  reaction 
is  inhibited  by  excitation  of  the  extensor  or  stepping  reflex.  As  soon  as  the 
'  stepping  '  reflex  has  passed  off,  the  scratch  reflex  returns  with  an  intensity 
greater  than  before.  This  successive  spinal  induction  explains  the  tendency 
which  exists  in  the  spinal  cord  to  an  alternation  of  response  ;  every  act  tend- 
ing to  come  to  an  end  by  fatigue  and,  as  a  result  of  negative  spinal  induction, 
inducing  the  opposed  or  antagonistic  act.  Thus  if  a  spinal  dog  be  held  up  in 
the  vertical  position,  so  that  the  hind  limbs  hang  freely,  these  latter  execute 
a  series  of  alternate  movements  of  flexion  and  extension.  The  starting-point 
of  these  is  the  stretching  of  the  anterior  thigh  muscles.  Once  .started 
they  continue  of  themselves,  each  act  exciting  the  alternating  antagonistic 
act. 

A  reflex  act  has  often  been  distinguished  from  other  reactions,  described 
as  conscious  or  purposive,  by  its  fatality — i.e.  by  the  invariability  with 
which  it  results  on  a  given  stimulus,  whether  the  reaction  be  for  the  good  of 
the  animal  as  a  whole  or  not.  Thus  a  decapitated  eel  will  wind  itself  u  it  h 
equal  readiness  around  a  stick  or  a  hot  poker.  All  reactions  are  however 
purposive.  The  machinery  for  them  has  been  evolved  and  the  paths  laid 
down  in  the  spinal  cord  under  the  action  of  natural  selection,  so  that  they 
must  act,  at  any  rate  in  the  average  of  cases,  towards  the  well-being  <>l  the 
animal  as  a  whole.  Since  the  nerve  path  involved  in  any  reaction  includes  a 
number  of  synapses,  each  of  which  may  be  influenced  from  other  parts  of  the 
body  in  a  positive  or  negative  direction,  an  absolute  uniformity  of  response 
cannot  be  predicated  for  any  one  reaction.  There  will  be  changes  in  the 
facility  with  which  it  is  evoked  and  changes  in  its  extent,  and  these  will 
become  the  more  operative  the  greater  the  complexity  of  the  arc,  and  the 
larger  the  number  of  other  impulses  to  which  it  may  be  subject.  The 
fatality  of  response  is  therefore  shown  only  at  its  best  in  the  very  simplest 
of  reflexes,  or  the  most  lowly  organised  nervous  systems. 

The  purposive  character  of  the  reflexes  obtained  from  the  spinal  frog  has  some- 
times led  writers,  especially  in  pre-Darwinian  days,  to  endow  the  spinal  cord  with  a 
guiding  intelligence.  At,  the  present  time  we  recognise  that  every  reaction  of  a  living 
being  must  be  purposive,  in  the  sense  of  being  adapted  to  the  preservation  of  the  species, 
if  the  latter  is  to  survive  in  the  struggle  for  existence.  The  question  as  to  whether 
we  are  justified  in  predicating  the  existence  of  even  a  germ  of  consciousness  or  volition 
in  the  spinal  animal  must  be  decided  in  the  negative.  "  Associative  memory  would 
seem  to  be  a  postulate  for  the  very  existence  of  perception.  Where  even  simplest 
ideas  are  not,  there  cannot  be  consciousness.  Animal  movements  that  are  appropriate 
not  only  for  an  immediate  but  also  for  a  remote  end  indicate  associative  memory. 


THE  MECHANISM   OF  CO-ORDINATED  MOVEMENTS      345 

The  approach  of  a  dug  in  answer  to  the  falling  of  its  name,  the  return  of  an  animal 
when  hungry  to  the  place  where  it  has  been  wont  to  receive  food,  such  movements 
may  be  taken  as  indicative  of  consciousness  since  they  indicate  the  working  of  associative 
memory.  Examined  by  this  criterion  all  purely  spinal  reactions  fail  to  evince  features 
of  consciousness  "  (Sherrington). 

THE  PART  PL*¥ED  BY  AFFERENT  IMPRESSIONS  IN  THE  CO- 
ORDINATION OF  MUSCULAR  MOVEMENTS.  Every  reflex  act  is  initiated 
in  the  first  place  by  some  form  of  sensory  stimulus.  In  the  carrying  out  of 
the  muscular  contractions  and  the  resultant  movements  of  the  limbs,  other 
impulses  are  set  up  in  the  structures  which  subserve  deep  sensibility,  in- 
cluding those  of  muscles.  These  secondary  afferent  impulses  in  their  turn 
affect  the  excitability  and  the  activity  of  the  motor  neurons,  and  are  im- 
portant whether  the  movements  be  aroused  by  immediate  sensory  stimula- 
tion of  the  surface  of  the  body,  or  through  the  higher  parts  of  the  brain, 
as  in  volitional  movements. 

Their  significance  is  shown  by  the  marked  disorders  of  movement  pro- 
duced in  a  limb  by  section  of  some  or  all  of  its  afferent  nerves.  Thus  if 
all  the  posterior  roots  supplying  one  hind  limb  of  the  frog  be  divided,  the 
posture  of  the  desensitised  limb  is  abnormal,  whether  the  frog  be  suspended 
or  be  hi  a  sitting  posture.  Such  a  frog  generally  swims  with  the  desensitised 
limb  in  permanent  extension.  The  complete  absence  of  muscular  tone  under 
these  circumstances  has  already  been  mentioned.  When  a  contraction  of 
the  quadriceps  extensor  is  induced  by  a  single  shock  applied  to  the  intact 
motor  nerve,  the  curve  obtained  shows  a  relaxation  line  much  slower  and 
more  prolonged  than  when  the  cut  nerve  is  similarly  excited.  In  the  latter 
case,  or  when  the  posterior  roots  alone  are  divided,  the  lever  at  the  end  of  re- 
laxation dips  below  the  base  line  with  an  inertia  fling,  which  is  never  present 
while  the  nerve  is  intact.  The  contraction  of  the  muscle,  when  its  afferent 
path  is  intact,  seems  to  develop  reflexly  in  the  muscle  itself  a  condition  of 
tone  which  damps  the  inertia  swing  of  the  contraction.  In  the  dog,  after 
section  of  the  afferent  nerves  of  one  hind  limb,  this  limb  is  not  at  first  used 
for  walking  ;  it  is  kept  more  or  less  flexed  at  hip  and  knee,  and  later,  when 
it  is  employed  in  walking,  it  is  lifted  too  high  with  each  step.  After  division 
of  the  afferent  fibres  of  both  limbs  these  appear  as  if  they  were  affected 
with  motor  paralysis.  At  first,  during  walking,  the  fore  limbs  simply  drag 
the  hind  limbs  after  them,  though  later,  as  the  hind  limbs  are  drawn  along, 
they  make  alternate  movements  and  may  ultimately  afford  a  certain  amount 
of  support  to  the  body. 

Still  more  striking  effects  are  observed  in  complete  apaesthesia  of  the  fore 
limb  in  monkey  or  man.  The  limb  is  permanently  paralysed  ;  it  is  never  used 
in  climbing  or  in  the  taking  of  food.  That  the  peripheral  motor  mechanism 
is  intact  is  shown  by  the  fact  that  stimulation  of  the  appropriate  area  of  the 
cerebral  cortex  in  such  animals  elicits  at  once  a  perfectly  normal  movement 
of  the  hand  or  limb.  It  seems  however  impossible  for  the  cortex  to  initiate 
Hi  1 1  movements  in  the  absence  of  all  afferent  impulses  arriving  from  the  limb. 
Similar  paralysis  was  observed  by  Chas.  Bell  in  the  upper  lip  of  the  ass  after 


346  PHYSIOLOGY 

section  of  the  corresponding  branches  of  both  lift  h  nerves,  and  was  interpreted 
by  him  as  indicating  a  possible  motor  function  for  these  nerves. 

In  these  phenomena  of  sensory  paralysis  we  are  dealing  with  the  effects 
produced  by  the  deprivation  of  two  distinct  classes  of  afferent  impressions, 
viz.  those  from  the  skin  and  those  from  the  deep  structures  and  muscles. 
The  phenomena  due  to  these  two  factors  may  be  studied  separately.  If  in  the 
monkey  all  the  afferent  brachial  roots  except  the  last  cervical,  which  supplies 
cutaneous  sensations  to  the  whole  hand,  be  divided,  the  monkey  uses  the 
arm  and  hand  both  in  climbing  and  in  taking  food.  A  marked  ataxy  of  the 
movement  is  however  observed.  Whereas  the  normal  monkey,  in  taking 
grains  of  rice  out  of  the  observer's  hand,  exhibits  perfect  precision  of  move- 
ment so  that  he  rarely  touches  the  hand  on  which  the  grains  are  lying. 
the  monkey  with  only  cutaneous  sensibility  remaining  grasps  clumsily  with 
the  whole  hand,  and  the  arm  sways  as  it  is  put  out,  often  missing  the  object 
aimed  at  altogether.  Cutaneous  insensibility  of  the  hind  limb  causes  very 
little  disturbance  of  locomotion,  the  alternate  movements  ot  which  seem  to  be 
started  by  the  stretching  of  the  structures  at  the  front  of  the  thigh.  On  the 
other  hand,  a  patient  affected  with  such  a  loss  may  be  the  subject  of '  static- 
ataxy,'  i.e.  he  is  unable  to  stand  with  his  feet  together  and  his  eyes  shut. 
The  afferent  impressions  from  the  skin  of  the  feet  appear  therefore  to  be 
necessary  for  the  maintenance  of  static  equilibrium. 

In  the  carrying  out  of  co-ordinated  movements,  such  as  those  of  loco- 
motion, the  impressions  from  the  muscles  play  a  more  important  part. 
Division  of  the  afferent  nerves  from  the  muscles  gives  rise  to  a  condition  of 
tonelessness,  and  the  passive  mobility  of  the  joints  is  greater  than  usual,  so 
that  the  hip  with  the  limb  extended  at  the  knee  may  be  flexed  to  an  abnor- 
mal extent.  The  effect  of  this  loss  of  tone  is  more  apparent  in  the  case 
of  certain  muscles.  The  disturbance  of  co-ordination  resulting  from  the 
cutting  off  of  afferent  muscular  impressions  is  well  seen  in  cases  of  tabes 
dorsalis,  or  locomotor  ataxy,  in  man,  and  to  a  slighter  extent  in  cases  of 
peripheral  neuritis  affecting  chiefly  the  sensory  nerves  of  rauscles.  The 
ataxic  gait  of  such  patient  is  characteristic.  There  is  no  loss  of  power  in 
the  muscles,  but  there  is  loss  of  control.  The  patient  is  unaware  of  the 
position  of  his  limbs  and  has  to  guide  his  walk  by  visual  impressions  ;  even 
then  the  movements  are  inco-ordinated.  The  contraction  of  every  muscle 
is  exaggerated,  so  that  in  walking  the  leg  is  first  raised  too  high  and  then  is 
brought  down  on  to  the  ground  with  a  stamp.  As  thedisease  progresses  the 
loss  of  control  becomes  more  and  more  pronounced,  so  that  attempts  to  walk 
simply  give  rise  to  a  profusion  of  disordered  movements,  the  legs  being  thrown 
in  all  directions  with  the  patient's  efforts,  but  with  no  effective  result.  The 
centres  are  no  longer  informed  of  the  degree  to  which  each  muscle  is  con- 
tracted, and  the  impressions  are  wanting  which  should  cut  short  the  con- 
traction of  a  muscle  when  it  has  attained  its  optimum,  and  which  should 
inhibit  the  antagonists  during  the  contraction  and  induce  activity  of  the 
antagonists  in  successive  alternation  to  those  of  the  other  muscles.  In  such 
a  patient  therefore  walking  finally   becomes  impossible    and,   with   well- 


THE   MECHANISM  OF  CO-ORDINATED  MOVEMENTS      347 

nourished  muscles  and  a  motor  path  which  is  intact,  he  is  condemned  to  pass 
the  rest  of  his  days  in  bed. 

THE  EFFECT  OF  POISONS  ON  THE  SPINAL  CORD 
The  reflex  functions  of  the  spinal  cord  may  be  abolished  by  the  same 
drugs,  such  as  ether,  chloral,  &c,  which  abolish  conductivity  in  a  nerve 
fibre.     The  central  effect  of  these  drugs  is  obtained  with  much  smaller  con- 


ARM   '-'- 


BODY 

prosthotonic 

NECK  . 

turning 


NECK 

retraction 


Fia.   173.     Diagram  by  Sherrington  to  show  influence  of  tetanus  toxin  on  the 
response  to  excitation  of  the  motor  area  of  the  cortex  in  the  monkey. 

A,  normal  animal.  B,  after  poisoning  with  tetanus.  F  and  /  =  flexion  of  leg 
and  arm  respectively.  E  and  e  signify  extension.  <  signifies  opening  of  mouth  ; 
=  signifies  closing  of  mouth. 

centrations  than  is  the  case  with  the  peripheral  nerves.      Hence  their  value 
as  general  anaesthetics. 

More  interesting  from  the  point  of  view  of  the  physiologist  is  the  action 
of  such  a  drug  as  strychnine,  or  the  somewhat  similar  action  of  the  toxin 
formed  by  the  tetanus  bacillus.  If  a  small  dose  of  strychnine  be  injected 
into  a  spinal  frog,  after  a  short  period  of  heightened  irritability  the  slightest 
stimulus  applied  to  the  surface  will  cause  spasms,  which  may  affect  every 


348  PHYSIOLOGY 

muscle  in  the  body.  Pinching  the  foot,  instead  of  causing  it  to  be  drawn  up 
now  causes  the  lens,  arms  and  back  to  be  rigidly  extended.  The  extension 
is  not  a  co-ordinated  act,  but  is  associated  with  strong  contraction  of  the 
flexi  >rs,  the  final  position  of  the  Limbs  being  determined  by  the  preponderating 
strength  of  the  extensor  muscles.  The  real  meaning  of  this  condition  is  seen 
if,  in  a  spinal  mammal,  the  extensor  muscles  be  connected  with  a  lever  and 
the  flexor  muscles  cut.  <  >n  exciting  the  flexor  reflex  by  pricking  the  foot, 
there  is  instantaneous  relaxation  of  the  extensor  muscles.  A  small  dose  of 
strychnine  is  now  given,  insufficient  to  cause  general  convulsions.  It  is  now 
found  that  on  pricking  the  foot  the  extensor  muscles  respond,  not  with 
inhibition,  but  with  a  contraction.  Strychnine  acts  by  abolishing  the 
inhibitory  side  of  every  co-ordinated  act  and  converting  the  process  of 
inhibition  into  one  of  excitation.  Co-ordination  therefore  becomes  an  im- 
possibility-, and  stimulation  of  any  spot  excites  contractions  not  only  of  the 
appropriate  muscles  but  also  of  the  antagonists  of  these  muscles,  the  direction 
of  the  resulting  movement  being  determined  simply  by  the  relative  strength 
of  the  two  sets  of  muscles. 

The  same  effect  is  produced  by  tetanus  toxin  and,  since  the  action  of  this 
toxin  may  be  confined  in  its  early  stages  to  one  limb,  it  is  possible  to  show 
the  abolition  of  the  inhibitor  side  of  the  reflexes  in  this  one  limb  while  the 
limb  of  the  other  side  reacts  normally  to  the  stimulus.  The  same  abolition  of 
inhibition  is  found  whether  the  response  be  excited  by  stimulation  of  the 
skin  or  by  voluntary  excitation  from  the  cortex  of  the  brain.  Thus  in  the 
monkey,  on  stimulating  the-  cortex,  opening  of  the  mouth  may  be  excited 
from  all  the  spots  marked  "  <^  "  in  the  diagram,  closure  being  obtained  only 
from  those  spots  marked  "  =  "  (Fig.  173).  Under  the  influence  of  the 
tetanus  toxin  excitation  of  every  one  of  the  spots,  whether  "  <^  "  or  "  =," 
causes  closure  of  the  jaw.  It  is  impossible  for  a  patient  under  these  circum- 
stances to  open  his  mouth,  because  every  willed  impulse  for  opening  in- 
nervates at  the  same  time  the  stronger  masseter  muscles  and  effectively 
closes  the  mouth. 


SECTION    IX 
TROPHIC   FUNCTIONS   OF   THE   CORD 

The  reflexes  which  are  excited  by  painful  or  nocuous  stimuli  must  be 
regarded  as  prepotent  in  that  their  inhibitory  efiect  on  other  reflexes  is 
more  marked  than  that  produced  by  any  other  quality  of  stimulus.  In  the 
struggle  for  existence  the  reaction  to  nocuous  stimuli  must  predominate  over 
those  due  to  any  other  kind,  since  it  is  essential  for  the  survival  of  the  animal 
that  the  stimulus  should  be  removed  or  avoided,  so  that  the  animal  should 
escape  from  its  injurious  effects. 

It  is  natural  therefore  that  after  complete  section  of  the  afferent  nerves 
from  any  part  of  the  surface  of  the  body  there  should  be  a  tendency  to 
trophic  disturbances,  such  as  the  formation  of  ulcers.  &c.  Such  ulceration  is 
lie;  jiiently  observed  in  patients  suffering  from  spinal  disease.  After  section 
of  the  first  division  of  the  fifth  nerve  ulceration  of  the  cornea  is  often  produced. 
These  effects  are  however  merely  due  to  the  absence  of  the  normal  protective 
reactions  of  the  part,  and  can  be  prevented  by  scrupulous  cleanliness  and 
protection  of  the  apsBsthetic  part  from  all  possible  injuries.  There  are  other 
trophic  effects  caused  by  nerve  lesions  which  cannot  be  ascribed  to  the  mere 
absence  of  protective  reflexes.  Thus  inflammation  of  the.  posterior  root 
ganglia  often  sets  up  herpes  roster,  or  '  shingles,'  in  the  region  of  cutaneous 
distribution  of  the  corresponding  sensory  nerve.  Changes  in  the  skin  ( '  gL  issy 
skin  ')  nails  and  hair  are  often  seen  after  irritative  injuries  of  nerves  to  the 
part.  Section  of  a  motor  nerve  causes  rapid  changes  in  the  skeletal  muscles 
supplied,  which  become  smaller  and  after  months  or  years  may  disappear 
altogether,  beinj;  replaced  by  connective  tissue.  The  changes  in  the  excita- 
bility of  the  muscles  produced  under  these  circumstances  have  already  been 
described. 

It  seems  that  the  nutrition  of  a  tissue  is  determined  by  its  activity,  and 
this  in  turn  is  under  the  control  of  some  nerve  path.  Section  of  the  nerve 
path,  by  cutting  away  the  impulses  which  normally  maintain  the  activity  of 
the  part,  must  at  the  same  time  seriously  affect  its  nutrition.  Thus  the 
muscles  which,  though  striated,  are  not  so  immediately  under  the  control 
of  the  central  nervous  system,  such  as  the  sphincter  ani.  do  not  undergo 
degeneration  after  section  of  their  nerves,  or  after  extirpation  of  the  lower 
part  of  the  spinal  cord. 

On  the  other  hand,  it  is  only  during  post-fcetal  life  that  the  activity  of 
the  skeletal  muscles  is  determined  by  the  motor  nerves  of  the  cord.     Thus 

349 


350  PHYSIOLOGY 

they  may  be  developed  normally  even  in  the  complete  absence  of  a  central 
nervous  system.  Whether  we  are  justified  in  assuming  the  existence  of 
trophic  nerves  exercising  an  influence  on  the  nutrition  of  the  part  they  supply, 
apart  from  any  influence  on  its  other  functions,  the  experimental  evidence 
before  us  is  not  sufficient  to  decide  ;  nor  can  we  as  yet  give  a  physiological 
analysis  of  the  changes  in  nutrition  which  may  be  brought  about  in  hysterical 
patients  under  the  influence  of  eihotion. 


SECTION    X 

THE    SPINAL   CORD    AS    A   CONDUCTOR 

The  nervous  system  is  built  up  of  chains  of  neurons  which  subserve  reactions 
of  varying  complexity.  The  complexity  increases  with  the  interference  of 
the  higher  parts  of  the  brain  in  the  reactions  and  becomes  therefore  more 
and  more  marked  as  we  ascend  the  animal  scale.  Whatever  the  course  taken 
by  the  impulses  in  the  central  nervous  system  they  must  all  finally  make  use 
of  the  motor  common  path,  represented  by  the  anterior  spinal  roots  and  by 
the  motor  roots  of  the  cranial  nerves. 

The  co-operation  in  any  co-ordinated  movement  of  widely  separated 
portions  of  the  central  nervous  system  necessitates  the  existence  of  long 
paths,  i.e.  the  axons  of  certain  nerve  cells  must  extend  through  a  considerable 
distance  in  the  central  nervous  system  before  they  arrive  at  the  next  relay 
in  the  chain  of  which  they  form  part.  During  this  course  the  axons  run  in 
the  white  matter  of  the  central  nervous  system  and  are  surrounded  by 
medullary  sheaths.  The  white  matter  of  the  cord  consists  almost  exclusively 
of  medullated  nerve  fibres  running  for  the  most  part  longitudinally.  These 
are  of  various  sizes,  some  of  the  smaller  fibres  being  collaterals,  which  have 
been  given  off  from  the  larger  ones  and  which  will  shortly  turn  into  the  grey 
matter.  In  section  they  resemble  closely  the  fibres  of  an  ordinary  peripheral 
nerve,  but  differ  from  these  in  that  they  have  no  primitive  sheath  or  neuri- 
lemma. Each  consists  of  an  axis  cylinder  surrounded  by  a  thick  sheath  of 
myelin,  the  whole  embedded  in  a  tube  formed  by  the  neuroglia. 

Of  these  fibres  part  belong  to  the  spinal  cord,  the  proprio-spinal  or 
interimiicial  fibres,  which  we  have  studied  previously.  The  greater  number 
serve  to  establish  connection  between  the  grey  matter  of  the  cord  or  the 
afferent  roots  entering  the  cord  and  the  different  levels  of  the  brain,  and  these 
fibres  may  carry  impulses  either  up  towards  the  brain  or  down  towards  the 
spinal  cord  ;  they  may  be  ascending  or  afferent,  so  far  as  the  brain  is  con- 
cerned, or  descending  and  efferent.  No  fibre  takes  an  isolated  course  on  its 
way  through  the  cord  ;  practically  every  one  sends  off  fine  branches  or 
collaterals,  which  run  into  the  grey  matter  at  various  levels,  there  making 
connection  or  having  synapses  with  the  local  reflex  mechanisms  contained  in 
each  segment. 

On  inspection  the  white  matter  is  seen  to  be  divided  by*  the  anterior 
and  posterior  fissures  of  the  cord  into  two  symmetrical  halves,  and  the 
nerve  i -uots  divide  each  half  into  anterior  or  ventral,  lateral,  and  posterior 

351 


352  PHYSIOLOGY 

or  dorsal  columns.  On  account  of  the  scattered  distribution  of  the  anterior 
mot  fibres  over  a  considerable  area  of  the  surface  of  the  cord,  the  division 
between  the  anterior  and  the  lateral  columns  is  ill  defined,  and  the  whole 
region  is  often  called  as  the  antero-lateral  column.  In  the  cervical  and 
upper  dorsal  region  of  the  cord,  slight  grooves'  on  the  surface  of  the  cord 
indicate  a  division  of  the  anterior  column  into  the  antero-median  and  antero- 
lateral columns,  and  of  the  posterior  column  into  the  postero-median  and 
postero-lateral  columns.  These  two  posterior  columns  are  often  designated 
as  the  columns  of  Goll  and  Burdach.  In  order  to  determine  the  origin, 
course,  and  destination  of  the  fibres  which  make  up  these  white  columns,  we 
must  have  recourse  to  the  indirect  methods  of  development  and  of  degenera- 
tion which  were  described  on  p.  319.  By  these  means  we  may  divide 
the  white  matter  into  ascending  and  descending  tracts.  An  '  ascending  ' 
tract  means,  not  that  the  direction  of  conduction  of  the  impulse  is  necessarily 
in  the  upward  direction,  i.e.  from  spinal  cord  to  brain,  but  that  the  nerve  cell 
which  gives  off  the  fibres  sends  its  axons  towards  the  brain,  while  a  descending 
fibre  in  the  cord  is  the  axon  of  a  nerve-cell  situated  in  the  upper  part  of  the 
cord  or  in  some  part  of  the  brain.  If  the  assumption  which  we  have  made 
as  to  the  normal  direction  of  conduction  in  axons  and  dendrites  be  correct, 
an  ascending  fibre  will  also  conduct  impulses  in  an  ascending  direction. 
After  section  of  the  cord,  say  in  the  mid-dorsal  region,  transverse  sections 
of  the  cervical  and  lumbar  regions  of  the  cord,  taken  at  the  appropriate 
period  after  the  lesion  has  been  inflicted,  show  patches  of  degenerated  fibres 
in  the  white  matter.  The  fibres  which  are  degenerated  above  the  section 
represent  the  ascending  tracts,  whereas  those  which  degenerate  below  the 
section,  i.e.  in  the  lumbar  region,  are  the  descending  tracts  of  the  cord  (cp. 
Figs.  174  and  175). 

In  this  way  the  following  tracts  have  been  distinguished  : 

A.     DESCENDING  TRACTS 

(1)  PYRAMIDAL  TRACTS.  If  the  spinal  cord  be  divided  in  the  upper  cervical 
region,  degeneration  of  two  distinct  tracts  on  each  side,  in  the  anterior  and  postero-lateral 
columns,  is  produced.  These  are  the  anterior  or  direct  and  the  crossed  pyramidal 
tracts.  The  fibres  composing  these  tracts  are  derived  from  large  nerve-cells  in  the 
motor  area  of  the  cerebral  cortex,  and  therefore  degenerate  if  the  motor  area  of  the  cortex 
is  destroyed.  The  pyramidal  tracts  are  derived  from  the  cerebral  cortex  of  the  opposite 
side,  having  crossed  the  middle  line  at  the  lower  level  of  the  medulla  oblongata  in  the 
pyramidal  decussation.  The  anterior  pyramids  represent  a  certain  number  of  fibres 
which  have  not  crossed  with  the  others,  but  continue  the  course  of  medullary  pyramids 
for  a  time,  crossing  gradually  by  the  anterior  commissure  on  their  way  down  the  cord, 
so  that  as  a  rule  they  come  to  an  end  in  the  mid-dorsal  region,  all  the  fibres  having 
passed  into  the  lateral  columns  of  the  opposite  side.  A  few  fibres  of  the  pyramids  on 
their  way  from  the  cerebral  cortex  pass  into  the  lateral  columns  of  the  same  side  ;  these 
are  the  uncrossed  pyramidal'Iibres.  The  greater  number  of  the  fibres  however  finally 
reach  the  crossed  pyramidal  tracts,  in  which  they  can  be  traced  as  far  as  the  lower  end 
of  the  cord.  They  end  iu  the  spinal  cord  by  turning  into  the  grey  matter  where  they 
break  up  into  a  fine  bunch  of  fibrils  in  close  connection  with  the  motor  cells  of  the 
anterior  horn  or,  according  to  Schafer,  with  the  cells  of  the  posterior  horn. 


THE    SPINAL  CORD   AS  A  CONDUCTOR 


353 


On  their  way  down  the  cord  they  give  off  fine  side  branches  or  collaterals,  which 
run  into  the  grey  matter,  thus  establishing  connections  between  one  cortical  cell  and  the 
anterior  cornual  cells  of  several  different  segments  of  the  spinal  cord.  These  fibres 
carry  voluntary  motor  impulses  from  the  cerebral  cortex  to  the  reflex  motor  mechan- 
isms of  the  cord.  Their  destruction  by  disease,  or  otherwise,  causes  the  abolition 
of  voluntary  control  over  the  muscles,  without  however  interfering  with  the  reflex 
motor   functions   of   the   cord   which. 

as  a  ma  iter  of  fact,  are   increased   in  ^-- ^ -^  ^e*zzz^xrr&> 

cases  where  these  tracts   have  under- 
gone degeneration. 

(2)  RUBROSPINAL  OR  PRE- 
PYRAMIDAL  TRACT  (also  called 
Monakow's  Bundle).  This  is  a  fairly 
compact  group  of  fibres  which  degene- 
rate downwards  after  section  of  the 
cord.  It  is  situated,  in  cross-section, 
ventral  to  the  pyramidal  tracts.  Its 
fibres  can  be  traced  up  to  the  cells  in 
the  red  nucleus,  a  mass  of  grey  matter 
in  the  mid-brain  lying  ventrally  to 
the  nucleus  of  the  third  nerve.  Thev 
are  probably   chiefly  concerned    with    Fl0"  17f:     Diagram   (/r^  SonAFER)  showmg  the 

ascending  (right  side)  ana  the    descendmg   (left 


carrying  motor  impulses  involving 
maintenance  of  posture,  and  are  the 
main  efferent  channels  of  the  cere- 
bellum— red  nucleus  co-ordinating 
mechanism . 


side)  tracts  in  the  spinal  cord. 
1,    crossed    pyramidal ;    2,    direct    pyramidal ; 
3j  antero-lateral     descendmg ;    3a,   spino-olivarv 
descending  (bundle  of  Helweg) ;  4,  pre-pyramidal 
(rubro-spinal) ;   5,    comma  ;      6,    postero-mesial ; 
7,  postero-lateral ;  8,  Lissauer's   tract  ;    9,    dorsal 
(3)  VESTIBULOSPINAL  TRACT,    (ascending)   cerebellar;  10,  antero-lateral   ascend- 
This  consists  of  scattered  fibres  in  the    ing  ;    *m>  septo-marginal ;  spl,  dorsal  root  zone  ; 
antero-lateral  column,  which  degene-    ■»  anterior  horn-cells  ;  i,  intennedio-lateral  horn; 
e  p,   cells   of   posterior  horn  :     a.   (.  larkes   column, 

rate  m  the  downward  direction.    Tbey    The    fae    dots  represent   the    situation    of   the 
were  formerly  supposed  to  be  derived    '  internuncial '  or  '  endogenous  '  fibres  of  the  spinal 
from  the  cerebellum  of  the  same  side,    e°rd. 
but   it  has  been  shown   that  they  are 

in  all  probability  derived  from  Deiters'  nucleus  in  the  inedulla— an  important    trans- 
mitting station  between  the  cerebellum  and  cord. 

(4)  OLIVOSPINAL  AND  THALAMICO-SPINAL  TRACTS  (Bundle  of  Helweg). 
This  tract  is  also  situated  in  the  antero-lateral  column,  opposite  the  head  of  the  anterior 
horn.  It  consists  mainly  of  fibres  which  pass  from  the  thalamus  (the  fore  brain)  through 
the  inferior  olive  of  the  medulla  downwards  in  the  cord  as  far  as  the  -lower  cervical 
region. 

(5)  COMMA  TRACT.  This  tract  lies  in  the  posterior  columns  at  the  junction  of 
the  postero-median  and  postero-lateral  portions.  It  consists  for  the  most  part  of  the 
descending  branches  of  the  afferent  dorsal  nerve  roots.  These  divide  as  they  enter 
the  cord,  and  their  descending  branches  pass  down  for  two  or  three  segments  in  the 
comma  tract  before  turning  into  the  grey  matter.  The  tract,  however,  contains  fibres 
of  other  origin,  some  of  which  begin  and  end  in  the  spinal  cord  itself. 

(6)  TRACT  OF  MARIE.  This,  also  in  the  anterior  column,  contains  both  descend- 
ing and  ascending  fibres  and  is  largely  a  continuation  of  the  posterior  longitudinal  bundle, 
the  connections  of  which  we  shall  have  to  study  later  on.  A  small  tract  of  fibres,  which 
degenerate  in  the  descending  direction,  is  also  found  in  the  posterior  part  of  the  cord 
adjoining  the  posterior  longitudinal  fissure. 

(7)  SEPTOMARGINAL  BUNDLE.  This  is  largely  proprio-spinal,  but  may 
contain   fibres  coming  from  the  mid-brain. 


23 


354  PHYSIOLOGY 

B.      ASCENDING  TRACTS 

These  may  be  divided  according  as  they  are  situated  in  the  posterior,  the  lateral, 

or  the  anterior  columns. 

(a)  THE  POSTERIOR  COLUMNS.  Almost  the  whole  of  the  fibres  making 
iij >  these  columns  are  exogenous,  being  axons  of  cells  in  the  posterior  cool  ganglia. 
They  can  be  divided  into  long,  medium,  and  short  fibres,  all  of  which,  on  their  way  up, 

give  off  collaterals,  which  pass  into  the  grey  matter  and  ramify  round  nerve  cells,  especi- 
ally in  the  posterior  horns  (cp.  Fig.  160).  The  longest  lilacs  pass  to  the  upper  end  of 
the  cord,  where  they  end  in  the  posterior  column  nuclei,  the  nucleus  gracilis  and  the 
nucleus  cuneatus  of  the  medulla.  These  fibres  remain  entirely  on  the  side  of  the  cord 
on  which  they  have  entered.  As  they  pass  up  they  are  displaced  towards  the  middle 
line  l>v  each  incoming  and  higher  placed  root.  Thus  in  the  cervical  region,  and  indeed 
from  the  fifth  dorsal  segment  upwards,  two  columns  can  be  distinguished  in  the  postci  ior 
part  of  the  cord,  viz.  the  postero-median  and  postero-lateral  columns,  the  division 
between  which  is  indicated  by  a  small  groove  on  the  surface.  The  postero-median 
column  contains  from  within  outwards  the  fibres  from  the  sacral  region,  those  from  the 
lumbar  region,  and  those  from  the  inferior  dorsal  region.  The  postero-lateral  column,  or 
column  of  Burdach,  contains  mesially  the  four  upper  dorsal  mot  fibres  and  more  laterally 
the  fibres  from  the  cervical  nerves. 

{!>)  THE  LATERAL  COLUMNS.  In  these  columns  are  found  the  two  cerebellar 
tracts,  as  well  as  scattered  fibres  passing  to  the  fore-  and  mid-brain. 

(1)  The  Direct  or  Dorsal  Cerebellar  Tract  arises  from  the  cells  of  Clarke's 
column  on  its  own  side.  It  consists  of  large  fibres,  which  pass  through  the  grey  matter 
to  the  lateral  columns  of  the  same  side,  and  ascend  in  the  cord  immediately  ventral  to 
the  incoming  posterior  root  fibres,  and  external  to  the  crossed  pyramidal  tract.  In 
the  medulla  they  are  joined  by  a  bundle  of  fibres  from  the  opposite  inferior  olive  and 
pass  with  the  restiform  body  into  the  cerebellum,  where  they  terminate  in  the  superior 
vermis  of  this  organ. 

(2)  The  Ventral  or  Anterior  Cerebellar  Trait,  often  called  the  tract  of  Gowers, 
arises  in  cells  scattered  through  the  grey  matter,  chiefly  of  the  posterior  horn  of  the  oppo- 
site side,  though  a  few  fibres  are  derived  from  cells  of  the  same  side.  The  tract  consists 
of  fine  fibres  which  pass  upwards  in  the  peripheral  margin  of  the  lateral  column,  extend- 
ing from  the  direct  cerebellar  tract  behind  to  the  level  of  the  anterior  roots  in  front  :  it 
passes  upwards  through  the  cord,  the  medulla,  and  the  pons,  then  turns  round  to 
enter  the  cerebellum  through  the  superior  cerebellar  peduncle,  ending  chiefly  in  the 
ventral  portion  of  the  superior  vermis. 

(i3)  THE  SpINO-THALAMIC  AND  SPINO-TECTAL  TRACTS.      These   fibres   form   a   scattered 

bundle  lying  internally  to  the  anterior  cerebellar  tract,  and  are  practically  part  of  Gowers' 
tract.  They  may  be  traced  through  the  cord,  medulla,  and  pons,  and  end  partly  in  the 
anterior  corpora  quadrigemina  of  both  sides,  but  to  a  greater  extent  in  the  optic 
thalamus  of  the  same  side. 

(c)  ANTERIOR  COLUMNS.  A  number  of  scattered  fibres  pass  up  the  anterior 
columns,  mingled  with  the  descending  fibres  of  the  tract  of  Marie  in  the  angleof  the 
anterior  fissure.  Others  pass  up  partly  to  end  in  the  olivary  body,  partly  to  run  on 
with  the   mesial  fillet  towards  the  thalamic  region. 

The  white  matter  of  the  cord  can  thus  be  regarded  as  made  up  of  short 
and  of  long  tracts,  which  maintain  direct  connection  between  the  following 
parts  of  the  central  nervous  system  : 

(1)  Different  levels  of  the  cord  itself  by  means  of  the  proprio-spinal 
fibres. 

(2)  Hind-brain  and  spinal  cord,  by  the  anterior  and  posterior  cerebellar 
tracts,  the  posterior  columns,  and  thc'spino-olivarv  fibres  among  the  ascend- 


THE  SPINAL  CORD  AS  A  CONDUCTOR 


355 


Fig.  I  To.  Diagram  of  sections  of  the  spinal  cord  of  the  monkey  showing  the  position  of 
degenerated  tracts  of  nerve  fibres  alter  specific  Lesions  of  the  cord  itself,  the  afferent 
nerve  roots,  anil  of  tlie  motor  region  of  flu-  cerebral  cortex.  (Sch  \fkk.)  (The  degenera- 
tions are  shown  h\  the  method  of  Marchi.)  The  left  side  of  the  cord  is  at  the  reader's 
left   hand. 

I.  Degenerations  resulting  from  extirpation  of  the  motor  area  of  the  cortex  of  the 
I'll  ,  erebral  hemisphere. 

II.  Degenerations  produced  by  section  of  the  posterior  longitudinal  bundles  in  the 
upper  part  of  the  medulla  oblongata. 

HI  and  IV.  Result  of  section  of  posterior  loots  of  tin  first,  second,  and  third  lumbar 
m-vves  on  the  right  side.  Section  III  is  from  tin  jegmen1  of  cord  between  the  last 
thoracic  and  first  lumbar  roots  :   section  IV  from  the  same  cord  in  the  cervical  region. 

V  to  VIII.  Degenerations  resulting  from  (right)  semi-section  of  the  cord  in  the 
upper  thoracic  region.  V  is  taken  a  short  distance  above  the  level  of  section  ;  VI 
higher  up  the  cord  (cervical  region);  VII  a  little  below  the  level  of  section;  VIII 
lumbar*  region. 


356  PHYSIOLOGY 

iag  tracts,  and  the  vestibulospinal  and  olivospinal  among  the  descending 
tracts. 

(3)  The  mid-brain  and  cord  connections  are  represented  by  the  spino- 
tectal tracts  in  the  lateral  columns  as  a  direct  ascending  path,  and  by  the 
rubro-spinal  tract  which  furnishes  a  direct  efferent  connection  between 
mid-brain  and  cord. 

(■i)  The  fore-brain,  viz.  the  thalamus,  receives  the  spino-thalamic  fibres 
which,  though  scattered,  are  of  considerable  importance.  They  run  chiefly  in 
the  lateral  and  anterior  columns.  Its  efferent  fibres  cannot  be  traced  below 
the  lower  cervical  region. 

(5)  The  cerebral  cortex,  the  master  tissue  of  the  body,  receives  no  fibres 
directly  from  the  cord  or  periphery  of  the  body,  but  by  the  pyramidal  tracts 
is  able  to  influence  directly  the  activities  of  the  motor  mechanisms  at  every 
level  of  the  cord.  These  fibres,  so  far  as  is  knowr,  exist  only  in  mammals, 
and  show  a  great  increase  in  relative  extent  when  traced  from  lower  to  higher 
types.  While  in  the  rabbit  the  pyramidal  tract  is  hardly  perceptible,  in  the 
monkey  it  is  the  best  marked  of  all  the  tracts,  and  in  man  is  still,  more  highly 
developed.  This  relative  increase,  which  is  probably  associated  with  the 
shunting  of  more  and  more  of  the  reactions  of  the  body  from  the  region  of 
the  unconditioned  reflex  to  that  of  the  educatable  reaction,  is  shown  not 
merely  by  the  tract  occupying  a  larger  proportion  of  the  transverse  area 
of  the  cord,  but  by  its  fibres  being  more  densely  set  within  that  area. 

THE  PATHS  OF  IMPULSES  IN  THE  CORD 
The  greater  part  of  the  white  matter  is  thus  concerned  in  transmitting 
impulses  to  nerve  cells  in  the  brain,  and  from  the  brain  towards  the  cord. 
The  complex  reactions  determined  by  these  impulses  are  in  many  cases  as 
unconscious  and  automatic  as  those  we  have  studied  in  the  spinal  cord,  even 
though  they  may  involve  the  activity  of  the  cerebral  cortex  itself.  Others 
however  influence  consciousness,  so  that  their  afferent  side  appears  in  con- 
sciousness as  sensations  of  various  qualities,  and  their  efferent  side  as  the 
result  of  volition,  i.e.  as  willed  or  emotional  movements. 

The  posterior  spinal  (sensory)  roots  at  their  entrance  into  the  cord  divide 
into  two  bundles.  The  smaller  of  the  two,  situated  more  laterally  and 
consisting  of  fine  fibres,  enters  opposite  the  tip  of  the  posterior  horn  and  turns 
up  at  once  in  Lissauer's  tract,  a  bundle  of  fine  longitudinal  fibres  close  to  the 
periphery  of  the  cord.  The  fibres  seem  to  pass  into  and  end  in  the  substance 
of  Rolando.  The  larger  median  bundle  of  coarse  fibres  passes  into  the  pos- 
tero-external  column.  Here  each  fibre  divides  into  a  descending  and  an 
ascending  branch,  the  former  running  in  the  comma  tract,  the  latter  in  the 
posterior  columns  up  as  far  as  the  gracile  and  cuneate  nuclei  of  the  medulla. 
Both  of  these  branches  give  off  collaterals  in  the  whole  of  their  course,  most 
numerous  near  the  point  of  entry  of  the  nerve.  These  collaterals  may  be 
divided  into  four  sets  according  to  their  destination  : 

(1)  Fibres  ending  round  cells  of  anterior  horn  on  same  side  or  crossing  by 
posterior  commissure  to  grey  matter  on  other  side. 


THE  SPINAL  CORD  AS  A  CONDUCTOR  357 

(2)  Fibres  ending  in  grey  matter  of  posterior  horns. 

(3)  Fibres  ending  round  cells  of  Clarke's  column. 

(4)  Fibres  to  lateral  horn. 

Since  the  motor  nerves  arise  from  the  anterior  horn-cells,  the  first  set, 
the  '  sensori-motor  '  collaterals,  represents  the  shortest  possible  spinal  reflex 
path.  The  second  group  may  also  represent  a  spinal  reflex  path  with  two 
relays  of  cells,  and  therefore  greater  choice  of  response  and  longer  reaction 
time  The  third  set  puts  into  action  the  cerebellar  tracts  which  arise  from 
the  cells  of  Clarke's  column,  and  therefore  calls  into  play  a  much  more  com- 
plicated mechanism,  the  limits  of  whose  action  it  would  be  difficult  to  define. 
The  collaterals  to  the  lateral  horn  probably  represent  the  afferent  tracts  of 
the  various  visceral  and  vaso-motor  reflexes  which  we  shall  study  later. 

We  find  no  special  tracts  devoted  to  those  impulses  which  affect  con- 
sciousness as  sensations.  All  tracts  going  towards  the  cerebral  hemispheres 
are  interrupted  by  cell  relays,  in  the  medulla,  cerebellum,  or  optic  thalamus, 
and  must  serve  as  afferent  channels  for  unconscious  as  well  as  for  conscious 
reactions.  The  quality  of  an  afferent  impulse  can  be  defined  only  by  its 
origin,  or  by  its  effect  on  consciousness,  and  much  discussion  has  arisen 
as  to  the  exact  path  of  the  various  cutaneous  and  muscular  sensations  in 
the  cord. 

It  is  evident  that  an  impulse  might  travel  to  the  cortex  by  way  of  the  two 
cerebellar  tracts  through  the  cerebellum,  or  by  way  of  the  posterior  columns 
through  the  intermediation  of  the  bulbar  nuclei,  or  by  the  spino-thalamic 
fibres,  or  by  a  series  of  relays  from  one  segment  of  the  cord  to  another 
through  grey  and  white  matter  alternately.  It  is  supposed  that  all  of  the 
ascending  tracts  may  convey  afferent  impulses  from  the  posterior  spinal 
roots  to  the  brain,  although  evidence  as  to  the  part  taken  by  each  tract  is 
very  conflicting.  The  following  account  represents  the  views  which  may 
be  regarded  as  the  most  probable  (Page  May)  (Fig.  176)  :  Pain  impulses, 
on  entering  the  cord  by  the  posterior  roots,  cross  to  the  other  side  at  once, 
and  then  pass  up,  chiefly  in  the  antero-lateral  column,  by  the  spino-thalamic 
til >ies  as  far  as  the  optic  thalamus.  Sensations  of  heat  and  cold  take  a 
very  similar  course.  Hence  they  are  generally  affected  by  lesions  of  the 
cord  in  the  same  way  as  pain  sensations.  Impulses  of  touch  and  pressure, 
after  entering  the  cord,  pass  up  in  the  posterior  column  of  the  same  side  for 
four  or  five  segments,  then  cross  gradually  and  pass  up  in  the  opposite  anterior 
column.  Impulses  serving  muscular  sensibility,  including  the  impulses 
from  joints  and  tendons,  take  two  courses.  Those  which  do  not  reach 
consciousness  and  are  involved  in  the  involuntary  guidance  of  muscular 
movements,  run  up  chiefly  in  the  anterior  and  posterior  cerebellar  tracts 
of  the  same  side.  Those  which  furnish  the  material  for  conscious  sensations 
and  give  information  as  to  the  position  of  the  limbs,  &c,  are  entirely  homo- 
lateral, and  travel  up  in  the  posterior  columns  of  the  same  side  of  the  cord. 
All  impulses  which  reach  the  brain  cross  finally  to  the  optic  thalamus  and 
thence  to  the  cerebral  cortex  of  the  opposite  side. 


358 


PHYSIOLOGY 


5-  § 


THE  SPINAL  COED  AS  A  CONDUCTOK  359 

Hemisection  of  the  cord  on  one  side,  as  was  first  pointed  out  by  Brown 
Sequard,  causes  the  following  symptoms: 

1)  Paralysis  of  the  voluntary  motor  conductors  on  the  same  side. 

(2)  A  paralysis  also  of  the  vaso-motor  conductors  on  the  same  side  and, 
asa  i  onsequence,  a  greater  afflux  of  blood  and  a  higher  temperature.  There 
may  be  some  degree  of  hyperesthesia  on  this  side. 

1 3)  There  is  anaesthesia  affecting  all  kinds  of  sensibility,  excepting  the 
muscular  sense,  in  the  opposite  side  to  that  of  the  lesion,  owing  to  the  fact 
thai  the  conductors  of  sensitive  impressions  from  the  trunk  and  limbs 
decussate  in  the  spinal  cord  ;  so  that  an  injury  in  the  cervical  region  of  that 
organ  in  the  right  side,  for  instance,  alters  or  destroys  the  conductors  from 
the  left  side  of  the  body. 

it)  There  is  some  degree  of  anaesthesia  also  on  the  side  of  the  lesion,  in 
a  very  limited  zone,  above  the  hyperaesthetic  parts,  and  indicating  the  level 
of  the  lesion  in  the  cord.  This  anaesthesia  is  due  to  the  fact  that  the  con- 
ductors  of  sensory  impressions,  reaching  the  cord  through  the  posterior  roots, 
at  t  he  level  or  a  little  below  the  seat  of  the  alteration,  have  to  pass  through 
the  altered  part  to  reach  the  other  side  of  the  cord 

The  only  direct  unbroken  cortico-spinal  fibres  are  those  contained  in  the 
pyramidal  tracts.  Motor  impulses,  which  start  from  the  cerebral  cortex  on 
one  side,  pass  down  that  side  till  they  reach  the  lower  part  of  the  medulla. 
Here  the  greater  number  of  the  fibres  crossover  in  the  pyramidal  decussation 
to  run  down  in  the  crossed  pyramidal  tract  on  the  other  side  of  the  cord." 
The  few  fibres  which  do  not  cross  over  in  the  pyramidal  decussation  are 
continued  as  the  direct  or  anterior  pyramidal  tract.  These  however  also 
cross  to  the  other  side  in  their  passage  down  the  cord  before  becoming  con- 

;ted  with  the  anterior  coniual  cells.     Hemisection  therefore  of  the  spinal 

cord  in  the  dorsal  region  will  produce  paralysis  of  voluntary  movement  and 
loss  of  or  impaired  muscular  sensation  in  the  parts  supplied  by  the  nerves 
on  the  same  side  below  the  lesion. 

\  great  part  of  the  white  matter  of  the  cord  is  concerned  then  in  main- 
taining connection  between  the  brain  and  higher  parts  of  the  nervous  system 
and  the  periphery,  through  the  intermediation  of  the  cells  of  the  grey  matter 
of  the  cord.  Corresponding  to  this  function  we  find  a  gradual  increase  in 
the  number  of  fibres  in  the  white  matter  as  we  ascend  from  the  sacral  part 
of  the  cord  to  the  medulla,  the  white  matter  being  continually  reinforced  as 
it  ascends  the  cord  by  fibres  establishing  connection  with  the  ganglion-cells 
forming  the  nuclei  of  the  nerve  roots. 

Vaso-motor  impulses  to  the  limbs  travel  down  the  lateral  columns  of  the 
tin'  same  side. 


THE    BRAIN 

SECTION  XI 
THE    STRUCTURE    OF   THE    BRAIN   STEM 

The  physiology  of  the  brain  falls  naturally  into  two  main  divisions;  namely, 
that  of  the  brain  stem,  including  the  medulla,  the  pons.  Sylvian  iter,  corpora 
quadrigemina  and  third  ventricle,  and  that  of  the  cerebral  hemispheres.  It 
is  usual,  in  treating  of  the  structure  of  the  brain  stem,  to  consider  it  as 
a  prolongation  forwards  of  the  spinal  cord  and  as  consisting,  like  this,  of  a 
central  tube  of  grey  matter  surrounded  by  a  tube  of  white  matter.  Like  the 
spinal  cord,  the  brain  stem  may  be  regarded  as  originating  primitively  by 
the  fusion  of  a  series  of  ganglia  presiding  over  the  local  reactions  of  their 
respective  somites.  The  modifications  in  this  segmental  arrangement,  which 
have  occurred  in  the  course  of  evolution,  have  been  so  profound  that  little 
trace  of  the  primitive  segmental  arrangement  is  to  be  observed.  At  the 
fore  end  of  the  body  have  been  developed  the  organs  of  special  sense,  which 
are  the  most  important  in  determining  the  reactions  of  the  animal  in  response 
to  present  or  approaching  changes  in  its  environment.  Indeed  the  whole 
course  of  evolution  is  conditioned  by  the  development  of  the  brain  stem  in  the 
first  place,  and  of  its  outgrowth,  the  cerebral  hemispheres,  in  the  second. 
Hence  we  cannot  expect  to  find  in  the  brain  stem  the  regularity  of  arrange- 
ment of  grey  and  white  matter  that  we  have  studied  in  the  cord.  The  typical 
division  of  the  grey  matter  into  cornua  becomes  altogether  lost.  While  some 
nerves  take  their  origin  from  or  terminate  in  the  central  tube  of  grey  matter, 
in  other  cases  the  collections  of  nerve  cells  and  fibres  forming  the  nuclei 
of  the  cranial  nerves  have  become  more  or  less  separated  from  the  central 
axis.  Moreover  the  central  grey  matter  is  by  itself  quite  inadequate  to  deal 
with  the  flood  of  afferent  impressions  entering  the  central  nervous  system 
through  the  organs  of  special  sense,  or  to  co-ordinate  these  with  one  another 
or  with  those  arriving  from  the  skin  and  lower  part  of  the  body.  Masses 
of  grey  matter,  which  have  no  representative  in  the  cord,  make  their  appear- 
ance, and  may  be  regarded  as  additional  sorting  stations  or  fields  of  conjunc- 
tion for  the  afferent  and  efferent  impulses  which  determine  the  nervous 
activities  of  the  animal. 

The  general  features  of  the  structure  of  the  brain  will  be  best  understood  by  reference 
to  the  mode  of  development  of  this  part  of  the  central  nervous  system.  At  the  front 
end  of  the  body,  the  primitive  neural  tube,  formed  by  the  invagination  and  growing  over 

360 


THE  STRUCTURE   OF  THE   BRAIN  STEM 


361 


Fig.  177.  Diagram  of  the 
cerebral  vesicles  of  the 
brain  of  a  chick  at  the 
second  day.     (Cadiat.) 

1,  2,  3,  cerebral    vesi- 
cles ;  0,  optic  vesicles. 


of  the  epiblast,  is  somewhat  enlarged  and  is  marked  off  by  two  constrictions  into  the  three 
primitive  cerebral  vesicles,  which  are  named  respectively  the  fore-,  the  mid-,  and  the 
hind-brain,  or  the  prosencephalon,  the  mesencephalon,  and  the  rhombencephalon  (Fig. 
177).  At  their  first  formation  the  walls  of  these  vesicles  are  composed  of  simple  epithe- 
lial cells,  and  show  no  trace  of  nervous  structm'e.  A  little  later  the  cells  fprming  tin- 
walls  present  a  differentiation  into  neuroblasts  and  spongio- 
blasts, the  former  developing  into  nerve  cells,  while  the 
latter  form  the  neuroglial  supporting  tissues  of  the  brain  and 
probably  also  furnish  the  cells  of  the  sheath  of  Schwann  to 
the  outgrowing  cranial  nerves.  In  some  places  the  wall  of 
the  vesicles  remains  undifferentiated  :  no  nervous  tissues 
develop  in  it,  and  it  forms  a  layer  of  epithelium  known  as 
ependyma.  By  the  varying  growth  of  nervous  tissue  in 
different  parts  of  the  wall,  the  typical  structure  of  the  adult 
brain  is  brought  about  (Fig.  178).  Thus  in  the  hind-brain. 
or  rhombencephalon,  the  roof  of  the  neural  canal  posteriorly 
fails  to  develop,  so  that  in  the  adult  brain  there  is  merely 
a  layer  of  epithelium  covering  the  expanded  central  canal, 
here  known  as  the  fourth  ventricle.  Tins  back  part  of  the 
hind-brain  is  often  called  the  myelencephalon,  the  anterior 
portion  being  the  metencephalon.  The  Moor  of  the  mye- 
lencephalon undergoes  considerable  thickening  and  forms 
the  future  medulla  oblongata.  In  the  metencephalon,  ner- 
vous tissue  is  developed  all  round  the  canal,  the  floor  of  the 
canal  forming  the  pons  Varolii,  while  the  cerebellum  is  developed  by  an  outgrowth 
of  the  dorsal  wall.  In  the  region  of  the  constriction  between- the  hind-  and  mid-brain 
known  as  the  isthmus,  the  roof  or  dorsal  wall  forms  the  superior  cerebellar  peduncles 
at  the  side,  and  between  them  a  thin  layer  of  nervous  matter  known  as  the  valve  of 
Vieussens,  or  superioi  medullary  velum.  The  cavity  of  the  third  vesicle  corresponds 
in  the  adult  brain  in  whal   is  known  as  the  fourth  ventricle. 

The    mesencephalon,    or    second 
i'S?.*, '""  cerebral  vesicle,  takes  a  relatively 

small  part  in  the  formation  of  the 
adult  human  brain,  though  very  con- 
spicuous in  manj'  of  the  lower  types 
of  brain.  The  whole  of  its  wall  is 
transformed  into  nervous  tissue  t  he 
roof  or  dorsal  wall  forming  the  cor- 
pora quadrigemina,  while  the  two 
crura  cerebri  are  developed  in  its 
ventral  wall.  The  cavity  of  the 
second  cerebral  vesicle  is  retained  as 
a  narrow  canal  known  as  the  aque 
duct  of  Sylvius,  and  connects  the 
fourth  ventricle  with  the  third  ven- 
tricle. 

Very  soon  after  its  first  appearance 
the  first  cerebral  vesicle  is  modified 
by  the  formation  of  lateral  expansions,  known  as  the  .  ,ptic  vesicles,  which  later  on  are  con- 
stricted off  from  the  central  part  of  the  ca  vity  so  as  to  be  connected  with  this  by  two  short 
tubular-  passages,  the  optic  stalks.  From  the  optic  vessels  are  ultimately  developed  the 
retinae  of  the  eyes.  By  the  development  of  nerve  cells  in  the  optic  cup  the  ganglion- 
cell  layer  of  the  retinaj  is  produced,  and  from  these  cells  fibres  grow  back  along  the 
optic  stalk  and  make  connection  with  the  grey  matter  developed  in  the  lateral  wall  of 
the  fore-brain  and  with  the  adjacent  parts  of  the  mid-brain,  viz.  the  superior  corpora 


Fig.  178.  Longitudinal  section  through  brain  of 
chick  of  ten  days.  (After  Mihalkovicz.) 
oil,  olfactory  lobes ;  h,  cerebral  hemisphere  ; 
U\  lateral  ventricle  ;  pin,  pineal  gland  ;  bg,  cor- 
pora bigemina  ;  chl.  cerebellum  ;  oc,  optic  com- 
missure :  pit,  pituitary  body;  po,  pons  Varolii; 
mo,  medulla  oblongata  :  »*,  i-1.  third  and  fourth 
ventricles. 


362 


PHYSIOLOGY 


quadrigemina.  The  Large  masses  of  nervous  tissue  developed  in  the  lateral  walls  of  the 
fore-brain  are  the  optic  thalami,  which  represent  the  head  ganglia  of  the  brain  stem. 
The  front  portion  of  the  first  cerebral  vesicle  expands  in  a  forward  and  downward 
direction,  and  from  the  upper  and  lateral  aspects  of  the  outgrowth  thus  formed  the 
cerebral  hemispheres  are  produced  as  two  hollow  pouches.  The  original  hack  part  of 
the  fore-brain  is  sometimes  spoken  of  as  the  diencephalon,  while  the  anterior  part 
of  the  cerebral  hemisphere  growing  from  it,  is  the  telencephalon.     The  floor  or  ventral 


l.uminu  truiiualis 
Optic  recess 

<  tptie  nerve 
<  '[I  n   i  iiNiinissurt' 

Hypophysis 


ebellun 

^  Medulla  oblongata 
entricle 
'  Superior  medullary  velum 
/Corpora  quadrigemina 


Suprapineal  rer 
Pineal  bodj 
Cerebral  aqueduct ' 
Fig.  179.     Median  section  of  an  adult  human  brain.     (J.  Symington.) 


wall  of  the  fore-brain  undergoes  moderate  thickening  to  form  the  nervous  structures 
which  occupy  the  '  interpeduncular  space  '  at  the  base  of  the  brain,  viz.  the  posterior 
perforated  spot,  the  corpora  mammillaria  and  the  tuber  cinereum.  The  roof  of  the 
first  cerebral  vesicle  remains  thin  and  in  its  primitive  epithelial  condition,  like  the  roof 
of  the  back  part  of  the  fourth  ventricle. 

In  the  course  of  development  the  cerebral  hemispheres  become  larger  than  the 
whole  of  the  rest  of  the  brain  put  together,  growing  backwards  over  the  latter  as  far 
as  the  middle  of  the  cerebellum  (Fig.  179).     Their  dorsal  and  lateral  walls  become  much 


THE  STRUCTURE   OF  THE   BRAIN  STEM  363 


Fig.  ISO.     Diagrammatic  view  of  the  brain  in  different  classes  of  vertebrates. 

(G  ISKEIA.) 

i  B,  cerebellum  j   ft.  pituitary  body  ;   pn,  pineal  body  :   C.STR,  corpus  striatum 
ghr,  right  ganglion  habenulse  ;  i,  olfactory  ;   n,  optic  nerves. 


:;c,l 


PHYSIOLOGY 


thickened  and  consist  of  white  mattei  internally  and  grey  matter  externally.  The  part 
oi  the  hemisphere  which  lies  over  the  first  cerebral  vesicle  is  undifferentiated  and  remains 
as  a  simple  epithelial  layer.  This  becomes  closely  applied  to  the  similar  layer  forming 
the  roof  of  the  third  ventricle,  from  whieli  il  is  separated  only  by  a  process  of  the  pia 
mater  carrying  numerous  blood-vessels  (the  velum  inter pesitum).  In  the  adult  brain  the 
eavities  of  the  cerebral  hemispheres  are  known  as  the  lateral  ventricles,  the  remains 
ol  the  first  cerebral  vesicle  receiving  the  name  of  the  third  ventricle.  The  lower  and  outer 
part  of  the  hemispheres,  i.e.  the  part  whieli  is  first  formed,  becomes  much  thickened  and 
forms  the  corpus  striatum,  which  is  closely  applied  to  the  front  and  outer  part  of  the 
optic  thalamus.  In  the  corpus  striatum  two  masses  of  grey  matter  are  developed, 
namely,  the  nucleus  caudatus  and  the  nucleus  lenticularis.  A  layer  of  nerve  fibres  ascends 
from  the  brain  stem  to  be  distributed  throughout  the  whole  of  the  cerebral  hemispheres. 
This  forms  a  sort  of  capsule  to  the  optic  thalamus,  lying  between  this  body  and  the  corpus 
striatum  behind,  but  in  front  piercing  the  corpus  striatum  between  its  two  nuclei.  It 
is  called  the  internal  capsule. 

The  development  of  the  different  parts  of  the  brain  stem  from  the  three  cerebral 
vesicles  and  their  gradual  subordination  and  overshadowing  in  the  course  of  development 
by  the  cerebral  hemispheres  is  well  shown  if  we  compare  the  brain  of  a  fish  with  that  of  a 
reptile  and  again  with  that  of  a  mammal  (Fig.  180).  Man's  position  in  the  scale  of 
animal  life  is  determined  not  by  increasing  complexity  of  the  structures  forming  his 
brain  stem,  but  by  the  gradual  subordination  of  these  to  the  latest  formed  cerebral 
hemispheres,  and  by  the  enormous  growth  of  his  capacity  to  adapt  himself  to  a  varying 
environment  consequent  on  the  increase  in  size  of  his  cerebral  hemispheres. 

THE  HIND-BRAIN 
It  will  be  convenient  to  trace  first  the  modifications  undergone  by  the 
axial  part  of  the  nervous  system  in  the  brain"  and  then  to  deal  with  the 
new  masses  of  grey  mutter  which  have  no  homologies  in  the  spinal  cord,  as 


Fig.  181.  Section  through  the  lower  border  of  the  medulla  oblongata,  at  the 
pyramidal  decussation.  (Bechtekew.) 
fla,  anterior  fissure  ;  d,  decussation  of  the  pyramids  ;  1",  anterior  columns  ; 
C'd.  anterior  cornu  ;  cc,  central  canal ;  »S'.  lateral  columns  ;  fr,  formatio  reti- 
cularis ;  ce,  neck,  and  </,  head  of  the  posterior  cornu  ;  rpC'l,  posterior  root  of 
first  cervical  nerve  ;  nc,  beginning  of  nucleus  cuneatus  ;  ng,  nucleus  gracilis  ; 
Hl,  funiculus  gracilis  ;    H".  funiculus  cuneatus  ;    sip,  posterior  fissure. 

well  ;is  the  long  tracts  of  white  matter  serving  to  connect  different  levels 
or  different  sides  of  the  brain. 


THE   STRUCTURE  OF  THE   BRAIN  STEM 


365 


In  examining  successive  sections  from  the  spinal  cord  up  through  the 
medulla,  the  first  change  which  makes  its  appearance  is  due  to  the  decussa- 
tion of  the  pyramids  (Fig.  181).  Throughout  the  spinal  cord,  fibres  have 
been  crossing  from  one  side  to  the- other  through  the  anterior  white  com- 
missure, many  of  them  belonging  to  the  pyramidal  system.  But  at  tlnj 
lower  border  of  the  medulla  we  see  a  large  mass  of  fibres  crossing  between  the 
anterior  columns  and  the  postero-lateral  columns,  at  first  cutting  off  the  head 
of  the  anterior  horn  and  later  on  breaking  this  up  altogether,  so  that  the 
onlv  definite  collection  of  grey  matter  left  in  this  situation  is  a  small  part 
of  the  lateral  column  of  grey  matter  known  as  the  lateral  nucleus.  In  this 
way  arc  formed  the  big  anterior  columns  of  the  medulla,  which  are  known 
as  the  pyramids,  and  contain  all  the  fibres  that  in  the  cord  are  represented  by 
tht"  direct  and  crossed  pyramidal  tracts. 


Funiculus  gracil 
!  uuieulus  cuneatus 


Sp.  root  of  5th  n.t-^jW?' 


Fonnatio   retlcula 


Gracile  nucleus 

Cuneate  nucleus 

Subst.  gel.  Eolandi 

Decussation  of  fillet 

Int.  access  olivary  n. 
Nerve  XII. 


Fig.  182.     Transverse  section  through  medulla  of  foetus,  immediately  above  pyramidal 
decussation.     (Cunningham.)     Stained  by  Pal-Weigert  method. 

The  next  change  is  due  to  the  ending  of  the  posterior  columns  (Fig.  182). 
These  are  the  central  ascending  branches  of  dorsal  nerve  roots,  having  there- 
fore an  origin  outside  the  cord.  On  their  way  up  the  cord  they  send  in 
collaterals  to  end  in  the  grey  matter  of  the  posterior  horn.  The  main  mass 
terminates  in  the  medulla,  just  above  the  pyramidal  decussation,  in  two 
collections  of  grey  matter — the  nucleus  gracilis  and  the  nucleus  cuneatus — 
which  are  formed  by  a  great  hypertrophy  of  the  grey  matter  at  the  root 
of  the  posterior  horn.  The  effect  of  this  development  in  the  dorsal  region 
of  the  medulla  is  to  push  the  head  of  the  posterior  horn  outwards.  At  the 
same  time  this  mass  of  gelatinous  substance  becomes  enlarged,  so  that  in 
section  we  have  three  grey  masses  from  within  outwards,  the  nucleus  gracilis, 
the  nucleus  cuneatus,  and  the  nucleus  of  Rolando. 

The  fibres  of  the  postero-median  column,  which  are  derived  chiefly  fr<  >m 
the  lower  limb,  end  in  arborisations  round  the  cells  of  the  nucleus  gracilis, 
while  those  of  the  postero-extemal  column,  or  column  of  Burdach.  of  which 
the  majority  is  formed  by  fibres  from    the  upper  limbs,  terminate    in   the 


366 


l'rlYSiOLOfJY 


grey  matter  of  the  nucleus  cuneatus.  The  cells  of  these  two  masses  of 
grey  matter  of  course  give  off  axons,  which  can  carry  on  the  impulses 
brought  to  them  by  the  fibres  of  the  posterior  columns.  These  axons  speedily 
leave  the  dorsal  aspect  of  the  medulla,  bending  round,  as  the  arcuate  fibres, 
to  the  deeper  parts  of  its  structure.  Thus  nothing  is  left  to  take  the  place 
of  the  posterior  columns  on  the  posterior  aspect  of  the  cord.  With  the  dis- 
appearance of  these  columns  and  the  development  of  the  pyramids  we  get  a 
practical  obliteration  of  the  anterior  fissure  and  a  displacement  of  the  central 
canal  towards  the  dorsal  surface.  A  little  higher  up  (Fig.  183)  the  canal 
opens  out  altogether,  forming  the  fourth  ventricle,  covered  on  its  dorsal 
surface  only  by  a  thin  layer  of  ependyma.  a  simple  epithelium  representing 


s        «&. 


Posterior  longitudinal  fascicul 

~i'l>-T.tnti:i  <,'■!. it  ui"~:i  Kolandi, 
■*|.in;il  root,  ot  tilth  nerve 
—  Nucleus  amoiguus 
erebello-olivary  fibres 
sal  acci    -my  olivary  nucleus 
tor  superficial  arcuate  fibres 

!  accessory  olivary  nucleus 


Inferior  olivary  nucleu5 


Fig.  1s:j.    Transvers 


section  thrum 
medulla. 


Pyramid 

uate  nucleus 

Anterior  superficial  arcuate  fibres 

h  the  middle  of  the  olivary  region  of  the  human 
(<  luKNINGHAM.) 


all  that  is  left  of  the  dorsal  wall  of  the  primitive  cerebral  vesicle.  The 
appearance  of  the  section  is  now  modified  by  two  structures.  In  the  first 
place,  a  new  mass  of  grey  matter,  consisting  of  a  thin  layer  shaped  like  a 
flask  with  its  orifice  directed  inwards,  is  developed  in  the  lateral  part  of  the 
medulla,  between  the  pyramids  in  front  and  the  tubercle  of  Rolando  behind. 
This  is  the  olivary  body,  and  has  on  its  inner  and  dorsal  sides  two  little  grey 
masses  which  are  the  accessory  olivary  bodies.  The  other  feature  is  the  new 
relay  of  sensory  fibres  which  start  from  the  dorsal  nuclei,  the  nuclei  gracilis 
and  cuneatus.     These  fibres  run  outwards  and  forwards  from  the  nuclei 


THE  STRUCTURE   OF  THE   BRAIN  STEM 


367 


riulit  round  the  medulla.  Some  fibres  pass  into  the  restiform  body  of  the 
same  side.  A  larger  number,  forming  the  superficial  arcuate  fibres,  pass 
superficially  to  the  olive  to  join  the  restiform  body  of  the  opposite  side, 
while  others,  the  deep  arcuate  fibres,  pass  deeply  to  the  olives,  and  crossing 
in  the  median  raphe  turn  upwards  in  the  broken  mass  of  grey  and  white 
matter  which  lies  between  the  olives  and  the  superficial  grey  matter  of  the 


-.-C  01.  Fibres 


Subdfl.-Bol:- 


FlG.  184.      Diagram  to  show  the  sources  of  the  fibres  making  up  the  restiform  body. 

Ar.N,  arcuate  nucleus  ;   Ar  fibres,  arcuate  fibres  ;   Pyr,  pyramid ;   C.Sp. 

Tract,   direct    cerebellar  tract;    C.01   fibres,   cerebello-olivary   fibres;  (Pl.B, 

posterioi  longitudinal  bundle  :   f  >X.  nucleus  of  Deiters  ;  NB,  nucleus  of  Bech- 

t'-n  w  ;    I'o.X,  roof  nuclei;  Vest.  N,  vestibular  nerve. 

fourth  ventricle.  This  decussation,  which  is  known  as  the  'decussation 
of  the  fillet  '  or  the  sensory  decussation,  takes  place  immediately  above  the 
level  of  the  decussation  of  the  pyramids.  In  its  upward  course  it  forms  a 
conspicuous  strand  of  fibres,  lying  close  to  the  mesial  plane  and  separated 
from  its  follow  of  the  opposite  side  simply  by  the  median  raphe.  To  this 
collection  of  fibres  is  given  the  name  of  the  fiUei  or  lemniscus.    It  is  perhaps 


368  PHYSIOLOGY 

the  most  important  of  the  afferent  tracts  of  the  brain  stem,  receiving 
as  it  does  continuations  of  the  posterior  columns  of  the  cord  as  well  as 
contributions  from  the  various  sensory  cranial  nerves.  It  may  be  traced 
forwards  as  far  as  the  thalamus  and  subthalamic  region,  where  its  fibres 
terminate.  The  region  corresponding  to  the  anterior  column  of  the  spinal 
cord  is  thus  invaded  in  the  medulla  by  two  great  longitudinal  tracts  of 
fibres  namely,  the  pyramids  and  the  tracts  of  the  fillet.  The  region  corre- 
sponding to  the  anterior  basis  bundle,  i.e.  that  part  of  the  anterior  columns 
occupied  chiefly  by  intra-spinal  fibres,  is  thus  pushed  further  backwards  and 
finally  comes  to  lie  immediately  beneath  the  grey  matter  of  the  floor  of  the 
fourth  ventricle.  Immediately  dorsally  to  the  fillet  is  to  be  seen  another 
well-marked  bundle  of  longitudinal  fibres,  known  as  the  posterior  longi- 
tudinal bundle.  These  fibres,  which  serve  to  connect  the  nuclei  of  many  of 
the  cranial  nerves,  can  be  regarded  as  analogous  to  the  constituent  fibres  of 
the  anterior  basis  bundle  in  the  cord,  and  can  in  fact  be  traced  into  this  part 
of  the  anterior  columns  in  the  first  and  second  cervical  segments  of  the  cord. 
The  fourth  ventricle  is  covered  in  by  the  cerebellum,  which  is  attached 
to  the  axial  part  of  the  brain  by  three  peduncles,  the  inferior  peduncles 
or  restiform  bodies,  the  lateral  peduncles,  which  form  the  great  mass  of 
transverse  fibres  known  as  the  pons  Varolii,  and  the  superior  peduncles, 
which  run  forward  to  the  posterior  corpora  quadrigemina.  The  restiform 
bodies  can  be  regarded  as  the  direct  continuation  forwards  of  the  lateral 
columns  of  the  cord,  minus  the  pyramidal  tracts,  the  chief  remaining  tract 
therefore  being  the  posterior  or  direct  cerebellar  tract.  In  the  region 
of  the  dorsal  nuclei  however,  it  receives  accession  of  fibres  from  the  gracile 
and  cuneate  nuclei  of  the  same  side  and,  through  the  superficial  arcuate 
fibres,  from  the  nuclei  of  the  opposite  side,  and  thus  passes  as  a  thick  white 
bundle  into  the  cerebellum.  Among  these  arcuate  fibres  are  also  a  number 
derived  from  the  olivary  body  of  the  opposite  side,  known  as  the  cerebello- 
olivary  fibres.  On  its  way  it  is  joined  by  a  smaller  bundle,  the  '  internal 
restiform  body,'  which  conveys  fibres  from  the  vestibular  division  of  the 
eighth  nerve  and  also  serves  to  connect  Deiters'  nucleus  with  the  cerebellum. 
The  restiform  body  is  thus  made  up  of  the  following  fibres  (Fig.  184)  : 

(1)  The  direct  or  posterior  cerebellar  tract,  derived  from  the  cells  of 
Clarke's  column  on  the  same  side  of  the  cord. 

(2)  The  posterior  superficial  arcuate  fibres,  derived  from  the  gracile  and 
cuneate  nuclei  of  the  same  side. 

(3)  The  anterior  superficial  arcuate  fibres,  from  the  gracile  and  cuneate 
nuclei  of  the  opposite  side. 

(4)  The  cerebello-olivary  fibres. 

(5)  The  vestibulocerebellar  fibres. 

A  section  through  the  pons  shows  the  fourth  ventricle  widely  dilated, 
with  a  floor  formed  of  grey  matter  as  in  the  medulla.  The  chief  difference 
in  the  appearance  of  the  section  is  due  to  the  great  masses  of  transverse 
fibres  which  pass  into  the  pons  by  the  lateral  peduncles  of  the  cerebellum, 
cross  by  the  median  raphe,  and  turn  either  upwards  or  downwards  on  the 


THE  STRUCTURE   OF   THE   BRAIN  STEM 


369 


opposite  side  or  end  in  connection  with  the  nerve  cells  which  are  scattered 
throughout  the  white  fibres.  The  pyramids  can  still  be  seen  as  thick  longi- 
tudinal bundles  on  each  side  in  the  midst  of  the  transverse  fibres.  They  are 
considerably  larger  than  in  the  medulla  and  become  larger  as  we  trace  them 
up  towards  the  mid-brain,  owing  to  the  presence  of  a  number  of  fibies 
which  are  derived  from  the  cortex  cerebri  and  end  in  the  grey  matter  of  the 


Supr.  ccr.  peduncle 


Valu  of  Yi<ii*seiis 


Motor  nucleus*  ol  5tl 


Motor  root,  of  ."it li  n.  —  —^d 


Sensory  nucleus  of  5th 
Supr.  olive  — -^ 


Fig.  ]s.">.     Transverse,  ection  I ugh  middle  of  pons  Varolii  (if  orang  on  level  of 

nuclei  of  fifth  nerve.     (Ct/nsdigham.) 

pons.  The  tract  of  the  fillet  lies  on  each  side  of  the  middle  line  dorsally  to 
the  transverse  fibres.  A  little  to  the  outside  of  the  fillet  is  seen  a  special 
mass  of  grey  matter,  known  as  the  superior  olive.  The  nervous  mass  lying 
behind  the  transverse  fibres  of  the  pons,  between  them  and  the  grey  matter 
of  the  floor  of  the  fourth  ventrit  le,  is  known  as  the  formatio  reticularis.  It 
is  divided  into  a  lateral  and  mesial  part  by  the  fibres  of  the  hypoglossal 
nerve.  In  the  lateral  portions  there  is  a  considerable  quantity  of  grey 
matter,  which  can  be  regarded  as  continuous  with  the  grey  matter  of  the 
lateral  horns  of  the  cord.  The  '  lateral  nucleus  '  is  simply  a  condensed  part 
of  this  grey  matter,  lying  between  the  olive  and  the  gelatinous  substance  of 
Rolando.  The  mesial  part  of  the  formatio  reticularis  is  almost  free  of  nerve 
cells.     The  reticular  appearance  of  this  part  of  the  pons  is  due  to  the  inter- 

24 


370 


PHYSIOLOGY 


section  of  fibres  which  run  longitudinally  and  transversely.  The  transverse 
fibres  are  a  continuation  of  the  deep  arcuate  fibres.  The  longitudinal  fibres 
in  the  miter  part  of  the  formatio  reticularis  are  the  representatives  of  the 
lateral  columns  of  the  cord  after  the  removal  of  the  direct  cerebellar  and  the 
crossed  pyramidal  tracts.  They  include  therefore  the  anterolateral  ascend- 
ing tract  (tract  of  Gowers)  and  a  number  of  other  fibres  corresponding  to  the 
lateral  basis  bundle  in  the  cord.      In  the  mesial  part  of  the  formatio  retiou- 


4th  ventriele 
Mesenc.  root  of  5th  n.  • — .        t^'^S 

Postr.  long,  bundle 

Form,  reticularis 
Nucleus  of  lateral  fillet 


Valve  of  Vieussens 
Floor  of  4th  ventricle 
s.  Supr.  cerebellar 

peduncle 


ing  de- 
cussation of  supr. 
3§gffl  cerebellar  pcd. 

Mesial  fillet 


Bf'      Pyramids 


Fig.  186.     Section  across  upper  part  of  pons  Varolii  of  the  orang.     (Cunningham.) 

laris  the  longitudinal  tracts  are  the  tract  of  the  fillet  and  the  posterior  longi- 
tudinal bundle  on  each  side  of  the  middle  line.  In  the  upper  part  of  the  pons 
Varolii  a  well-marked  collection  of  transverse  fibres  are  to  be  seen  lying 
dorsally  to  the  tracts  of  the  fillet.  This  collection  is  called  the  corpus 
trapezoides  and  is  made  up  of  ascending  fibres  derived  from  the  nuclei  of  the 
cochlear  nerve,  the  auditory  part  of  the  eighth  nerve. 

A  little  further  forward  a  section  will  escape  the  cerebellum  altogether, 
being  bounded  ventrally  by  the  upper  or  anterior  part  of  the  pons  and 
dorsally  by  a  thin  mass  of  grey  matter,  the  valve  of  Vieussens  (Fig.  186). 
On  each  side  of  the  valve  of  Vieussens  may  be  seen  the  superior  peduncles  of 
the  cerebellum.  As  these  peduncles  are  traced  upwards  they  sink  gradually 
deeper  into  the  pons  until  they  lie  on  the  outer  side  of  the  tegmental  region 
or  formatio  reticularis.  They  are  made  up  of  fibres  which  run  from  the 
dentate  nucleus  of  grey  matter  in  the  cerebellum  to  the  mid-brain,  where 
they  decussate  below  the  Sylvian  iter  and  end  in  the  red  nucleus  and  in  the 
thalamus  of  the  opposite  side.  They  also  contain  the  continuation  upwards 
of  the  antero-lateral  ascending  tract  which,  passing  up  in  the  superior 
peduncles,  bends  dorsally  round  the  fourth  nerve  and  then,  turning  back- 
wards, ends  in  the  superior  vermis  of  the  cerebellum.     In  a  section  through 


THE  STRUCTURE   OF  THE   BRAIN  STEM 


371 


the  upper  part  of  the  pons,  the  division  into  the  formatio  reticularis  or 
tegmentum  and  the  part  made  up  of  transverse  and  longitudinal  fibres,  the 
pedal  portion,  is  well  marked  (v.  Fig.  186).  The  fourth  ventricle  has  now 
become  constricted  to  a  narrow  canal  triangular  in  section  and  closed  above 
by  the  valve  of  Vieussens.  It  is  surrounded,  especially  on  its  ventral  side, 
by  grey  matter  containing  the  cells  of  origin  of  the  fourth  nerve.     In  the 


'  Inf.  corpus  quadri 


.  Mesenc.  root  of  5th  n. 
Nucleus  of  4th  nerve 


UPostr.  long,  bundle 
>\  Mesial  fillet 


Grey  matter 1 

Aqueduct  of  Sylvius_  __/\ 


Raphe 


Pupr.  cer.  pi  duncle. 


Substantia  nier; 


Fio.  187.     Transverse  section  through  human  mid-brain,  on  level  of   the  inferior 
corpora  quadrigemina.     (Cunningham.) 

tegmental  portion  we  may  distinguish  on  each  Side  the  superior  cerebellar 
peduncle.  Outside  the  longitudinal  fibres  of  this  peduncle  are  a  number 
of  transverse  fibres  derived  from  the  corpus  trapezoides  seen  in  the  previous 
section.  To  these  fibres  is  given  the  name  of  the  '  lateral  fillet.'  They  are 
on  their  way  to  end  in  the  roof  of  the  mid-brain  in  the  posterior  corpora 
quadrigemina.  The  posterior  longitudinal  bundle  lies  near  the  middle  line, 
immediately  under  the  grey  matter  of  the  floor  of  the  fourth  ventricle,  while 
the  longitudinal  fibres  of  the  fillet,  now  called  the  mesial  fillet,  form  a  distinct 
mass  in  the  ventral  portion  of  the  formatio  reticularis.  The  pedal  portion 
contains  the  longitudinal  fibres  of  the  pyramids,  now  much  increased  in 
amount,  cut  up  into  bundles  by  transverse  fibres  derived  from  the  middle 
peduncles  of  the  cerebellum. 

The  cerebellum,  which  covers  in  the  fore  part  of  the  fourth  ventricle, 
will  have  to  be  described  in  greater  detail  later  on.  At  present  it  will  suffice 
to  say  that  it  consists  of  a  middle  and  two  lateral  lobes.     The  surface  of  the 


;$72 


PHYSIOLOGY 


middle  lobe  turned  towards  the  fourth  ventricle  is  known  as  the  inferior 
vermis,  the  dorsal  surface  forming  the  superior  vermis.  Each  vermis  and 
each  lateral  lobe  is  subdivided  into  a  number  of  smaller  lobes.  The  intimate 
structure  of  all  parts  of  the  cerebellum  is  however  very  uniform.  It  consists 
of  a  mass  of  white  matter  internally,  covered  by  a  layer  of  grey  matter,  the 
extent  of  grey  matter  being  largely  increased  by  the  formation  of  numerous 
parallel  and  more  or  less  curved  grooves  or  sulci  which  give  the  whole  organ 
a  laminate  appearance.     In  the  mass  of  white  matter,  which  forms  the 


Transverse  section  through  human  mid-brain  at  the  level  of  the  superior 
corpus  quadrigeminum.     (Cunningham.) 

core  of  each  lateral  hemisphere,  is  an  isolated  nucleus  of  grey  matter  known 
as  the  corf  as  dentatum.  In  the  white  matter  of  the  middle  lobe  is  another 
mass  of  grey  matter  known  as  the  roof  nucleus  or  nucleus  fastigii.  Be- 
tween the  nucleus  fastigii  and  the  nucleus  dentatum  are  two  other  nuclei, 
the  nucleus  globosus  and  the  nucleus  emboliformis. 

THE  MID-BRAIN 
A  little  further  forward  the  fourth  ventricle  comes  to  an  end,  and  the 
section  passes  through  the  mid-brain  (Fig.  187),  the  cavity  of  the  second 
cerebral  vesicle  being  represented  by  the  narrow  Sylvian  aqueduct,  bounded 
dorsally  by  the  corpora  quadrigemina  and  ventrally  by  the  crura,  the  stalks 
of  the  brain.  The  crura  are  divided  by  an  irregular  mass  of  grey  matter,  the 
substantia  nigra,  into  two  parts.     The  ventral  portion  is  known  as  the  pes  or 


THE  STRUCTURE   OF  THE   BRAIN  STEM  373 

orusta.  It  is  composed  almost  entirely  of  longitudinal  white  fibres,  among 
which  is  the  continuation  forwards  of  the  pyramids  of  the  medulla.  The 
pyramids  however  form  only  about  two-fifths  of  the  total  mass  of  white 
fibres,  the  rest  consisting  of  fibres  which  run  from  the  different  parts  of  the 
cerebral  cortex,  especially  from  the  frontal  and  temporal  lobes,  to  end  in  the 
formatio  reticularis  of  the  pons,  probably  in  relation  with  the  grey  matter  in 
this  situation  and  with  the  endings  of  the  transverse  fibres  derived  from  the 
cerebellum  and  forming  the  middle  peduncles  of  the  cerebellum.  The  dorsal 
part,  the  tegmentum,  is  a  direct  prolongation  forwards  of  the  formatio  reticu- 
laris of  the  medulla  and  pons,  and  like  this  contains  much  scattered  grey 
matter.  On  a  level  with  the  inferior  corpora  quadrigemina  a  number  of 
decussating  fibres  are  to  be  seen  in  the  tegmentum,  which  are  derived  from 
the  superior  cerebellar  peduncles.  Their  decussation  is  complete  at  the  level 
of  the  upper  border  of  the  inferior  corpora  quadrigemina.  Here  each 
peduncle  turns  upwards,  and  a  large  proportion  of  its  fibres  end  in  the  red 
nucleus  (Fig.  188),  a  mass  of  grey  matter  forming  a  conspicuous  feature  of 
sections  through  the  anterior  part  of  the  mid-brain.  Many  of  the  fibres  pass 
round  the  red  nucleus,  forming  a  sort  of  capsule  over  it,  to  the  ventral 
I  in  it  of  the  optic  thalamus,  in  which  they  probably  end.  It  is  possible  that  a 
certain  proportion  pass  through  the  optic  thalamus  and  run  straight  to  the 
cerebral  cortex  of  the  Rolandic  area.  The  lateral  fillet  has  disappeared  from 
the  region  of  the  tegmentum  and  passed  into  the  inferior  corpora  quadri- 
gemina. The  mesial  fillet  forms  a  flat  band  lying  to  the  outer  side  of  the  red 
nucleus  and  comes  into  close  relation  with  a  ganglion  of  the  fore-brain,  known 
as  the  internal  geniculate  body.  The  roof  of  the  mid-brain  is  formed  by  the 
corpora  quadrigemina.  The  inferior  corpora  quadrigemina  are  composed  of 
central  grey  matter  encapsulated  by  white  matter,  derived  chiefly  from 
the  lateral  fillet.  The  superior  corpora  quadrigemina  are  composed  of  several 
layers  of  grey  matter  traversed  by  nerve  fibres,  derived  partly  from  the 
fillet,  partly  from  the  optic  tract,  and  partly  from  the  occipital  lobe  of  the 
cerebral  hemisphere. 

THE  FORE-BRAIN 
In  the  fore-brain  the  most  important  feature  is  the  optic  thalami,  the 
two  head  ganglionic  masses  of  the  brain  stem  (Fig.  189).  In  this  region 
the  central  neural  canal,  which  in  the  mid-brain  forms  the  Sylvian  iter, 
widens  out  to  the  third  ventricle,  in  the  lateral  walls  of  wThich  are  developed 
the  two  optic  thalami.  It  is  a  narrow  cleft,  rapidly  increasing  in  depth  from 
behind  forwards.  As  wTe  trace  sections  forwards  we  see  that  the  two  crura 
cerebri  diverge  from  one  another.  The  floor  of  the  third  ventricle  is  thus  left 
thin.  It  is  formed  from  behind  forwards  by  a  thin  layer  of  grey  matter  witn 
numerous  vessels,  the  locus  perforates  posticus,  two  small  eminences,  he 
corpora  mammillaria,  and  in  front  of  these  another  lamina  of  grey  matter 
known  as  the  tuber  cinereum.  In  front  of  the  tuber  cinereum  is  the  infun- 
dibulum,  which  leads  to  the  posterior  lobe  of  the  pituitary  body.  In  front 
of  the  infundibuluin  the  optic  chiasnia  is  closely  attached  to  the  lowest  part 
of  the  anterior  wall  of  the  ventricle.     The  front  wall  is  formed  by  a  thin  layer 


374 


PHYSIOLOGY 


of  nervous  matter,  the  lamina  emerea, at  the  upper  border  of  which,  project- 
ing slightly  into  the  ventricle,  is  a  strand  of  white  fibres  connecting  the  an- 
terior parts  of  the  two  optic  thalami  and  known  as  the  anterior  commissure. 
The  roof  of  the  third  ventricle  is  formed  entirely  of  epithelium,  the  ependyma, 


Corpus  callosum 

Lateral  ventricle 

Nucleus  caudatus 

Internal  capsule 

Thalamus 

Nucleus  lcntiforniis 

Anterior  commissure 


Collicuhis  superior 
Inferior  brachium 

Colliculus  Inferior 
4  th 

Trigonum  Iemniscl 

5th  nerve / 

Brachium  conjunctivum 
Pons. 

8th  nerve 

Rrstifonn  body 

9th  nerve 

lOth  nerve 


Vl2th  nerve 
Fig.  189.     Right  lateral  aspect  of  brain  stern,  with  a  part  of  the  cerebrum. 

(J.  Symington.) 

along  the  upper  surface  of  which  is  the  layer  of  pia  mater,  the  velum  inter- 
position. The  roof  is  invaginated  into  the  cavity  by  two  delicate  vascular 
fringes,  the  choroid  plexuses.  At  the  back  part  of  the  roof  is  attached  the 
stalk  of  the  pineal  body,  and  behind  this  stalk,  between  the  anterior  parts 
of  the  anterior  corpora  quadrigemina,  is  a  small  space  known  as  the  trigomnn 
habenulw,  which  contains  a  well-marked  collection  of  nerve  cells  known  as  the 
ganglion  habemdw.  The  lateral  walls  are  formed  entirely  by  the  optic 
thalami.  The  upper  surface  of  the  optic  thalamus  looks  into  the  lateral 
ventricle  of  the  cerebral  hemispheres,  from  which  it  is  separated  by  the 
velum  interpositum  and  by  the  ependyma,  the  epithelium  completing  the 
inferior  wall  of  the  lateral  ventricle  in  this  region.     It  consists  of  three 


THE   STRUCTURE   OF  THE   BRAIN  STEM 


375 


masses  of  grey  matter- — the  anterior  nucleus,  the  lateral  nucleus  (the  largest 
of  the  three),  and  the  mesial  nucleus.  Its  outer  surface  is  in  contact  with  the 
layer  of  nerve  fibres  formed  by  the  crusta  of  each  crus  cerebri  as  it  diverges 
from  its  fellow  to  pass  up  into  the  cerebral  hemispheres.  Into  this  layer, 
'  the  internal  capsule,'  fibres  proceed  from  all  parts  of  the  thalamus  to  pass 
to  the  cerebral  cortex.  The  anterior  extremity  of  the  thalamus,  known  as  the 
anterior  tubercle,  forms  a  marked  projection  into  the  lateral  ventricle.  In 
front  of  this,  the  foramen  of  Monro  leads  from  the  third  ventricle  into  the 
lateral  ventricle.  This  foramen  is  bounded  anteriorly  by  a  strand  of  fibres, 
known  as  the  '  anterior  pillar  of  the  fornix,'  which  lies  just  behind  the  anterior 


Fig.  190,  Transverse  section  through  upper  part  of  mid-brain. 
Th,  thalamus ;  brs,  brachium  superior ;  cqs,  anterior  (or  superior)  corpus 
quadrigeminum  ;  cgi,  cge,  internal  and  external  geniculate  bodies  ;  /,  fillet ;  «,  aque- 
duct ;  pi,  posterior  longitudinal  bundle ;  r,  raphe  ;  III,  third  nerve  ;  nlll,  its 
nucleus  ;  Ipp,  posterior  perforated  space  ;  sn,  substantia  nigra  ;  cr,  crusta  ;  II, 
optic  tract ;  H,  medullary  centre  of  the  hemisphere  ;  nc,  nucleus  caudatus  ;  st, 
stria  terminahs. 

commissure  and  forms  a  conspicuous  feature  in  the  anterior  part  of  the 
lateral  wall  of  the  third  ventricle.  It  passes  in  the  wall  down  to  the  corpus 
mammillare.  From  the  corpus  mammillare  a  well-marked  bundle  of  fibres 
passes  up  into  the  optic  thalamus  to  end  round  the  large  cells  in  the  anterior 
nucleus  of  the  thalamus.  The  posterior  extremity  of  the  thalamus  forms 
a  definite  prominence,  the  pulvinar.  To  the  outer  and  back  part  of  the 
pulvinar  two  bodies  are  developed,  known  as  the  geniculate  bodies.  These 
may  be  regarded  as  special  outgrowths  of  the  grey  matter  of  the  optic 
thalamus,  one  of  which,  the  external  geniculate  body,  is  in  close  connection 
with  the  fibres  from  the  optic  tracts,  while  the  other,  the  internal  geni- 
culate body,  receives  fibres  from  the  lateral  fillet  ultimately  derived  from 
the  organ  of  hearing.  In  a  section  through  the  fore  part  of  the  mid-brain 
(Fig.  190)  these  two  bodies  may  be  seen  lying  to  the  outer  side  of  the  anterior 
corpora  quadrigemina,  so  that  the  fore-brain,  to  a  certain  extent,  enfolds  the 
anterior  part  of  the  mid-brain.     Below  the  thalamus  at  its  back  part  is  the 


37G 


PHYSIOLOGY 


prolongation  forwards  of  the  tegmentum  of  the  crus.  This  is  often  spoken 
of  as  the  subthalamic  region.  The  red  nucleus  is  a  conspicuous  object  in 
sections  through  the  back  part  of  this  region,  but  gradually  diminishes  as  we 
proceed  forwards,  and  disappears  before  the  level  of  the  corpora  mammillaria 
is  reached.  The  mesial  fillet,  which  in  the  mid-brain  lies  on  the  lateral  and 
dorsal  aspect  of  the  red  nucleus,  is  prolonged  upwards  together  with  fibres 
from  the  superior  cerebellar  peduncle  into  the  ventral  part  of  the  thalamus, 
where  probably  all  of  the  fibres  end  in  connection  .with  the  thalamic  cells. 
The  substantia  nigra  gradually  disappears.  Before  it  has  disappeared  we 
may  see  on  its  outer  side  a  special  collection  of  grey  matter  called  the  nucleus 
of  Luys  or  the  corpus  suithalamicum.  In  addition  to  the  anterior  and 
posterior  commissures  already  described  as  connecting  the  two  optic  thalami 
at  the  front  and  back  of  the  third  ventricle,  the  two  sides  are  connected  about 
the  middle  of  the  cavity  by  the  middle  or  soft  commissure.  The  optic 
thalamus  is  often  described  together  with  the  corpus  striatum  as  forming 
the  basal  ganglia.  The  corpus  striatum  is  however  genetically,  and 
probably  functionally,  part  of  the  cerebral  hemispheres,  and  its  connections 
will  therefore  be  best  dealt  with  when  describing  the  latter  bodies. 

THE   AXIAL  GREY  MATTER 
In  the  spinal  cord  we  could  distinguish  between  the  anterior  grey  matter 
giving  origin  to  the  motor  nerves,  the  posterior  grey  matter  serving  as  an  end 


Cross-section  of  medulla  showing 
(Cunningham.) 


XII. 

[HYPOGLOSSAL] 


nuclei  of  nerves  X  and  xn. 


station  for  a  number  of  the  sensory  posterior  root  fibres,  and  a  lateral  horn, 
less  well  marked,  probably  giving  origin  to  the  visceral  system  of  nerves. 
As  the  central  canal  widens  out  to  form  the  fourth  ventricle,  the  relative 


THE  STRUCTURE    OF  THE   BRAIN  STEM 


377 


position  of  these  various  parts  becomes  altered,  the  anterior  grey  matter 
being  now  neatest  the  median  line,  while  the  posterior  grey  matter  lies  more 
laterally.  Part  of  the  lateral  grey  matter  seems  to  lie  deeper  than  the  rest, 
from  which  it  is  separated  by  the  tangle  of  fibres  and  cells  known  as  the 
formatio  reticularis.  All  the  cranial  nerves  from  the  third  to  the  twelfth 
arise  or  end  in  the  axial  grey  matter,  or  in  close  proximity  to  it.  So  great 
however  is  the  complexity  of  this  part  of  the  nervous  system,  and  so  in- 
volved are  the  genetic  relations  of  the  various  nerves,  that  it  is  difficult  or 


Fig.  192.  Diagram  showing  the  brain  connections  of  the  vagus,  glosso-pharyngeal, 
auditory,  facial,  abducent,  and  trigeminal  nerves.  (Cunningham  after  Ober- 
steiner..) 

impossible  in  many  cases  to  state  definitely  the  spinal  analogies  of  these 
nerves. 

The  cranial  nuclei  (of  origin  or  termination)  may  be  roughly  classed  as 
follows  : 

(1)  Motor  Somatic  Nuclei «  These  consist  of  an  almost  continuous  column 
of  multipolar  cells.  Iving  close  to  the  middle  line  on  each  side  in  the  floor  of 
the  fourth  ventricle,  the  Sylvian  iter,  and  the  back  part  of  the  third  ventricle. 
From  below  upwards  these  groups  of  cells  give  origin  to  the  fibres  of  : 


378 


PHYSIOLOGY 


(a)  The  hypoglossal  nerve. 

(b)  The  sixth  nerve. 

(c)  The  fourth  nerve. 

(d)  The  third  or  oculo-motor  nerve. 

(2)  Splanchnic  Sensory  Nuclei.  Immediately  outside  the  column  of 
motor  cells  is  a  column  of  grey  matter  which  receives  the  terminations  of 
the  afferent  fibres  belonging  to  the  ninth,  tenth,  and  eleventh  nerves,  and 
is  sometimes  called  the  vago-glossopharyngeal-accessory  nucleus.     This  grey 


Fig.  193.     Plan  of  the  course  and  connections  of  the  fibres  forming  the  cochlear 
root  of  the  auditory  nerve.     (Schafer.) 
r,  restiform  body  ;    V,  descending  root  of   the  fifth  nerve  ;   tub.ac,  tuberculum 
acusticum  ;    n.acc,  accessory  nucleus  ;    s.o,  superior  olive  ;   n.tr,  nucleus  of  trape- 
zium ;   n.  VI,  nucleus  of  sixth  nerve  ;    VI,  issuing  root-fibre  of  sixth  nerve. 

matter  of  course  does  not  give  rise  to  the  fibres  of  these  nerves  which,  like 
other  sensory  nerves,  are  axons  of  ganglion-cells  lying  outside  the  central 
nervous  system. 

(3)  Splanchnic  Motor  Nuclei.  These  lie  more  deeply  at  some  distance 
from  the  middle  line,  and  include  the  nucleus  ambiguus  for  the  efferent  fibres 
of  the  vaso-glossopharyngeal,  the  nucleus  of  the  seventh  or  facial  nerve 
(originally  splanchnic  or  branchial,  now  typically  somatic),  and  the  motor 
nucleus  of  the  fifth  nerve  with  its  prolongation  into  the  mid-brain. 

(4)  Sensory  Somatic  Nuclei.  The  chief  representative  of  this  group 
is  the  great  sensory  root  of  the  fifth  nerve.  The  fibres  of  this  nerve  arise 
from  the  Gasserian  ganglion,  pierce  the  fibres  of  the  pons  Varolii,  and  run 
to  the  dorso-lateral  part  of  the  pons,  where  they  divide  into  ascending  and 
descending  fibres.  These  fibres  form  a  cap  to  the  substantia  gelatinosa, 
the  descending  branches,  which  are  longer,  being  conspicuous  in  sections  of 
the  medulla  as  low  down  as  the  first  or  second  cervical  nerve.  This  nerve 
gives  common  sensation  to  practically  the  whole  of  the  head. 

It  is  doubtful  in  what  group  we  should  place  the  fibres  of  the  eighth 
nerve.  This  nerve  really  consists  of  two  parts  very  different  in  function, 
the  cochlear  or  auditory  nerve,  and  the  vestibular  or  labyrinthine  nerve. 


THE  STRUCTURE  OF  THE   BRAIN  STEM 


379 


The- fibres  of  each  are  derived  from  ganglion-cells  in  the  internal  ear,  pass  to 
the  medulla  at  its  widest  part  and  then,  dividing  into  two,  terminate  in 
masses  of  grey  matter  situated  at  the  extreme  lateral  part  of  the  floor  of  the 
fourth  ventricle. 

The  branches  of  the  cochlear  nerve  (Fig.  193)  make  connection  with  two 
collections  of  cells,  the  dorsal  nucleus,  apparently  embedded  in  the  fibres  of 
the  root  itself,  and  the  accessory  nucleus,  a  little  triangular  mass  of  grey 
matter  situated  in  the  angle  between  the  cochlear  and  vestibular  nerves. 


TO   HEMISPHERE 


FIBRES    OF 

VESTIBULAR 

ROO~ 


NERVE 
ENDINGS 
IN  MACUL/E 
&  AMPULL/E 


p.l.i 


Fig.  194.  Plan  of  the  course  and  connections  of  the  fibres  forming  the  vestibular 
root  of  the  auditory  nerve.  (Schafer.) 
r,  restiform  body ;  v,  descending  root  of  fifth  nerve ;  p.  cells  of  principal  nucleus 
of  vestibular  root  ;  d,  fibres  of  descending  vestibular  root  ;  nil,  a  cell  of  the  descend- 
ing vestibular  nucleus  ;  d,  cells  of  nucleus  of  Deiters  ;  B,  cells  of  nucleus  of  Bech- 
terew;  nt,  cells  of  nucleus  tecti  (fastigii)  of  the  cerebellum  ;  plb,  fibres  of  posterior 
longitudinal  bundle.  No  attempt  has  been  made  in  this  diagram  to  represent  the 
actual  positions  of  the  several  nuclei.  Thus  a  large  part  of  Deiters'  nucleus  lies 
dorsal  to  and  in  the  immediate  vicinity  of  the  restiform  body. 

From  these  miclei  fibres  are  given  off  which  take  two  courses.  Some,  follow- 
ing the  previous  course  of  the  cochlear  nerve,  pass  across  the,  surface  of  the 
fourth  ventricle  as  the  strim  medullares  or  stria  acousticce,  and  then  bending 
inwards  pass  into  the  tegmentum  of  the  opposite  side.  Others  pass  deeply 
and  form  a  mass  of  transverse  fibres  in  the  ventral  part  of  the  tegmentum,  the 
corpus  trapezoides  or  trapedum.  After  making  connections  with  the  superior 
olivary  body  and  a  special  nucleus,  they  join  the  superficial  set  of  fibres,  and 
run  up  in  the  tegmentum  to  the  inferior  corpora  quadrigemina,  forming  the 
■lateral  fillet. 

The  vestibular  nerve  (Fig.  194)  also  has  two  nuclei  of  termination,  the 
median  nucleus  with  small  cells,  and  the  lateral  or  Deiters'  nucleus  with  large 
cells.  Some  fibres  pass  also  to  the  nucleus  of  Bechtereiv,  which  is  in  close 
relation  with  the  roof  nuclei  of  the  cerebellum.  The  descending  fibres  end 
chiefly  in  the  median  nucleus,  while  the  ascending  fibres  end  in  Deiters' 


380 


PHYSIOLOGY 


nucleus.  From  the  latter  a  distinct  band  of  fibres  passes  up  to  the  cere- 
bellum, forming  the  median  division  of  the  restiform  body,  while  other  fibres 
run  across  to  the  tegmentum  of  the  opposite  side,  where  they  take  part  in  the 
formation  of  the  posterior  longitudinal  bundle. 

In  a  section  through  the  fourth  ventricle  through  the  middle  of  the  pons, 
a  group  of  large  cells  is  seen  in  the  position 
occupied  by  the  nucleus  of  the  hypoglossal 
below.  These  cells  give  rise  to  the  fibres  of 
the  sixth  nerve.  Another  group  is  seen  lying 
laterally  and  more  deeply,  evidently  belong- 
ing to  the  lateral  horn  system.  This  is  the 
nucleus  of  the  seventh  or  facial  nerve,  the 
fibres  id  which  pass  dorsallyand  anteriorly, 
looping  round  the  sixth  nerve-nucleus,  before 
issuing  as  the  root  of  the  seventh  nerve. 

In  the  upper  part  of  the  pons  we  find  the 
lit ih  nerve  (Fig.  195)  with  its  two  roots. 
The  fibres  of  the  sensory  root  derived  from 
the  cells  of  the  Gasserian  ganglion  bifurcate. 
The  upper  divisions,  which  are  short,  end  in 
a  mass  of  grey  matter  at  the  lateral  part  of 
the  formatio  reticularis,  the  so-called  sensory 
root,  while  the  descending  divisions  form  a 
long  strand  of  white  fibres  passing  down  as 
far  as  the  second  cervical  nerve  and  lying 
over  the  substantia  gelatmosa  of  Rolando, 
around  the  small  cells  of  which  the  fibres 
finally  terminate.  The  motor  fibres  arise 
partly  from  the  motor  nucleus,  a  mass  of 
Fig.  j  95.     Diagram  showing  ceu-  ceUs  lymg  internally  to  the  sensory  nucleus, 

tral    connections   ot    fifth,   nerve.  " .         .  .  . 

(Cajal.)  and  belonging  probably  to  the  lateral  horn 

a,  Gasserian  ganglion ;   b,  acces-   system.     A  large  number  are  derived  from 

sory  motor  nucleus  ;   c,  main  motor  J                               ° 

nucleus  ;D,  facial  nucleus;  b,  nucleus  along      column    of     cells,     which     stretches 

of  hypoglossal;  f,  sensory  nucleus  of  fonvar(j  from  the  nucleus  as  far  as  the  level 

fifth  nerve;  a,  cerebral  tract  (fillet)  .                                       ... 

of  fifth  nerve.  of     the     anterior     corpora    quadrigemina. 

These  fibres  are  known  as    the  descending 
motor  root  of  the  fifth  nerve. 

In  the  region  of  the  mid-brain,  besides  the  root  of  the  fifth  nerve  just 
mentioned,  we  find  only  the  motor  nuclei  of  the  third  and  fourth  nerves, 
which  are  situated  near  the  median  line  in  the  ventral  part  of  the  central  grey 
matter,  corresponding  in  situation  to  the  sixth  and  twelfth  nerves  lower 
down. 


INTERMEDIATE  GREY  MATTER  OF  THE  CEREBRAL  AXIS 
The  masses  of  grey  matter  which  are  found  throughout  this  region  may 
be  regarded  as  extra  shunting  stations  (or  association  centres  for  various 


THE  STRUCTURE   OF  THE   BRAIN  STEM  381 

systems  of  nuclei  and  conducting  paths),  which  have  arisen  in  consequence 
of  tlie  great  complexity  of  reaction  required  of  the  nerve  mechanisms  in 
connection  with  the  organs  of  special  sense.  We  must  confine  ourselves 
here  to  little  more  than  the  enumeration  of  the  chief  masses,  though  we 
shall  have  occasion  to  refer  to  some  in  more  detail  when  dealing  with  the 
co-ordinating  mechanisms  of  the  cerebral  axis.  From  below  upwards  we 
may  enumerate  the  following  grey  masses  : 

In  the  medulla  is  the  large  olivary  body,  with  the  accessory  olive  lying  on 
its  inner  side.  Each  olive  sends  fibres  across  the  middle  line  to  the  opposite 
cerebellar  hemisphere,  and  must  be  regarded  as  connected  with  this  body 
in  its  functions,  since  atrophy  or  removal  of  one  side  of  the  cerebellum  is 
followed  by  atrophy  of  the  opposite  olive. 

In  the  pons  wTe  find  a  similar  but  smaller  body,  the  superior  olive,  in  the 
neighbourhood  of  the  nucleus  of  the  seventh  nerve.  The  superior  olive  is 
closely  connected  with  the  co-ordination  of  visual  and  auditory  impressions 
with  the  eye  movements. 

Deiters'  nucleus,  which  occurs  in  the  same  region,  although  described  as 
one  of  the  nuclei  of  the  eighth  nerve,  might  equally  well  be  included  in  this 
class  owing  to  its  manifold  connections  with  both  afferent  and  efferent 
mechanisms. 

In  close  connection  with  Deiters'  nucleus  are  a  number  of  grey  masses 
in  the  cerebellum,  the  roof  nuclei  in  the  roof  of  the  fourth  v.entricle. 

In  the  mid-brain  we  must  mention  the  superficial  grey  matter  covering 
the  corpora  quadrigemina. 

On  the  ventral  side  of  the  Sylvian  iter  are  the  various  masses  of  grey 
matter  in  the  crura,  the  red  nucleus,  a  large  mass  in  the  tegmentum  just  below 
the.  oculo-motor  nucleus,  and  the  substantia  nigra,  which  divides  each  crus 
into  two  parts,  the  dorsal  tegmentum  and  the  ventral  pes  or  crusta. 

Finally  at  the  fore  part  of  the  cerebral  axis  we  come  to  the  great  ganglionic 
mass  already  described,  the  optic  thalamus  and  the  geniculate  bodies.  The 
geniculate  bodies  may  be  regarded  as  outgrowths  of  the  optic  thalamus 
which  have  developed  in  connection  with  the  terminations  of  the  auditory  and 
the  optic  nerve  fibres.  The  optic  thalamus  is  connected  by  fibres  with  all 
parts  of  the  cortex  and  represents  the  termination  of  the  whole  tegmental 
system,  so  that  in  many  ways  it  may  be  regarded  as  a  sort  of  foreman  of  the 
central  nervous  system,  controlling  the  activities  of  the  lower  level  centres 
and  bringing  all  parts  of  this  system  in  relation  with  the  supreme  cerebral 
cortex. 

THE  CHIEF  LONG  PATHS  IN  THE  BRAIN  STEM 

In  dealing  with  the  spinal  cord  we  were  able  to  treat  it  as  one  organ, 
very  largely  on  account  of  the  uniformity  of  the  afferent  and  efferent 
mechanisms  connected  with  its  various  segments.  Every  afferent  impulse 
arriving  at  the  cord  has  many  possible  paths  open  to  it,  on  account  of  the 
branching  of  the  nerve  fibres  as  they  enter  ttie  cord  and  the  connection  of 
these  branches  with  different  neurons  of  varying  destination.     The  exact 


382  PHYSIOLOGY 

path  taken  by  any  given  impulse  under  any  given  set  of  circumstances 
is  determined  by  the  varying  resistance  at  the  synapses  which  intervene 
between  the  terminations  of  the  afferent  fibres  conveying  the  impulse 
and  the  next  relay  of  neurons.  These  resistances  in  their  turn  are  altered 
by  the  process  of  facilitation  and  inhibition,  which  may  be  due  to  con- 
temporaneous or  previous  events.  A  conspicuous  example  of  these  con- 
ditions is  afforded  by  the  phenomena  of  simultaneous  and  successive  spinal 
induction. 

The  uniformity  of  afferent  and  efferent  mechanisms  disappears  when  we 
include  the  brain  stem  with  the  spinal  cord.  The  main  efferent  channel 
of  impulses  is  still  through  the  spinal  cord,  since  here  are  found  the  efferent 
mechanisms  for  all  the  skeletal  muscles  of  the  trunk  and  limbs,  the  chief 
servants  of  the  central  nervous  system  in  the  daily  events  of  life.  Other 
efferent  channels  are  added,  which  acquire  special  importance  with  the 
growth  of  the  upper  brain  or  cerebral  hemispheres.  These  mechanisms 
include  those  for  the  movements  of  the  eye  muscles,  those  concerned  in  facial 
expression,  and  those  responsible  for  the  movements  of  the  mouth  in  mastica- 
tion and  deglutition,  and  in  man,  in  speech.  Important  visceral  efferent 
fibres  are  also  contained  in  the  vago-glossopharyngeal  nerves,  which  leave 
the  brain  stem  at  its  hindmost  part  in  the  region  of  the  medulla  oblongata, 
and  influence  the  condition  of  the  heart  and  the  alimentary  canal  with 
its  accessory  organs.  On  the  other  hand,  the  afferent  mechanisms  of  the  brain 
stem  far  transcend  in  importance,  i.e.  in  their  influence  on  the  reactions  of 
the  animal,  those  of  the  spinal  cord.  Among  these  afferent  mechanisms  are 
those  which  we  have  spoken  of  as  '  projicient '  sense  organs  or  organs  of 
foresight,  the  impulses  from  which  must  predominate  over  all  reactions 
determined  by  the  immediate  environment  of  the  animal.  Into  the  medulla 
oblongata  are  poured  the  impulses  from  the  greater  part  of  the  alimentary 
canal  and  from  the  heart  (the  chief  factor  in  the  circulation)  and  the  lungs. 
At  the  junction  of  the  medulla  and  pons  is  the  great  eighth  nerve,  really  con- 
sisting of  two,  one  of  which,  the  cochlear  nerve,  carries  impulses  from  the 
projicient  sense-organ  of  hearing,  while  the  other,  the  vestibular  nerve,  has 
its  terminations  in  the  labyrinth,  the  sense-organ  of  equilibration.  To  the 
impressions  received  from  this  organ  all  the  complex  co-ordinating  motor 
mechanisms  of  the  spinal  cord  have  to  be  subordinated,  in  order  that  they 
may  co-operate  in  the  maintenance  of  the  equilibrium  of  the  body  as  a  whole. 
Into  the  pons  enters  the  fifth  nerve,  carrying  sensory  impressions  from  the 
whole  of  the  head,  while  in  the  mid-  and  fore-brain  we  find  the  endings  of 
the  optic  tracts  derived  from  the  eyes  and  carrying  visual  impressions.  From 
the  front  of  the  fore-brain  are  produced  the  olfactory  lobes. 

At  each  segment  or  level  in  the  brain  stem  the  afferent  fibres  from  these 
various  sense-organs  enter  and  join  afferent  tracts,  carrying  impulses  on  from 
the  spinal  cord — impulses  originally  derived  from  the  muscles  and  skin  of 
the  trunk  and  limbs.  At  each  level  there  may  be  an  immediate  '  reflection  ' 
back  to  the  cord,  so  that  the  spinal  afferent  impressions  may  co-operate 
with  the  cranial  afferent  impressions  in  the  production,  through  the  spinal 


THE  STRUCTURE  OF  THE   BRAIN  STEM 


383 


cord,  of  reactions  affecting  the  viscera  or  the  skeletal  muscles.  On  the 
other  hand,  both  kinds  of  afferent  impressions  may  pass  on  up  the  brain  stem 
to  involve  higher  centres  and,  mingling  with  impulses  from  other  afferent 
nerves  or  from  the  projicient  sense-organs,  may  result  at  some  higher  level 
in  an  efferent  discharge,  which  may  include  reactions  not  represented  in  the 
cord,  or  reactions  of  far  greater  complexity  than  are  possible  in  the  purel) 
spinal  animal. 

In  consequence  of  the  endless  complex  intermingling  of  afferent  im- 
pulses, any  diagrammatic  representation  of  tracts  is  apt  to  be  misleading, 
unless  it  be  remembered  that  at  each  break  or  synapse  in  the  chain  of  neurons 
there  are  numerous  possibilities  of  branching  discharge,  and  that  in  our 
diagrams  we  can  only  give  the  course  of  such  impulses  as,  by  the  frequency 
of  repetition  in  the  average  life  of  the  animal,  have  involved  the  grouping 
of  a  large  number  of  nerve  paths  of  similar  function  into  tracts.  The  con- 
stituent elements  of  these  tracts  will  present  similar  destinations  and  possi- 
bilities of  interruption,  i.e.  of  reactions  involving 
the  motor  mechanisms  at  the  different  levels  in 
the  brain  stem.  It  is  thus  much  more  difficult  in 
the  brain  stem  than  in  the  spinal  cord  to  describe 
a  '  way  in  '  and  a  '  way  out.'  In  a  chain  consist- 
ing, say,  of  six  neurons,  a,  b,  c,  d,  e,  /  (Fig.  196), 
though  a  is  certainly  afferent  and/  efferent,  it 
must  always  be  more  or  less  a  question  of  words 
whether  we  regard  neurons  c  and  d  as 
afferent  or  efferent  in  character.  It  is 
usual  in  our  classifications  to  be 
guided  chiefly  by  the  direction  of  such 
impulses  in  relation  to  the  cerebral 
hemispheres.  All  tracts  going  up  to 
the  cerebral  hemispheres  may  be 
involved  more  or  less  in  the  production 
nervous  matter  of  these  hemispheres  as  are 
scions  sensation.  In  the  same  way  there  is  a  possibility  that  the 
chains  of  neurons  which  carry  impulses  in  a  descending  direction  may  be 
involved  in  the  production  of  voluntary  movement.  It  is  therefore  usual 
to  classify  these  two  sets  of  tracts  as  ascending  and  descending,  or  as  afferent 
and  efferent.  If  we  adopt  such  a  classification  it  must  be  with  a  distinct 
reservation  that  tracts  which  apparently  are  going  downwards  may  play 
a  greater  part  in  the  determination  of  sensation  than  in  the  determination 
of  movement,  and  that  there  may,  and  indeed  must,  be  a  reverberation  of 
impulses  through  these  ascending  and  descending  tracts,  so  that  it  must 
be  difficult  to  dissociate  the  various  elements  in  the  extremely  complex  neural 
events  which  are  involved,  say,  in  the  simplest  kind  of  conscious  sensation. 

As  we  trace  out  the  evolution  of  the  brain  we  find  an  ever-increasing 
subordination  of  the  lower  to  the  higher  centres,  so  that  in  man  himself 
many  reactions  which  in  the  lower  animals  are  carried  out  by  the  spinal 


of 


such     changes    in 
associated    with 


the 


384  PHYSIOLOGY 

cord  alone,  involve  the  educated  co-operation  of  the  cerebral  hemispheres. 
With  this  increased  control  there  is  a  corresponding  increase  in  the  develop- 
ment of  long  paths.  In  the  brain  of  a  fish,  for  instance,  the  cerebral  hemi- 
spheres are  connected  only  with  the  fore-brain  ;  a  little  higher  in  the  scale 
there  are  connections  between  the  hemispheres  and  the  mid-brain  as  well. 
The  chief  long  tracts  are  those  which  run  between  the  thalamus,the  mid-brain 
or  the  hind-brain,  and  the  spinal  cord.  With  the  huge  development  of  the 
cerebral  hemispheres  in  man  there  is  also  development  of  long  paths,  the 
pyramidal  tracts,  from  the  hemispheres  down  to  all  the  motor  mechanisms 
of  the  cord,  and  of  tracts  which  connect  all  parts  of  the  cortex  with  the  grey 
matter  of  the  pons  and  indirectly  with  the  cerebellum.  The  tracts  which  in 
the  lower  animals  were  of  supreme  importance  in  determining  subordination 
of  lower  to  higher  centres,  of  immediate  reactions  to  those  determined  by  the 
organs  of  foresight,  dwindle  therefore  in  importance.  Those  tracts,  such  a  s 
the  thalamo-spinal,  tecto-spinal,  vestibulo-spinal,  which  form  the  main  mass 
of  the  white  matter  of  the  brain  stem  in  lower  types  of  vertebrates,  become 
reduced  to  a  few  scattered  fibres  in  the  brain  of  man  and  are  insignificant 
as  compared  with  the  great  cerebro-bulbar  and  cerebro-spinal  tracts. 

ASCENDING  TRACTS 
The  Tracts  of  the  Fillet.  The  fibres  which  enter  the  spinal  cord 
by  the  posterior  roots  pass  into  the  posterior  columns  and  along  these  to 
the  dorsal  column  nuclei,  the  nucleus  gracilis  and  the  nucleus  cuneatus, 
where  they  end  by  arborisations  among  the  cells  composing  these  nuclei. 
From  these  nuclei  the  axons  of  the  cells  pass  in  various  directions,  the  chief 
mass  of  them  forming  the  deep  arcuate  fibres.  These  emerge  from  the  inner 
side  of  the  nuclei  and  pass  through  the  raphe  to  the  other  side  of  the  medulla 
where  they  join  the  spino-thalamic  fibres  and  form  the  definite  collection 
of  longitudinal  fibres,  lying  dorsallv  to  the  pyramids,  which  is  known 
as  the  main  tract  of  the  fillet  or,  often,  the  mesial  fillet.  As  these  fibres 
traverse  the  pons  they  are  joined  at  the  outer  side  by  a  number  of  bundles 
which  are  derived  from  the  central  continuation  of  fibres  connected  with 
those  derived  from  the  cochlear  nerve.  This  part  is  known  as  the  lateral 
fillet.  The  cells  of  the  accessory  and  lateral  nuclei  of  the  cochlear  nerve 
send  their  axons  by  the  trapezium  to  the  superior  olivary  nucleus  and 
other  small  masses  of  grey  matter  on  the  other  side.  In  these  nuclei  the 
fibres  for  the  most  part  terminate,  but  a  fresh  relay  of  neurons  carries 
on  the  impulses  and  forms  the  main  part  of  the  lateral  fillet.  These  pass 
up,  getting  more  dorsal  as  they  ascend,  and  finally  terminate  in  the  inferior 
corpora  quadrigemina.  The  mesial  fillet,  which  we  can  regard  as  a  con- 
tinuation  of  certain  spinal  tracts  upwards,  is  reinforced  throughout  the 
whole  extent  of  the  medulla  and  pons  by  fibres  originating  from  the  masses 
of  grey  matter  in  which  the  sensory  cranial  nerves  terminate.  Certain 
of  these  fibres  may  form  a  distinct  tract  in  the  formatio  reticularis,  known 
as  the  central  or  thalamic  tract  of  the  cranial  nerves.  Another  similar 
tract  in  the  formatio  reticularis  is  derived  from  the  central  terminations 


TIIK   STRUCTURE   OF  THE   BRAIN  STEM 


385 


(crbusCoJIosum  ,__ 


Thalamo-CorfKjl  FibrfS 


Rtd   Nucleus  , 

Substantia  Nipr& 

Peduncle    - 

Ctrtbellum   -  '~~~~a 


\  Muscular  Tons 


Pyramid 

Dttp  Arcuift  Fibres 


Dorsal  Column  (dirtcD 
lUnst  of  pcufion 
\  inovtmenf, 

Spinal  Ganglion 
Spirr&l  Nerve  _ 


Sbmo-Ctrebtllar 

Tracfs    \\ 

/Co-ordination  %t\  \^ 


TRACT5. 


rl0.  197      Diagram  of  ascending  tracts  between  the  spinal  cord  and  brain  (Gordon 
ll"i  mi>).  with  the  probable  path  oi  sensory  impulses. 


25 


386 


PHYSIOLOGY 


of  the  fifth  nerve,  and  is  known  as  the  trigemino-thalaniic  tract.  All 
these  fibres  pass  up  in  the  tegmentum  of  the  mid-brain  and  finally  end,  partly 
in  the  grey  matter  of  the  subthalamic  region  and  parti}-  in  the  grey  matter  of 
the  thalamus  itself.  To  the  thalamus  are  also  continued  a  few  fibres  from  the 
lateral  fillet.  By  this  means  the  head  ganglion  of  the  fore-brain  is  in  a  posi- 
tion to  receive,  so  to  speak,  samples  of  the  afferent  impressions  derived  from 
every  sense-organ  of  the  body. 

The  Visual  Taths.     Two  classes  of  afferent  impressions  which  arrive  at 

the  optic  thalamus  are  probably  of 
equal  importance  to  all  the  other 
afferent  impressions  taken  together. 
These  are  impulses  derived  from 
the  organs  of  vision  and  of  smell. 
The  greater  part  of  the  fibres  com- 
posing the  optic  nerves  arise  as 
axons  of  the  ganglion-cells  of  the 
retinae.  Passing  backwards,  the 
nerves  of  the  two  sides  join  in  the 
optic  chiasma,  which  is  dosely 
attached  to  the  floor  of  the  third 
ventricle.  After  joining  in  the 
chiasma  the  optic  nerves  are  ap- 
parently continued  round  the  crura 
cerebri  as  the  optic  tracts.  These 
pass  round  on  each  side  and  can  be 
seen  to  make  coimection  with  the 
back  part  of  the  thalamus,  the 
external  geniculate  body,  and  the 
superior  corpus  quadrigeininum. 
Part  of  the  tract,  which  is  some- 
times called  the  mesial  root,  passes 
into  the  internal  geniculate  body. 
This  part  of  the  tract  has  probably 
nothing  to  do  with  vision  and 
forms  a  commissure  running  in 
the  optic  chiasma  connecting  the  internal  geniculate  bodies  of  the  two 
sides.  The  course  of  the  optic  fibres  is  shown  in  the  diagram  (Fig.  198).  In 
man  and  in  some  other  mammals,  e.g.  dog,  monkey,  the  nerve  fibres  decussate 
incompletely  in  the  chiasma.  The  uncrossed  bundle  is  derived  from  the 
outer  half  of  the  retina  of  the  same  side,  whereas  the  crossed  bundle  is  derived 
from  the  mesial  half  of  the  retina  on  the  other  side.  The  right  optic  nerve 
thus  carries  all  the  impulses  originating  in  the  right  eye.  The  right  optic 
tract  carries  all  the  impulses  originating  from  stimuli  occurring  in  the  left 
field  of  vision.  It  must  be  remembered  that  vision  in  man  is  binocular,  both 
retinas  being  concerned  in  the  perception  of  each  field  of  vision.  The  external 
and  internal  geniculate  bodies  may  be  regarded  as  extensions  of  the  optic 


Fig.  198.  Diagram- 
matic representa- 
tion of  the  optic 
tracts  and  their 
connections. 
(Cunningham.) 


THE  STRUCTURE  OF  THE  BRAIN  STEM  387 

thalamus,  the  former  in  special  relation  with  the  organ  of  vision,  the  latter 
with  the  organ  of  hearing. 

The  olfactory  bulb  is  also  connected  by  tracts  with  the  thalamic  region, 
probably  through  the  column  of  the  fornix  and  the  bundle  of  Vicq  d'Azyr. 
Since  however  the  chief  connections  of  the  olfactory  lobe  are  with  the 
more  primitive  portions  of  the  cerebral  hemispheres,  the  olfactory  tracts 
will  be  more  conveniently  treated  of  in  connection  with  the  latter. 

The  Cerebellar  Paths.  We  have  already  traced  out  the  course  of 
spinal  fibres  which  terminate  in  the  cerebellum.  They  may  be  shortly 
summarised  as  follows  : 

(1)  The  posterior  or  direct  cerebellar  tract,  originating  in  Clarke's 
column  of  cells  of  same  side,  passing  up  in  the  lateral  columns  and  by 
the  restiform  body  into  the  superior  vermis  of  the  middle  robe  of  the 
cerebellum. 

(2)  The  anterior  cerebellar  tract  or  tract  of  Gowers,  originating  in  the  grey 
matter  of  both  sides  of  the  cord  and  passing  in  the  lateral  columns  through 
the  lateral  part  of  the  medulla  and  pons,  and  finally  attaining  the  superior 
vermis  through  the  superior  cerebellar  peduncles. 

(3)  The  posterior  columns,  ending  chiefly  in  the  homolateral  posterior 
column  nuclei.  From  these  nuclei,  though  the  great  mass  of  fibres  passes 
into  the  fillet,  a  certain  number  from  the  nuclei  of  both  sides  join  the  resti- 
form body  to  pass  into  the  middle  lobe  of  the  cerebellum. 

In  the  medulla  these  afferent  tracts  of  the  cerebellum  are  joined  by  the 
following  sets  of  fibres  : 

1.  The  olivo-cerebellar. 

"2.  The  vestibulocerebellar. 

3.  A  few  fibres  from  the  chief  sensory  nuclei,  including  those  of  the  vago 
glossopharyngeal  nerves. 

All  these  fibres  terminate  in  the  cortex,  chiefly  of  the  middle  ldbe.  From 
the  cortex  of  this  lobe  fibres  pass  to  the  central  and  roof  nuclei  of  the  cere- 
bellum, namely,  the  nucleus  dentatus,  the  nucleus  emboliformis,  the  nucleus 
tastigii,  and  the  nucleus  giobosus.  The  efferent  tracts  of  the  cerebellum 
start  from  these  central  nuclei,  no  fibres  which  originate  in  the  cortex  of  the 
cerebellum  apparently  leaving  the  precincts  of  this  organ.  Some  of  these 
efferent  fibres  of  the  cerebellum  will  be  better  described  with  the  descending 
tracts  of  the  brain  stem.  Of  those  which  take  an  ascending  direction,  the 
great  bulk  are  contained  in  the  superior  cerebellar  peduncles.  These  origin- 
ate for  the  most  part  in  the  dentate  nucleus  and  the  nuclei  emboliformis  and 
giobosus.  As  the  superior  peduncles  run  forwards  they  sink  below  the 
posterior  corpora  quadrigemina,  and  in  the  tegmentum,  below  the  Sylvian 
iter,  decussate  with  the  tract  of  the  opposite  side  to  pass  to  the  red  nucleus. 
In  the  red  nucleus  many  of  the  fibres  end  some  however  passing  through  the 
nucleus  together  with  fibres  derived  from  the  cells  of  the  red  nucleus  itself 
to  end  in  the  thalamus  and  in  the  grey  matter  of  the  subthalamic  resion. 


388 


PHYSIOLOGY 


Optic 

Tha.lj>mus|~ 


Infernal  1 
CApsulej- 


Lenficutarl    '' 
Nucleus  J 

Substantia  Ni(Sr& !ji\ 

RubroSpin*!  Iract 


Outers  Nucleus  — i 


L^-  -  CUusfrui 


-Red  Nucleus 


Pyramidal  Tract- 


Wsfibulo  Spinal  Tract s 


>cssed  Pyramidal  Tract 


Dentate  Nucleus 


^ Inferior  Olive 


Direct  Pyraniulal  Tract 

D€SC6MDING~h£RV/£ 
TRACTS. 


Fig.  199.  Schema  of  course  taken  by  chief  descending  tracts  of  brain  stem.  (Cordon 
Holmes.)  The  tract  in  red.  to  the  right  of  the  rubro-spinal  tract,  includes  the  pi  sterioX 
longitudinal   bundle,  together  with   the   fibres  of  the   thalamo-spinal  and   tecto-spinal 

tracts. 


THE  STRUCTURE   OF  THE   BRAIN  STEM  389 

DESCENDING  TRACTS 

The  chief  descending  tracts  having  their  origin  in  the  brain  stem  are  the 
rubro-spina]  bundle  or  bundle  of  Monakow,  the  complex  system  of  fibres 
known  as  the  posterior  longitudinal  bundle,  and  the  vestibulo-spinal  fibres 
from  the  upper  part  of  the  medulla. 

(1)  The  rubrospinal  fibres  originate  in  the  red  nucleus.  They  cross 
the  median  line  and  run  down,  at  first  in  the  tegmentum  and  later  in  the 
lateral  column  of  the  medulla  oblongata  and  cord.  In  their  passage  they 
communicate  with  the  various  motor  nuclei  of  the  cranial  nerves.  They 
can  be  traced  to  all  segments  of  the  cord,  where  they  terminate  in  connection 
with  the  anterior  horn-cells. 

(2)  The  posterior  longitudinal  bundle.  This  bundle  is  to  be  seen  in 
ajl  sections  through  the  brain  stem  below  the  level  of  the  oculo-motor  nucleus. 
It  consists  of  fibres,  some  of  which  pass  upwards,  while  others  pass  down- 
wards. Most  of  the  fibres  take  origin  in  the  cells  of  Deiters'  nucleus  and  of 
the  reticular  formation  of  the  pons,  medulla,  and  mid-brain,  as  well  as  from 
certain  cells  in  the  sensory  nucleus  of  the  fifth  nerve.  The  fibres  traced 
upwards  can  be  seen  to  send  collaterals  to  end  in  the  various  parts  of  the 
nuclei  of  the  third,  fourth,  and  sixth  nerves..  Lower  down  it  becomes  con- 
tinuous with  the  anterior  basis  bundle  of  the  spinal  cord  and  merges  in  the 
mternuncial  fibres  which  serve  to  connect  the  various  levels  of  the  cord. 
Some  of  the  fibres,  which  are  descending,  are  derived  from  a  small  nucleus, 
the  so-called  nucleus  of  the  posterior  longitudinal  bundle,  which  is  found  in 
the  grey  matter  at  the  side  of  the  posterior  part  of  the  third  ventricle.  This 
bundle  also  receives  fibres  from  the  superior  olivary  body.  It  is  one  of  the 
earliest  to  undergo  myelination  in  the  foetus  (cp.  also  Fig.  205,  p.  407). 

(3)  The  vestibulo-spinal  tract  takes  origin  for  the  most  part  in  the 
cells  of  Deiters'  nucleus.  The  fibres  pass  down  in  the  anterior  part  of  the 
spinal  cord  and  terminate  in  the  anterior  horns.  They  are  sometimes  known 
as  the  antero-lateral  descending  tract.  It  is  probably  through  this  tract 
that  the  cerebellum  is  able  to  affect  indirectly  the  activity  of  the  motor 
mechanisms  of  the  cord. 

Two  other  descending  tracts  which  are  important  in  the  lower  vertebrates 
arc  insignificant  in  man.  These  are  the  thalamo-spinal  tract,  consisting  of 
descending  fibres  derived  from  the  optic  thalamus,  and  the  tecto-spinal  tract, 
containing  fibres  derived  from  the  roof  of  the  mid-brain.  In  the  mid-  and 
hind-brain  these  fibres  run  in  the  tegmentum.  In  the  cord  they  are  found 
in  the  anterior  columns.  The  olivo-spinal  tract,  which  is  supposed  to 
on-mate  in  the  olivary  body,  forms  a  small  tract  in  the  cervical  region  near 
the  surface,  opposite  the  lateral  angle  of  the  anterior  horn. 


SECTION  XII 

THE    FUNCTIONS    OF   THE    BRAIN   STEM 

The  brain  stem  may  be  taken  to  include  all  those  parts  lying  between  the 
cerebral  hemispheres  and  the  spinal  cord,  from  the  optic  thalamus  in  front 
to  the  medulla  oblongata  behind.  The  brain  may  be  divided  into  the  follow- 
ing parts  from  before  back  : 

(1)  Thalamencephalon,  including  the  corpus  striatum,  the  cerebral 
hemispheres  and  rhinencephalon,  or  olfactory  lobes. 

(2)  Diencephalon,  i.e.  the  fore-brain,  especially  the  optic  thalamus. 

(3)  Mesencephalon,  or  mid-brain,  including  the  quadrigemina,  the  iter  of 
Sylvius,  and  the  crura  cerebri. 

(4)  Metencephalon,  composed  of  the  pons  Varolii,  the  upper  part  of  the 
fourth  ventricle,  and  cerebellum. 

(5)  Mvelencephalon,  or  bulb,  consisting  of  the  medulla  oblongata. 
We  may  get  some  idea  of  the  part  played  by  these  different  regions  of 

the  brain  in  determining  the  reactions  of  the  individual  as  a  whole  by 
examining  the  behaviour  of  the  animals  in  whom  all  the  rest  of  the  brain 
in  front  of  the  part  in  question  has  been  removed.  If  however  we  take 
into  account  the  numberless  connections  existing  between  the  different  levels 
in  the  central  nervous  system,  the  interdependence  between  the  different 
portions,  and  the  subordination,  especially  in  the  higher  animals,  of  the 
functions  of  the  lower  to  those  of  the  higher  levels,  we  must  acknowledge 
that  such  experiments  can  give  us  but  an  imperfect  idea  of  the  possibilities 
of  each  level  when  in  connection  with  all  other  portions  of  the  nervous  sy~t.-n;. 

THE  FUNCTIONS  OF  THE  MEDULLA  OBLONGATA 
OR  MYELENCEPHALON 

The  possibilities  of  any  given  nervous  centre  are  determined  by  the 
afferent  impressions  which  enter  it,  and  by  the  connections  made  by  the 
nerves  carrying  these  impulses  with  the  motor  tracts  within  the  centre.  The 
bulb  receives  afferent  impressions  of  '  taste  '  from  the  tongue  through  the 
nervus  intermedins,  from  the  alimentary  canal  as  low  as  the  ileocolic  sphinc- 
ter, from  the  lungs,  the  heart,  and  the  larger  blood-vessels,  i.e.  from  the  most 
important  of  the  viscera  of  the  body,  by  the  fibres  of  the  vagoglossopharyn- 
geal nerves.  Its  only  skeleto-motor  centre  is  that  for  the  muscles  of  the 
tongue  (the  hypoglossal).  It  sends  also  to  the  viscera  efferent  fibres,  which 
arise  from  cells  in  the  nucleus  ambiguus.     These  fibres  carry  motor  impulses 

390 


THE  FUNCTIONS  OF  THE   BRAIN  STEM  391 

to  the  muscles  of  the  larynx  and  bronchi  and  to  the  oesophagus  stomach 
and  intestines,  secretory  fibres  to  the  stomach  and  inhibitory  fibres  to  the 
heart. 

At  the  upper  border  of  the  bulb  enter  also  the  fibres  of  the  eighth  nerve, 
carrying  important  impressions  from  the  organ  of  hearing  and  the  organ  of 
static  sense.  These  will  be  in  all  probability  divided  or  injured  in  isolating 
the  bulb  from  the  higher  portions  of  the  brain.  While  in  connection  with  the 
upper  portions  of  the  brain,  the  bulb  receives  also  afferent  impressions 
from  the  skin  of  the  face,  and  the  mucous  membrane  of  the  nose  and  mouth 
through  the  descending  branches  of  the  root  of  the  fifth  nerve,  which  pass 
down  superficially  to  the  tubercle  of  Rolando.  When  in  connection  with  the 
cord,  the  medulla  receives  afferent  impressions  from  the  whole  surface  of  the 
body  and  from  all  the  muscles  and  joints  through  the  posterior  column 
nuclei. 

The  bulbo-spinal  animal,  i.e.  one  in  whom  a  section  has  been  carried  out 
at  the  upper  boundary  of  the  medulla,  differs  from  the  spinal  animal  chiefly 
in  the  maintenance  of  the  nexus  between  the  visceral  functions  and  the 
skeleto-motor  functions  of  the  body.  After  removal  of  all  the  brain  in 
front  of  the  bulb,  the  animal  still  continues  to  breathe  regularly  and  auto- 
matically. The  blood  pressure  and  the  pulse  rate  remain  normal,  and  all 
three  mechanisms,  respiration,  pulse  rate,  blood  pressure,  may  be  affected 
reflexlv  bv  appropriate  stimuli,  or  may  be  altered  in  consequence  of  central 
.stimulation  of  the  medulla. 

In  addition  to  the  reflex  mechanisms  of  locomotion,  which  are  evident 
in  the  spinal  animal,  the  bulbo-spinal  animal  shows  a  greater  degree  of 
solidarity  in  its  responses.  It  is  easier  to  evoke  movement  of  all  four  limbs. 
In  the  frog,  if  the  eighth  nerve  has  been  left  intact,  there  is  a  certain  power 
of  equilibration  left,  and  the  animal  when  laid  on  its  back  tries  to  right  itself 
and  usually  succeeds. 

It  is  in  this  portion  of  the  central  nervous  system  that  have  been  located 
the  great  majority  of  the  so-called  centres.  By  a  statement,  that  the  centre 
nf  such-and-such  movement  or  function  is  situated  in  the  medulla,  we  mean 
merely  that  the  integrity  of  the  medulla,  or  certain  parts  of  it,  is  essential  for 
the  carrying  out  of  the  function.  Every  function,  for  instance,  in  which 
impulses  passing  up  the  vagus  nerves  are  involved,  is  necessarily  dependent 
on  the  integrity  of  these  nerves  and  their  central  connections,  and,  since  these 
are  situated  in  the  medulla,  the  centres  for  these  functions  are  also  located 
in  this  region.  From  a  broad  standpoint  the  medulla  or  bulb  may  be  looked 
upon  as  a  ganglion,  or  a  collection  of  ganglia,  whose  main  office  is  to  guard  and 
preside  over  the  working  of  the  mechanisms  at  the  anterior  opening  of  the 
body  ;  by  means  of  which  food  is  seized,  tasted,  taken  into  the  alimentary 
canal,  and  finally  digested.  The  respiratory  apparatus  belongs  to  the  same 
system  and  is  innervated  through  the  same  nerve  channels.  Hence  the 
various  events  in  alimentation,  such  as  deglutition,  vomiting,  mastication, 
or  in  the  allied  respiratory  functions,  such  as  phonation,  coughing,  and 
respiration  itself,  are  endowed  with  centres  in  this  part  of  the  brain.     In 


392  PHYSIOLOGY 

connection  with  the  termination  of  the  vagus  nerves  of  this  pari  "I  the  brain 
is  the  location  here  of  the  chief  vaso-motor  centre,  i.e.  in  a  region  which  is 
in  close  proximity  to  the  endings  of  the  chief  afferent  nerves  from  the  heart 
and  larger  blood-vessels  and  to  the  nucleus  of  the  efferent  controlling  nerve 
to  the  heart. 

THE  METENCEPHALON  (PONS  VAROLII  AND  CEREBELLUM) 
Destruction  of  the  brain  at  the  front  of  the  fourth  ventricle  and  just 
behind  the  posterior  quadrigemina  will  leave  the  animal  with  a  central 
nervous  system,  which  is  in  connection  by  efferent  nerves  with  the  whole 
musculature  of  the  body  (with  the  exception  of  certain  eye  muscles)  and 
which  receives  impressions  through  the  spinal  cord  from  the  whole  surface 
of  the  trunk  and  limbs,  and  through  the  fifth  nerve  from  the  face  and  head, 
and  also  the  higher  specialised  impressions  from  the  organ  of  hearing  and 
the  organ  of  static  sense.  The  impressions  from  the  two  great  projieient 
senses  of  smell  and  sight  would  be  wanting. 

Such  an  animal  presents  considerable  advance  in  the  complexity  of  its 
reactions  above  one  possessing  only  spinal  cord  and  bulb.  The  frog,  for 
instance,  after  such  an  operation,  can  still  walk,  spring,  and  swim  :  when 
placed  on  a  turntable  it  reacts  to  passive  rotation  by  turning  its  head  in  the 
opposite  direction.  On  stroking  its  back  it  croaks.  If  the  cerebellum  be 
also  removed, the  animal  becomes  spontaneouslyactive  and  crawls  about  until 
it  is  blocked  by  some  obstacle.  In  this  condition  there  is  great  activity  of  the 
swallowing  reflex.  Anything  which  touches  the  mouth  is  snapped  at.  If 
placed  on  its  back  the  frog  at  once  rights  itself. 

In  the  mammal  a  similar  increase  of  reflex  activity  is  observed  though  the 
power  of  progression  is  not  retained. 

THE  MESENCEPHALON  OR  MID-BRAIN 

A  section  in  front  of  the  anterior  corpora  quadrigemina  would  leave 
the  animal  with  the  nervous  system  receiving  all  normal  sensory  impressions. 
with  the  exception  of  the  olfactory,  and  with  efferent  paths  to  all  the  muscles 
of  the  body,  including  those  of  the  eye.  In  the  mammal  such  an  operation 
brings  about  a  condition  known  as  '  decerebrate  rigidity.'  Though  respira- 
tory movements  continue  normally,  the  whole  musculature  is  in  a  cataleptic- 
condition,  the  elbows  and  knees  being  extended  and  resisting  passive  flexion  ; 
the  tail  is  stiff  and  straight,  the  neck  and  head  retracted,  i  This  condition 
seems  to  depend  on  an  over-activity  of  the  reflex  toni&functions  of  the  lower 
centres.V/That  it  is  reflex  is  shown  by  the  fact  tha|_the  rigidity  is  at  once 
abolished  in  a  limb  on  dividing  the  appropriate  posterior  roots^J  The 
position  of  the  limbs  may  be  also  modified  by  sensory  stimuli.  A  similar 
condition  of  increased  tonus  is  observed  in  the  frog. 

The  apparatus  for  emotional  expression  is  still  intact  though  somewhat 
modified,  and  an  impression  which  would  give  rise  to  pain  in  the  intact 
animal  may  cause  vocalisation  in  an  animal  in  whom  the  brain  above  the 
mesencephalon  has  been  destroyed. 


THE   FUNCTIONS  OF  THE   BRAIN  STEM  393 

THE  BRAIN  STEM  AS  A    WHOLE  (INCLUDING  THE  THALAM- 
ENCEPHALIC, OR  OPTIC  THALAMI) 

The  introduction  of  the  head  ganglia  of  the  brain  stem,  viz.  the  optic 
t  ha  la  mi.  completes  in  the  lower  animals  at  all  events  the  apparatus  for  im- 
mediate response  to  stimulus.  The  powers  of  such  an  apparatus  may  be 
studied  by  examining  the  behaviour  of  an  animal  in  whom  the  cerebral 
hemispheres  have  been  destroyed.  The  result  of  this  operation  varies 
according  to  the  type  of  animal  chosen,  though  all  types  present  certain 
common  features.  When  a  frog's  cerebral  hemispheres  have  been  excised,  a 
casual  observer  would  not  at  first  notice  anything  abnormal  about  the  animal. 
It  sits  up  in  its  usual  position,  and  on  stimulation  may  be  made  to  jump 
away,  guiding  itself  by  sight,  so  that  it  avoids  any  obstacles  in  its  path. 
Movements  of  swallowing  and  breathing  are  normally  carried  out.  The 
animal  thrown  on  to  its  back,  immediately  turns  over  again.  If  put  into 
water,  it  swims  about  until  it  comes  to  a  floating  piece  of  wood  or  any  support 
when  it  crawls  out  of  the  water  and  sits  still.  If  it  be  placed  on  a  board  and 
the  board  be  inclined,  it  begins  to  crawl  slowly  up  it,  and  by  gradually  in- 
creasing the  inclination  may  be  made  to  crawl  up  one  side  and  down  the 
other.  But  a  striking  difference  between  it  and  a  normal  frog  is  the  almost 
entire  absence  of  spontaneous  motion — that  is  to  say,  motion  not  reflexly 
provoked  by  changes  immediately  taking  place  in  its  environment.  All 
psychical  phenomena  seem  to  be  absent.  It  feels  no  hunger  and  shows  no 
fear,  and  will  suffer  a  fly  to  crawl  over  its  nose  without  snapping  at  it.  "  In 
a  word,  it  is  an  extremely  complex  machine,  whose  actions,  so  far  as  they  go, 
tend  to  self-preservation  ;  but  still  a  machine  in  this  sense,  that  it  seems  to 
contain  no  incalculable  element.  By  applying  the  right  sensory  stimulus 
to  it,  we  are  almost  as  certain  of  getting  a  fixed  response  as  an  organist  is 
when  he  pulls  out  a  certain  stop." 

According  to  Schrader  and  Steiner,  if  care  be  taken  not  to  injure  the 
optic  thalami,  spontaneous  movements  may  be  occasionally  observed  after 
removal  of  the  cerebral  hemispheres.  On  the  approach  of  winter  such  a 
frog  has  been  observed  to  bury  itself  in  order  to  hibernate,  and  with  spring  to 
resume  activity  and  to  feed  itself  by  catching  insects.  The  behaviour  of 
such  decerebrate  animals  depends  on  the  part  taken  in  the  initiation  of 
movement  and  adapted  reactions  by  stimuli  entering  through  the  higher 
sense-organs.  Thus  an  ordinary  bony  fish  after  ablation  of  the  cerebral 
hemispheres  maintains  its  normal  equilibrium  in  water.  It  is  continually 
swimming  about,  stopping  only  when  it  reaches  the  side  of  the  vessel  or  when 
worn  out  by  fatigue.  Here  again,  if  the  thalami  and  optic  lobes  be  intact, 
the  fish  has  been  observed  to  show  very  little  difference  from  a  normal 
animal  and  to  possess  the  power  of  distinguishing  edible  from  non-edible 
material.  On  the  other  hand,  in  the  elasmobranch  fishes,  which  depend 
mainly  upon  their  olfactory  apparatus  as  a  guide  to  movement,  the  removal 
of  the  cerebral  hemispheres  with  the  olfactory  lobes,  or  of  the  latter  alone, 


394  PHYSIOLOGY 

produces  complete  immobility  and  absence  of  spontaneous  movement, 
even  though  the  optic  thalami  and  optic  lobes  may  be  intact. 

In  the.  bird  the  cerebral  hemispheres  may  be  removed  with  ease.  A 
decerebrate  pigeon,  if  its  optic  lobes  be  intact,  walks  about  avoiding  all 
obstacles,  and  may  even  fly  a  short  distance.  In  the  dark,  i.e.  in  the  absence 
of  visual  impressions,  it  remains  perfectly  still.  The  bird  however  is  unable 
to  recognise  food,  or  enemies,  or  individuals  of  the  opposite  sex  ;  it  shows 
no  fear  and  responds  to  stimuli  like  the  brainless  frog  described  above. 

Goltz  has  succeeded  in  the  dog  in  removing  the  whole  of  the  cerebral 
hemispheres  in  three  operations.  The  dog  was  kept  alive  for  eighteen 
months  after  the  final  operation.  It  was  able  to  walk  in  normal  fashion 
and  spent  the  greater  part  of  the  day  in  walking  up  and  down  its  cage. 
At  night  it  would  sleep  and  then  required  a  loud  sound  to  awaken  it.  It 
reacted  to  stimuli  in  a  normal  fashion,  shutting  its  eyes  when  exposed  to  a 
strong  light,  shaking  its  ears  in  response  to  a  loud  sound.  On  pinching  its 
skin  it  attempted  to  get  away,  snarling  or  turning  round  and  biting  clumsily 
at  the  experimenter's  hand.  It  had  no  power  to  recognise  food  and  had  to  be 
fed  by  placing  food  in  its  mouth,  though,  if  this  food  were  mixed  with  a 
bitter  substance  such  as  quinine,  it  was  at  once  rejected.  The  dog  never 
showed  recognition  of  the  persons  that  fed  it,  nor  any  signs  of  pleasure  or 
fear.  Removal  of  the  hemispheres  had  thus  produced  loss  of  all  understand- 
ing and  memory.  There  was  no  sign  of  conscious  intelligence,  and  all  the 
actions  of  the  animal  must  be  regarded  as  reflex  responses  to  immediate 
excitation. 

With  the  development  of  the  cerebral  hemispheres  in  the  higher  mammals 
there  is  a  considerable  shifting  of  motor  reactions  from  those  which  are 
immediate  and  '  fatal  '  or  inevitable  to  those  which  are  edueatable.  The 
cerebral  hemispheres  in  man  take  a  large  part  in  the  determining  of  even 
the  common  reactions  of  everyday  life.  Ablation  of  the  hemispheres 
therefore,  or  even  part  of  the  hemispheres,  in  the  ape  and  man  gives  rise 
to  much  more  lasting  symptoms  than  is  the  case  in  the  animals  we  have  just 
studied.  These  defects  we  shall  have  to  consider  more  fully  later.  The 
results  however  obtained  on  the  lower  animals,  from  the  dog  downwards, 
show  that  the  brain  stem,  from  the  head  ganglion  of  the  optic  thalamus  back 
to  the  medulla,  with  the  spinal  cord,  represents  a  complex  mechanism  which 
can  be  played  upon  by  impulses  received  through  all  the  sensory  apparatus 
of  the  body,  and  is  able  to  adjust  the  motor  and  visceral  reactions  to  the 
immediate  environment  of  the  animal. 

Certain  of  these  immediate  reactions  are  susceptible  of  further  physiologi- 
cal analysis.  We  have  seen  that  the  spinal  cord  contains  the  co-ordinated 
mechanism  for  the  movement  of  the  limbs.  We  may  now  discuss  how  the 
movements  of  the  limbs  are  co-ordinated  with  thosa  of  the  trunk  and  head  in 
the  maintenance  of  the  unstable  position  of  the  animal  in  standing  and  in 
locomotion.  For  this  purpose  there  has  been  developed  the  great  mass  of 
nerve  matter  in  the  roof  of  the  metencephalon,  viz.  the  cerebellum. 


SECTION  XIII 

THE    FUNCTIONS   OF   THE   CEREBELLUM 

The  carrying  out  of  co-ordinated  movements  is  associated  with  and  regu- 
ated  by  afferent  impressions  which  can  be  divided  into  two  main  groups. 

In  the  first  group  may  be  placed  those  due  to  the  changes  in  the  environ- 
ment of  the  animal,  working  on  sensory  structures  or  '  receptors,'  of  varying- 
qualitative  sensibility,  in  the  surface  of  the  body.  These  receptors  may  be 
excited  by  the  mechanical  stimuli  of  pressure,  by  changes  of  temperature, 
or  by  nocuous  or  harmful  impressions,  such  as  would,  in  the  presence  of 
consciousness,  give  rise  to  pain.  At  the  fore  end  of  the  body  we  have  in 
addition  the  special  receptor  organs  excited  by  waves  of  light  or  of  sound. 
The  action  of  any  of  these  impressions,  if  of  sufficient  intensity,  is  to  evoke 
an  appropriate  reflex  movement,  such  as  the  flexor  reflex  in  response  to 
nocuous  stimulus  applied  to  the  foot,  or  the  stepping,  or  extensor,  reflex 
excited  by  steady  pressure  on  the  sole  of  the  foot. 

The  integrity  of  the  nerve  paths  carrying  these  afferent  impressions  and 
of  the  motor  paths  to  the  muscles  is  not  however  sufficient.  A  secondar}T 
set  of  afferent  impulses  is  essential  in  order  to  i>,uide  and  regulate  the  extent 
of  the  resultant  discharge.  These  secondary  afferent  impulses  start  in  the 
deep  tissues,  viz.  the  muscles,  joints,  and  ligaments,  which  are  provided  with 
special  sense-organs  capable  of  being  stimulated  by  the  mechanical  changes 
of  tension  or  pressure  set  up  by  the  movements  themselves.  The  importance 
of  these  impressions  for  the  carrying  out  of  muscular  movements  is  shown 
by  the  ataxia  which  is  the  result  of  injury  to  the  corresponding  afferent 
nerves.  Degeneration  of  the  nerves  to  muscles,  or  section  of  the  afferent 
roots,  causes  marked  ataxia  of  the  movements  of  the  limb,  whereas  no  such 
result  follows  section  of  all  the  cutaneous  nerves  supplying  the  surface  of  the 
limb  with  sensibility.  To  this  system  of  afferent  nerves  Sherrington  has 
given  the  name  of  the  '  proprioceptive  '  system,  since  it  is  excited,  not  directly 
by  changes  in  the  environment,  but  by  alteration  in  the  animal  itself.  It  is 
responsible  for  reactions  differing  in  many  respects  from  those  which  are  the 
immediate  result  of  stimulation  of  the  other  system,  the  '  exteroceptive.' 
which  is  distributed  over  the  surface  of  the  body.  Since  it  is  excited  by 
the  movement  of  the  muscles  themselves,  i.e.  by  the  first  result  of  the  reaction 
to  external  stimulus,  it  Serves  as  a  governing  mechanism  to  regulate  the 
extent  of  each  motor  discharge.  Its  excitation  not  only  prevents  over-action 
of  the  muscles,  but  may  evoke  a  compensatory  reflex  in  an  opposite  direction 
to  the  reflex  immediately  excited  from  the  skin.     A  marked  feature  of  this 

395 


396  PHYSIOLOGY 

system  is  its  tendency  to  continued  01  tonic  activity.  The  steady  slight  con- 
traction, or  '  tone,'  which  is  observable  in  most  skeletal  muscles,  is  inde- 
pendent of  the  surface  sensibility  and  depends  entirely  on  the  proprioceptive 
system  of  the  muscles  and  their  accessory  structures. 

In  the  decerebrate  animal  the  rigidity  of  a  limb  disappears  at  once  after 
section  of  its  afferent  roots,  though  it  is  unaltered  by  division  of  the  main 
skin  nerves.  This  tonus  does  not  affect  all  muscles  to  an  equal  degree. 
In  every  limb  there  is  a  predominance  of  tonus  in  certain  muscles,  so  that 
the  result  on  the  whole  limb  is  an  attitude  br  posture  which  is  typical 
of  the  limb  or  the  animal.  Thus  the  spinal  frog  takes  up  an  attitude  which 
is  very  different  from  that  which  would  be  impressed  on  it  by  gravity 
in  the  absence  of  muscular  activity.  If  one  of  its  hind  limbs  be  extended 
gently,  it  soon  draws  it  up  to  reproduce  the  same  crouching  position.  The 
posture  of  the  limb  is  therefore  a  result  of  afferent  impressions  continually 
ascending  its  proprioceptive  nerves  and  exciting  a  tonic  activity  which 
predominates  in  certain  definite  muscles.  This  posture,  as  carried  out  by 
the  spinal  cord,  is  a  segmental  response.  It  determines  the  relation  of  the 
limb  to  the  trunk,  and  to  a  less  extent  of  the  four  limbs  to  one  another.  It  is 
not  concerned  with  the  relation  of  the  animal  as  a  whole  to  its  environment, 
and  only  to  a  slight  extent  with  the  maintenance  of  equilibrium  in  the 
presence  of  the  continually  acting  force  of  gravity. 

In  the  evolution  of  the  nervous  system  there  has  been  a  continual 
subordination  of  the  hinder  parts  to  the  head  end,  in  consequence  of  the 
development  at  this  end  of  the  all-important  distance  receptors,  the  impulses 
from  which  take  a  predominating  part  in  determining  the  reactions  of 
the  body  as  a  whole.  In  fact  the  subordination  of  one  part  of  the  central 
nervous  system  to  another  is  in  direct  relation  to  the  importance  of  the 
afferent  impulses  arriving  at  each  portion  of  the  system.  Thus  the  vaso- 
motor centres  segmentally  distributed  throughout  the  spinal  cord  are 
subject  to  the  vaso-motor  centre  in  the  medulla,  which  is  developed  at  the 
point  of  entry  of  the  vagus  nerves,  i.e.  the  chief  afferent  nerves  from  the  heart 
and  large  blood-vessels.  The  collections  of  grey  matter  presiding  over  the 
segmental  reactions  of  the  intercostal  muscles  are  entirely  subordinated  to 
the  grey  matter  in  the  medulla  around  the  entry  of  the  vagus  fibres  from 
the  lungs. 

This  subordination  of  the  hinder  to  the  anterior  sense-organs  is  paralleled 
in  the  case  of  the  proprioceptive  system.  Entering  the  hind-brain  at  the 
upper  border  of  the  medulla  is  the  eighth  nerve,  composed  of  two  parts  which 
differ  widely  in  functions,  viz.  the  cochlear  division  and  the  vestibular 
division.  The  former  is  entirely  concerned  with  the  reception  of  sound 
waves,  and  is  therefore  the  auditory  nerve.  The  vestibular  nerve,  which  is 
distributed  to  the  rest  of  the  membranous  labyrinth,  must  be  assigned  to  the 
proprioceptive  system.  The  labyrinth  is  practically  a  double  organ.  The 
primitive  auditory  sac  arises  as  a  simple  involution  of  the  surface.  In  the 
course  of  development  the  front  part  is  modified  to  form  the  canal  of  the 
cochlea,  which  is  set  apart  entirely  for  the  reception  of  sound.     From  the 


THE  FUNCTIONS   OF  THE  CEREBELLUM 


397 


back  part  there  are  formed  two  sacs — the  saccule  and  utricle — and  the  three 
semicircular  canals.  The  saccule  and  the  utricle,  which  receive  each  a  large 
branch  of  the  vestibular  nerve,  represent  the  otolith  organ,  which  is  found 
in  almost  all  classes  of  animals.  The  crayfish,  for  instance,  at  the  base 
of  its  antenna1  presents  a  small  sac  lined  with  hairs  and  richly  supplied 
with  nerves.  In  this  sac  a  small  calcareous  particle  rests  on  the  hairs. 
It  is  evident  that  the  incidence  of  the  pressure  of  the  small  stone  or  otolith 
on  the  bail's  will  vary  according  to  the  position  of  the  animal  (Fig.  200), 
so  that  any  change  in  the  position  of  the  head  will  be  attended  by  altera- 
A 


a  be 
I'm:.  200.     Diagram  of  an  otolith  organ,  I"  show  how  alterations 
in  its  position  will  cause  the  weight  of  the  otolith  [ot.)  to  press  on 
different  sense  cells,  and  therefore  to  affect  different  nerve  fibres. 

tion  in  the  nerve  fibres  which  have  been  stimulated  by  the  pressure  of 
the  otolith,  and  therefore  in  the  nature  of  the  impulses  flowing  to  the  central 
nervous  system.  The  importance  of  these  impulses  in  regulating  the  loco- 
motion and  the  maintenance  of  the  equilibrium  of  the  animal  is  well  shown 
if  the  otolith  be  replaced  by  a  small  fragment  of  iron.  Under  normal 
circumstances  the  iron  particle  will  act  quite  as  well  as  an  otolith.  If 
however  a  powerful  magnet  be  brought  in  the  neighbourhood  of  the  animal, 
the  pressure  of  the  particle  will  not  be  determined  simply  by  gravity  and 
therefore  by  the  position  of  the  animal,  so  that  there  will  be  a  discordance 
between  the  impulses  arriving  from  the  otolith  organ  and  those  arising  from 
the  sense-organs  of  the  body,  and  marked  disorders  of  equilibrium  are  the 
result. 

In  the  saccule  and  utricle  the  vestibular  nerve  ends  in  similar  otolith 
organs  known  as  the  maculae  acousticse.  These  are  small  elevations 
covered  with  long  hairs  and  supplied  with  nerves.  One  or  two  calcareous 
secretions  or  otoliths  are  embedded  in  the  hairs,  so  that  any  change  in  position 
will  cause  a  corresponding  change  in  the  nerve  fibres  which  are  being  excited 
by  the  weighl  i  if  the  otoliths.  The  semicircular  canals,  which  lie  in  the  three 
planes  of  space,  are  also  provided  with  end  organs,  somewhat  similar  in 
structure  to  the  maculae  acousticse,  but  devoid  of  otoliths.  The  end  organs 
are  excited  by  mass  movements  of  the  fluid  endolympli,  which  arc  set 
up  by  rotation  of  the  head. 

Since  the  nervous  apparatus  of  the  labyrinth  is  excited  not  by  changes 
in  the  environment,  from  which  it  is  carefully  shielded,  but  by  changes  in  the 


398  PHYSIOLOGY 

animal  itself,  we  are  justified  in  assigning  it  to  the  proprioceptive  system,  of 

which  indeed  it  represents  the  most  important  receptor,  .rust  as  the  pro- 
prioceptive nerves  of  a  limb  are  responsible  for  the  tonus  of  tin'  limb  muscles. 
so.  as  Ewald  has  shown,  each  labyrinth  is  responsible  to  a  considerable  degree 
for  the  tonus  of  the  corresponding  side  of  the  body.  Extirpation  of  one 
labyrinth  causes  a  lasting  loss  of  tone  in  the  muscles  of  the  same  side.  A 
further  functional  resemblance  lies  in  the  part  played  by  the  labyrinth  in  the 
determination  of  posture.  The  resultant  effect  of  the  impulses  arising  in  it 
is  to  maintain  a  reflex  posture  of  the  head  and  eyes,  so  that  the  optic  axes  in 
a  position  of  rest  are  directed  towards  the  horizon.  Stimulation  of  the 
labyrinth  causes  therefore  movements  of  the  eyes  which  may  or  may  not  be 
associated  with  correlated  movements  of  the  head. 

As  in  the  case  of  the  other  sense-organs  of  the  anterior  end  of  the  body, 
the  reflexes  excited  from  the  labyrinth  dominate  over  those  evoked  by  pro- 
prioceptive impulses  from  the  hinder  portions  of  the  body.  At  the  entry 
of  its  nerve  into  the  brain  stem,  a  mass  of  grey  matter  is  developed  which 
must  be  regarded  as  the  head  ganglion  of  the  proprioceptive  system,  and 
the  chief  co-ordinating  organ  of  all  the  reflex  systems  which  determine 
posture  of  the  limbs  and  of  the  whole  animal,  and  therefore  the  maintenance 
of  equilibrium  both  at  rest  and  during  locomotion.  This  organ  is  the 
cerebellum,  associated  with  the  grey  matter  in  the  upper  part  of  the  fourth 
ventricle  at  the  point  of  entry  of  the  vestibular  nerves.  The  cerebellum 
commences  in  early  foetal  life  as  a  small  elevation  in  the  dorsal  wall  of  the 
neural  tube,  where  the  eighth  nerve  enters.  Simple  in  structure  and  small 
in  extent  in  most  of  the  fishes  and  amphibia,  it  grows  in  extent  with  increasing 
complexity  of  the  animal's  motor  reactions,  and  attains  its  greatest  develop- 
ment in  the  mammalia.  In  this  class  the  cerebellum,  like  the  cerebrum,  is 
most  highly  developed  in  man  and  the  higher  apes.  It  is  generally  described 
in  man  as  consisting  of  a  middle  lobe,  composed  of  the.  superior  and  inferior 
vermis,  with  two  lateral  hemispheres,  and  these  are  subdivided  by  anatomists 
according  to  the  situation  of  the  chief  sulci.  From  the  physiological  point 
of  view  the  structure  of  the  organ  is  relatively  simple,  as  is  shown  by  the 
uniformity  of  its  structure  throughout  all  parts.  It  may  be  considered  as 
formed  of  two  main  structures,  viz.  the  cortex  and  the  central  or  roof  ganglia. 

The  surface  of  the  cerebellum  is  increased  by  being  thrown  into  folds  or  laminae, 
so  that  a  section  of  this  organ  has  a  tree-like  appearance.  A  section  through  a  lamina 
shows  three  distinct  zones  :  an  outer  molecular  layer  presenting  a  granular  appearance 
with  a  few  nuclei ;  internal  to  this  a  granule  layer  composed  of  many  nuclei  of  nerve 
cells  ;  and  most  deeply  a  central  core  of  white  matter.  Between  the  molecular  and 
granular  layers  are  situated  the  cells  of  Purkinje,  large  flask -shaped  cells  each  with  one 
apical  dendrite,  distinguished  above  all  other  dendrites  of  the  central  nervous  system 
by  the  richness  of  its  branching,  and  with  one  axon,  which  leaves  the  base  of  the  cell 
and  passes  down  into  the  central  white  matter,  giving  off  collaterals  in  its  course. 
In  preparations  made  by  Golgi's  method  we  are  able  to  distinguish  the  various  elements 
composing  these  layers  and  their  relations.  The  molecular  layer,  besides  neuroglia- 
cells  and  the  brandling  dendrites  of  the  cells  of  Purkinje,  contains  certain  star-shaped 
cells  (a  Fig.  201),  which  give  off  an  axon  running  parallel  with  the  surface  in  the 
molecular  layer.     From  this  axon  branches  dip  down  towards  the  cells  of  Purkinje. 


THK    Fl'XCTIOXS   OF   TIIK   <  KREBKLLUM 


399 


where  they  end  in  a  rich  basket-work  of  fibres  around  the  body  and  beginning  of  the 
axon  of  these  cells.  The  nuclear  or  granular  layer  presents  two  kinds  of  cells.  The 
most  numerous  is  a  small  cell  with  a  few  short  dendrites,  each  of  which  terminates 
in  a  claw-shaped  arborisation,  and  a  single  lung  axon,  which  passes  straight  up  into 
the  molecular  layer,  where  it  bifurcates.  The  two  branches  run  parallel  with  the 
surface  in  a  direction  at  right  angles  to  the  plane  of  expansion  of  the  dendrites  of 
Purkinje's  cells,  apparently  resting  against  the  serial  inns  on  the  edges  of  these  processes. 
The  second  kind  of  cell  in  the  granular  layer  is  the  so-called-  Golgi's  cell — a  large  cell 


Central 

white 

matter. 


Fig.  201.  Schema  of  constituent  elements  of  cerebellum.  (Modified  from  Boh.u 
and  Davidoff.  )  On  the  left  is  a  section  of  the  cortex  as  it  appears  when 
stained  by  ordinary  methods.  The  middle  portion  represents  diagrammaticallv 
a  section  at  right  angles  to  the  lamina",  while  to  the  right  of  the  dotted  line  the 
section  is  taken  in  the  same  plane  as  the  lamina?. 
a,  star-shaped  cells  of  molecular  layer  ;  b,  b,  cells  of  Purkinje  ;   c,  '  Golgi  cell '  ; 

d,  small  cells  of  nuclear  layer  ;    e,  '  tendril  fibre  '  ;  f,    •  moss  fibre  '  ;  g,  axon  of  cell 

of  Purkinje. 

with  many  dendrites  and  an  axon  which  terminates  by  frequent  branches  in  the  neigh- 
bouring grey  matter. 

The  fibres  making  up  the  white  matter  are  of  three  kinds — two  afferent  and  one 
efferent.  The  moss  fibres,  so  called  from  the  curious  thickenings  they  present  in  the 
nuclear  layer,  pass  up  into  the  grey  matter  and  terminate  by  frequent  branches  in 
this  layer.  The  tendril  fibres,  also  afferent,  end  in  a  rich  arborisation  which  surrounds 
the  distal  part  of  the  bodies  and  the  bases  of  the  dendrites  of  the  cells  of  Purkinje. 
Tin'  efferent  fibres  are  represented  by  the  axons  of  the  cells  of  Purkinje,  which  acquire 
a  medullary  sheath  and  run  down  into  the  white  matter. 

This  slight  sketch  of  the  anatomy  gives  us  a  conception  of  the  extreme  complexity 
of  choice  presented  to  nervous  impulses  traversing  the  cerebellar  cortex.  Thus  a 
discharge  along  an  axon  of  the  cell  of  Purkinje  may  be  excited  (1)  by  an  impulse  ascend 
nag  the  tendril  fibres;  or  (2)  by  one  ascending  the  moss  fibres  through  the  grannie 
nil-,  and  then  passing  by  their  bifurcating  axon  i"  the  dendrites  of  the  cells  of  Pur- 
kinje; or  (3)  by  the  star-shaped  cells  of  the  molecular  layer  and  their  basket-work 
round   the  body  of   Purkinje's  cells. 


400  PHYSIOLOGY 

The  roof  ga  nuclei  fastigii  near  the  middle  line,  the  nuclei  em- 

boliformes  situated  just  dorsal  to  these,  and  the  nuclei  dentati.  large  crenated  capsules 
of  grey  matter  lying  in  the  middle  of  each  lateral  lobe.    'II 

matter  of  the  central  nuclei  are  large  and  multipolar,  resembling  those  found  in  the 
nuclei  of  motor  nerves. 

The  cerebellum  receives  fibres  from  all  the  receptor  apparatus  of  the  body  which 
can  be  classed  in  the  proprioceptive  system.  The  greater  number  of  these  fibres 
ran  directly  to  the  cortex,  especially  of  the  vermis,  and  there  is  no  evidence  of  the 
passage  of  any  efferent  fibres  from  the  cortex  directly  to  the  motor  apparatus  of  the 
cord. 

The  connections  of  the  cerebellum  are  established  by  means  of  its  three  peduncles, 
and  may  be  classified  a*  follows: 

AFFERENT  TRACTS.  Inferior  Peduncle.  By  this  peduncle  afferent  fibres 
pass  to  the  superior  vermis: 

1     Prom  Clarke's  column  of  the  same  side  by  the  posterior  cerebellar  tract. 
_'     From  the  dorsal  column  nuclei,  viz.  the  nucleus  gracilis  and  nucleus  cuneatus 
of  each  side,  so  that  connection  is  established  in  this  way  with  the  prolongations  of  the 
posterior  sensory  roots  which  run  into  the  posterior  columns  of  the  cord. 

(3)  Bv  the  internal  restiform  body  from  the  vestibular  division  of  the  eighth  nerve, 
part  of  the  fibres  passing  through,  and  perhaps  making  connections  with,  Deiters' 
nucleus. 

(4)  A  strong  band  of  fibres  passes  from  the  inferior  olivary  body  into  the  opposite 
cerebellar  hemisphere.  Atrophy  of  one  side  of  the  cerebellum  induces  a  corresponding 
atrophy  in  the  opposite  olivary  body. 

Middle  Peduncle.  The  broad  mass  of  fibres  making  up  these  peduncles  is  partly 
afferent  and  partly  efferent.  Many  fibres  originate  in  the  cells  in  the  formatio  reticu- 
laris of  the  pons,  cross  the  middle  line,  and  pass  up  into  the  lateral  cerebellar  hemi- 
sphere of  the  opposite  side.  F:l  from  the  cerebellum  to  the  pons  to  end 
round  cells  in  the  same  region.  By  this  means' connection  is  established  between  the 
cerebellar  hemispheres  and  the  corticopontine  fibres  which  pass  by  the  crura  cerebri 
between  the  pons  and  the  frontal  and  temporal  portions  of  the  cerebral  cortex  of  the 
-  ••■  side.  On  account  of  this  connection  there  is  a  close  association  between  the 
development  of  each  cerebellar  hemisphere  and  the  contralateral  cerebral  hemisphere. 
Atrophy  of  one  half  of  the  cerebrum  brings  about  atrophy  of  the  opposite  hemisphere  of 
the  cerebellum. 

The  Superior  Peduncle.  By  this  path  fibres  from  the  superior  corpora  quadri- 
gemima,  i.e.  from  the  terminations  of  the  optic  nerve,  pass  into  the  cortical  grey  matter 
of  the  cerebellum  (Fig.  202 

EFFERENT  TRAClS.  The  cerebellar  cortex  must  be  regarded  as  a  receiving 
rather  than  as  a  discharging  station.  Stimulation  of  it  has  little  effect  uuless  strong 
currents  are  employed,  and  a  motor  response  is  obtained  more  easily  the  deeper  the 
electrodes  are  sunk  below  the  grey  matter.  The  fibres  which  form  the  axons  of  the 
cells  of  Purkinje  pass  partly  towards  the  pons  by  the  middle  peduncle,  largely,  how- 
ever, towards  the  roof  nuclei,  where  they  terminate.  These  nuclei  form  the  efferent 
stations  of  the  cerebellum.  From  them  fibres  pass  in  various  directions.  A  large 
bundle  leaves  the  dentate  nucleus,  runs  into  the  superior  peduncle,  or  brachium, 
and  passing  deeply  across  to  the  tegmentum  of  the  opposite  side,  traverses  the  red 
nucleus  to  end  in  the  subthalamic  region  of  the  opposite  side  of  the  brain.  A  certain 
number  of  fibres,  chiefly  derived  from  the  central  nuclei,  such  as  the  nucleus  fastigii, 
i  ward  to  the  corpora  quadrigemina  chiefly  on  the  same  side.  From  the  cerebellum 
itself  no  direct  tract  runs  into  the  spinal  cord.  The  nuclei  of  Dieters  and  of  Bechterew 
(the  paraeerebellar  nuclei),  which  are  connected  with  the  ending-  oi  the  vestibular 
nerve,  are.  however,  closely  associated  with  the  roof  nuclei,  and  give  rise  to  descending 
fibres  which  pass  into  the  antero-lateral  region  of  the  cord  as  the  vestibulospinal 
tract. 


THE   FUNCTIONS   OF   THE   CEREBELLUM 


401 


The  cerebellum  is  a  receiving  station,  not  only  for  impulses  which  arise  in 
the  skin  and  eyes,  i.e.  on  the  surface  of  the  body,  but  especially  for  those 
which  have  been  defined  as  proprioceptive,  and  originate  either  in  the  muscles 
and  tendons  or  in  the  labyrinth.  Activity  of  this  apparatus  is  roused  as  a  rule 
by  the  movement  of  the  organism  itself,  and  is  only  a  secondary  result  of  the 
environmental  stimulation  which  provoked  the  original  movement.  By  its 
efferent  tracts  starting  in  the  roof-  and  paracerebellar  nuclei,  the  cerebellum 
is  -able  In  affect  the  musculature  of  the  same  side  <>{  the  body  by  a  direct 
influence  on  the  anterior  horns,  it  also  enters  to  a  much  greater  extent  into 
relation  with  the  opposite  cerebral  hemi- 
spheres, so  that  it  is  in  a  position  to 
controloi  modify  the  actiyityof  these, 
whether  exerted  on  their  sensor)-  or  on 
their  motor  sides. 

STIMULATION  OF  THE  CEREBEL- 
LUM. It  was  first  shown  by  Ferrier 
that  movements  of  the  same  side  of 
the  body  can  be  excited  by  stimulation 
either  of  the  cerebellar  hemispheres  or 
of  the  superior  vermis.  These  results 
have  been  confirmed  by  subsequent 
observers,  and  point  to  each  half  of  the 
cerebellum  being  connected  functionally 
with  the  skeletal  muscular  apparatus  of 
the  corresponding  side  of  the  body. 
The  cortex  cerebelli  is  not  excited 
with  ease.  To  evoke  movements  much 
stronger  stimuli  are  necessary  than 
e.g.  for  the  excitation  of  the  motor  area 
of  the  cerebral  cortex.  This  again 
is  in  accordance  with  what  we  should 
expect  from  the  anatomy  of  the  organ, 
knowing  as  we  do  that  the  cortex  is  an   Fig.  202.     Diagram  of  afferent  and  efferent 

end-station  for  a    number   of    afferent  tracts  of  cerebellum 

(After  v.  Gehuchten.) 
paths,  but  has  no  direct    efferent  paths       ot,  optic  thalamus;    en,  red  nucleus; 

from  it   to  the  lower  motor  mechanisms    PCTV P^or  cerebellar  tract;  ACT.  anterior 

cerebellar  tract  ;   v.  fifth  nerve, 
of  the  cord.     On  the  other  hand,  move- 
ments  are    excited    by    minimal    stimuli  from  the  intrinsic    nuclei  of  the 
cerebellum. 

As  a  result  of  his  experiments  Horslev  concluded  that  the  cortex 
cerebelli  must  be  regarded  as  an  afferent  receptive  centre  from  which  axons 
pass  1..  lb.'  ventrally  placed  efferent  nuclei,  viz.  the  nuclei  dentati.  fastigii, 
emboliformes,  as  well  as  Deiters'  nuclei.  Whereas  excitation  of  the  roof  nuclei 
produces  more  especially  movements  of  the  eyes  and  head,  the  paracere- 
bellar (e.g.  Deiters'  nucleus)  are  responsible  more  especially  for  the  move- 
ments of  the  trunk  and  limbs.     The  movements  of  the  body  which  are  thus 

26 


402 


1'IIYSIOUHiY 


C.R.V- 


evoked  arc  those  concerned  in  maintaining  equilibrium  and  are  involved  in 
every  alteration  in  the  position  of  the  body. 

EFFECTS  OF  ABLATION  OF  THE  CEREBELLUM.  Complete  unilateral 
extirpation  of  the  cerebellum,  after  the  irritative  effects  of  the  lesion  itself 
lia  vi>  passed  away,  brings  about  a  condition  of  the  animal  characterised  by  : 

(1)  Slight  loss  of  power  on  the  same  side  of  the  body. 

(2)  Considerable  loss  of  tone  on  the  same  side. 

(3)  Tremors  or  rhythmical 
SupA/ermis  movements  of  the  muscles  on 

the.  same    side    accompanying 
any  willed  movements. 

These  three  symptoms  are 
denoted  by  Luciani  as  asthenia, 
atonia,  and  astasia.  At  first 
the  animal  is  quite  unable  to 
stand,  and  lies  on  the  side  of 
the  lesion  with  neck  and  trunk 
curved  in  the  same  direction  ; 
when  it  attempts  to  stand  it 
always  falls  to  the  same  side. 
After  two  or  three  weeks  the 
power  to  stand  is  regained, 
though  when  it  attempts  to 
walk  the  hindquarters  drag 
and  tremors  accompany  every 
effort.  The  animal  endeavours 
to  correct  the  tendency  to  fall 
towards  the  side  of  the  lesion 
by  an  exaggerated  abduction 
of  the  limbs  to  that  side,  and 
is  always  ready  to  take  ad- 
en.  restiform  body  ;  en,  roof  nuclei ;  SF,  sagittal  vantage  of  the  Support  of  a 
iibres  from  cortex  to  roof  nuclei;  cvt,  cerebello-  ,  „n  .  „„„i.i„  ;+  i„  ™„:„i„4„  it- 
vestibular   tract  ;     Dx,    Deitcrs'     nucleus;     III.    vr,    wall  to  enable  it  to  maintain  its 

nuclei  of  third  and  sixth  nerves;  plf.  posterior  equilibrium.  Swimming  is  much 
longitudinal  bundle;  viii,  vestibular  division  of  better  carried  out  than  walking 
eighth  nerve  ;    sc,  semicircular  canals  ;    vst,  vesti-    Detter  Carried  OUT.  man  walking. 

bulo-spinal  fibres.  the  contact  of  the  water  with  the 

skin  furnishing  guidance  to  the 
spinal  mechanism  which  is  lacking  when  the  animal  attempts  to  walk. 

When  the  whole  cerebellum  is  removed  the  animal  is  unable  to  walk, 
sometimes  for  months.  After  a  time  it  gradually  learns  to  walk,  but  this  is 
carried  out  by  an  alteration  of  the  method  of  progression.  The  disorders  of 
locomotion  are  quite  distinct  from  the  spinal  ataxia  observed  after  interfer- 
ence with  the  afferent  tracts  from  the  muscles.  The  difficulty  now  is  that 
each  diagonal  movement  of  the  limbs  in  progression  tends  to  throw  the 
centre  of  gravity  to  one  side  or  other  of  the  basis  of  support,  and  it  is  the 
mechanism  for  maintaining  the  right  position  of  the  centre  of  gravity,  i.e.  the 


THE  FUNCTIONS  OF  THE  CEREBELLUM  403 

posture  of  the  body  as  a  whole  in  relation  to  its  environment,  which  is  at 
fault.  The  animal,  in  the  case  of  the  dog,  therefore  attempts  to  correct  the 
tendency  to  fall  to  one  side  or  other  at  each  step  by  making  its  basis  of 
support  as  wide  as  possible,  and  gradually  acquires  a  peculiar  gait,  consisting 
of  a  series  of  springs,  in  which  the  two  fore  limbs  and  two  hind  limbs  act 
together,  the  diagonal  movements  of  the  fore  limbs  being  practically 
abandoned.  That  the  compensation,  which  is  slowly  acquired  after  extirpa- 
tion of  the  cerebellum,  is  of  cerebral  origin  is  shown  by  the  fact  that  subse- 
quent removal  of  the  cerebral  hemispheres,  or  even  of  the  motor  areas  of 
the  hemispheres,  at  once  abolishes  the  power  of  movement  which  has  been 
reacquired  ;  and  after  the  motor  areas  are  destroyed  on  both  sides,  the  loss 
of  power  of  progression  is  permanent. 

These  experiments  show  that  the  cerebellum,  in  Sherrington's  words, 
must  be  regarded  as  the  head  ganglion  of  the  proprioceptive  system,  acting 
as  a  centre  where  arrive  the  afferent  impulses  from  the  cord,  the  fifth  nerve 
and  especially  from  the  labyrinth.  It  influences,  through  the  superior 
peduncle,  the  cerebral  cortex  and  furnishes  the  subconscious  basis  for  the 
guidance  of  the  motor  functions  of  the  latter  organ.  Through  its  connections 
with  the  nuclei  of  the  bulb  and  the  efferent  tracts  arising  therefrom,  it  aug- 
ments the  tonic  activity  of  all  the  muscles  of  the  body,  especially  of  those 
concerned  in  the  maintenance  of  posture,  an  effect  which  is  especially 
marked  in  the  absence  of  the  cerebral  hemispheres  and  is  responsible  for 
the  condition  known  as  decerebrate  rigidity.  As  a  centre  of  conjunction 
for  the  afferent  impressions  from  the  muscles  and  those  from  the  laby- 
rinth, it  co-ordinates  the  segmental  reflexes,  which  determine  the  relative 
posture  of  each  limb,  with  those  originating  in  the  labyrinth  and  determining 
the  position  of  the  head.  Thus  the  whole  mechanism  provides  for  a  mainten- 
ance of  equilibrium  of  the  body  as  a  whole,  and  for  the  proper  balancing 
of  the  reflex  movements  of  the  different  limbs  with  those  of  the  trunk 
during  all  the  changes  in  the  position  of  the  centre  of  gravity  attending 
locomotion. 

The  view  here  put  forward  really  includes  the  various  descriptions  of  the  functions 
of  the  cerebellum  which  have  been  given  by  different  authorities.  Thus  Luciani 
describes  the  cerebellum  as  an  organ  which  by  unconscious  processes  exerts  a  continual 
reinforcing  action  on  the  activity  of  all  the  spinal  centres.  Munk  ascribes  to  the 
cerebellum  the  function  of  maintaining  bodily  equilibrium.  Lewandowsky  regards  the 
cerebellum  as  the  central  organ  of  the  muscular  senses.  Hughlings  Jackson  expressed 
many  years  ago  an  important  characteristic  of  the  cerebellum  when  he  wrote  that  the 
cerebellum  is  the  centre  for  continuous  movements,  and  the  cerebrum  for  changing 
movements.  All  these  descriptions  come  under  Sherrington's  conception  of  the 
cerebellum  as  head  ganglion  of  the  proprioceptive  system. 

DESTRUCTIVE    LESIONS    OF    THE    CEREBELLUM    IN    MAN 

The  general  results  of  the  lesions  of  the  cerebellum  in  man  are  broadly  similar  to 
those  described  for  animals.  As  in  these,  the  effects  of  unilateral  lesions  are  always 
limited  to  the  same  side  of  the  body. 

One  invariable  result  is  diminished  tone  of  the  muscles  on  the  same  side  of  the  body. 
This  does  not  necessarily  involve  diminution  or  absence  of  the  tendon  reflexes  ;  in  fact, 


lol  PHYSI0L0G1 

there  may  I"-  some  exaggeration  of  these  reflexes  accompanying  the  diminished  tone. 

The  loss  of  ("lie  is  easily  perceived  on  lifting  up  the  leg  and  letting  it  drop,  hi 
on  taking  the  fore  arm  and  shaking  the  hand.  The  knee-jerk  in  these  circumstances 
differs  from  the  normal  jerk  in  the  absence  of  the  tonic  contraction  which  ordinarily 
follows  and  continues  the  short  sharp  contraction;  the  leg  thus  falls  after  the  jerk, 
in-lead  of  being  held  up  for  a  short  time  by  the  continued  contraction  of  the  quadriceps 
muscle. 

Associated  with  this  atonia  is  a  loss  of  voluntary  power — asthenia  «  bich  is  generally 
mi  ire  marked  in  the  arm  than  in  the  leg.  The  initiation  and  the  execution  of  voluntary 
movements  are  slower  than  normal,  and  the  end  of  the  movement  is  delayed,  so  thai 
there  is  a  tendency  to  over-action  of  the  muscles.  Sustained  effort  is  difficult,  the  con- 
tractions becoming  intermittent,  or  giving  place  to  coarse  tremor-  so-called  astasia. 
There  may  lie  defective  maintenance  of  equilibrium  in  walking,  so  that  a  staggering  gait 
is  produced,  closely  resembling  that  of  a  drunken  man.  There  is  a  tendency  to  fall  or 
deviate  to  the  injured  side,  hut  this  defect  is  not  nearly  so  marked  as  in  the  case  of  the 
dog,  already  described. 

Even  when  the  cerebellar  gait  is  not  marked,  there  is  always  some  ataxy  of  the  arm 
or  hand  muscles  ;  the  usual  co-operative  antagonism  of  opposing  muscles  is  faulty, 
and  these  may  contract  together  instead  of  alternately,  or  the  wrong  muscles  may  be 
used.  When,  for  instance,  the  man  tries  to  approximate  one  finger  to  the  thumb,  In- 
tends to  move  all  the  others. 

Speech  is  often  slurred,  drawling,  or  '  scanning  '  in  character,  and  the  difficulty  ex- 
perienced by  the  man  in  articulation  frequently  gives  rise  to  explosive  utterance. 
The  head  is  generally  inclined  towards  the  injured  side  and  rotated  to  the  opposite 
side.  Abnormal  position  of  the  eyes  is  always  a  prominent  symptom.  Both  eyes 
are  deviated  to  the  opposite  side,  and  there  is  nystagmus  owing  to  the  difficulty 
experienced  in  moving  the  eyes  towards  the  side,  of  the  lesion.  When  a  patient  w  ith  a 
lesion  on  the  right  side  attempts  to  look  towards  the  right,  the  eyes  move  slowly  towards 
the  right  and  then  drop  back  rapidly  towards  their  position  of  rest,  to  be  slowly  moved 
up  again  towards  the  right.  The  movements  are  similar  to  those  which  may  be  seen 
in  any  person  looking  out  of  the  window  of  a  rapidly  moving  train. 

There  is  no  loss  of  sensation  or  of  muscular  sensibility. 


SECTION  XIV 


VISUAL    REFLEXES 


Foremost  among  the  afferent  impulses  determining  the  reactions  of  higher 
animals  are  those  arising  in  the  eyes.  Each  retina,  or  rather  the  two 
retinae  acting  together  as  a  single  organ,  can 
be  regarded  as  a  sensory  surface,  every  point 
of  which  corresponds  to  a  point,  or  series 
of  points,  lying  in  a  given  direction  outside 
the  body.  Each  optic  nerve  contains  about 
half  a  million  nerve  fibres,  i.e.  as  many  as 
enter  the  cord  by  the  posterior  roots  from 
the  whole  of  the  body.  The  two  optic  nerves 
coming  from  the  retinas  meet  together  in  the 
floor  of  the  fore-brain  and  form  the  chiasrna. 
At  the  chiasrna  a  decussation  of  fibres  takes 
place  which,  in  animals  such  as  the  rabbit 
with  no  fusion  of  the  fields  of  the  two  eyes. 
is  practically  complete.  In  man  only  those 
fibres  which  arise  in  the  mesial  half  of  each 
retina  cross  the  mesial  plane  ;  these,  together 
with  the  uncrossed  fibres  from  the  temporal 
half  of  the  other  retina,  form  the  optic  tract 
of  the  opposite  side  (Fig.  20:>).  The  optic  tract 
passes  backwards  across  the  eras  cerebri  and 
finally  divides  in  the  roof  of  the  mid-  and 
fore-brain  into  three  branches,  which  end  in 
the  grey  matter  of  the  anterior  corpora  quad- 
rigemina  and  in  the  external  geniculate  body 
and  the  pulvinar  of  the  optic  thalamus. 
Running  in  the  optic  tract  are  also  fibres 
which  are  simply  commissural ;  these  form 
the  mesial  root  of  the  optic  tract.  They  cross 
in  the  optic  chiasrna  and  serve  to  connect  the 
two  internal  geniculate  bodies.  In  addition 
to  the  afferent  fibres  from  the  retina  to  the  brain  the  optic  tract  contains 
a  certain  number  of  efferent  fibres  which  pass  out  and  end  in  the  retinae 
It  is  evident  from  these  connections  thai  whereas  section  oi  one  optic 
405 


Fig.  203.  Diagram  to  show  con- 
nections of  optic  tracts.  (After 
Sherrington.) 

L,  left,  and  R,  right  retina;  OD, 
optic  decussation  (chiasrna)  ;  OpT, 
optic  tract;  NC,  nucleus  caudatus  : 
I  X.  lenticular  nucleus  ;  Th.  optic 
thalamus  ;  G,  external  geniculate 
hody  ;  At,',  anterior  corpus cruadri- 
geminum  ;  P,  pulvinar  :  OpR,  opi  ic 
radiations  running  to  OC,  the  occi- 
pital cortex  :  Illn.  nucleus  of  third 
nerve  in  floor  of  Sylvian  aqueduct  ; 
IV,  fourth  ventricle. 


406 


PHYSIOLOGY 


nerve,  say  the  right,  will  only  cause  loss  of  vision  in  the  right  eye,  section 
of  the  right  optic  tract  will  divide  the  fibres  coming  from  the  right  halves  of 
both  retinae.  This  portion  of  the  retina  in  each  eye  is  stimulated  in  the 
normal  position  of  the  eyes  by  rays  of  light  coming  from  the  objects  lying  to 
i  lie  lei  t  ( il  the  field  of  vision.  Section  of  the  right  ojotic  tract  therefore  causes 
blindness  to  all  objects  to  the  left  of  the  median  line,  left  hemianofia. 
Section  of  both  ojjtic  tracts  of  course  causes  complete  blindness. 

Every  movement  of  the  head  involves  compensatory  movements  of  the 
eyes,  and  conversely,  in  any  change  in  the  environment  of  the  animal  which 

demands  its  attention,  there  is 
a  movement  of  the  eyes  so  as  to 
turn  the  gaze  on  to  the  origin  of 
the  disturbance  as  an  antecedent 
to  any  body  movement.  In  the 
absence  of  normal  regulative  im- 
pulses from  the  skin  or  from  the 
semicircular  canals,  the  afferent 
impressions  from  the  eyes  may 
serve  for  the  maintenance  of 
fairly  well  co-ordinated  move- 
ments—a compensation  which  is 
rendered  possible  by  the  power 
of  the  cerebral  cortex  to  learn 
new  reactions  by  experience. 

The  centres  for  the  eye  move- 
ments are  contained  in  the  grey 
matter  in  the  floor  of  the  back 
part  of  the  third  ventricle  and  of 

Diagram  to  show  origin  of  the  different    the  iter  of  Sylvius.    Here  We  find 

the  nucleus  of  the  third  or 
oculo-motor  nerve.  The  oculo- 
motor nucleus  consists  of  several  divisions,  viz.  a  lateral  part  containing 
large  motor  cells,  a  superficial  median  nucleus  with  small  cells,  and  a 
deeper  median  nucleus  with  large  cells.  By  localised  stimulation  it  has  been 
found  possible  to  differentiate  the  functions  of  the  various  parts  of  the 
nucleus  (Fig.  204).  Stimulation  of  the  back  part  of  the  third  ventricle  causes 
contraction  of  the  ciliary  muscles,  and  of  the  part  immediately  behind  this 
contraction  of  the  pupil.  On  stimulating  the  floor  of  the  iter  from  before 
backwards,  we  obtain  contractions  in  order  of  the  rectus  internus,  the  rectus 
superior,  the  levator  palpebra?  superioris,  the  rectus  inferior,  and  the  inferior 
oblique  muscle.  On  stimulating  more  laterally,  or  exciting  the  corpora 
quadrigemina,  dilatation  of  the  pupil  is  obtained. 

It  seems  probable  that  the  optic  thalamus  and  the  closely  related  external 
geniculate  body  are  mainly  concerned  with  the  reception  of  visual  impulses 
and  their  forwarding  to  the  cerebral  cortex.  On  the  other  hand,  the  anterior 
or  superior  corrjora  quadrigemina  are  mainly  concerned  with  the  co-ordination 


fibres  of  the  third  and  fourth  nervea  from  the 
oculo-motor  nuclei. 


VISUAL  REFLEXES 


407 


of  visual  impressions  and  visual  movements  with  the  movements  of  every 
part  of  the  body,  and  especially  with  the  complex  mechanism  we  have  already 
studied  in  connection  with  the  labyrinth  and  cerebellum.  Stimulation  of  the 
corpora  quadrigemina  therefore  evokes  movements  of  the  eyes  and  of  the 
head  ;  extirpation  of  this  part,  even  when  bilateral,  though  it  may  inter- 
fere with  co-ordination,  does  not  necessarily  involve  loss  of  sight. 

The  multifarious  intercourse  which  is  continually  taking  place  between 


Vlll.Vest.n 


(tJ  Jy  j*  \Anf- 'basis  bun  die 


Fig.  205.     Diagram  of  connections  of  posterior  longitudinal  bundle. 
Ant.C.Quad,  anterior  corpus  quadrigeminum  ;    oc.m.n,  oculo-motor  nucleus  ; 
IV.n,  nucleus  of  fourth  nerve ;  Vl.n,  nucleus  of  sixth  nerve  ;  D.N,  Deiters'  nucleus  ; 
S.O,  superior  olive  ;    VIII.  Veat.n,  vestibular  nerve  ;    p.l.b,  posterior  longitudinal 
bundle ;    1st  c.n,  first  cervical  nerve. 


the  eye  centres  and  those  for  the  movements  of  the  body,  and  between 
afferent  impressions  from  the  eyes  and  those  from  the  semicircular  canals  and 
the  proprioceptive  system  generally,  is  effected  to  a  large  extent  through  the 
intermediation  of  the  posterior  longitudinal  bundle,  which  extends  through- 
out the  whole  length  of  the  mid-brain  and  the  hind-brain,  and  in  the  spinal 


408  '  PHYSIOLOGY 

cord  becomes  continuous  with  the  anterior  basis  bundle  of  the  anterior 
columns.  Receiving  fibres  above  through  the  anterior  commissure  from 
the  optic  thalamus  and  from  the  superior  corpora  quadiigemina3  it  is 
associated  in  its  course  with  the  three  motor  nuclei  that  give  origin  to  the 
nerves  supplying  the  muscles  of  the  eyeball,  viz.  the  third,  fourth,  and  sixth 
nerves.  Fibres  enter  the  posterior  longitudinal  bundle  Erom  the  auditory 
system  and  from  the  superior  olive,  and  connections  are  also  established 
between  this  bundle  and  the  facial  nucleus,  and  the  nucleus  of  Deiters, 
representing  the  central  station  of  impulses  from  the  labyrinth.  The  general 
connections  of  the  bundle  art1  shown  in  Fig.  205. 


SECTION  XV 

SUMMARY   OF   THE   CONNECTIONS    AND    FUNCTIONS 
OF   THE   CRANIAL   NERVES 

Crdnial  nerves.  The  cranial  nerves  are  generally  reckoned  as  twelve  in 
number  :  1st,  olfactory  ;  2nd,  optic  ;  3rd,  oculo-motor  ;  4th,  or  trochlear  : 
5th,  or  trigeminus  ;  6th.;  7th,  or  facial ;  8th,  auditory  ;  9th,  glossopharyn- 
geal ;  10th,  vagus  or  pneumogastric  ;  11th,  spinal  accessory  ;  12th,  hypo- 
glossal. 

Of  these  the  first  two  stand  on  a  different  footing  from  the  rest  which, 
like  the  spinal  nerves,  are  outgrowths  of  nerve  fibres  from  the  central  tube 
of  grey  matter  surrounding  the  neural  canal  or  from  ganglia  corresponding 
to  the  spinal  posterior  root  ganglion. 

The  olfactory  bulb  and  the  retinas,  from  which  the  majority  of  the 
fibres  forming  the  olfactory  tract  and  the  optic  nerve  respectively  take  their 
origin,  are  analogous  rather  to  lobes  of  the  brain  than  to  peripheral  sense- 
organs.  Thus  in  the  retina  there  are  three  relays  of  neurons  through  which 
the  visual  impulse  must  pass  before  it  arrives  at  the  optic  nerve.  The 
olfactory  tract  and  optic  nerve  are  thus  comparable  with  the  association  or 
commissural  nines  connecting  different  parts  of  the  central  nervous  system. 
The  connections  of  these  sensory  fibres  have  already  been  fully  dealt  with,  and 
i  lie  structure  of  the  peripheral  sense-organ  will  be  treated  of  under  the  physi- 
ology of  the  special  senses.  Among  the  cranial  nerves  proper  we  may 
therefore  reckon  the  third  to  the  twelfth. 

The  third  or  oculo-motor  arises  from  an  elongated  nucleus  which  ex- 
tends on  either  side  from  the  back  part  of  the  third  ventricle  along 
almost  the  whole  length  of  the  ventral  part  of  the  aqueduct  of 
Sylvius  close  to  the  middle  line  (Fig.  204).  The  anterior  part  is  com- 
posed of  small  cells  which  give  origin  to  the  fibres  innervating  the  intrinsic 
muscles  of  the  eye,  namely,  the  ciliary  muscle  and  the  sphincter  pupillae. 
The  rest  of  the  nucleus  is  made  up  of  large  multipolar  cells,  arranged  in 
groups,  and  gives  origin  to  the  fibres  passing  to  most  of  the  extrinsic  muscles 
of  the  eye.  The  fibres  of  the  third  nerve  pass  through  the  tegmentum  to 
emerge  at  the  inner  margin  of  the  crusta  of  the  same  side.  The  fibres  from 
the  posterior  large-celled  nucleus  supply  the  following  muscles  ;  levator 
palpebrarum,  superior  rectus,  inferior  rectus,  internal  rectus,  ami  inferior 
oblique. 

Stimulation  of  the  trunk  of  the  third  nerve  causi     thi    eyeball  to  look 

409 


410  PHYSIOLOGY 

upwards  and  inwards,  wit  li  conl  i  action  of  the  pupil  and  spasm  of  accommo- 
dation. 

Thegtiucleus  of  the  fourth  nerve  is  situated,  just  behind  that  for  the  third, 
in  the  floor  of  the  Sylvian  aqueduct,  on  a  level  with  the  inferior  corpora 
quadrigemina.  The  fibres  run  from  here  down  towards  the  pons,  then  turn 
sharply  backwards  to  pass  into  the  valve  of  Vieussens,  which  they  cross  hori- 
zontally, decussating  with  the  nerve  of  the  opposite  side.  The  superficial 
origin  is  therefore  from  the  valve  of  Vieussens.  This  nerve  supplies  the 
superior  oblique  muscle  of  the  eyeball.  Its  stimulation  causes  the  eyeball  to 
look  downwards  and  outwards. 

The  sixth  nerve,  the  motor  nerve  for  the  external  rectus  muscle  of  the 
eyeball,  arises  from  a  group  of  large  multipolar  cells  lying  on  each  side  of 
the  middle  line  in  the  floor  of  the  fourth  ventricle.  The  fibres  of  the 
nerve  pass  directly  outwards  to  emerge  from  the  anterior  ventral  surface 
of  the  medulla  between  the  pyramids  and  the  olivary  eminence,  at  the 
lower  border  of  the  pons.  Stimulation  of  this  nerve  causes  the  eyeball 
to  look  directly  outwards.  All  these  three  oculo-motor  nuclei  receive 
collaterals  from  the  fibres  forming  the  posterior  longitudinal  bundle,  many 
of  which  are  axons  of  cells  in  Deiters'  nucleus.  It  is  by  this  means  that  the 
contractions  of  the  muscles  moving  the  eyeball  are  co-ordinated.  Sherring- 
ton has  shown  that,  although  the  third,  fourth,  and  sixth  nerves  arise  directly 
from  the  brain  stem  and  have  no  ganglion  on  their  course,  they  are  really 
mixed  afferent-efferent  nerves.  Their  afferent  fibres,  which  must  arise 
from  the  cells  in  the  central  nervous  system  itself,  run  to  the  receptor  nerve 
endings  with  which  all  the  extrinsic  eye  muscles  are  richly  provided.  They 
are  exclusively  proprioceptive,  and  supply  no  organs  outside  the  muscles 
innervated  by  the  motor  fibres.  The  occurrence  of  afferent  fibres  in  these 
nerves  explains  the  fact  previously  observed  by  Sherrington  that,  after  total 
desensitisation  of  the  eyeball  by  means  of  cocaine,  or  by  section  of  the  first 
division  of  the  fifth  nerve,  the  ocular  movements  are  carried  out  with  as 
much  precision  as  in  the  normal  animal.  As  we  have  seen,  such  precision 
of  movement  requires  the  co-operation  of  afferent  impressions  from  the 
muscle,  and  the  only  possible  channels  for  these  impressions  are  the  pro- 
prioceptive sense-organs  and  the  afferents  of  the  third,  fourth,  and  sixth 
nerve  pairs  themselves. 

The  fifth  nerve,  or  trigeminus,  resembles  a  spinal  nerve  in  that  it  has  a 
motor  as  well  as  a  sensory  root.  The  motor  root  is  much  the  smaller  of  the 
two.  The  fibres  of  the  sensory  root  take  their  origin  in  the  cells  of  the 
Gasserian  ganglion,  which  is  in  all  respects  similar  to  the  ganglion  of  a 
posterior  spinal  nerve  root.  The  sensory  root  represents  the  somatic 
afferent  part  of  all  the  motor  cranial  nerves  from  the  third  to  the  hypoglossal 
and  has  a  correspondingly  wide  field  of  termination  in  the  brain  stem.  The 
afferent  fibres  of  the  fifth  nerve,  as  they  enter  the  pons,  bifurcate,  like  a  spinal 
afferent  nerve,  into  ascending  and  descending  branches.  The  ascending 
branches  are  short  and  pass  to  an  upper  sensory  nucleus,  situated  below  the 
lateral  part  of  the  fourth  ventricle  in  the  upper  part  of  the  pons.     The 


CONNECTIONS  AND  FUNCTIONS  OF  CRANIAL  NERVES -11  I 

descending  branches,  which  are  much  longer,  are  collected  into  one  or  more 
bundles  which  pass  downwards  in  the  lateral  part  of  the  reticular  formation, 
accompanied  by  the  downward  extension  of  the  sensory  nucleus  known  as  the 
substantia  gelatinosa.  The  descending  root  can  be  traced  down  in  the 
upper  part  of  the  cervical  cord,  its  fibres  in  this  region  forming  a  cap  to  the 
gelatinous  substance  of  Rolando.  From  the  cells  of  the  sensory  nucleus 
fibres  pass  towards  the  median  raphe,  crossing  to  the  other  side  to  take  part 
in  the  formation  of  the  tract  of  the  fillet  (the  trigemino-thalamic  tract).  The 
efferent  fibres  forming  the  motor  root  arise  from  two  nuclei.  The  chief  motor 
nucleus  consists  of  large  pigmented  multipolar  cells  situated  just  below  the 
surface  of  the  lateral  margin  of  the  fourth  ventricle  at  the  upper  part  of 
the  pons.  The  accessory  or  mesencephalic  nucleus  is  composed  of  large 
unipolar  cells,  situated  in  the  central  grey  matter  along  the  lateral  aspect  of 
the  anterior  end  of  the  fourth  ventricle,  and  in  a  corresponding  position  in 
mid-brain  as  far  as  the  upper  border  of  the  inferior  corpora  quadrigemina. 

The  fifth  nerve  is  the  motor  nerve  for  the  muscles  of  mastication,  and  for 
the  tensor  tympani  and  tensor  palati  muscles.  It  is  the  sensory  nerve  for  the 
whole  of  the  face  (including  eyeball,  mouth,  and  nose).  It  also  contains 
dilator  fibres  to  blood-vessels  derived  from  the  chorda  tympani,  and  is 
said  to  have  trophic,  functions.  The  latter  conclusion  is  from  the  fact 
that  section  of  the  fifth  nerve  in  the  skull  is  followed  by  ulceration  and 
sloughing  of  the  cornea,  and  finally  by  destructive  changes  involving  the 
whole  eyeball.  Since  however  these  results  may  be  prevented  by  carefully 
shielding  the  eye  from  all  dust  and  deleterious  influences,  it  is  probable  that 
the  ulceration  is  merely  a  secondary  consequence  of  the  anaesthesia.  The 
cornea  being  anaesthetic,  foreign  objects  that  fall  on  its  surface  are  allowed 
to  remain  there,  and  so,  give  rise  to  injurious  changes  and  ulceration. 

The  fifth  is  also  said  to  be  the  nerve  of  taste  for  the  anterior  third  of  the 
tongue,  but  it  is  probable  that  the  taste  fibres  which  run  in  the  fifth  arc 
derived  from  the  glossopharyngeal  or  from  the  nervus  intermedius. 

The  eighth  nerve  and  its  connections  have  been  discussed  already  on 
several  occasions.  We  may  here  briefly  summarise  what  has  already  been 
stated.  In  describing  the  eighth  nerve  it  is  necessary  to  consider  separatelv 
its  two  divisions,  the  dorsal  or  cochlear  division  and  the  ventral  or  vestibular 
nerve.  The  fibres  of  the  cochlear  nerve  originate  in  the  bipolar  cells  of  the 
spiral  ganglion  of  the  cochlea.  They  carry  impulses  from  the  auditory  end- 
organ.  On  entering  the  medulla  they  bifurcate  into  ascending  and  descend- 
ing branches  which  terminate  in  two  nuclei,  the  ascending  branches  in  the 
ventral  nucleus,  the  descending  branches  in  the  dorsal  nucleus.  The  ventral 
or  accessory  nucleus  lies  between  the  cochlear  and  vestibular  divisions  ven- 
trally  to  the  restiform  body.  The  dorsal  nucleus,  often  called  the  acoustic 
tubercle,  forms  a  rounded  projection  on  the  lateral  and  dorsal  aspects  of  the 
restiform  body.  From  these  two  nuclei  new  relays  of  fibres  start,  pass  to  the 
other  side,  by  crossing  the  median  raphe  (where  they  form  the  trapezium)  to 
run  up  in  the  lateral  fillet  of  the  opposite  side.  From  the  ventral  nucleus 
the  fibres  pass  directly  to  the  opposite  side,  forming  the  greater  part  of  the 


412  PHYSIOLOGY 

trapezium,  maid  Tig  conned  ion  on  their  way  with  the  nucleus  of  the  trapezium 

and  with  the  superior  olive.  From  the  dorsal  nucleus  most  of  the  axons  pass 
dorsally,  forming  the  stria?  acousticse  at  the  middle  of  the  floor  of  the  fourth 
ventricle.  On  arriving  at  the  middle  line  they  dip  down  and  join  the  fibres 
of  the  trapezium  of  the  opposite  side.  The  further  course  of  these  fibres 
up  to  the  internal  geniculate  body,  the  posterior  corpora  quadrigemina,  and 
1  he  auditory  radiations  of  the  cerebral  cortex,  have  been  described  on  p.  378. 

The  ventral  division  of  the  eighth  nerve,  or  vestibular  nerve,  originates 
in  the  bipolar  cells  of  the  vestibular  ganglion  or  ganglion  of  Scarpa.  These 
cells,  like  those  of  the  spiral  ganglion,  retain  the  primitive  bipolar  character. 
The  fibres  divide  into  ascending  and  descending  branches  which  become 
connected  with  two  nuclei.  The  dorsal  or  vestibular  nucleus,  or  principal 
nucleus,  which  receives  the  ascending  fibres,  is  a  mass  of  grey  matter  lying 
laterally  of  the  vago-glosso-pharyngeal  nucleus  and  corresponding  to  the 
lateral  triangular  area,  the  trigonuni  acoustici,  which  is  seen  on  the  surface 
of  the  fourth  ventricle  outside  the  ala  cinerea.  The  descending  vestibular 
nucleus,  receiving  the  descending  branches  of  the  vestibular  nerve,  lies 
below  but  continuous  with  the  principal  nucleus.  The  fibres  of  the  vestibular 
nucleus  send  also  collaterals  to  the  nucleus  of  Deiters  and  the  nucleus  of 
Bechterew,  two  accumulations  of  large  multipolar  cells  lying  ventrally  and 
internally  to  the  vestibular  nucleus,  both  nuclei  being  in  close  relation  to  the 
roof  nuclei  of  the  cerebellum.  Many  fibres  of  the  vestibular  nerve  pass 
apparently  through  these  various  nuclei  on  the  inner  side  of  the  restiform 
body  into  the  cerebellum,  where  they  make  connection  with  the  roof  nucleus 
or  nucleus  fastigii.  By  the  nuclei  of  Deiters  and  Bechterew  the  vestibular 
nerve  is  connected  through  the  dorsal  longitudinal  bundle  and  the  descending 
vestibulo-spinal  tract  with  the  motor  nuclei  of  the  cranial  and  spinal  nerves. 

The  use  of  the  vestibular  nerve  is  entirely  connected  with  the  function 
of  equilibrium.  It  is  probably  not  concerned  in  conveying  auditory  im- 
pressions, all  its  nerve  fibres  being  derived  ultimately  from  the  nerve-endings 
in  the  saccule  and  utricle  and  semicircular  canals. 

The  seventh  cranial  nerve  or  facial  nerve  emerges  from  the  brain  at  the 
inferior  margin  of  the  pons,  lateral  to  the  point  of  exit  of  the  sixth  nerve. 
It  is  almost  entirely  a  motor  nerve,  but  carries  also  some  sensory  blues 
for  taste  and  general  sensibility  which  it  receives  from  the  nervus  intermedins 
of  Wrisberg.  The  motor  nucleus  of  the  seventh  nerve  lies  in  the  reticular 
formation,  dorsally  to  the  superior  olive,  at  some  depth  below  the  floor 
of  the  fourth  ventricle.  From  this  nucleus  the  fibres  first  pass  inwards 
and  dorsally  towards  the  floor  of  the  ventricle,  where  they  collect  to  form 
a  bundle  which  runs  upwards  in  the  grey  matter  for  a  short  distance  and  then 
turns  sharply  in  a  ventro-lateral  direction  to  emerge  on  the  lateral  aspect  of 
the  pons.  The  fibres  from  the  motor  nucleus  supply  the  muscles  of  the  face. 
the  scalp,  and  the  ear.  Secretory  fibres  also  run  in  the  chorda  tympani, 
which  is  a  branch  of  the  facial.  These  are  probably  derived,  like  the 
sensory  fibres,  from  the  nerve  of  Wrisberg.  The  sensory  fibres  of  the 
nerve  of  Wrisberg  originate  in  the  nerve  cells  of  the  geniculate  ganglion,  and 


CONNECTIONS   AND   FUNCTIONS   OF  CRANIAL  NERVES    413 


passing  inwards  with  the  main  root  of  the  facial,  divide  into  ascending  and 
descending  branches  and  end  in  the  upper  part  of  the  column  of  grey  matter 
which  receives  also  the  sensory  fibres  of  the  ninth  and  tenth  cranial  nerves. 
The  ninth  and  tenth  cranial  nerves  arise  by  a  series  of  bundles  of  nerve 
fibres  from  the  side  of  the  medulla.  Both  the  ninth  and  tenth  are  mixed 
visceral  sensory  and  motor  nerves.  The  sensory  nucleus  is  a  column  of 
grey  matter  lying  laterally  to  the  hypoglossal  nucleus  just  below  the  promin- 
ence on  the  floor  of  the  fourth 
ventricle  known  as  the  ala 
cinerea.  The  descending  fibres 
of  these  nerves  form  a  well- 
marked  bundle  of  white  fibres 
known  as  the  fasciculus  soli- 
tarius,  or  sometimes,  from  its 
supposed  connection  with  the  &\ 
regulation  of  respiration,  the 
'respiratory  bundle  of  Gierke.' 
It  may  be  traced  down  as  far 
as  the  uppermost  part  of  the 
cervical  cord,  its  fibres  losing 
themselves  on  their  way  down 
among  the  cells  of  the  enclos- 
ing grey  matter.  The  efferent 
fibres  of  the  ninth  and  tenth 
nerves  are  derived  partly  from 
the  dorsal  nucleus  of  the  vagus 
and  accessory  nerves  lying  ex- 
ternallv  to  the  nucleus  of  the 
twelfth  nerve,  and  partly 
from  the  nucleus  ambiguus, 
a  mass  of  grey  matter  lying  deeper  in  the  medulla  (Fig.  206). 

The  ninth  or  glossopharyngeal  nerve  supplies  motor  fibres  to  the  muscles 
of  the  pharynx  and  the  base  of  the  tongue,  and  secretory  fibres  to  the  parotid 
gland.  The  sensory  fibres  convey  impulses  from  the  tongue,  the  mouth,  and 
pharynx,  the  fibres  originating  outside  the  central  nervous  system  in  the 
ganglion  cells  of  the  ganglion  petrosum  and  the  ganglion  superius.  It  also 
contains  inhibitory  fibres  to  the  respiratory  centre. 

The  tenth  nerve,  vagus  or  pneumogastric,  is  joined  by  the  accessory  part 
of  the  spinal  accessory,  so  that  the  two  nerves  may  be  considered  together. 
It  has  both  afferent  and  efferent  functions  : 
Efferent  functions  : 

Motor  to  levator  palati  and  three  constrictors  of  pharynx. 

Motor  to  muscles  of  larynx. 

Inhibitory  to  heart. 

.Motor  to  muscular  walls  of  oesophagus,  stomach,  and  small  intestine. 

Motor  to  unstriated  muscle  in  walls  of  bronchi  and  bronchioles. 


Fig. 


Plan 


tenth    ami 


I  the  origin  of  tin 
I  uiUth  nerves. 
pyr,  pyramid;  nXII.  nucleus  of  hypoglossal; 
XII.  hypoglossal  nerve  ;  il/iX,  XI.  dorsal  nucleus  of 
vagus  and  accessory;  n.amb,  nucleus  ambiguus; 
ft,  fasciculus  solitarius  (descending  root  of  vagus  and 
glossopharyngeal)  ;  fun,  its  nucleus  ;  A",  crossing 
motor  fibre  of  vagus  ;  r/,  cell  in  ganglion  of  vagus 
giving  origin  to  a  sensory  fibre  ;  d  V,  descending  root 
of  fifth  ;    cr.  corpus  restiforme ;  o,  olivary  nucleus. 


•114  PHYSIOLOGY 

Secretory  to  glands  of  stomach  and  to  pancreas. 

Afferent  functions  : 

Regulate   respiration.     Stimulation    of   central    end   may   quicken 
respiration  and  promote  inspiration,  or  may  inhibit  inspiration. 
Stimulation  of  central  end  of  superior  laryngeal  branch  causes 
stoppage  of  inspiration,  expiration,  cough. 
Depressor  and  pressor  (from  heart  to  vaso-motor  centre). 
Reflex  inhibition  of  heart. 

Its  afferent,  fibres  arise  from  cells  in  the  ganglia  on  the  trunk  of  thf> 
vagus,  namely,  the  jugular  ganglion  and  the  ganglion  triinci  vagi.  The 
spinal  accessory  nerve  arises  partly  in  connection  with  the  vagus,  partly  by 
a  series  of  roots  from  the  lateral  region  of  the  spinal  cord  as  low  as  the  sixth 
cervical  segment.  The  spinal  portion  of  the  nerve  is  purely  motor  and 
supplies  fibres  to  the  sterno-mastoid  and  trapezius  muscles. 

The  twelfth  or  hypoglossal  nerve  arises  from  a  collection  of  large  multi- 
polar cells  in  the  floor  of  the  fourth  ventricle  at  its  lower  end  close  to  the 
middle  line.  The  nerve-trunk  issues  from  the  ventral  part  of  the  medulla 
in  the  groove  between  the  anterior  pyramid  and  the  olivary  body.  The 
hypoglossal  is  purely  motor  in  function,  supplying  the  muscles  of  the  tongue, 
the  extrinsic  muscles  of  the  larynx,  as  well  as  those  moving  the  hyoid  bone. 

Since  the  integrity  of  the  nuclei  of  the  cranial  nerves  is  a  necessary  con- 
dition for  the  carrying  out  of  various  reflex  acts  in  which  those  nerves  are 
involved,  the  grey  matter  of  the  fourth  ventricle  and  aqueduct  is  often 
spoken  of  as  if  it  were  cut  up  into  a  series  of  centres  distinct  for  every  act. 
The  chief  of  these  are  the  respiratory  and  the  vaso-motor  centres.  Other 
centres  that  may  be  enumerated  are  : 

Centres  for  movements  of  intrinsic  and  extrinsic  ocular  muscles. 

Cardiac  inhibition. 

Mastication,  deglutition. 

Sucking. 

Convulsive  (connected  with  respiratory). 

Vomiting. 

Diabetic  (connected  with  vaso-motor). 

Salivary. 

Centres  of  phonation  and  articulation. 

We  shall  have  to  consider  the  action  of  these  centres  more  fully  in  treating 
of  the  several  functions  of  the  body.  It  must  be  remembered  however 
that,  when  a  dozen  or  more  centres  are  enumerated  as  being  situated  in  the 
fourth  ventricle,  it  is  not  meant  that  we  can  anatomically  distinguish  a  group 
of  cells  for  each  act  or  group  of  actions  named.  When  we  say  that  a  part  of 
the  nervous  system  is  a- centre  for  any  action,  we  merely  mean  that  this  part 
forms  a  necessary  link,  or  meeting  of  the  ways,  in  the  complicated  directing  of 
nerve  impulses  that  takes  place  in  every  co-ordinated  act. 


THE   CEREBRAL    HEMISPHERES 

SECTION  XVI 

GENERAL   STRUCTURAL    ARRANGEMENTS   OF 
THE   CEREBRUM 

The  cerebral  hemispheres  form  the  most  important  part  of  the  brain.  It  is 
bo  the  development  of  this  part  that  is  due  the  rise  in  type  in  vertebrates. 
In  development  they  are  formed  as  two  diverticula  from  the  front  part  of  an 
outgrowth  of  the  first  cerebral  vesicle.  In  the  lowest  vertebrates  these 
outgrowths  are  connected  entirely  with  the  olfactory  sense  organs,  and  we 
may  regard  the  olfactory 
part  of  the  brain  as  a  fun- 
damental part  on  which 
has  been  built  up  all  the 
rest  of  the  cerebral  hemi- 
spheres. In  a  cartilaginous 
fish  the  whole  of  the  upper  ,^)  !  \  '/  //  .  j 
brain  is  connected  with  HiV  A-  * 
the  organ  of  smell,  and  I. ...  ¥  , 
consists     of    a     thickening 

ill     the     floor     of    the     Out-  Fig.  207.     Section  through  cerebral  cortex  of  the  frog. 

growth  from  the  fore-brain.  (After  Edi™er-> 

The  roof  of  the  outgrowth  is  formed  of  simple  epithelium.  With  the 
development  of  the  visual  sensations  in  the  bony  fishes  there  is  still  very 
little  corresponding  growth  of  the  fore-brain,  most  of  the  fibres  from  the 
optic  nerves  going  to  the  roof  of  the  mid-brain  (the  optic  lobes).  The 
beginning  of  the  cerebral  hemispheres  is  associated  with  the  development 
of  nervous  tissue  in  the  roof  of  the  prosencephalon.  At  its  first  appear- 
ance this  higher  brain  material  still  receives  chiefly  olfactory  impressions. 
But  the  structure  of  the  cerebral  cortex  thus  laid  down  differs  from  that 
of  the  centres  forming  the  brain  stem  or  the  olfactory  lobe  itself  in  that 
it  provides  for  a  very  rich  association  of  impulses  between  all  its  parts. 
The  fibres  entering  the  cortex  break  up  into  a  fine  meshwork  of  fibres 
which  run  tangentially  to  the  surface  and  come  in  contact  with  innumer- 
able dendrites  of  nerve  cells  situated  at  some  little  distance  below  the 
surface  (Fig.  207).  We  have  here  the  first  germ  of  an  apparatus  in  which 
the  nerve  paths  can  be  determined  by  education,  i.e.  in  consequence  of 
inhibitions  by  pain,  rather  than  by  the  limits  set  by  Hereby-  T"  *'"' 
amphibian  brain,  and  still  more  in  the  brain  of  the  reptile,  the  cerebral 

415 


in 


PHYSIOLOGY 


cortex  extends  over  the  whole  of  the  roof  of  the  cerebral  hemispheres, 
though  even  here  a  very  large  proportion  of  it  is  devoted  to  the  association 
of  olfactory  impulses.  The  importance  of  these  olfactory  association  fibres 
is  well  shown  in  the  figure  (Fig.  208)  of  a  diagrammatic  section  through  a 
lizard's  brain.  Above  the  reptiles  there  is  a  divergence  in  the  course  of 
development.  The  wider  reactive  powers  of  birds  are  based  chiefly  on  an 
enormous  development  of  the  corpus  striatum,  whereas  in  mammals  the 
corpus  striatum  remains  relatively  small  and  the  chief  development  occurs 
in  the  roof  of  the  cerebral  hemispheres,  the  so-called  pallium  or  mantle. 
With  the  increased  entry  of  fibres  from  the  optic  thalamus  into  the  cerebral 
hemispheres,  carrying  impulses  from  the  eyes.  ears,  and  all  the  other  sense 
organs  of  the  body,  the  olfactory  part  of  the  brain  diminishes  in  importance, 


FlG.  208.     Schematic  section  through  brain  of  lizard  showing  the  chief 
nerve  tracts.     (After  Kdinger.) 


and  in  the  higher  mammals  and  man  is  altogether  overshadowed  by  the  newly 
formed  structures  of  the  pallium.  On  this  account  those  parts  of  the 
cerebral  hemispheres  in  special  connection  with  the  olfactory  sense  organs 
are  often  spoken  of  as  the  archif allium,  in  distinction  to  all  the  rest  of 
the  more  newly  formed  brain  substance,  known  as  the  neopallium. 

In  man  the  cerebral  hemispheres  form  a  great  ovoid  mass  exceeding 
in  size  all  the  rest  of  the  brain  put  together.  The  two  hemispheres  are 
separated  by  a  deep  fissure,  the  great  longitudinal  fissure.  Before  and 
behind,  this  fissure  extends  to  the  base  of  the  cerebrum,  but  in  the  middle  the 
two  hemispheres  are  connected  by  a  mass  of  transverse  fibres  known  as  the 
corpus  callosum.  On  the  outer  side  each  cerebral  hemisphere  presents  a 
deep  cleft,  the  Sylvian  fissure.  The  whole  surface  of  the  brain  is  thrown 
by  fissures  (or  sulci)  into  convolutions,  by  which  means  a  very  large  increase 
of  the  surface  grey  matter  is  obtained.  By  these  fissures  the  brain  surface 
is  divided  into  lobes.  The  general  arrangement  is  shown  in  Figs.  209  and  210. 
The  chief  lobes  are  the  frontal,  the  parietal,  the  occipital,  the  temporal,  the 
insular,  the  limbic,  and  the  olfactory.  On  the  inner  side,  from  before 
backwards,  we  have  the  marginal,  the  paracentral,  the  pre-cuneus,  the 
cuneus  ;    and  in  close  proximity  to  the  corpus  callosum,  the  cingulum  or 


STRUCTURAL   ARRANGEMENTS   OF  CEREBRUM  417 

S.precentral.s  inferior      5f,recentratlS  supei 


S-fr'ontatiS  Inferior 
S.  frontalis  superior 
7.  frontalis  medius 


S.centralis  (Rolandi) 

,     S. postcentrals  inferior 

5. post '■centralis  intermedius 

postcentrals  superior 

ntrapariefafis 


Ramus 
anthorizontalis 
Ramus  ant  ascendens 
S.  diagonal  is 
Ramus  post,  of  Sylu 


S  occipitalis  lateralis 

S.occipitaiis  transuersu 

Fig.  209.     Lefl  cerebral  hemisphere  of  mmi.  lateral  aspect.     (Symington. 


Sprecenfralis  mesiahs 
S.centralis  (Roland/) 
■Pars  marainalis s.cinduli 
Spanetalis  superior 
S. pane  to  -occipitalis 


5  cm  fuh 


Scorporis  catlosi 


S.subpanetalts 


>.cotianratis 
5.  temporalis  infer/oj- 


Fasc/'a  denfata 


!'  '■  -  210.     Lefl   cerebral   hemisphere  of  num.  from  tKe  mesial  aspect.     (Symj 

27 


418 


PHYSIOLOGY 


supra-callosal  convolution  above,  and  the  liippocampal  convolution  and  the 
uncus  below.     The  chief  fissures  separating  these  are  the  Sylvian  fissure,  the 


Midbrain 

Cerebellum 


Eye  I' 


-■-  Occipital  cortex 
radiate    Midbrau 


Fig.  211.  Diagrams  from  Monakow,  showing  the  evolution  of  the  neopallium, 
and  the  gradual  shifting  of  the  visual  sensory  tracts  from  the  mid-brain  to  the  fore- 
brain,  and  thence  to  the  Occipital  cortex. 

A,  a  bony  fish.     B,  brain  of  a  lizard.     C,  brain  of  a  mammal  (cat). 

central  sulcus  or  fissure  of  Rolando,  the  parieto-occipital  fissure,  the  cal- 
carine  fissure,  the  collateral  fissure,  and  the  calloso-marginal  fissure.  Each 
of  the  main  lobes  (or  gyri)  mentioned  above  is  further  subdivided  by  smaller 


STRUCTURAL  ARRANGEMENTS   OF  CEREBRUM 


419 


fissures.  The  extent  of  these  secondary  fissures  varies  from  brain  to  brain, 
the  higher  types  of  brain  being  richer  in  convolutions  than  those  of  the  more 
primitive  races. 

The  gradual  evolution  of  the  cerebral  cortex,  and  the  concomitant  shifting 
of  the  chief  afferent  impulses,  arising  in  the  projicient  sense  organs,  from  the 
lower  ganglia  to  the  higher  educatable  cortex,  is  well  shown  in  the  diagrams 
from  Moankow  (Fig.  211,  p.  418).  In  the  lower  fishes  practically  all  the 
reactions  to  visual  impressions  are  carried  out  by  the  optic  lobes.  In  the 
higher  types  the  reflexes  through 
these  lobes  become  subordinated,  first 
to  the  more  complex  organ  of  the 
optic  thalamus  (where  representatives 
from  all  the  afferent  tracts  of  the  body 
assemble),  and  later  to  the  still  more 
complex  occipital  cortex,  when  the 
reactions  are  determined  not  only  by 
inherited  nerve  paths  but  also  by 
the  various  blocks  and  facilitations 
imprinted  on  the  nerve  paths  by 
the  experience  of  the  individual 
himself. 

The  original  cavities  of  the  hemispheres 
form  the  lateral  ventricles,  each  of  which, 
in  the  adult  brain,  is  prolonged  into  the  main 
divisions  of  the  hemispheres  as  the  anterior 
horn,  the  posterior  horn,  and  the  inferior 
horn.  Each  lateral  ventricle  is  roofed  over  by 
the  corpus  callosum  and  the  adjoining  white 
matter  of  the  hemispheres.  On  opening  the 
ventricle  we  see  on  its  floor  the  body  of  the 
fornix,  a  flattened  tract  of  white  matter  with 
longitudinal  fibres,  which  in  front  bifurcates  FlG  212.  Horizontal  section  through  the 
into  two  cylindrical  bundles  which  pass  verti-  optic  thalamus  and  corpus  striatum,  the 
cally  downwards  in  front  of  the  foramen  of  'basal  ganglia.'  (Natural  size.)  (Quahj.) 
Monro  into  the  mesial  part  of  the  subthala-  vl,  lateral  ventricle,  its  anterior  cornu  : 
mic  tegmentum.  Internal  to  the  fornix  is  a  <*■  corP"s  ^Uosum  ;  si.  septum  tacidnm: 
6        .  .     ,  ,,        ,        . ,    af.  anterior  pillars  of  the  fornix  ;    r3,  third 

layer  of  pia  mater,  including  the  choroid  ventricie  .  th,  thalamus  opticus  ;  nt,  stria 
plexus.  On  removing  this  the  third  ventricle  medullaris  :  nc,  nucleus  caudatus.  and 
is  opened,  so  that  in  this  region  the  wall  of   nl,  nucleus  lenticularis  of  the  corpus  stria- 

the  cerebral  hemispheres,  like  the  roof  of   tum:    ie>  mt^m.al  f  W^  '    '•  lts  "$V* 
r  .  genu  ;     nc,    tail    of    the    nucleus    caudatus 

the  third  ventricle,  is  limited  to  a  simple   appeai.ing  ^  the  descending  cornu  of  the 
layer  of  ependyma.     At  the    margin  of  the    lateral  ventricle  ;    <•'.  claustrum  ;    /,   island 
choroid  plexus  can  be  seen  a  part  of  the  supe-    of  Reil. 
rior  surface  of  the  optic  thalamus,  separated 

however  from  the  cavity  of  the  ventricle  by  a  layer  of  ependyma.  Outside 
and  in  front  of  the  optic  thalamus  are  the  masses  of  nervous  material  con- 
stituting the  corpus  striatum.  These  present  two  nuclei  of  grey  matter,  known 
as  the  nucleus  caudatus  and  the  nucleus  lenticularis  (Fig.  212).  The  crusta 
of  the  crura  cerebri  as  it  ascends  to  the  cerebral  hemispheres  passes  behind  between 
the  optic  thalamus  and  the  corpus  striatum,  and  in  front  between  the  nucleus  lenticu- 


420  PHYSIOLOGY 

laris  and  nucleus  caudatus  of  the  corpus  striatum.  Outside  the  corpus  striatum  we  find 
another  mass  of  white  fibres,  known  as  (he  external  capsule,  and  this  is  separated  from 
the  white  matter  of  the  cortex  cerebri  by  a  thin  layer  of  grey  matter  known  as  the  clans- 
t  rum.  In  a  horizontal  section  through  the  brain,  the  part  of  the  internal  capsule 
which  pierces  the  corpus  striatum  forms  an  angle  with  the  posterior  pari  separating  the 
optic  thalamus  from  the  lenticular  nucleus.  The  part  where  the  two  limlis  come  in 
contact  is  known  as  the  genu  of  the  internal  capsule  (Kig.  212). 

THE  OLFACTORY  APPARATUS  OF  THE  BRAIN 
In  mini  the  olfactory  sense  is  luit  feebly  developed,  and  the  parts  of  the 
brain  connected  therewith  are  inconspicuous  in  comparison  with  those  en- 
gaged in  the  reception  of  impressions  from  the  other  two  main  projicienl 
sense  organs,  namely,  sight  and  hearing.  On  this  account  it  is  not  easy  to 
make  out  the  connections  of  the  olfactory  lobe  proper,  the  rhmencepkalon, 
with  the  primitive  part  of  the  cortex,  the  arcJiipaUium,  subserving  the  olfac- 
tory sense  and  probably  the  allied  sensations  derived  from  the  mouth  cavity. 
The  wide  connections  of  the  olfactory  sense  organs  with  the  different  parts 
of  the  brain  in  the  lower  vertebrate  are  shown  in  the  diagrammatic  figure  of 
the  brain  of  a  reptile  (Fig.  208,  p.  416). 

It  is  interesting  to  note  that  the  olfactory  nerve  fibres  are  derived  from  cells  situated 
actually  on  the  surface  of  the  body.  These  are  bilateral,  spindle-shaped  cells,  lying 
in  the  olfactory  mucous  membrane  at  the  upper  part  of  the  nasal  cavity.  The  peri- 
pheral process  is  short  and  passes  towards  the  surface,  while  the  deep  process  passes 
as  a  non-medullated  nerve  fibre  through  the  cribriform  plate  of  the  ethmoid  to  sink 
nito  the  olfactory  bulb.  The  bulb,  in  man.  is  a  greyish  enlargement  at  the  anterior' 
end  of  the  olfactory  tract.  In  sections  stained  by  (iolgi's  method  of  impregnation  it 
may  be  seen  that  the  olfactory  fibres  terminate  in  an  arborisation  in  close  connection 
with  a  thick  end  arborisation  derived  from  a  dendrite  of  a  large  nerve  cell,  known  as 
a  mitral  cell.  The  synapses  between  these  two  sets  of  fibres  are  prominent  objects 
in  a  section  through  the  olfactory  bulb  and  form  the  'olfactory  glomeruli  '  (Fig.  213). 
The  axons  of  the  mitral  cells  pass  back  in  the  olfactory  tracts.  Each  olfactory  tract- 
divides  posteriorly  into  two  roots,  the  mesial  root  which  curves  inwards  behind  Broca's 
area  and  passes  into  the  end  of  the  callosal  gyrus,  and  the  lateral  root  which  runs  back- 
wards and  over  the  outer  part  of  the  anterior  perforated  spot.  Its  fibres  pass  into  the 
uncinate  extremity  of  the  liippocampal  gyrus.  The  small  triangular  field  of  grey 
matter  between  the  diverging  roots  of  the  olfactory  tract  is  known  as  the  olfactory 
tubercle.  The  primitive  rhineneephalon  includes  in  the  adult  human  brain  the  olfactory 
bulb  and  tract,  together  with  the  anterior  perforated  space,  the  anterior  part  of  the  unci- 
nate gyrus,  the  subcallosal  gyrus,  the  septum  lucidum.  and  the  liippocampal  convolution. 
The  two  sides  of  the  rhineneephalon  are  united  by  fibres  passing  through  the  anterior 
commissure.  Other  tracts  subserving  this  apparatus  include  the  habenula  passing 
from  the  fornix  to  the  ganglion  of  the  habenula.  the  fasciculus  retroflexus  passing  from 
this  to  the  interpeduncular  ganglion,  and  the  corpus  mammillare  which  is  connected 
with  the  column  of  the  fornix  on  the  one  hand  and  through  the  bundle  of  Vieq  d'Azyr 
with  the  thalamus  on  the  other. 

THE   CHIEF   TRACTS   OF   THE   CEREBRAL   HEMISPHERES 
We  may  divide  the  tracts  of  the  upper  brain  or  cerebral  hemispheres  into 
three  classes  : 

I,  Tracts  connecting  the 'brain  with  lower  levels  of  the  central  nervous 

system. 


STRUCTURAL   ARRANGEMENTS   OF  CEREBRUM 


421 


II.  Tracts  connecting  different  parts  of  the  cortex  of  one  hemisphere 
and  serving  as  a  means  of  association  between  these  different  parts. 

III.  Tracts   (commissural)   connecting   the   two   cerebral   hemispheres 
together. 

I.     THE    PROJECTION  FIBRES 
These  are  the  fibres  which  connect  the  cerebral  cortex  with  the  different 
lower  levels  of  the  central  nervous  system.     They  form  a  great  part  of  the 


Fig.   l'I:'..     Schema  of  oourse  of  olfactory  impulses.     (Ramon   y  Cajal.) 
A,   olfactory   mucous   membrane;     B,   olfactory   glomeruli;     C,   mitral   cells; 
e.  granule  cells  ;    D,  olfactory  tract  ;    L,  centrifugal  fibres. 

fibres  of  the  corona  radiata  and  are  condensed  at  the  base  of  the  brain  into 
the  broad  band  of  fibres  known  as  the  internal  capsule.  A  few  of  the  fibres 
of  the  projection  system  may  gain  the  cortex  through  the  lenticular  nucleus 
and  by  the  external  capsule.  The  projection  fibres  may  be  divided  into 
two  groups  according  as  they  conduct  impulses  to  or  away  from  the  cere)  ira  1 
cortex  :    the  afferent  or  corticipetal,  and  the  efferent  or  corticifugal. 


A.     AFFERENT   TRACTS   OF   THE   CEREBRUM. 

( I )  The  thalamo-cortical.  From  all  parts  of  the  optic  thalamus  fibres 
arise  as  axons  of  the  cells  of  its  grey  matter  and,  streaming  out  from  its  outer 
and  under  surfaces,  pass  to  every  part  of  the  cortex.  Although  there  is  no 
division  of  them  into  distinct  groups  as  they  leave  the  thalamus,  fchej  are 
often  described  as  constituting  a  frontal,  a  parietal,  an  occipital,  and  a  vent  ra  I 
stalk.  The  front  fibres  pass  through  the  anterior  limb  of  the  internal  capsule 
to  reach  the  cortex  of  the  frontal  lobe,  many  of  the  fibres  however  termina- 
ting in  the  caudate  and  lenticular  nuclei.  The  parietal  fibres  issuing  from 
the  lateral  surface  of  the  thalamus  pass  through  the  internal  capsule  to  be 
distributed  chiefly  to  the  parietal  lobe.  The  occipital  fibres  issue  from 
the  outer  part  of  the  pulvinar  and  the  external  geniculate  body  and  constitute 
the  so-called  '  optic  radiation,'  passing  outwards  and  backwards  to  be 
distributed  to  the  cortex  <>f  the  occipital  lobe.  The  ventral  fibres  pass 
downwards  and  outwards  below  the  lenticular  nucleus  and  end  partly  in  the 


422 


PHYSIOLOGY 


latter  nucleus  and  partly  in  the  cortex  of  the  temporal  lobe  and  of  the  insula 
or  island  of  Reil. 

(2)  The  fillet  system  of  fibres.  This  great  mass  of  ascending  fibres 
has  been  already  described  (cp.  Fig.  197)  as  gathering  up  the  impulses  from 
the  different  sensory  nerves  of  the  cerebro-spinal  system  and  terminating 
in  the  thalamus  and  subthalamic  region. 

(3)  The  superior  cere- 
bellar pedunclk.  These 
fibres,  from  the  central 
ganglia  of  the  cerebellum, 
terminate  for  the  most  part 
in  the  thalamus  and  sub- 
thalamic region.  It  is  pos- 
sible that  some  of  them  may 
pass  through  the  hinder  end 
of  the  internal  capsule,  with- 
out interruption  in  the  thal- 
amus, to  end  in  the  Rolandic 
area. 

(4)  The  optic  radiation. 
These  diverging  fibres  in  the 
back  part  of  the  corona- 
radiata  are  mixed  up  with 
fibres  which  are  partly  corti- 
cifugal.  The  corticipetal 
fibres  arise  in  the  pulvinar 
and  the  external  geniculate 
body  and  end  in  the  occipital 
cortex. 

(5)  The  auditory  radia- 
tion. These  fibres  consist  of 
the  axons  of  cells  situated  in 
the  internal  geniculate  body. 

They  pass  through  the   posterior  limb  of  the  internal  capsule  under  the 
lenticular  nucleus  to  end  in  the  temporal  lobe. 


Pig.  l>I4. 


<-       UOBL 

Schema  of  projection   fibrea  of  cortex. 
(Cunningham.) 


B.     THE    EFFERENT   PROJECTION   FIBRES. 

( 1 )  The  pyramidal  tract.  This  is  composed  of  fibres  which  arise  from 
the  large  Betz  cells  in  the  ascending  frontal  convolution,  the  '  motor  area.' 
They  pass  through  the  corona  radiata  into  the  internal  capsule,  where  they 
occupy  the  genu  and  the  anterior  two-thirds  of  the  posterior  limb.  Hence 
they  pass  into  the  crusta,  where  they  occupy  the  middle  two-fifths  of  this 
structure,  and  are  continued  as  the  pyramids  of  the  pons  and  medulla  to 
the  upper  part  of  the  spinal  cord,  where  most  of  them  decussate  to  the  other 
side  to  form  the  crossed  pyramidal  tracts.     Some  of  the  fibres  do  not  cross 


STRUCTURAL  ARRANGEMENTS  OF  CEREBRUM 


423 


at  the  pyramidal  decussation,  but  are  continued  down  in  the  same  position 
in  the  anterior  columns  of  the  spinal  cord  of  the  same  side,  forming  the  direct 
or  anterior  pyramidal  tracts.  These  fibres  cross  for  the  most  part  lower  down 
in  the  cord,  so  that  the  direct  pyramidal  tract  is  not  seen  below  the  cervical 
region.  The  pyramidal  tracts  are  not  found  in  lower  vertebrates,  and  make 
their  first  appearance  in  the  mammalia.  Their  development  corresponds 
with  the  gradual  increase  in  the  direct  interference  of  the  cerebral  cortex 
in  the  reactions  of  the  organism  as  a 
whole  and  is  an  index  to  the  gradual 
shifting  of  these  reactions  from  the 
inevitable  to  the  educated  reflex.  The 
fibres  of  the  pyramidal  tract  end  at 
various  levels  of  the  spinal  cord  and 
can  be  traced  to  the  lower  end  of  the 
sacral  region.  According  to  Schafer 
they  end  in  the  posterior  cornua,  so 
that  their  action  is  to  set  going  a  reac- 
tion which  could  otherwise  be  elicited 
by  stimulation  of  the  afferent  fibres 
entering  by  the  posterior  root  at  the 
level  of  the  cord  where  they  end. 

(2)  The  fronto-pontine  fibres. 
These  arise  from  cells  in  the  cortex  of 
the  frontal  lobe,  and  pass  down  in  the 
anterior  limb  of  the  internal  capsule 
to  gain  the  mesial  part  of  the  crusta  of 
the  Crus  cerebri.  The  fibres  end  in 
the  grey  matter  of  the  formatio  reti- 
cularis of  the  pons,  the  nucleus  pontis. 

(3)  The  temporopontine  fibres. 
These  arise  from  the  two  upper 
temporal  convolutions,  especially  from  that  area  which  is  associated  with 
hearing.  They  pass  inwards  under  the  lenticular  nucleus  through  the  hinder 
limb  of  the  internal  capsule  to  gain  the  outer  part  of  the  crusta.  In  this 
situation  this  tract  passes  down  into  the  pons,  where  it  ends  in  the  nucleus 
pontis. 

As  part  of  these  projection  fibres  we  Ought  probably  to  reckon  the  fibres 
which  take  origin  or  end  in  the  corpus  striatum.  The  afferent  fibres  of  this 
body  are  derived  chiefly  from  the  thalamus,  forming  the  thalamo-striate 
fibres.  Other  fibres  arise  in  the  nuclei  of  the  corpus  striatum  and  pass  down 
in  the  dorsal  portion  of  the  crusta  to  end  for  the  most  part  in  the  pons,  the 
strio-pontine  fibres. 

The  relative  position  of  these  various  fibres  in  the  internal  capsule 
and  in  the  crusta  is  shown  in  the  accompanving  diagrams  (Figs.  215  and 
216). 

The  fronto-pontine  and  temporo-pontine  fibres,  which  end  in  the  nucleus 


Fig.  215.  Diagrammatic  representation 
of  the  internal  capsule,  as  seen  in  hori- 
zontal section.     (Cunningham.) 


424 


PHYSIOLOGY 


pontis,  come  there  in  relationship  with  thcfibres  Eorming  the  middle  peduncles 
of  the  cerebellum  and  derived  chiefly  from  the  lateral  lobes  of  the  cerebellum. 
These  fibres  may  therefore  be  regarded  as  the  efferent  side  of  the  greal 
cerebro-cerebellar  connections  of  which  the  afferent  side  is  represented 
by  the  fibres — efferent  so  far  us  concerns  the 
cerebellum- -which  pass  from  the  cerebellar 
cortex  to  the  dentate  nucleus  and  thence  by 
a  fresh  relay  in  the  superior  cerebellar 
peduncles  to  the  red  nucleus,  optic  thalamus, 
and  cortex  of  the  opposite  side.  The  devel- 
opment of  these  fibres,  as  of  the  lateral 
lobes  of  the  cerebellum,  is  largely  proportional 
to  the  growth  of  the  cerebral  hemispheres.  In 
cases  where  there  has  been  congenital  atrophy 
of  one  cerebral  hemisphere,  the  crusta  of  the. 
same  side  and  the  lateral  lobe  of  the  cerebellum 
of  the  opposite  side  also  fail  to  develop. 


Fig.  21(i.     Transverse  section 
through   mid-brain   t<>  show 
position  of  fillet  and  pyramid. 
AQ,  anterior  corpus  quadri- 
geminum  ;  dV,  descending  roof 
of  fifth  nerve  ;F,fillet  (I,  lateral, 
and  m,  mesial  fillet) ;  Pyr.  pyra- 
mid ;  Fr.  fibres  from  frontal  lobe 
to  pons  ;  TO,  fibres  from  tem- 
poral   and    occipital    lobes    to 
pons  ;  Ne,  fibres  from  nucleus 
caudatus  to  pons  ;    ITT,  mot  of 
third  nerve  ;    8,  .Sylvian   iter  ; 
Rn.  red  nucleus. 


II.     ASSOCIATION    FIBRES 


These  tidies  serve  to  unite  different  portions 
of  the  cortex  of  the  same  hemisphere  ami  may 
be  classified  into  short  and  long  association 
fibres.  The  short  association  fibres  pass  round 
the  bottom  of  the  sulci  in  U-shaped  loops 
connecting  adjacent  convolutions.  These  fibres  are  some  of  the 
latest  to  acquire  a  medullary  sheath  and  probably  first  become  functional 


Fio.  217.     Chief  association  bundles  of  the  cerebral  hemispheres.     (Ccnningh  \m.) 
A.  Outer  aspect    of  hemisphere.     B.  Inner  aspect  of  hemisphere. 


as  associated  activity  between  the  various  portions  of  the  cortex  is  gradually 
acquired  by  education. 

The  long  association  fibres  may  be  divided  into  five  groups  as  follows  : 
(a)  The  uncinate  fasciculus  passes  from  the  orbital  convolutions  of    the  frontal  lobe 
to  the  front  part  of  the  temporal  lobe  round  the  stem  of  the  Sylvian  fissure  (Fig.  217). 


STRUCTURAL  ARRANGEMENTS   OF  CEREBRUM 


425 


(t)  The  (-ingnluai  is  closely  associated  with  those  parts  of  the  cerebral  cortex  known 
together  as  the  limbic  lobe.  In  front  it  originates  in  the  neighbourhood  of  the  anterior 
perforated  space,  passes  round  the  genu  of  the  corpus  callosum,  and  then  is  carried 
backwards  over  the  upper  surface  of  this  body  to  its  hinder  end,  where  it  turns  round 
and  is  distributed  to  the  hippocanipal  gyrus  and  to  the  temporal  lobe. 

(c)  The  longitudinal  superior  fasciculus  lies  in  the  base  of  the  frontal  and  parietal 
lobes,  and  passing  from  before  backwards  connects  the  frontal  occipital,  and  temporal 
parts  of  tlic  cerebral  cortex. 

(d)  The  longitudinal  inferior  fasciculus  runs  along  the  whole  length  of  the  occipital 
.mil  temporal  lobes,  being  situated  behind  on  the  outer  aspect  of  the  optic  radiation. 

(e)  The  occipito-frontal  fasciculus  lies  on  the  inner  aspect  of  the  corona  radiata  in 
intimate  relation  to  the  caudate  nucleus,  and  projects  out  over  the  upper  and  outer 
aspect  of  the  lateral  ventricle  immediately  outside  the  ependyma. 


III.     THE   COMMISSURAL   FIBRES 

These  are  arranged  in  three  groups  : 

(a)  The  corpus  callosum  forms  a  great  mass  of  while  fibres  passing  trans- 
\'i  ely   in   both  directions  between  the  two  hemispheres,     [ts  fibres  are 


Flo.  218.     Schematic  section  through  cerebral  hemispheres,  to  show  chief  classes 
of  nerve  tracts.     (After  Ram6n  y  Cajal.) 
a,  corpus  callosum  ;    B,  anterior  commissure  ;    c,   pyramidal  tract  ;    a,  cell 
giving  off  projection  fibre  ;    ').  cell  giving  off  commissural  fibre  ;    c,  cell  with  a  son 
forming  association   fibres. 

derived  from  every  part  of  the  cerebral  cortex  with  the  exception  of  the 
olfactory  bulb  and  the  hind  and  fore  parts  of  the  temporal  lobe.  As  the 
fibres  cross  the  middle  line  they  become  gradually  scattered,  so  that  tiny 
tend  to  connect  wholly  dissimilar  parts  of  the  cortex  of  opposite  hemispheres. 
Each  callosal  fibre  arises  in  one  hemisphere  and  ends  by  fine  arborisations  in 
the  opposite  hemisphere.  It  may  represent  either  the  axon  of  one  oi  the 
cortical  cells  or  a  collateral  from  a  fibre  of  association  or  a  collateral  from  a 
projection  fibre  (Fig.  218). 

(6)  The  anterior  commissure  is  situated  in  the  anterior  wall  of  the  third 
ventricle  in  front  of  the  two  pillars  of  the  fornix.  It  connects  together  the 
two  olfactory  lobes  and  portions  of  the  opposite  temporal  lobes.  In  lower 
vertebrates  it  is  almost  entirely  olfactory  in  function,  but  in  man  the  olfad  ory 


426  PHYSIOLOGY 

fibres  form  only  a  small  proportion  of  the  total  number  making  up  the 
bundle. 

(c)  The  psalterium  or  hippocampal  commissure  is  a  thin  lamina  formed 
of  transverse  fibres  filling  up  the  small  triangular  space  on  the  under  surface 
of  the  hinder  part  of  the  corpus  callosum  formed  by  the  divergence  of  the 
posterior  pillars  of  the  fornix.  Like  the  anterior  commissure,  the  hippo- 
campal commissure  is  closely  associated  with  the  sense  of  smell.  Its  fibres 
arise  from  the  pyramidal  cells  in  the  cornu  ammonis  or  hippocampus  and  pass 
for  the  greater  part  to  the  cornu  ammonis  of  the  opposite  side. 

MINUTE  STRUCTURE  OF  THE  CEREBRAL  CORTEX 
The  cortex  of  the  cerebral  hemispheres  consists  of  a  layer  of  grey  matter 
covering  a  central  mass  of  white  fibres.  With  the  growth  in  size  of  the 
brain,  which  accompanies  the  development  of  increased  intelligence  and 
powers  of  adaptation,  the  necessary  increase  in  cortex  is  rendered  possible  by 
the  folding  of  the  surface  into  convolutions  and  fissures.  The  chief  of  these 
convolutions  have  already  been  indicated  in  the  sketch  of  the  anatomy  of  the 
brain  (Fig.  209). 

On  section  the  grey  matter  is  seen  to  consist  of  many  layers  of  nerve 
cells  embedded  in  neuroglia  and  nerve  fibres,  both  medullated  and  non- 
medullated.  The  nerve  cells  vary  in  size  and  shape  :  one  kind  of  cell  is 
however  typical  of  this  part  of  the  central  nervous  system.  This  is  the 
pyramidal  cell  (Fig.  219),  a  cone-shaped  or  pear-shaped  cell  with  one  large 
apical  dendrite  which  runs  towards  the  surface  and  breaks  up  in  the  most 
superficial  layer  into  a  number  of  branches.  Dendrites  are  also  given  off  from 
the  sides  and  lower  angles  of  the  cell.  The  axon,  which  arises  from  the  axon 
hillock  in  the  middle  of  the  base  of  the  cell,  passes  downwards  into  the  white 
matter,  giving  off  collaterals  in  its  course.  Some  of  these  axons  pass  by  the 
corona  radiata  into  the  internal  capsule  and  into  the  crura  cerebri,  including 
those  which  form  the  pyramidal  tracts  ;  others,  or  their  collaterals,  may  pass 
into  the  adjacent  regions  of  the  cortex,  or  across  by  the  corpus  callosum  into 
the  opposite  hemisphere. 

Although  varying  in  structure  at  different  parts,  it  is  generally  possible 
to  distinguish  four  or  five  layers  in  the  cortex. 

(1)  The  most  superficial  layer,  known  as  the  outer  fibre  lamina,  or 
'molecular  layer,  contains  very  few  cells.  It  is  composed  generally  of  the  den- 
drites of  cells  from  the  deeper  layers.  It  contains  a  few  cells  which  are 
spindle-shaped  and  are  provided  with  several  processes  running  parallel 
to  the  surface.  These  are  sometimes  called  association  cells.  It  is  probable 
that  afferent  fibres,  entering  the  cortex,  pass  up  towards  the  surface  and  end 
for  a  large  part  in  this  molecular  layer. 

(2)  Below  this  is  a  layer  of  pyramidal  cells,  the  outer  cell  lamina,  which 
is  divided  by  some  observers,  e.g.  Campbell,  into  three,  viz.  : 

(a)  The  small  pyramidal  cells. 

(b)  Medium-sized  pyramidal  cells. 

(c)  Internal  layer  of  large  pyramidal  cells. 


STRUCTURAL  ARRANGEMENTS  OF  CEREBRUM 


127 


(3)  Below  the  pyramidal  layer  we  find  a  stratum  of  small  cells,  most  of 
which  are  stellate  in  form.  This  is  known  as  the  stellate  or  granule  layer, 
or  middle  cell  lamina. 

(4)  Internal  to  the  granule  layer  is  the  inner  fibre  lamina.  In  the 
motor  cortex  and  in  certain  other  parts  of  the  brain  this  contains  large 
solitary  cells,  which  in  the  motor  area  receive  the  name  of  the  cells  of  Betz. 

(5)  Most  internal  of  all,  lying  next  to  the  white  matter,  is  the  poly- 


l'lo.   219.     Schematic   representation  of  the  neuro-hbrillar  apparatus  of    a    cortical 

pyramidal  cell.     (After  Cajal.) 

o,  axon  ;    dh,  dendrites. 

morphous  layer  or  inner  cell  lamina,  composed  of  many  types  of  cells,  among 
which  spindle-shaped  cells  predominate.  Other  cells  are  also  found  resem- 
bling pyramidal  cells  of  the  more  superficial  layer,  but  directed  in  the  reverse 
direction,  so  that  their  axons  take  a  course  towards  the  surface.  These 
are  the  cells  of  Martinotti.  We  also  find  Golgi  cells  with  a  freely  branching 
axon,  which  terminates  in  the  adjacent  grey  matter. 


128 


PHYSIOLOGY 


If  sections  of  the  cortex  be  stained  by  some  method  such  as  Weigert's, 
which  displays  medullated  nerve  fibres,  sheaves  of  radial  fibres  may  be 
seen  running  from  the  white  centre  towards  the  surface  and  giving  of!  a  rich 


Fig.  220.     Diagrammatic  section  of  cerebral  cortex.     (From  Barker  after  Starr, 
Strong,  and  Leamtng.) 
I,  molecular  layer  with  a,  bipolar  cell ;    II,  liyer  of  small  pyramidal  cells  ; 
III,  layer  of  large  pyramidal  cells  ;    IV,  polymorphous  layer  ;    V,  white  matter. 

meshwork  of  fibres  to  the  intervening  portions  of  the  grey  matter.  In 
addition,  bands  of  tangential  fibres  are  seen  running  parallel  to  the  surface 
in  certain  situations,  viz.  : 


STRUCTURAL  ARRANGEMENTS  OF  CEREBRUM 


429 


(a)  A  layer  of  very  fine  fibres  just  under  the  surface  of  the  cortex.  This 
layer  is  especially  marked  in  the  hippocampal  convolution  and  is  but  slightly 
developed  in  other  regions  of  the  cortex. 

(b)  A  layer  between  the  molecular  layer  and  the  layer  of  pyramidal 
cells,  known  as  the  mi/cr  live  <>j   Bailh  rger. 


ill  Molecular   or   mil 
Hlnv  lamina. 
Il-.'tl   mm. 


a,  Tangential  laye 


Fig.  221.    Motor  leg 


(c)  Internal  to  the  granule  layer  is  another  zone  of  fibres,  the  inner 
1 1 in'  nj  Baillarger,  giving  its  name  to  the  inner  fibre  lamina. 

[(I)  In  the  part  of  the  occipital  cortex,  distinguished  as  the  visuo-sensory 
area,  which  receives  fibres  of  the  optic  radiations,  a  special  layer  of  tangential 
fibres  is  observed  running  through  the  middle  of  the  granular  layer  and 
dividing  it  into  two  parts.     This  is  known  as  the  line  of  Gennari  (Fig.  222). 

A  careful  study  of  the  histology  of  the  different  parts  of  the  cortex  in 
man  enables  us  to  distinguish  certain  types  of  structure  characteristic  of 
various  regions  of  the  grey  matter.  In  attempting  by  such  means  an 
histological  localisation  of  functions  we  have  to  take  into  account  : 

(a)  The  thickness  of  the  cortex. 


430 


PHYSIOLOGY 


(b)  The  relative  thickness  of  the  various  layers. 

(c)  The  character  of  the  cells  found  in  the  various  layers. 

(d)  The  •arrangement  and  degree  of  development  of  the  systems  of 
medullated  fibres,  both  radial  and  transverse. 

The  possibilities  in  such  a  method  are  at  once  apparent  if,  as  in  Figs.  221, 
222  and  223,  we  compare  the  structure  of  the  cortex  from,  e.g.  the  pre-central 


T7*  <v; 

x    l  *  i  <K  *  r 


^i, 


V  * 


Fig.  222.     Visuo-sensory. 


Fig.  223.     Viauo-psychic. 


motor  convolution,  the  visuo-sensory  area  of  the  occipital  convolution,  and 
the  '  visuo-psychic  '  area.  The  finer  differences  are  not  so  readily  perceptible 
without  careful  study  and  measurement  of  the  various  layers  and  the  elements 
constituting  them.  By  this  method  we  can  mark  out  the  cortex  into  areas, 
which  agree  closely  with  the  localisation  of  functions  as  arrived  at  by 
experimental  methods  or  by  a  study  of  the  systems  of  fibres  in  the  brain  or 
of  the  functional  defects  observed  under  pathological  conditions. 

The  localisation  arrived  at  in  this  way  is  represented  in  the  diagrams 
taken  from  Campbell  (Fig.  224).     Thus  in  the  motor  area,  the  precentral 


STRUCTURAL  ARRANGEMENTS  OF  CEREBRUM 


431 


or  ascending  frontal  convolution,  we  find  below  the  granular  layer  the  well- 
marked  pyramidal  cells  or  Betz  cells,  which  are  larger  than  any  other  element 
in  the  cerebrum.     The  layer  of  pyramidal  cells  is  also  very  thick,  while 

A. 


I''i'..  224.  Human  brain  showing  outer  (A)  and  mesial  (B)  surfaces,  and  the  situation 
"f  I  he  chief  motor  and  sensory  areas.  The  different  shading  represents  the  extent 
of  each  of  these  areas  as  determined  by  a  study  of  the  histological  structure  of  the 
cortex.     (Campbell.) 

the  granular  layer  is  but  slightly  developed.     In  this  area  the  actual  average 
thickness  of  the  different  layers  is  as  follows  : 

Molecular  or  outer  fibre  lamina         ....     0-34  mm. 
Pyramidal  or  outer  cell  lamina  ....     0-90  mm. 

Granular  or  middle  cell  lamina         ....     0-22  mm. 
Betz  or  inner  fibre  lamina        .  .  .  .  .0-22  mm. 

Polymorphous  layer  or  inner  cell  lamina  .  .  .     0-31  mm. 


432  PHYSIOLOGY 

In  the  visuo-sensory  area  the  granular  layer  is  the  thickest,  and  is 
divided  into  two  layers  by  the  band  of  tangential  fibres  forming  the  line 
of  Gennari.  In  the  association  areas  (both  those,  such  as  the  intermediate 
precentral  and  visuo-psychic,  which  arc  normally  associated  with  motor 
or  sensory  processes,  as  well  as  the  higher  association  centres  of  Flechsig, 
i.e.  the  frontal,  parietal  and  temporal  lobes),  the  most  marked  feature  in  the 
section  is  the  great  development  of  and  the  large  number  of  cells  observed 
in  the  outer  cell  lamina  or  pyramidal  cell  layer.  It  will  be  noticed  Ion  thai 
the  audito-sensory  area  is  but  small  in  extent  and  lies  almost  entirely  wit  hin 
the  lips  of  the  fissure  of  Sylvius,  while  the  greater  part  of  the  superior 
temporal  convolution,  w7hich  on  the  left  side  is  associated  with  the  auditory 
images  and  associations  necessary  for  the  comprehension  of  speech,  partakes 
of  the  character  of  an  intermediate  or  psychic  sensory  area. 

The  same  method  may  be  applied  to  a  comparison  of  the  relative  develop- 
ment of  the  cerebral  functions  in  different  types  of  animals.  A  comparison  of 
the  brain  of  the  dog,  ape.  and  man  shows  that,  while  the  absolute  amount  of 
brain  substance  devoted  to  the  elementary  functions  of  movement  and 
sensation  remains  practically  the  same  throughout,  in  man  these  areas  are, 
relatively  to  the  whole  brain,  very  much  diminished  in  size,  the  greater  part 
of  the  brain  surface  being  taken  up  with  the  nervous  material  of  the  type 
which  is  connected  with  the  functions  of  association  involved  in  the  higher 
processes  of  reflection,  intelligence,  and  volition. 

If  we  draw  still  lower  animals  into  the  sphere  of  our  observations,  we  are 
enabled  to  form  some  idea  as  to  the  relative  significance  of  the  various 
elements  of  the  cortex.  Thus  in  an  animal,  such  as  the  rabbit,  the  poly- 
morphous layer  is  three  times  the  thickness  of  the  pyramidal  layer  :  whereas 
in  man,  with  an  infinitely  greater  range  of  reaction,  it  is  only  one-third  of  the 
thickness  of  this  layer.  If  we  may  roughly  assign  a  function  to  each  of  the 
types  of  cells  found  in  the  cortex,  we  may  say  that  the  pyramidal  cell  layer 
is  generally  associative  in  functions.  The  large  pyramidal  cells  of  Betzare 
motor  ;  the  granular  layer  is  sensory,  while  the  polymorphous  layer  presides 
over  the  lowest  cortical  functions,  such  as  those  concerned  in  the  getting  of 
food,  the  sexual  instincts,  and  so  on. 

The  description  given  above  applies  to  the  whole  of  the  neopallium. 
In  the  more  primitive  part  of  the  brain,  the  archipallium,  represented 
by  the  hippocampus,  we  find  only  two  cell  laminae  which  are  homologous 
with  the  middle  (granule)  and  the  inner  polymorphous  cell  layers  of  the 
neopallium. 


SECTION    XVII 

THE    FUNCTIONS   OF   THE   CEREBRAL 
HEMISPHERES 

In  an  animal  possessing  cerebral  hemispheres  if  is  impossible  to  foretell 
with  certainty  what  particular  reaction  may  be  evoked  by  any  stimulus. 
The  animal  which  has  been  deprived  of  its  hemispheres  can.  as  we  have 
seen,  be  played  on  at  will,  whereas  the  intact  animal  is  an  individual  whose 
actions — to  judge  by  our  own  experience — are  guided  by  intelligence,  and 
influenced  by  motives  or  by  feelings  of  fear,  hunger,  pain,  and  the  like.  In 
short,  its  behaviour  is  analogous  to  that  which  in.  man  we  associate  with 
conscious  feeling  and  volition.  This  association  of  the  volitional  manifesta- 
tions with  the  cerebral  hemispheres  has  long  been  assumed,  and  is  borne  ou1 
by  the  exact  parallelism  existing  between  the  degree  of  intelligence  with 
which  an  animal  is  endowed  and  the  extent  of  developmenl  of  its  cerebral 
hemispheres.  Moreover  in  man  himself  there  is  a  proportionality  between 
the  average  size  of  the  brain,  i.e.  of  the  cerebral  hemispheres,  and  the 
average  intelligence  of  the  race. 

Earlier  attempts  to  analyse  the  factors  entering  into  the  sphere  of 
consciousness  and  to  associate  with  these  factors  localised  parts  of  the 
brain  failed,  largely  on  account  of  a  faulty  psychological  analysis  and  the 
absence  of  any  proper  experimental  groundwork  for  the  conclusions  put 
forward.  Gall,  the  founder  of  phrenology,  recognised  more  clearly  than 
previous  authors  that  the  cerebral  hemispheres  must  be  regarded  as  the 
material  basis  of  consciousness.  Impressed  however  by  the  fact  that  there 
was  no  proportionality  between  the  acuteness  of  the  senses  and  the  degree 
of  development  of  the  cerebral  hemispheres,  lie  considered  that  any  division 
of  functions  among  different  parts  of  the  hemispheres  must  relate  to  highly 
complex  psychical  conditions,  and  thereforeon  very  slender  groundshe  allotted 
to  parts  of  the  brain  functions  such  as  those  i  I  intelligem  e,  memory,  judg 
inent.  amativeness,  and  so  on.  These  conclusions  of  Gall  were  overthrown 
by  Flourens  on  both  theoretical  and  experimental  grounds.  In  the  firsl 
place,  Flourens  pointed  out  that  the  mental  faculty  of  man  cannot  be  dividi  d 
up  into  a  number  of  different  independent  qualities  or  faculties,  such  as  those 
proposed  by  Gall.  In  the' second  place,  he  showed  that  in  the  pigeon, 
although  loss  of  the  whole  cerebral  hemispheres  destroyed  intelligem  e 
associative  memory  with  the  actions  founded  on  such  endowments,  removal 
of  portions  of  the  brain  caused  simply  a  lowering  of  these  functions,  and  it 

433  28 


131 


PHYSIOLOGY 


COR 


COR 


was  a  matter  of  indifference  whether  the  brain  substance  was  taken  from  the 
anterior  or  from  the  posterior  portions  of  the  hemispheres.  Flourens  there- 
fore concluded  that  the  cerebral  hemispheres  acted  as  a  whole  as  the  seat  of 
the  will  and  intelligence.  There  is  no  doubt  that  Flourens  was  so  far  per- 
fectly correct,  since  all  parts  of  the  brain  must  co-operate  in  determining 
the  psychical  condition  of  any  individual  in  any  given  moment.  He  was 
however,  as  later  researches  showed,  in  error  in  thinking  that  no  difference 
could  be  distinguished  between  the  parts  contributed  by  the  various  con- 
volutions of  the  brain  to  the  organic  whole  which  is  called  consciousness. 

As  we  have  seen,  histological 
ASG  evidence,  which  in  the  case  of 

the  cerebellum  displays  a 
marked  uniformity  throughout 
the  whole  cortex,  in  t  be  ca  le 
of  the  cerebrum  reveals  strik- 
ing differences  between  its 
various  areas.  The  demarca- 
tion of  the  cerebral  cortex  into 
areas  according  to  the  histo- 
logical structure  of  their  grey 
matter  agrees  with,  and  in 
many  cases  supplements,  the 
results  procured  by  an  experi- 
mental inquiry  into  the  func- 
tions of  the  different  parts. 
That  there  is  a  localisation 
Fro.  225.  Upper  surface  of  dog's  brain,  showing  «f  function  in  the  cortex  so 
results  of  excitation.     (Fritsch  and  Hitzic)  far  as  concerns  the  movement  - 

A,    neck    m  uncles ;     +,    movements    of    fere    limb;        -   , ,  .,  ,    , ,       ,      •, 

jf.  movements  of  hind  limb;  O,  movements  of  ot  the  two  Sides  of  the  body 
face  ;  ASG,  anterior  sigmoid  gyrus  ;  PSG,  posterior  was  kllOWIl  to  Galen,  who  meil- 
Bigmoid  gyrus ;  COR,  coronary  fissures ;    Scr,  crucial  ,,  ,  , 

sulcus.     *  tions  the  occurrence  oi  paraly- 

sis on  one  side  of  the  body  as  a 
result  of  lesions  in  the  brain  of  the  opposite  side.  In  1861  a  French  physician 
Broca,  confirming  older  statements  by  Dax  and  Bouillaud.  maintained  that 
aphasia,  i.e.  loss  of  power  of  speech,  when  it  occurred  in  right-handed  people 
was  always  associated  with  a  lesion  of  the  third  frontal  convolution  of  the 
left  hemisphere,  which  has  ever  since  that  time  been  known  as  Broca's 
convolution.  Hughlings  Jackson  in  1864  drew  attention  to  the  connection  of 
localised  spasms  (Jacksonian  epilepsy)  with  lesions  of  certain  parts  of  the 
central  convolutions.  On  anatomical  grounds  Meynert  considered  that  the 
posterior  portions  of  the  hemispheres  were  probably  more  nearly  connected 
with  sensation,  and  the  anterior  with  the  power  of  movement ;  but  direct 
evidence  of  motor  localisation  was  first  brought  by  Fritsch  and  Nitzig  in 
1870.  These  observers  pointed  out,  in  contradiction  of  the  then  received 
idea,  that  the  grey  matter  of  the  cortex  was  excitable,  and  that  it  was 
possible  to  evoke  co-ordinated  movements  of  the  limbs  on  stimulating  the 


FUNCTIONS   OF  THE  CEREBRAL  HEMISPHERES 


435 


front  part  of  the  hemispheres  in  dogs  with  weak  currents.  The  results  of 
their  experiments  are  shown  in  Fig.  225.  These  experiments  were  soon 
after  repeated  and  confirmed  by  Ferrier,  who  extended  his  observations 
lo  the  monkey,  and  more  lately  by  Horsley,  Schafer,  Beevor,  Sherrington, 
and  others  in  the  higher  apes  and  man.  It  was  formerly  a  subject  of  dispute 
whether  the  movements  resulting  from  stimulation  of  the  cortex  were  due 
to  the  excitation  of  the  grey  matter  or  of  the  underlying  white  matter.  The 
following  facts  show  that  the  seat  of  the  excitation  is  in  the  grey  matter  : 

( 1 )  A  smaller  strength  of  current  is  required  to  excite  the  grey  matter 
than  the  underlying  white  matter,  after  removal  of  the  grey  matter. 

(2)  In  animals  poisoned  by  chloral  the  grey  matter  is  inexcitable,  though 
movements  can  still  be  aroused  on  stimulating  the  white  matter.  A  similar 
inexcitability  of  the  grey  matter 

can    be   produced  by  painting  it 
with  cocaine. 

(3)  The  latent  period  elapsing 
between  the  beginning  of  the  A. 
stimulation  and  the  occurrence  of 
the  movement  in  the  correspond- 
ing limb  is  longer  when  the  grey 
matter  is  excited  than  when  the 
stimulus  is  applied  to  the  white 
matter.  The  results  obtained  by 
Francois  Franck  give  a  latent  B 
period  of  -065  sec.  for  the  grey 
matter  and  "045  sec.  for  the 
white  matter  (Fig.  226). 

Whether  the  stimulus  acts  directly 
on  the  pyramidal  cells  of  the  <-<>itex:,  or 
win1  her,  as  seems  more  likely,  it  is  the 
endings  of  the  afferent  nerves  to  the 
cortex  which  are  really  excited  by  the 
stimulus,  wo  cannot  at  present  deter 
mine. 

When  we  compare  different  animals,  such  as  the  dog,  monkey,  and  man, 
we  find  there  is  a  much  finer  differentiation  of  movements  evoked  by  stimula- 
tion of  the  cortex  in  the  higher  than  in  the  lower  type.  Whereas  in  the  dog 
the  excitable  areas  shade  into  one  another,  in  the  higher  ape  and  man  the 
areas  are  much  more  circumscribed  and  are  often  separated  from  adjoining 
areas  by  an  inexcitable  zone.  The  localisation  of  motor  functions  in  the 
cortex  of  the  chimpanzee  is  indicated  in  the  accompanying  diagrams  by 
Sherrington  (Figs.  227,  228).  It  will  be  seen  that  the  motor  cortex  is  limited, 
on  the  convex  side  of  the  brain,  to  the  precentral  convolution,  or  ascending 
frontal  convolution,  situated  immediately  in  front  of  the 'fissure  of  Rolando. 
On  the  inner  aspect  of  the  hemispheres  only  the  corresponding  part  of  this 
convolution  gives  motor  responses  on  excitation.     We  may  say  broadly  that, 


FlG.   "220.     Tracings  to   show   latent   periods 
of  movements  obtained  by   stimulating  r 
A,  grey  matter ;  B,  underlying  white  matter 
of  cortex.     Time-marking  =  T,'„-  sec. 

(V.  Franck.) 


436 


PHYSIOLOGY 


from  above  downwards,  by  stimulation  of  the  precentral  convolution  we  gel 
movements  of  the  leg,  arm,  and  face  ;  though,  as  is  shown  in  the  diagram, 
within  those  larger  areas  smaller  areas  can  be  distinguished  for  definite 
co-ordinated  movements  of  the  different  parts  of  the  body. 


Anus &i 


Ear-  ■■      / 
Eyelid, --'Closure 

Nose  °f  jav/  Opening 

of  jaw    Vocal 

cords    Mastication 

Fig.  22s. 


Sulcus  centralis 


Sulc  precentr  mary 


Sulc.calcarin 


C.S  S.  del. 


FlG.  227,  outer  surface  ;     Fig.  228.  inner  surface  of  brain  of  chimpanzee,    showing 
movements  obtained  by  excitation  of  the  motor  areas.     (Sherrington.) 

NATURE  OF  MOVEMENTS  EXCITED.  The  movements  obtained  by 
excitation  of  these  areas  resemble  in  every  respect  the  co-ordinated  move- 
ments observed  during  the  normal  willed  or  spontaneous  activity  of  the 
animal.     Like  the  movements  evoked  by  stimulation  of  a  sensory  surface 


FUNCTIONS   OF   THE   CEREBRAL   HEMISPHERES         437 

they  involve  the  reciprocal  innervation  of  antagonistic  muscles.  Never 
do  we  find  simultaneous  contractions  of  antagonists,  even  where  two 
opposing  centres  are  excited  simultaneously  ;  one  reaction  is  prepotent,  as 
is  the  case  with  cutaneous  excitation,  and  this  reaction  is  attended  and 
brought  about  by  ordered  contraction  of  certain  muscles  accompanied  by 
an  ordered  relaxation  of  their  antagonists.  Thus  the  movement  of  opening 
t  he  jaw,  which  can  be  excited  from  a  fairly  large  area  of  the  cortex,  involves 
a  relaxation  of  the  normal  tone  of  the  masseter  muscle.  Flexion  of  the  leg 
demands  relaxation  of  the  extensor  muscles.  As  in  the  case  of  the  spinal 
reflexes,  this  relaxation  or  inhibition  can  be  abolished  under  the  action  of 
strychnine  or  the  toxin  of  tetanus.  After  administration  of  either  of  these 
it  is  impossible  to  evoke  inhibition  of  any  muscle.  Excitation  of  the  cortical 
centre  for  the  movements  of  the  jaw  causes  contraction  of  both  closers  and 
openers  of  the  jaw,  i.e.  a  strife  in  which  the  stronger  masseter  muscles 
predominate,  so  that  the  jaw  is  firmly  closed. 

The  part  played  by  muscular  relaxation  in  the  response  to  cortical 
stimulation  is  also  well  seen  in  the  case  of  the  eye  muscles.  Stimulation  of  the 
centre  for  eye  movements  on  the  convex  surface  of  the  frontal  lobes  on  the 
right  side  causes  '  conjugate  deviation  '  of  both  eyes  to  the  left.  This  move- 
ment involves  contraction  of  the  right  internal  rectus  and  left  external  rectus 
and  a  simultaneous  inhibition  of  the  tone  of  the  right  external  rectus  and  left 
internal  rectus.  If  all  the  muscles  of  the  right  eye  be  divided  except  the 
external  rectus,  this  eye  looks  permanently  towards  the  right  side,  i.e.  a  right 
external  st  rabismus  or  squint  is  produced.  On  now  exciting  the  right  cortex 
both  eyes  move  to  the  left,  although  the  right  internal  rectus  is  divided.  The 
movement  of  the  right  eye  stops  at  the  middle  fine,  and  is  brought  about 
simjilv  by  a  relaxation  of  the  tone  of  the  right  external  rectus  muscle 
(Sherrington). 

This  movement  of  both  eyes  on  stimulation  of  one  side  of  the  brain  shows 
that  the  function  of  each  hemisphere  is  not  entirely  unilateral  with  regard 
to  the  muscles  of  the  body.  As  a  rule  the  response  to  excitation  of  the  motor 
area  for  limbs  is  strictly  unilateral.  In  the  case  of  those  movements  how- 
ever which  arc  normally  carried  out  by  co-operation  of  the  muscles  of  the 
two  sides,  such  as  the  movements  of  the  trunk,  neck,  and  eyes,  stimulation  of 
I  he  motor  area  in  one  hemisphere  evokes  a  movement  involving  the  muscles 
of  both  sides  of  the  body,  i.e.  the  cortical  representation  is  one  of  movement 
rather  than  one  of  muscles.  Where  an  action  is  carried  out  by  similar  con- 
tractions of  corresponding  muscles  on  the  two  sides,  the  movement  itself 
is  bilaterally  represented  in  the  cortex.  Types  of  such  reactions  are  found 
in  closure  of  the  mouth,  contractions  of  the  abdominal  muscles,  erection  or 
flexion  of  the  trunk.  It  seems  that  under  such  circumstances  there  is  a  free 
communication  between  the  lower  motor  centres  of  the  two  sides,  since  the 
I'ilatcrality  of  the  response  is  not  altered  by  extirpation  of  the  cortex  of 
the  hemisphere  opposite  to  that  which  is  being  stimulated. 

CORTICAL  EPILEPSY.  When  electrical  excitation  of  any  strength 
over  the  minimum  effective  stimulation  is  applied  to  the  motor  area  of  the 


438 


PHYSIOLoiiV 


cortex,  the  movements  evoked  tend  to  persist  for  a  short  time  beyond  the 
duration  of  the  stimulus.  On  still  further  increasing  the  strength  of  the 
current,  the  contraction  spreads  to  adjoining  muscles,  and  finally  may 
affect  all  parts  of  the  body,  giving  rise  to  the  phenomenon  known  as  an 
epileptic  convulsion.  The  same  effect  may  often  be  caused  by  weak  stimuli, 
if  the  irritability  of  the  cortex  be  raised  in  consequence  of  repeated  previous 
stimulation.  A  typical  fit  consists  of  two  parts.  The  first  effect  of  t  lie  stimu- 
lation is  a  strong  tonic  contraction;  this  outlasts  the  stimulus  for  some 
time,  and  then  gives  way  to  a  series  of  clonic  contractions,  repeated  at  first  at 
intervals  of  from  six  to  ten  per  second,  but  gradually  getting  slower  as  the 
tit  dies  away.     The  tracing  of  such  a  contraction  is  given  in  Fig.  229. 


Fig.  229.     Tracing  of  muscular  contractions  durum  an  epileptic  convulsion  aroused 
by  strong  stimulation  of  the  motor  area.     (HOBSLEY  and   Schafer.) 

The  main  phenomena  of  a  fit,  due  to  irritation  of  any  portion  of  the 
motor  area,  were  described  by  Hughlings  Jackson  in  L864,  even  before  the 
experimental  proof  of  cortical  localisation  had  been  brought  forward  by 
Fritsch  and  Hitzig.  A  similar  condition  may  occur  in  the  human  subject 
as  a  result  of  irritative  lesions  of  this  part  of  the  cortex,  such  as  that  due  to 
t  he  presence  of  a  tumour  or  a  spicule  of  bone  pressing  on  the  brain.  Jackson 
showed  that  in  this  condition  the  convulsive  movements  follow  a  certain  order 
or  '  march.'  Thus  if  the  thumb  area  be  the  seat  of  stimulation,  the  fit 
begins  by  a  contraction  of  the  thumb  muscles,  then  spreads  to  the  muscles 
of  the  hand,  fore-arm  and  shoulder  of  the  same  side,  and  then  to  the 
face,  trunk,  and  leg.  If  it  begins  in  the  toes  the  order  would  be  up  the  leg  and 
down  the  arm.  The  same  '  march  '  is  observed  in  artificial  stimulation  of 
the  motor  area.  If  the  convulsions  are  very  strong  they  spread  to  the 
leg  of  the  opposite  side  and  then  to  the  whole  body.  The  spread  to  the  other 
side  of  the  body  is  not  prevented  by  division  of  the  corpus  callosum,  nor  by 
isolating  the  centres  from  one  another,  so  that  the  sequence  seems  to  be 
maintained  through  the  mediation  of  the  sub-cortical  centres.  Complete 
excision  of  the  cortical  centre  for  any  given  movement  excludes  this  move- 
ment from  participation  in  the  fit.  In  man  this  type  of  epilepsy  is,  in  the 
milder  cases  at  any  rate,  generally  unattended  with  loss  of  consciousness. 
In  animals  epileptic  convulsions  can  be  excited  by  stimulation  of  any  portion 
of  the  cortex,  though  it  is  obtained  by  a  weaker  stimulus  applied  to  the  motor 
cortex  "than  to  any  other  part.  Jacksonian  epilepsy  is  often  preceded  l>y 
a  sensation  of  numbness  or  tingling,  the  '  aura,'  in  the  part  in  which  such 
convulsions  begin.     In  ordinary  idiopathic  epilepsy  tactile  or  visual  sensory 


FUNCTIONS  OF  THE  CEREBRAL  HEMISPHERES  139 

aura?  may  precede  the  attack  ;  but  in  this  case  loss  of  consciousness  is  always 
a  prominent  symptom,  even  in  the  milder  form  of  the  disease.  UniversaJ 
epileptic  convulsions  can  be  excited  in  animals  by  the  injection  of  absinthe 
into  a  vein.  During  the  convulsion  there  is  a  rise  of  blood  pressure  and  a 
quickening  of  the  pulse ;  the  respiration  is  very  often  stopped  during  the  tonic 
pari  of  the  spasm,  so  that  the  patient  becomes  livid.  The  universal  con- 
dition of  excitation  affects  also  the  centres  from  which  the  secretory  nerves 
originate,  so  that  there  is  an  excessive  flow  of  saliva  which,  in  the  idio- 
pathic case,  is  responsible  for  the  characteristic  frothing  at  the  mouth. 

EFFECTS  OF  ABLATION  OF  THE  MOTOR  CENTRES 
We  have  seen  that  a  dog  may  preserve  complete  power  of  movement 
after  a  total  ablation  of  both  cerebral  hemispheres.  We  should  not  exped 
therefore  to  find  any  lasting  paralysis  as  a  result  of  extirpation  of  portions 
of  the  brain,  such  as  the  motor  centres.  Ablation  of  the  motor  areas  in 
these  animals,  during  the  first  few  weeks  after  the  operation,  gives  rise  to 
considerable  disorders  of  movement,  the  muscles  on  the  side  of  the  body 
opposite  to  the  lesion  being  markedly  weaker  than  those  on  the  same  side. 
These  symptoms  however  gradually  pass  off,  so  that  after  a  time  not  only 
are  both  limbs  employed  in  the  ordinary  automatic  movements  of  progression, 
hut  t  he  animal  can  be  taught  new  movements  in  the  limb,  the  cortical  centre 
for  which  has  been  excised.  We  must  conclude  therefore  that  in  the  dog  all 
the  movements,  including  those  which  are  voluntary  and  conscious,  can  be 
carried  out  in  the  absence  of  the  motor  centres,  although  destruction  of  these 
centres  may  impair  the  accuracy  with  which  some  of  the  finer  movements  are 
regulated. 

In  the  monkey  (Macacus)  the  effect  of  ablation  is  more  marked,  corre- 
sponding to  the  greater  degree  of  localisation  in  these  animals.  If  the  whole 
of  the  motor  area  on  the  external  surface  of  the  brain  be  excised,  e.g.  on  the 
right  side,  there  will  be  almost  complete  paralysis  of  the  left  arm  and  the  left 
side  of  the  lace,  and  weakness  of  the  muscles  of  the  left  leg.  The  animal 
will  continue  to  use  the  leg  in  walking  and  in  climbing.  If  the  lesion  extends 
to  the  medial  side  of  the  hemisphere,  paralysis  of  the  leg  is  more  marked,  and 
the  muscles  of  the  left  side  of  the  trunk  are  also  affected.  Many  of  these 
symptoms  disappear  in  the  course  of  time.  In  a  monkey,  in  which  Goltz  had 
destroyed  the  greater  part  of  the  left  side  of  the  cerebral  hemispheres,  it  was 
found  that  the  right  arm  and  hand  could  be  still  employed  alone  for  such 
purposes  as  taking  food,  although  the  movements  were  much  more  awkward 
than  those  of  the  left  hand. 

Still  less  complete  is  the  recovery  from  lesions  of  the  motor  area  in  man. 
We  possess  now  a  considerable  number  of  typical  histories  of  cases  in  which 
part  of  the  motor  cortex  has  been  destroyed  by  disease  or  by  operation,  and 
the  seat   of  the  lesion  verified  by  post-mortem  examination.     In  all  these 

e  ises  t  here  ha  s  l n  a  loss  of  voluntary  movement  corresponding  in  disl  ribvj 

lion  to  the  seat  of  the  lesion  and  proportionate  in  its  severity  to  the  extent 
of  the  lesion.     On  the  other  hand,  equally  extensive  lesions  outside  the 


110  PHYSIOLOGY 

ascending  frontal  convolution  have  been  shown  to  have  no  eff  eel  on  voluntary 
movements.  The  loss  of  movemenl  is  chiefly  confined  to  those  which  we 
regard  as  volitional.  Although,  for  instance,  the  arm  may  be  paralysed,  it 
can  be  still  raised  in  association  with  a  movement  involving  the  other  arm. 
A  certain  degree  of  recovery  from  the  immediate  effects  of  the  lesion  may  be 
observed,  but  tin-  recovery  is  never  complete. 

The  difference  in  the  reaction  of  various  animals  to  lesions  of  the  motor 
cortex  is  connected  with  the  gradual  shifting  of  functions  from  the  sphere 
of  fatal  necessary  read  ions  to  the  sphere  of  educatable  adaptations  (i.e.  from 
the  lower  centres  to  the  cerebral  cortex),  which  is  a  characteristic  of  the  evolu- 
tions of  the  higher  type  of  nervous  system,  and  is  a  concomitant  of  the  in- 
creased adaptability  which  distinguishes  man  from  all  the  lower  animals,  in 
I  he  animal  \\  it  bout  hemisphere  the  motor  mechanisms  for  all  the  movements 
of  the  body  are  present  and  can  be  set  into  action  from  any  point  on  the 
sensory  surface  of  the  body.  The  first  effect  of  adding  the  cerebral  hemi- 
spheres to  this  mechanism  is  to  increase  the  range  of  reactions,  to  modify 
them  or  to  inhibit  them,  by  diverting  the  stream  of  nervous  impulses  into 
channels  which  have  to  a  large  extent  been  laid  down  in  the  cortex  by  the 
past  experience  of  the  individual.  In  the  frog  and  bird  we  notice  an  auto- 
maticity  and  a  'conscious'  adaptation  of  movements  to  purpose,  although 
the  hemispheres  have  no  direct  connection  with  the  motor  centres  of  the 
cord,  and  present  no  areas  which  we  can  designate  as  motor.  In  the  dog, 
although  a  portion  of  the  brain  is  in  direct  connection  with  the  spinal  motor 
centres,  and  can  therefore  initiate  movements  without  making  use  of  the 
mid-brain  motor  machinery,  these  movements  play  only  a  small  part  in  the 
motor  life  of  the  animal,  and  the  removal  of  the  corresponding  centres  takes 
away  but  little  of  the  conscious  functions  of  the  animal.  In  man  the  enor- 
mous power  of  acquisition  of  new  movements  is  rendered  possible  by  the 
shifting  of  one  motor  function  after  another  to  the  sphere  of  influence  of  the 
cerebral  hemispheres.  Almost  every  act  of  life  in  man  has  become  one 
involving  co-operation  of  the  cerebral  cortex.  For  many  years  after  birth 
man  is  helpless  and  far  inferior,  as  a  reactive  organism,  to  animals  much 
lower  in  the  scale.  Even  the  lower  motor  functions,  such  as  those  of  loco- 
motion or  defence,  have  to  be  painfully  learnt,  and  this  learning  implies  the 
laving  down  of  paths  (Bahnung)  in  the  cortex.  On  this  account  the  sub- 
cortical centres  in  man  are  no  longer  complete.  Acting  in  every  instance 
of  life  as  a  subordinate  or  adjunct  to  the  cerebral  hemispheres,  they  are  unable 
to  carry  out  even  the  simpler  motor  reactions  of  the  body  after  removal 
of  those  portions  of  the  hemispheres  especially  engaged  in  the  control  of 
voluntary  movement.  The  motor  defect  therefore  which  is  brought  about 
in  man,  as  a  result  of  destruction  of  one  or  more  of  the  motor  centres,  is  to  a 
large  extent  permanent. 

If  the  lesion  in  man  be  strictly  limited  to  the  motor  areas  in  the  ascending 
frontal  convolution,  it  is  impossible  to  detect  any  loss  of  sensation  in  the 
affected  parts  of  the  body.  On  the  other  hand,  some  loss  of  sensation  is 
often  found  where  the  paralysis  is  widespread  and  occasioned  by  extensive 


FUNCTIONS   OF  THE  CEREBRAL  HEMISPHERES         441 

lesion  in  the  neighbourhood  of  the  Rolandic  area.  Moreover,  even  in  localised 
lesions  in  man,  an  epileptic  fit  may  be  preceded  by  a  sensory  aura  in  the  part 
which  is  the  starting-point  of  the  convulsive  movements.  Much  discussion 
has  taken  place  as  to  the  exact  significance  to  be  assigned  to  these  slight 
sensory  phenomena.  By  some  observers,  e.g.  .Munk,  it  has  been  thought 
that  the  motor  centres  were  the  end-stations  of  the  fibres  subserving  muscular 
sensations,  and  that  the  movements  resulting  from  their  stimulation  were 
due  1<>  the  revival  of  such  sensations.  Bastian  insisted  on  the  important 
pari  played  in  voluntary  actions  by  afferent  impressions,  and  these  centres 
have  sometimes  been  spoken  of  as  '  kinsesthetic  '  or  sensori-motor.  The 
discussion  has  however  now  resolved  itself  practically  into  one  of  terms. 
There  is  no  doubt  that,  when  the  lesion  is  strictly  localised  in  the  motor  aTea, 
paralysis  may  be  present  without  any  loss  of  sensation  whatsoever.  The 
paralysis  therefore  cannot  be  classed  with  the  sensori-motor  paralysis  dis- 
tinguished earlier  as  the  result  of  division  of  sensory  roots.  On  the  other 
hand,  when  we  say  that  this  part  of  the  brain  represents  a  'centre  fur 
voluntary  movements,'  we  do  not  mean  that  the  volitional  motor  impulses 
arise  de  novo  from  the  pyramidal  cells  in  its  grey  matter.  Every  neuron  in 
the  nervous  system  is  part  of  an  arc,  and  it  is  generally  difficult  to  label  any 
given  neuron  as  definitely  sensory  or  motor.  In  a  reaction  involving  a  chain 
of  neurons  we  can  assign  the  name  of  motor  to  that  neuron  which  sends 
its  axon  to  the  muscle,  and  of  sensory  or  afferent  to  that  neuron  which 
receives  the  impulses  at  the  periphery  of  the  body.  Where  in  the  chain  we 
are  to  draw  the  dividing  line  and  to  say  "  these  neurons  are  sensory  and  those 
motor,"  it  is  difficult  to  decide.  The  motor  areas  in  the  cortex  give  origin  to 
the  long  fibres  of  the  pyramidal  tract,  which  passes  right  through  the  central 
nervous  system  to  the  segmental  centres  of  the  cord.  We  know  that  the 
integrity  of  these  tracts  is  essential  for  the  carrying  out  of  voluntary  move- 
ment. It  is  therefore  convenient  to  speak  of  them  as  motor  or  efferent 
tracts,  and  their  origin  as  motor  centres;  although  these  tracts  have  the 
same  relation  to  the  motor  cells  of  the  spinal  segment  as  have  the  afferenl 
fibres  from  the  posterior  roots  by  which  similar  movements  may  be  evoked. 
On  the  other  hand,  the  activity  of  the  pyramidal  cells  of  the  cortex, 
like  those  of  the  motor  cells  of  the  spinal  cord,  is  determined  by  the  arrival 
at  them  of  afferent  impressions.  In  the  absence  of  these  afferent  impressions 
no  spontaneous  discharge  of  motor  impulses  takes  place.  Thus  in  the  spinal 
frog  we  have  seen  that  complete  inactivity  is  brought  about  by  section  of 
all  the  posterior  roots.  In  the  same  way  paralysis  of  the  arm  is  induced 
by  section  of  all  its  posterior  roots,  although  it  can  be  shown  that  the  motor 
cortex  is  still  excitable,  and  that  the  application  of  an  induced  current  to  the 
motor  centres  of  the  arm  evokes  a  movement  as  easily  as  in  the  normal 
animal.  The  motor  cells  in  the  cortical  motor  centres  are  normally  played 
upon  and  aroused  by  impressions  arriving  at  them  from  all  other  parts  ol  the 
brain  and  nervous  system,  and  determined  originally  by  impressions  falling 
on  tin'  surface  of  the  body. 


442  PHYSIOLOGY 

THE   FUNCTIONS   OF   THE   CORPUS   STRIATUM 

The  mass  of  grey  matter  known  aw  the  corpus  striatum,  which  consists 
of  the  nucleus  lenticularis  and  the  nucleus  caudatus,  is  the  basal  part  of  the 
outgrowth  from  which  each  cerebral  hemisphere  is  formed  and  in  the  lowest 
vertebrata  represents  almost  the  whole  of  the  telencephalon.  For  many 
years  the  corpus  striatum  was  classed  with  the  optic  thalamus  as  the  '  basal 
ganglia,'  and  these  two  ganglia  were  regarded  as  relay  stations  between  the 
cerebral  cortex  ami  the  lower  parts  of  the  central  nervous  system.  This  view 
u  as  correct  so  far  as  concerns  the  optic  thalamus,  in  which  end  all  the  afferent 
tracts  and  from  which  afferent  impressions  are  carried  on  by  fresh  relays  of 
fibres  to  the  cortex.  In  the  higher  mammals  the  motor  cortex  has  a  direct 
connection  with  the  motor  nuclei  of  the  bulb  and  spinal  cord  through 
the  pyramidal  tracts,  which  are  not  interrupted  anywhere  on  their  course. 
On  destroying  1  be  corpora  striata. degenerated  fibres  are  found  running  to  the 
optic  thalamus,  to  the  red  nucleus,  and  from  the  latter  to  the  posterior 
longitudinal  bundle.  On  the  other  hand  the  corpus  striatum  receives  fibres 
from  the  olfactory  tracts  and  from  the  optic  thalamus.  These  connections 
would  tend  to  show  that  the  corpus  striatum  serves  in  no  way  as  an  inter- 
mediary between  the  cortex  and  the  lower  parts  of  the  central  nervous 
system,  but  is  an  independent  mass  of  grey  matter,  receiving  impulses  from 
the  same  source  as  the  cortex  and  sending  impulses  which  may  join  in  the 
stream  of  impressions  which  play  upon  the  lower  motor  mechanisms  of  the 
bulb  and  cord. 

Isolated  excitation  of  the  caudate  and  lenticular  nuclei  has  no  visible 
effect,  provided  the  current  is  not  so  strong  as  to  spread  to  the  adjoining 
pyramidal  fibres  in  the  internal  capsule.  A  study  of  the  evolution  of  the 
central  nervous  system  in  different  classes  of  animals  points  to  a  diminishing 
importance  of  these  bodies  in  the  normal  life  of  the  animal.  In  the  carti- 
laginous fishes  it  probably  serves  to  a  greater  or  less  degree  the  same  functions 
in  the  determination  of  educated  reflexes  as  the  cerebral  hemispheres  in 
mammals.  In  birds  the  corpus  striatum  attains  its  greatest  relative  develop- 
ment, the  increased  powers  of  adaptation  in  these  animals  being 
apparently  procured  by  development  of  the  corpus  striatum  instead  of  the 
pallium  or  cerebral  hemispheres  as  is  the  case  in  mammals.  In  the 
monkey  Kinnear  Wilson  found  no  definite  results  to  follow  destruction  of 
the  grey  matter  in  these  bodies.  The  animals  were  however  allowed  to 
survive  the  operation  of  destruction  only  three  weeks,  and  the  same  observer 
has  pointed  out  that  destruction  of  the  corpora  striata  in  man  may  give  rise 
to  a  morbid  condition,  characterised  by  tremor  in  the  execution  of  willed 
movements  and  increased  tonicity  of  the  muscles.  He  therefore  ascribes 
to  these  bodies,  or  rather  to  the  sensori-motor  mechanism  which  has  its  chief 
meeting-place  in  their  nuclei  of  grey  matter,  a  steadying  effect  on  the  motor 
system,  and  places  this  system  by  the  side  of  the  other  systems  which  we 
have  already  studied,  namely,  the  vestibular,  the  cerebellar,  and  the 
pyramidal  systems. 


FUNCTIONS   OF   THE   CEREBRAL  HEMISPHERES         443 

According  to  Meyer  and  Barbour,  the  anterior  part  of  the  corpus  striatum 
plays  an  important  part  in  the  regulation  of  body  temperature.  In  the 
experiments  a  metal  tube,  closed  at  one  end,  was  introduced  through 
the  brain  so  as  to  lie  in  or  on  the  corpus  striatum.  Through  this  tube  water 
at  any  temperature  could  be  passed.  It  was  found  that  cooling  the  water 
gave  rise  to  shivering  and  increased  heat  production  in  the  body  with  a  rise 
of  body  temperature,  while  warming  the  water  had  the  reverse  effect.  They 
are  therefore  inclined  to  regard  this  part  of  the  nervous  system  as  representing 
the  chief  thermo-taxic  mechanism  of  the  body. 

THE  LOCALISATION  OF  SENSORY  FUNCTIONS  IN  THE  CORTEX 

It  was  pointed  out  by  Ferrier  that  movements  might  be  obtained  on 
electrical  excitation  of  regions  of  the  cortex  cerebri  other  than  those  we  have 
described  as  motor.  Thus  excitation  of  the  superior  temporal  convolution 
on  the  right  side  causes  the  animal  to  turn  its  head  and  eyes  to  the  left  and  to 
prick  tin  its  ears.  In  the  same  way  stimulation  of  the  right  occipital  lobe 
causes  movement  of  both  eyes  and  head  to  the  left  side.  These  portions 
ol  tin-  brain  cannot  be  regarded  as  having  a  direct  relationship  to  the  motor 
mechanisms  involved  in  the  above  movements,  since  their  ablation  leads  to 
no  defect  of  movement  but  does,  in  many  cases,  lead  to  defect  of  sensation. 
Thus  excision  of  the  right  occipital  lobe  in  the  monkey,  though  leaving  the 
eye  movements  intact,  causes  a  loss  of  power  to  discern  objects  lying  to  the 
left  of  the  middle  hue.  The  obvious  explanation  therefore  of  the  movements 
obtained  on  excitation  of  this  portion  of  the  cortex  is  that  they  are  due  to 
the  revival  or  arousing  of  sensory  impressions,  that  these  portions  of  the 
cortex  represent  the  cortical  receiving-stations  for  the  impulses  from 
definite  sense-organs,  and  that  the  movements  obtained  are  simply  those 
which  are  normally  associated  with  a  corresponding  sensory  excitation. 

This  conclusion  is  borne  out  by  the  fact  that  to  excite  movement  it  requires 
a  greater  strength  of  stimulus  when  applied  to  the  sensory  areas  than  is 
necessary  if  t  In-  stimulus  be  applied  to  the  Rolandic  area.  Moreover  Si  haier 
lias  shown  that  the  latent  period  which  intervenes  between  the  stimulus  and 
the  resulting  movement  is  considerably  longer  when  the  stimulus  is  applied 
to  the  sensory  centre  than  when  it  is  applied  to  the  motor  centre,  suggesting 
that  more  neurons  are  interpolated  between  the  point  of  stimulus  and  the 
discharging  motor  neuron  in  the  first  case  than  in  the  latter.  Thus  in  one 
experiment  the  latent  period  between  the  stimulus  and  the  resulting  move- 
ment of  the  eyes  amounted  to  0'2  sec.  when  the  frontal  lobes  were  stimulated 
and  0"4  sec.  when  the  occipital  lobes  were  stimulated.  Finally  the  anatomi- 
cal investigation  of  the  course  of  the  fibres  in  the  white  matter  of  the  cerebral 
hemispheres  points  to  a  concentration  of  sensory  fibres  from  different  sense- 
organs  towards  certain  regions  of  the  cortex.  The  diagrams  (Fig.  230 
and  231)  show  those  portions  of  the  brain  to  which  the  endings  of  i  he  sensory 
tracts  of  the  central  nervous  system  are  directed. 

From  the  purely  anatomical  standpoint  we  may  designate  as  '  sensory 
areas  '   of   the   coitex  : 


414 


PHYSIOLOGY 


(1)  An  area  including  Lot  li  cent  ral  convolutions,  i.e.  the  ascending  frontal 
and  the  ascending  parietal,  and  spreading  forward  into  the  frontal  lobes. 

(2)  An  area  occupying  the  hinder  portion  of  tin'  occipital  lobe  and  the 
greater  pari  of  its  inner  surface 


Auditory  area 
Fig.  230.     Outer  side  of  right  cerebral  hemisphere,  according  to  Flechsig.     The 

dotted  surface  indicates  the  regions  where  I  lie  majority  of  the  afferent  (sensory) 
fibres  end. 

(.'))  Aii  area  occupying  flip  superior  temporal  convolution  and  extending 
well  into  the  fissure  of  Sylvius. 

(4)  An  area  on  the 'inner  side  of  the  hemisphere,  occupying  the  hippo- 

'  Tactile  i 


Olfactory  area 
Fig.  231.     Inner  surface  of  the  same  hemisphere.     (Fi-echsio.) 

campal  gyrus  and  the  margin  of  the  gyrus  fornicatus  close  to  the  corpus 
callosum. 

Let  us  see  how   far  experimental  evidence  bears  out  this  localisation. 


FUNCTIONS    OF  THE  CEREBRAL    HEMISPHERES         445 


TACTILE  AND  MOTOR  SENSIBILITY 
A  lesion  limited  to  the  ascending  frontal  convolution  may  produce 
paralysis  of  definite  movements  or  groups  of  muscles  without  any  detectable 
interference  with  sensation.  When  however  in  man  a  widespread  injury, 
involving  both  the  Rolandic  area  and  the  adjacent  portions  of  the  brain, 
occurs  as  the  result  of  some  morbid  condition,  such  as  blockage  of  the  middle 
cerebral  artery,  the  resulting  hemiplegia  is  almost  always  associated  with  a 
greater  or  lesser  degree  of  hemiancBsthesia.  We  are  therefore  justified  in 
locating  tactile  and  muscular  sens- 
ibility somewhere  in  the  region  of  L£FT  RE,,NA  right  retina 
the  central  convolutions,  and  it  is 
probable  that,  while  it  may  in- 
clude the  motor  area,  its  chief 
representation  is  to  be  found  in 
the  post-central  gyrus,  i.e.  the 
ascending  parietal  convolution. 

The  sensory  aura  which  pre- 
cedes an  attack  of  Jacksonian 
epilepsy  points  to  the  motor  area 
itself  having  some  degree  of  sen- 
sory functions,  and  it  has  been 
observed  that  faradisation  of  the 
central  run  volution  in  man  may 
produce  tingling  sensations  in  the 
part  of  the  body  which  is  the 
'it  the  muscular  contractions 
induced  by  stimulation.  No  pain 
is  however  felt  as  a  result  of  the 
stimulation.  The  impulses  which 
subserve  cutaneous  and  muscular 
sensibility  travel  up  to  the  brain  in 
the  mesial  fillet.  This  tract  comes 
to  an  end  in  the-  ventro-lateral 
portion  of   the  thalamus  and  the 

subthalamic  region.  The  new  relays  of  fibres,  which  carry  on  impulses  to 
the  cortex,  arise  in  the  thalamus  and  pass  through  the  hinder  limb  of  the 
internal  capsule  to  be  distributed  to  the  central  convolutions.  Their  area 
of  distribution  is  however  much  wider  than  the  area  of  origin  of  the  pyra- 
midal fibres.  We  may  therefore  conclude  that  tactile  and  muscular  sensi- 
bility are  chiefly  subserved  by  the  central  convolutions,  including  the  motor 
area,  but  are  especially  dependent  on  the  integrity  of  the  post-central  gyrus. 
Flechsig  has  shown  that  fibres  from  the  thalamus,  which  may  probabbj  b< 
regarded  as  continuations  of  the  fillet  system,  arc  also  distributed  to  other 
portions  of  the  cortex,  i.e.  the  temporal,  the  frontal,  and  the  occipital  lobes. 
It  is  therefore  not  surprising  that  the  hemianaesthesia  produced  by  lesions 
in  the  central  convolutions  is  rarely  or  never  complete. 


Jco£7 


Fig.    232.     Diagram     showing    the    probable 
relations    between    the    parts  <>f   the  retinas 

and  the  visual  area  "I  I  he  coi  tex.    (Schafer.) 


in;  PHYSIOLOGY 

The  term  '  tactile  and  motor  sensibility  '  is  very  inadequate  as  describing 
the  complex  afferent  impressions  which  proceed  from  all  parts  of  the  body 
to  the  brain.  They  may  perhaps  be  better  grouped  under  the  term  '  somatic 
impressions,'  and  include  three  main  classes,  viz.  : 

Exteroceptive      .  .     From  the  surface  of  the  body 

Enteroceptive      .         .     From  the  viscera 

Proprioceptive     .  .     From   the   muscles   and   joints,    aroused    by 

changes    occurring    within    the    organism 

itself. 

Of  these,  the  exteroceptive  are  the  most  important  in  giving  information 
as  lo  the  external  world,  and  predominate  among  those  impressions  which 
reach  and  affect  consciousness.  The  enteroceptive  under  normal  conditions 
very  rarely  rise  to  the  conscious  level.  The  proprioceptive  impressions  are 
also  for  the  most  part  unconscious,  yet  those,  which  do  reach  consciousness, 
play  a  great  part,  in  conjunction  with  the  exteroceptive,  in  forming  the 
basis  of  our  schema  of  the  material  world. 

We  find — as  Head  has  shown — a  constant  regrouping  of  somatic  impres- 
sions as  we  trace  them  from  their  origin,  at  or  near  the  surface  of  the  body, 
through  the  spinal  cord  and  nerve  tracts  to  the  cerebral  cortex.  At  the 
periphery  these  impressions  are  divided  into  superficial  and  deep  sensations, 
and  the  former  again  into  the  epicritic,  which  determine  localisation,  dis- 
crimination and  the  finer  gradations  of  pressure,  heat,  and  cold,  and  the  proio- 
/niiliir,  comprising  pain,  the  coarser  degrees  of  heat  and  cold,  and  tactile 
sense  with  defective  localisation. 

When  these  various  impulses  reach  the  cord,  they  are  regrouped,  so- 
that  the  pain,  heat  and  cold,  and  tactile  sensations  are  collected  each  in  a 
separate  bundle,  with  no  distinction  between  the  coarser  kinds  of  tactile 
sense  and  the  finer  qualities  involved  in  discrimination  and  localisation. 
This  grouping' persists  as  far  as  the  thalamus,  and  even  beyond  the  thalamus 
a  similar  grouping  is  observed  in  the  sub-cortical  white  matter  through 
which  the  tracts  run  from  the  thalamus  to  the  sensory  cortex.  Lesions  at 
any  part  of  these  paths  may  therefore  affect  one  or  more  of  these  qualities 
of  sensation  separately.    . 

On  arrival  at  the  cortex  cerebri  all  these  different  kinds  of  sensation  are 
poured  into  the  grey  matter  to  form  the  basis  of  the  schema  of  the  external 
world  and  the  relations  thereto  of  the  individual.  The  cortical  type  of  loss 
of  sensation  differs  therefore  profoundly  from  the  loss  produced  by  a  lesion  in 
any  other  part  of  the  sensory  tracts.  It  may  occur  as  the  result  of  lesions 
of. the  pre-  and  post-central  convolutions,  of  the  internal  part  of  the  superior 
parietal  lobule  and  of  the  angular  gyri.  The  chief  feature  of  this  cortical 
loss  of  sensation  is  a  defect,  not  in  one  or  other  of  the  different  sensations 
which  have  been  described,  but  in  the  appreciation  of  the  meaning  of  these 
sensations,  i.e.  the  loss  appears  to  be  rather  psychical  than  physiological. 
Thus,  it  is  not  a  question  of  recognition  of  touch,  pain,  heat  and  cold,  but  of 
certain  discriminating  faculties  which  can  be  classed  as  : — (a)  recognition  of 


FUNCTIONS   OF  THE   CEREBRAL   HEMISPHERES  117 

spacial  relations,  (b)  appreciation  of  intensity  of  stimuli,  and  (c)  apprecia- 
tion of  similarity  and  difference  in  external  objects  which  are  brought  into 
contact  \Vith  the  surface  of  the  body. 

It  is  not  surprising  therefore  that  in  such  cases  the  answers  of  the  patient, 
when  his  sensibility  is  tested,  seem  to  be  confused,  and  it  is  this  confusion 
of  judgment  which  is  more  apparent  than  definite  loss  of  sensibility.  With 
regard  to  sensory  localisation,  it  should  be  noted  that  the  functions  rather 
than  the  anatomical  relations  of  any  one  part  of  the  body,  are  represented 
on  the  cortex  ;  hence,  as  in  the  motor  functions  of  the  brain,  those  portions, 
such  as  the  hand,  which  are  endowed  with  the  highest  powers  of  discrimina- 
bive  sensibility,  are  most  extensively  represented,  and  next  in  order  comes 
tin1  sole  (if  the  foot.  Thus,  after  a  cortical  lesion,  sensibility  of  the  hand  and 
loot  may  he  dist  ui'bed  without  there  being  any  alteration  in  that  of  the  elbow, 
shoulder  or  knee. 

VISUAL    IMPRESSIONS 

Bach  optic  t  pact,  carrying  impulses  arising  as  a  result  of  events  occurring 
in  the  opposite  field  of  vision,  ends  in  the  pulvinar  of  the  optic  thalamus,  the 
external  geniculate  body,  and  the  superior  corpora  quadrigemina.  The  last 
named  is  apparently  not  concerned  in  vision,  but  represents  a  centre  for 
the  co-ordination  of  visual  impressions  with  those  from  other  regions  of  the 
body  in  influencing  bodily  movements.  From  the  pulvinar  and  external 
geniculate  body  arises  a  shsaf  of  fibres,  which  pass  through  the  extreme  binder 
end  of  the  posterior  limb  of  the  internal  capsule  and  diverge  in  the  centrum 
ovale  to  hi'  distributed  to  the  occipital  lobes,  being  here  known  as  the  optic 
radiations.  The  anatomical  connexion  of  the  occipital  lobes  with  vision 
is  confirmed  by  evidence  derived  from  experiment.  .Movements  of  the 
e\  es  result  from  stimulation  of  almost  any  part  of  this  lobe.  If  the  upper 
surface  of  the  right  occipital  lobe  be  stimulated,  both  eyes  move  downwards 
and  towards  the  left.  Excitation  of  the  posterior  part  causes  movement 
ol  i  he  eyes  up  and  to  the  left ;  while  between  these  two  parts  there  is  an 
intermediate  zone,  most  marked  on  the  mesial  surface,  stimulation  of  which 
evokes  a  purely  lateral  deviation  of  the  eyes  to  the  left.  It  is  therefore  con- 
cluded not  only  that  there  is  representation  of  visual  impressions  in  the 
occipital  lobes,  but  that  there  is  a  certain  amount  of  localisation  within  the 
visual  area  itself,  as  is  represented  in  the  diagram  (Fig.  232). 

These  conclusions  are  fully  borne  out  by  the  results  of  ablation.  While 
extirpation  of  the  whole  occipital  lobe  on  one  side  in  animals  causes  crossed 
in  iniauopia.  i.e.  has  the  same  effect  as  division  of  the  corresponding  optic 
tract,  extirpation  of  these  lobes  on  both  sides  causes  complete  blindness. 
It  seems  that  the  fovea  centralis — the  region  of  distinct  vision — is  bilaterally 
represented,  so  that  central  vision  is  usually  retained  in  both  eyes  after 
destruction  of  one  occipital  lobe  (Fig.  233). 

The  area  connected  with  vision  seems  to  be  smaller  in  man  than  in  the 
ape,  and  in  the  ape  than  in  the  dog.  Thus  in  man  complete  blindness  has 
been  observed  as  the  result  of  localised  bilateral  lesions  of  the  internal  sur- 


IIS 


PHYSIOLOGY 


faces  df  1 1 ccipital  lobes,  and  we  find  the  same  relative  limitation  of  area 

as  we  proceed  from  lower  to  higher  forms  in  the  case  of  il tiler  sensory 

areas  of  the  cortex. 

THE  AUDITORY  AREA 
Anatomical  study  indicates  a  connexion  of  auditory  sensations  with  the 
superior  temporal  lobe.  The  impulses,  started  by  the  arrival  of  sound  waves 
at  the  ear,travel  by  the  cochlear  nerve  to  the  medulla,  From  the  I  wo  audi- 
tory nuclei  a  well-marked  set  of  fibres  passes  across  to  the  opposite  side  in 
the  corpustrapezoid.es,  then  turns  up  into  the  tegmentum  of  the  opposite  side 
to  form  the  tract  known  as  the  lateral  fillet.     The  fibres  of  this  tract  end 


Fig.  233.     Perimeter  charts  from  right  and  left  eye,  showing  the  limitation  of  the  field  of 
vision  (right  hemianopia)  produced  by  a  lesion  of  the"  left  occipital  cortex.     (Bechterew.) 

partly  in  the  inferior  corpora  quadrigemina,  partly  in  the  internal  geniculate 
body.  From  the  latter,  fibres  pass  into  the  internal  capsule,  and  thence  as 
'  auditory  radiations  '  directly  to  the  superior  temporal  convolution. 

In  the  monkey  stimulation  of  the  upper  two-thirds  of  this  lobe  of  the 
brain  causes  pricking  of  the  opposite  ear,  dilatation  of  the  pupils,  and  rotation 
of  the  head  and  eyes  to  the  opposite  side.  It  was  stated  by  Ferrier  that 
ablation  of  the  superior  temporal  convolution  causes  deafness,  but  Schafer 
found  that,  even  after  extirpation  of  the  superior  temporal  convolutions  of 
both  sides,  monkeys  showed  signs  of  hearing  quite  distinctly,  and  of  under- 
s1  anding  the  nature  of  the  sounds  heard.  One  must  conclude  therefore  that 
the  function  of  auditory  perception  is  not  entirely  confined'  to  the  temporal 
lobe,  though  its  focal  point  may  be  located  in  the  superior  temporal  eon- 
volution,  especially  in  that  part  which  is  seated  within  the  fissure  of  Sylvius. 
This  conclusion  is  strengthened  by  the  results  of  clinical  evidence  in  man,  in 
whom  cerebral  lesions,  which  have  produced  disturbances  of  auditory  per- 
ception, are  found  almost  invariably  to  be  closely  associated  with  the  superior 
temporal  convolution. 


FUNCTIONS   OF  THE  CEREBRAL   HEMISPHERES  119 

SMELL    AND   TASTE 

The  course  of  the  fibres  from  the  olfactory  lobe  may  be  used  to  throw 
light  upon  the  localisation  of  olfactory  sensation  in  the  cerebral  cortex. 
There  is  a  great  divergence  between  different  animals  in  the  degree  1"  which 
the  olfactory  sense,  is  developed,  and  with  this  divergence  we  find  corre- 
sponding variations  in  the  development  of  certain  portions  of  the  brain. 
In  those  species  with  highly  developed  olfactory  sense  the  following  parts 
of  the  brain  show  special  growth: 

(I)  The  olfactory  lobe,  including  the  olfactory  bulb,  and  the  olfactory 
tract. 

(•_')  The  posterior  part  and  the  inferior  surface  of  the  frontal  lobe. 

(v$)  The  hippocampal  gyrus  and  the  dentate  convolution. 

(4)  A  convolution  termed  the  gyrus  supracallosus  and  forming  that  pari 
of  the  gyrus  fornicatus  closely  encircling  the  corpus  callosum. 

("))  The  anterior  commissure. 

The  olfactory  lobe  is  connected  almost  exclusively  with  the  cerebral 
hemispheres  of  the  same  side.  Ferrier  found  that  electrical  excitation  of 
the  hippocampal  region  causes  contortion  of  the  lip  and  nostril  on  the  same 
sidi  i.e.  a  reaction  such  as  that  actually  induced  in  these  animals  by  applica- 
tion of  an  irritative,  or  pungent  odour  direct  to  the  nostril.  Ablation  ex- 
periments have  not  yielded  very  definite  evidence  on  the  question  oflocalisa- 
tion  of  t!n>  olfactory  sense.  So  widespread  are  the  connexions  of  the  olfac- 
tory tract  throughout  the  brain  that  it  would  be  extremely  difficult,  if  not 
impossible,  to  extirpate  all  those  parts  which  receive  fibres  from  this  tract. 
C  i-  usual  to  regard  the  sens.'  of  taste  as  associated  with  that  of  smell,  but 
hereagain  experimenl  and  clinical  evidence  have  yielded  very  little  that  i^ 
definite. 

GENERAL  CHARACTERISTICS  OF  CORTICAL  MOTOR  FUNCTIONS 
The  motor  phenomena,  which  may  be  observed  as  the  result  of  artificial 
excitation  of  the  motor  and  senspry  areas  in  the  cortex,  constitute  a  very 
small  fraction  of  the  activities  which  must  be  associated  with  the  cerebral 
hemispheres.  An  animal  with  its  cerebral  hemispheres  intact  differs 
markedly  from  a  decerebrate  animal  in  the  variety  of  combined  movements 
which  it  may  exhibit,  either  spontaneously  or  in  response  to  external  stimuli. 
When  however  we  excite  the  motor  areas  directly,  we  obtain  movements 
which  are  practically  identical  with  those  which  we  may  elicit  from  a  bulbo- 
spinal animal  by  appropriate  peripheral  stimulation.  The  movements  thus 
excited  from  the  skin  may  be  looked  upon  as  variations  from  tin-  tonic 
postural  activity  of  the  musculature  of  the  body.  We  have  seen  that  From 
i  he  end-organs  subserving  deep  and  muscular  sensibility  (the  proprioceptive 
system),  as  well  as  from  the  labyrinth,  impulses  are  continually  arising 
which  travel  up  to  the  spinal  cord.  bulb,  cerebellum,  and  mid-brain,  mid 
excite  a  tonic  activity  of  these  centres.  The  normal  attitude  of  the  animal 
depends  on  the  tonus  thereby  produced  in  certain  muscles.  .Muscular  lone 
is  indeed  a  qualitv  specially  found  in  certain  groups  of  muscles.      If  the  cere- 

29 


150 


PHYSIOLOGY 


bra!  hemispheres  be  removed,  as  l>v  a  section  through  the  crura  cerebri 

or  in  front  of  the  mid-brain,  this  postural  tonus  is  increased  and  the  animal 
enters  into  the  condition  of '  decerebrate  rigidity.'  Destruction  of  one  laby- 
rinth diminishes  the  tone  on  the  same  side  of  the  body  ;  section  of  all  the 
afferent  nerves  from  a  limb  abolishes  the  tone  in  that  limb,  so  that  its  post  hit 
thereafter  depends  entirely  on  gravity. 

The  movements  which  are  excited  in  such  animals  by  cutaneous  stimula- 
tion involve  as  a  necessary  factor  inhibition  of  the  postural  tone  as  well  as 

co-operative  inhibition  of  the  an- 
tagonistic muscles.  In  the  same 
way  excitation  of  the  motor  area  of 
the  cortex  lias  as  its  most  essential 
feature  an  inhibitory  action  on  the 
postural  tonus  in  addition  to  its  exci- 
tatory action  on  the  muscles  con- 
cerned in  the  movement.  A  cer- 
tain antagonism  is  evident  between 
the  total  action  of  the  cerebral  hemi- 
spheres and  that  of  the  propriocep- 
tive part  of  the  central  nervous  sys- 
tem. Whereas  in  the  decerebrate 
animal  there  is  increased  tonus  in 
the  masseters,  in  the  neck  muscles. 
the  muscles  of  the  trunk,  and  the 
extensor  muscles  of  the  limbs,  stim- 
ulation of  the  cortex  produces 
opening  of  the  mouth,  flexion  of  the 
fore  limb  or  of  the  hind  limb,  more 
easily  than  any  other  movements. 
That  an  essential  part  of  this  action 
is  inhibitory  is  shown  by  the  effects 
of  exciting  the  motor  area  of  the  cor- 
tex after  exhibition  of  strychnine  or 
during  the  local  action  of  tetanus 
toxin.  Whereas  in  the  normal  animal 
closure  of  the  jaw  and  extension  of 
the  fore  limb  are  obtainable 
only  from  one  or  two  points  on  the 
surface  of  the  brain,  after  the  injection  has  taken  place,  every  part  of 
the  jaw  area  gives  closing  of  the  jaw,  every  part  of  the  arm  area  gives 
extension  of  the  lirub  (op.  Fig.  173). 

Since  the  predominant  influence  of  the  motor  cortex  is  therefore  inhibitory 
of  the  stronger  muscles  of  the  body,  as  well  as  of  the  tonus,  which  is  con- 
tinually and  reflexly  maintained,  it  is  not  surprising  that  excision  of  both 
hemispheres  should  give  rise  to  decerebrate  rigidity,  or  that  destruction 
or  division  of  the  chief  direct  tracts  from  the  cortex  to  the  motor  spinal 


Fig.  234.  Diagram  (from  Mott  after  Mon- 
akow)  to  show  the  interaction  of  the 
different  levels  in  the  central  nervous 
system  in  the  production  of  co-ordinated 
'  volitional '  movements. 

s,  sensory  neuron  ;  B,  bulb  ;  Tir,  thala- 
mus ;  MA,  motor  area  ;  i>,  pyramidal  fibre  ; 
C,  cerebello-pontine  nuclei ;  vs,  vesti- 
bular neuron  (Deiters'  nucleus). 


FUNCTIONS   OF  THE  CEREBRAL  HEMISPHERES         451 

mechanisms,  viz.  the  pyramidal  tracts,  should  determine  increased  tonus  and 
rigidity  of  the  limbs — the  so-called  '  spastic  '  condition  observed  in  cere- 
bral paralyses. 

Two  separable  systems  of  motor  innervation  appear  thus  to  control  two 
sets  of  musculature.  One  system  exhibits  the  transient  phases  of  heightened 
reaction  which  constitute  reflex  movements  ;  the  other  maintains  that  steady 
tonic  response  which  supplies  the  muscular  tension  necessary  to  attitude. 
Hughlings  Jackson  long  ago  called  attention  to  this  contrast  between  the 
two  systems.  He  pointed  out  that  while  the  cerebrum  innervates  the  muscles 
in  the  order  of  their  action  from  the  most  voluntary  movements  (the  limbs) 
to  the  most  automatic  (trunk),  the  cerebellum,  or,  as  we  should  say  now, 
the  whole  proprioceptive  system,  innervates  them  in  the  opposite  order. 
The  cerebellum  therefore  he  regarded  as  the  centre  for  continuous  move- 
ments and  the  cerebrum  for  changing  movements.  The  increased  tone  of  the 
paralysed  muscles,  observable  after  hemiplegia,  he  ascribed  to  unbalanced 
cerebellar  influence.  While  there  is  no  doubt  that  the  cerebellum  must  play, 
and  does  play,  a  considerable  part  in  the  production  of  decerebrate  rigidity 
and  of  the  spastic  condition  of  hemiplegia,  it  is  not  the  only  element 
involved  ;  nor  is  it  essential,  since  decerebrate  rigidity  may  continue  after 
extirpation  of  the  cerebellum  and  an  exaggerated  knee-jerk  may  result  from 
section  of  the  spinal  cord  in  the  lower  cervical  region. 

HIGHER   ASSOCIATIVE   FUNCTIONS   OF   THE   CORTEX 

Tin'  simple  and  uncomplicated  nature  of  the  movements  elicited  on 
cortical  stimulation  shows  that  we  cannot  regard  these  motor  centres  as 
responsible  for  the  whole,  or  even  the  greater  part,  of  the  motor  functions  of 
the  cortex.  They  are  in  fact  simply  the  starting-point  for  the  motor  impulses 
which  run  down  the  long  pyramidal  tracts,  but  which  result  from  the 
activities  of  the  cerebral  hemispheres  as  a  whole.  In  the  lower  mammals 
they  do  not  even  represent  the  only  starting-point,  as  is  shown  by  the  almost 
perfect  recovery  of  volitional  motor  power  in  a  dog  deprived  of  its  motor 
cortex.  The  distinguishing  feature  of  the  response  of  an  animal  possessing 
cerebral  hemispheres  is  that  it  is  not  determined  solely  and  exclusively 
by  the  nature  and  position  of  the  peripheral  stimulation,  but  involves 
elements  connected  with  the  past  experiences  of  the  animal,  and  including 
therefore  the  results  of  previous  stimulation  of  many  of  the  sense-organs, 
either  directly,  or  indirectly  as  a  result  of  reflex  movements.  The  animal's 
reactivity  is  determined  by  its  past  history,  and  this  modifying  influence  on 
the  brain  must  involve  parts  connected  with  all  its  sense-organs.  In  any con- 
scious motor  act  we  may  say  therefore  that  the  brain  functions  as  a  whole,  or 
nearly  as  a  whole. 

In  endeavouring  to  arrive  at  some  idea  of  the  neural  processes  concerned 
in  voUtional  movements,  i.e.  movements  of  the  intact  animal,  we  are  dealing 
with  events  which  in  ourselves  come  within  the  sphere  of  consciouMH sss, 
so  that  some  assistance  is  derived  by  appealing  to  our  own  mental  experiences. 
Especially  is  this  necessary  in  the  case  of  the  sensations.     It   might   1  e 


152  PHYSIOLOGY 

imagined  thai  a  simple  sensation  would  ensue  as  the  result  "I  local  stimula- 
tion, say  of  the  visual  centre  on  one  side.     Our  knowledge  of  the  properties 

of  the  systems  of  neurons  composing  the  cenl  ral  nervous  system  would  teach 
us  that  no  excitatory  process  could  remain  confined  to  one  portion  of  the 
brain,  bu1  must  diverge  in  many  directions.  It  is  true  thai  excision  ol  the 
occipital  lobes  on  one  side  causes  blindness  to  objects  in  the  opposite  half 
of  the  field  of  vision.  This  is  however  merely  a  result  of  localisation  of  the 
end  of  visual  fibres,  and  the  same  effect  can  be  brought  about  by  division  of 
the  right  optic  tract,  or  damage  to  the  right  half  of  both  retina'. 

On  the  other  hand,  an  appeal  to  our  own  experience  shows  that  no 
sensation  can  be  regarded  as  simple,  i.e.  as  following  merely  stimulation  of 
visual  fibres  or  visual  centres.  Thus  the  sensation  of  a  luminous  point 
has  connected  with  it  not  only  luminosity  but  also  colour  and  intensity. 
Moreover  the  apparent  position  of  the  luminous  point  comes  into  conscious- 
ness at  the  same  tiine  as  the  consciousness  of  the  luminosity  itself,  and  this 
location  of  the  stimulation  involves  muscular  impressions  from  the  eyeballs 
and  an  association  between  certain  points  on  the  retina  and  certain  corre- 
sponding muscular  movements  of  the  eye  muscles,  of  the  head  and  neck,  and 
even  of  the  body  and  arm — movements  which  would  be  necessary  to  bring 
the  image  of  the  spot  on  to  the  fovea  centralis  and  to  approach  the  whole 
body  to  the  site  of  the  stimulating  object. 

As  the  visual  sensation  becomes  more  complex,  the  associated  sensations 
and  experiences  which  it  evokes  become  more  numerous.  Thus  the  image 
of  a  chair  falling  on  the  retina  excites  a  long  train  of  nervous  processes.  At 
once  we  become  aware  not  only  of  a  visual  impulse  but  of  an  object  which 
possesses  colour,  extension,  or  size  in  three  dimensions,  solidity,  hardness, 
distance  or  position  in  space,  etc.  These  qualities  are  founded  on  past  ex- 
periences— visual,  muscular,  and  tactile.  Moreover  we  are  at  once  aware 
of  the  uses  of  the  chair,  and  of  its  name  both  spoken  and  written,  a  mental 
activity  connoting  revival  of  higher  visual  and  auditory  sensations.  The 
higher  in  the  scale  of  intelligence,  the  greater  is  the  development  of  the 
cerebral  hemispheres  and  the  more  extensive  are  the  associations  arising  in 
connexion  with  any  single  sense  impression. 

Besides  the  portions  of  the  brain  which  send  out  the  motor  paths  and 
which  receive  the  endings  of  the  sensory  paths,  there  may  be  whole  regions 
taken  up  by  the  interconnecting  neurons  which  subserve  the  association  of 
the  activities  of  all  parts  of  the  cerebral  hemispheres,  and  the  higher  the 
animal  is  in  the  scale  of  intelligence  the  larger  must  be  the  relative  amount 
of  brain  substance  set  apart  for  these  functions  of  association.  This  is  very 
evident  if  we  compare  the  brain  of  three  animals,  such  as  the  dog.  the  ape. 
and  man.  Although  as  we  ascend  to  man  there  is  an  absolute  increase  in  the 
amount  of  brain  substance  involved — say  in  the  motor  areas  or  in  the  sensory 
areas — the  increase  is  very  small  as  compared  with  that  in  those  portions 
of  the  brain  which  give  no  response  on  stimulation,  and  in  man  these 
'  silent '  parts  of  the  brain  form  the  greater  part  of  the  cerebral  cortex. 
Although  every  phase  of  cerebral  activity,  every  conscious  event,  involves 


FUNCTIONS   OF  THE   CEREBRAL  HEMISPHERES         453 

co-operation  of  a  large  number  of  distant  portions  of  the  brain  substance,  in 
most  of  them  there  will  be  some  seat  of  sense  impressions  which  will  be 
predominant,  and  a  train  of  ideas  may  be  specially  visual,  or  auditory,  or 
tactile.  It  is  therefore  not  surprising  that,  in  the  immediate  neighbourhood 
of  the  cortical  areas  which  receive  the  endings  of  the  sensory  tracts  associa- 
t  n  m  areas  are  developed  which  may  be  labelled  according  to  the  sense-organ 
with  which  they  are  most  nearly  in  relation.  Thus  we' may  speak  of  the 
visual-sensory  and  the  visual  association,  or  psychic  area,  the  auditory- 
sensory  and  the  auditory-psychic,  and  so  on.  The  limits  of  these  areas  are 
indicated  in  Fig.  224.  p.  431. 

Conditioned  reflexes.  Until  recently,  our  study  of  the  processes  of  association 
and  therewith  all  tin-  higher  functions  of  the  cerebral  hemispheres  was  chiefly  carried 
nut  in  man,  and  in  most  cases  by  the  introspective  method.  Even  when  carried  out 
on  other  men.  it  was  chiefly  by  using  speech  as  an  index  to  the  introspective  experi- 
ences of  those  who  were  being  investigated.  During  the  last  fewyears  a  method  has 
been  introduced  by  Pawlow  for  investigating  the  higher  cerebral  functions  by  an 
objective  method  which  is  capable  of  very  wide  application.  When  a  hungry 
animal  is  shown  food,  we  say  that  'its  month  waters,'  i.e.  there  is  a  secretion  of 
saliva  ;  and  if  the  animal  be  provided  with  a  salivary  fistula  the  extent  of  the  emotion 
of  appetite  may  be  gauged  in  ee.  of  saliva  flowing  from  the  fistula.  It  is  found  in 
such  an  animal  that  a  flow  of  saliva  may  be  excited,  not  only  by  the  sight  or  adminis- 
tration of  food,  but  also  by  any  other  event  which  has  become  associated,  as  the  result 
of  experience,  with  the  taking  of  food.  We  may  use  this  method  in  order  to  deter- 
mine the  sensitiveness  of  the  animal's  perception  of  pure  tones.  Thus  if  we  wish  to 
know  whether  the  animal  can  recognize  the  difference  between  middle  C  and  middle 
i  "Z-.  as  produced  by  tuning-forks,  we  can  for  some  days  or  weeks  allow  him  to  hear  both 
i  hese  sounds  frequently  but  always  follow'  up  one  of  them,  say  C,  by  giving  him  a  piece 
of  meat.  After  a  time  it  is  found  that  not  onlj^  can  he  distinguish  between  the  two 
sounds,  but  that  he  has  a  memory  of  the  absolute  pitch,  so  that  whenever  the  note 
middle  ('  is  sounded  or  any  note  differing  from  it  by  not  more  thanSd.v.  per  second, 
there  is  a  How  of  saliva  from  the  fistula,  whereas  the  note  C;is  heard  without  producing 
any  response.  Such  an  acquired  reaction  is  designated  by  Pawlow,  a  'conditioned 
reflex  '  and  the  method  has  been  applied  by  him  to  study  the  association  between  the 
most  widely  different  impressions  and  the  condition  which  we  can  regard  as  appetite 
and  which  is  associated  psychically  with  the  idea  of  food. 

THE    FUNCTION   OF   SPEECH 

The  acts  of  a  conscious  individual,  i.e.one  possessing  cerebral  hemispheres, 
are  determined  by  Ins  experience.  The  wider  the  range  of  past  sense 
impressions  which  can  be  called  up  and  taken  into  the  chain  of  processes 
involved  in  any  reaction — the  more,  that  is  to  say,  the  individual  weighs  hi.s 
acts  in  the  light  of  past  experience — the  more  fitted  will  these  acts  be  to  his 
maintenance  amid  the  ever-changing  stresses  of  the  environment.  In  this 
guiding  of  behaviour  by  experience  man,  as  well  as  the  higher  mammals,  may 
profit  also  from  accumulated  racial  experience.  The  increased  complexity 
of  the  neural  processes  concerned  in  every  reaction  of  the  body,  anil  the 
excessive  '  lost  time  '  brought  about  by  the  intercalation  of  one  neuron  after 
another  in  the  chain  of  the  excitatory  process,  would  finally  counteract  the 
advantages  derived  from  the  growth  in  complexity  of  the  brain,  were  it  not 


I.'.l  PHYSIOLOGY 

that,  as  a  result  of  education  or  training,  short  cuts  are  laid  down,  by  means 
of  which  reactions  adapted  to  the  maintenance  of  the  individual  can  be  carried 
out  immediately,  without  thought  and  without  correlated  calling  up  of 
numberless  sense  impressions.  Education  in  fact  consists  in  laying  down 
these  '  short  cuts  '  which,  as  habits,  are  the  basis  of  the  behaviour  of  the 
animal.  The  more  complex  the  central  mechanism  and  the  wider  the  range 
of  environmental  change  to  which  adaptation  is  necessary,  the  longer  must  be 
the  time  involved  in  this  process  of  road-making  within  the  cerebral  hemi- 
spheres. The  behaviour  of  man  is  therefore  a  product  of  many  years' 
training,  during  which  time  he  is  in  a  state  of  subjection  and  unfit,  from 
the  absence  of  habit,  to  maintain  himself  as  a  unit  in  the  human  com- 
munity. The  neural  short  cuts  of  habit  are  however  of  advantage  to  the 
individual  only  in  dealing  with  those  events  which  are  of  everyday  occur- 
rence. Every  novel  circumstance  must  involve  a  revival  of  past  sense 
impressions  and  a  calling  up  of  activities  of  the  most  diverse  portions 
of  the  brain  in  order  to  arrive  at  the  safest  or  most  advantageous  mode 
of  action  adapted  to  the  circumstances.  Here  again  the  complexity  of 
the  process  would,  by  the  very  delay  involved,  put  a  stop  to  a  further 
rise  in  intellectual,  i.e.  associative,  capacities,  were  it  not  for  the  invention 
of  Speech. 

In  speech  we  have  a  symbolism  which  acts  as  an  economy  of  thought  or  of 
cerebral  activities.  An  object,  such  as  a  table,  with  its  associated  properties 
of  colour,  consistence,  spatial  extension,  and  resistance,  with  the  connoted 
acts  associated  with  its  use,  can  now  be  evoked  as  a  word,  involving  com- 
paratively simple  auditory  and  motor  processes,  which  itself  may  be  em- 
ployed as  a  unit  of  thought  and  brought  into  connexion  with  other  words, 
each  of  which  in  the  same  way  is  the  symbol  for  a  whole  series  of  sensory  and 
motor  processes.  The  training  of  the  cultivated  man  consists  in  a  constant 
extension  of  the  range  of  this  symbolism,  and  the  acquisition  of  words 
including  wider  and  wider  groups  of  neural  processes,  so  that  finally  we  arrive 
at  those  short  verbal  collections  which,  as  the  so-called  natural  laics,  sum- 
marize the  experience  not  only  of  the  individual  but  such  as  is  common  to  the 
whole  race  of  mankind.  All  science  may  in  fact  be  regarded  as  an  extension 
of  the  process  of  representation  of  neural  experience  in  symbolic  shorthand, 
which  in  the  child  begins  with  the  utterance  of  such  a  simple  word  as 
'  mamma,'  and  from  which  speech  has  arisen.  A  study  of  the  nervous 
mechanisms  involved  in  speech  is  therefore  of  interest  in  its  relations  to  t V  e 
development  of  the  intelligence,  and  heljis  us  to  realize  more  completely  the 
conditions  which  determine  the  activity  and  functioning  of  the  cerebral 
hemispheres.  Much  light  is  thrown  upon  this  mechanism  by  the  study  of 
disorders  in  man  grouped  together  under  the  name  Aphasia. 

It  has  been  usual  to  divide  the  disorders  of  speech  known  as  aphasia  into 
various  groups,  as  follows  : 

(1)  Motor  aphasia,  or  aphasia  of  Broca.  In  this  condition,  which  was  de- 
scribed fully  by  Broca  and  referred  by  him  to  a  lesion  of  the  third  left  frontal 
convoluti  Hi,  the  patient  is  unable  to  speak,  although  he  understands  what  is 


FUNCTIONS   OF  THE  CEREBRAL  HEMISPHERES         155 

said  to  him  and  lias  been  stated  to  suffer  from  no  impairment  of  his  intelli- 
gence. 

(2)  Sensory  aphasia,  or  aphasia  of  Wernicke.  This  condition  was  con- 
nected by  Wernicke  with  the  existence  of  lesions  in  a  fairly  -wide  area,  known 
as  the  area  of  Wernicke,  which  involves  the  supramarginal  and  angular  gyri 
and  the  hinder  portions  of  the  first  and  second  temporo-sphenoidal  convo- 
lutions. In  these  cases  there  may  be  limited  power  of  speech,  but  there 
is  serious  impairment  of  the  intelligence  and  especially  of  the  power  of 
appreciation  of  spoken  words,  so  that  the  patient  does  not  understand  what 
is  said  to  him.  This  condition  may  or  may  not  be  attended  with  alexia,  loss 
of  power  to  read.  Any  impairment  of  the  motor  processes  of  speech  which 
is  present  is  due  rather  to  the  inability  of  the  patient  to  appreciate  what 
he  himself  is  saying,  so  that  there  is  here  a  species  of  sensory  paralysis 
in  the  higher  sphere  of  neural  processes. 

(3)  Anarthria.  This  is  a  condition  in  which  there  is  marked  impairment 
of  the  motor  powers  of  expression,  although  intelligence  and  appreciation  of 
speech,  both  spoken  and  written,  may  be  unaltered.  This  condition  is 
generally  associated  with  lesion  of  the  white  matter  of  the  external  capsule 
as  it  passes  round  the  lenticular  nucleus. 

There  are  however  considerable  difficulties  in  the  acceptation  of  this 
traditional  classification.  Microscopic  examination  of  Broca's  convolution 
shows  a  type  of  cortex  entirely  different  from  that  part,  viz.  the  psycho- 
motor area  of  the  ascending  frontal  convolution,  which  is  concerned  with 
the  higher  cerebral  processes  resulting  in  movement.  Its  structure  is  in  fact 
identical  with  that  described  by  Campbell  as  the  '  intermediate  precentral 
area  '  and  regarded  as  characteristic  of  the  association  areas.  Moreover  it  is 
difficult  to  comprehend  how  a  function  such  as  speech,  with  its  enormously 
complex  mechanism,  could  be  limited  to  so  small  a  portion  of  the  brain  as 
Broca's  convolution.  The  neural  basis  of  language  must  in  fact  be  co- 
extensive with  the  sensory  centres  (the  projection  spheres)  and  with  the 
whole  region  of  lower  association.  AVe  might  indeed  speak  of  auditory  and 
visual  word-centres  as  located  in  the  visuo-psvehie  and  auditory  psychic 
i-entres.  There  is  probably  however  no  word,  still  less  a  collection  of  words, 
expressing  an  idea,  which  does  not  involve  the  activity  of  practically  all  parts 
of  the  cerebral  cortex.  As  Bolton*  points  out,  "  a  word,  such  as  '  mouse,'  at 
once  sets  in  effect  processes  of  association  which  puss  to  every  projection 
sphere  with  the  solitary  exception  of  the  gustatory,  and  even  this  may  be 
aroused  in  a  person  who  has  eaten  a  fried  mouse  in  the  hope  of  thereby 
recovering  from  an  attack  of  whooping-cough." 

A  careful  examination  of  an  extensive  series  of  cases  by  Marie  has  shown, 
in  fact,  that  Broca's  aphasia  does  not  exist  as  a  result  of  lesions  of  Broca's 
convolution.  This  part  of  the  brain  may  be  destri  >yed  without  anj7  disorder 
of  speech.  The  cases  described  by  Broca  of  motor  aphasia  are  really  cases  of 
sensory  aphasia  from  lesion  of  Wernicke's  area,  combined  with  anarthria  due 
to  subcortical  injury  of  the  fibres  of  the  external  capsule.     The  statement 

*  In  his  admirable  article  in  Hill's  "Further  Advances  in  Physiology." 


156 


piivsioi.ocv 


that  there  is  no  loss  of  intelligence  in  these  cases  of  so-called  motor  aphasia 
does  not  bear  invesfigation.  Although  as  patients  they  may  comport 
themselves  reasonably,  as  soon  as  they  have  to  performany  duties  which 
have  been  learnt  by  them  in  connexion  with  their  ordinary  avocations 
they  show  their  deficiency.    They  are  incapable  of  transacting  ordinary  busi- 


(i) 


(2) 


W 


(5) 


Pig.  2:{."j.  Types  of  lesions  giving  rise  to  deficient  intellectual  power,  [n  amentia, 
the  deficiency  is  due  to  failure  of  development;  in  dementia,  to  atrophy  of 
the  cells  (especially  small  pyramidal)  previously  present  in  the  cortex.     (Mott.) 

ness.  at  any  rate  to  the  extent  to  which  they  were  before  the  lesion.  The 
amount  of  impairment  of  intelligence  will  vary  in  different  cases  according 
to  the  extent  of  the  lesion.  Thus  softening  affecting  the  occipital  lobe 
may,  with  hemianopia,  cause  '  word-blindness'  or  alexia,  a  loss  of  power 
of  appreciating  the  meaning  of  written  words.  In  most  individuals,  and 
certainly  in  the  uneducated,  this  power  may  he  cut  out  altogether  without 
interfering  considerably  with  the  mental  powers.  On  the  other  hand, 
from  babyhood  upwards  we  have  learnt  the  meaning  of  words  and  their 


FUNCTIONS   OF   THE  CEREBRAL  HEMISPHERES         457 

grouping  by  auditory  impressions.  If  the  whole  of  the  auditory  associa- 
tions be  destroyed  by  an  extensive  lesion  in  the  first  and  second  temporal 
convolutions,  the  resulting  loss  of  word  appreciation,  sensory  aphasia,  will 
be  attended  with  great  diminution  of  mental  powers.  It  must  be  remem- 
bered  that  the  area  of  Wernicke  is  not  a  sensory  centre,  but  a  centre  of 
association  between  the  various  sense-impressions,  especially  I  hose  of 
hearing  and  sight.  It  may  therefore  be  spoken  of  as  an  intellectual  centre. 
Pure  muter  aphasia  of  course  exists,  but  is  always  anarthria  and  is  due  to  a 
lesion  in  the  lenticular  zone.  i.e.  in  the  lenticular  nucleus  and  its  neighbour- 
hood, in  the  anterior  part  and  the  genu  of  the  internal  capsule,  and  possibly 
in  the  external  capsule. 

It  is  important  to  make  a  distinction  between  loss  of  sanity  and  loss 
of  intellectual  powers.  The  essential  factor  of  sensory  aphasia  is  the  exist- 
ence of  intellectual  impairment,  though  in  his  behaviour  the  patient  may 
appear  perfectly  uormal.  On  the  other  hand,  in  insanity  there  may  he 
perfect  retention  of  the  intellectual  processes,  which  depend  on  the  proper 
working  ol'  the  lower  association  centres.  The  personality  of  the  individual, 
and  therefore  anally  his  behaviour,  involves  a  further  association  on  a  higher 
plane  of  these  intellectual  processes  and  therefore  control  in  accordance  with 
the  relation,  past,  present,  or  future,  of  the  individual  to  his  environment. 
The  prefrontal  region  is  in  all  probability  the  seat  of  this  highest  plane  of 
association.  Insanity  always  involves  alteration  of  personality  and  depends 
on  failure  of  development  or  on  disintegration  processes  (subevolution  or 
dissolution  of  this  region)  (Fig.  235).  In  monkeys  and  cats  Franz  has  found 
that  destruction  of  the  frontal  lobes  causes  a  loss  of  recently  formed  habits. 
He  concludes  from  his  experiments  that  the  frontal  lobes  are  the  means  by 
which  we  are  able  to  learn  and  to  form  habits,  i.e.  to  regulate  our  behaviour 
in  accordance  with  the  needs  of  our  position  in  society. 

THE  TIME  RELATIONS  OF  CENTRAL  NEURAL  REACTIONS 
In  the  spinal  animal  a  stimulus  of  any  particular  quality  and  localisation 
always  evokes  an  appropriate  reaction.  A  certain  period  of  time  necessarily 
elapses  between  the  moment  at  which  the  stimulus  is  applied  and  the  moment 
at  which  the  resulting  reaction  takes  place.  This  interval  is  spoken  of  as 
the  simple  reaction  time,  and  in  the  spinal  animal  is  entirely  independent 
of  consciousness.  .Many  reactions,  even  in  the  intact  animal,  are  also,  as  we 
may  say,  involuntary  and  are  not  modified  perceptibly  by  our  consciousness 
of  their  occurrence:  such  reflexes  as  the  withdrawal  of  the  hand  when  it 
conies  111  contact  with  a  hot  surface,  the  shutting  of  the  eyelid  when  the  con 
junctiva  is  touched,  the  drawing  up  of  the  leg  when  the  sole  of  the  foot  is 
tickled.  Not  only  are  these  carried  ou1  in  the  absence  of  voluntary  impulses, 
but  in  many  cases  it  is  almost,  if  not  quite,  impossible  to  check  the  reaction 
by  any  etiorl    of  the  will. 

When  the  leg  is  drawn  up  in  response  to  a  painful  or  nocuous  stimulus 
applied  to  the  foot,  a  certain  amount  of  time  is  involved  in  each  of  the 
following  links  in  the  chain  of  processes  which  determine  the  reaction  ; 


158 


I'JIYSIOLOCY 


(1)  The   conversion  in  the   peripheral   sense  organ   of   the   mechanical 
stimulus  into  a  nerve  process. 

(2)  The  passage  of  a  nerve  impulse  up  the  nerve  from  the  end  organ  to  the 
spinal  cord. 

(3)  The  passage  of  the  impulse  across  two  or  more  synapses  in  the  grey 
matter  of  the  cord. 

(4)  The  passage  of  the  impulse  down  the  motor  nerve  fibres  From  the 
spinal  curd  to  the  muscles. 


Fia.  236.     Arrangement  of  apparatus  for  determination  of  reaction  time. 

(Alcock  and  Ellison.) 
r,  coil;   E,  exciting  electrodes  ;   F,  tuning-fork  ;   a,  b,  keys  ;   s,  t,  electro- 
magnetic signals  ;    D,  drum. 


(5)  The  processes  occurring  in  the  end  organs  of  the  muscle. 

(6)  The  latent  period  in  the  muscle  fibre  itself. 

With  a  weak  stimulus  No.  I  is  impossible  to  measure.  With  a  strong 
stimulus  it  may  he  so  short  as  to  be  practically  negligible.  (2),  (4),  (5) 
and  (6)  represent  quantities  for  the  measurement  of  which  we  have  all  the 
necessary  data. 

In  any  given  reflex  therefore  we  may  add  these  periods  together  and 
subtract  them  from  the  total  reaction  time  ;  we  thus  get  a  '  reduced  re- 
action time,'  which  represents  the  time  involved  in  the  passage  of  the  impulse 
through  the  central  nervous  system,  and  in  the  conversion  of  an  afferent 
impulse  into  an  aggregate  of  co-ordinated  motor  impulse's.  It  is  found 
that  the  reduced  reaction  time  accounts  for  the  greater  part  of  the  total 
reaction  time.  Since  we  have  no  reason  to  assume  that  the  rate  of  passage  of 
an  impulse  through  the  intra-spinal  course  of  a  nerve  fibre  differs  appreciably 
from  the  rate  at  which  it  is  conducted  by  the  same  nerve  fibre  outside  the 


FUNCTIONS  OF  THE  CEREBRAL  HEMISPHERES         159 

cord,  the  extra  delay  which  occurs  in  the  passage  of  the  impulse  through  the 
cord  must  take  place  either  in  the  nerve  cells  themselves,  or  in  the  synapses, 
through  which  the  impulse  passes  from  one  neuron  to  the  next  in  the  chain  of 
reflex  elements. 

The  rate  of  passage  of  an  impulse  through  the  nerve  cell  can  be  deter- 
mined only  in  one  part  of  the  body,  viz.  in  the  posterior  spinal  root  ganglia, 
since  only  in  these  is  it  possible  to  detect  the  moment  of  passage  of  an  im- 
pulse across  a  given  section  of  a  nerve  fibre  on  both  sides  of  the  ganglion  cell 
in  which  the  nerve  fibres  arise.  Experiments  on  this  jjoint  have  been  made 
by  Steinach  and  by  Moore.  In  each  case  the  time  occupied  in  the  passage 
of  the  impulse  through  the  ganglion  was  not  appreciably  longer  than  if  the 
impulse  had  passed  through  a  corresponding  stretch  of  uninterrupted  nerve 
fibre.  We  are  therefore  justified  in  concluding  that  the  relatively  great 
delay  in  the  passage  of  an  impulse  through  the  central  nervous  system  has 
its  seat  in  the  synapses  across  which  the  impulse  has  to  pass.  This  con- 
clusion is  in  accordance  with  our  experience  on  the  latent  period  of  muscle, 
the  greater  part  of  which  is  due  to  changes  occurring  in  the  nerve  endings, 
i.e.  in  the  synapses  between  motor  nerve  and  muscle.  The  greater  the 
number  of  synapses  involved  in  any  given  reaction,  i.e.  the  greater  the  coin 
plexily  of  the  reaction,  the  longer  will  be  the  period  which  elapses  between 
the  moment  of  application  of  the  stimulus  and  the  moment  at  which  the 
response  takes  place.  Especially  is  this  the  case  when  the  complex  mesh- 
work  of  neurons  of  the  cerebral  hemispheres  is  involved,  or  when  the  occur- 
rence of  the  reaction  is  associated  with  the  conscious  processes  of  sensation 
and  volition.  In  the  latter  case  the  determination  of  the  reaction  time  has 
the  added  interest  that  it  gives  information  as  to  the  time  relations  of  the 
psychical  processes  which  are  the  representation  in  consciousness  of  the 
physiological  changes  occurring  in  the  neurons  of  the  central  nervous 
system. 

Many  methods  an-  employed  fur  the  measuring  of  the  reaction  linn-  oi  conscious 
processes.  In  most  methods  the  application  of  the  stimulus  is  arranged  mi  as  in  close 
the  circuit  of  a  currenf  which  flows  through  an  electro  magnel  ai  tivath  e  a  [ever  which 
writes  nil  a  rapidlj  moving  blackened  surface1.  The  reaction  of  the  individual  who 
is  flu-  subject  of  experiment  is  arranged  si.  that  tin-  resulting  movement  activates  a 
key  by  which  the  same  current  is  opened.  We  thus  obtain  a  tracing  on  flic  blackened 
surface  showing  the  moment  of  application  of  tin-  stimulus  and  the  moment  at  «  hich  the 
reaction  takes  place.  Thus,  if  tin-  reaction  tune  for  an  auditory  stimulus  is  to  he 
determined,  flu-  electric  current  is  arranged  so  as  to  pass  through: 

(1)  A  spring  contact  key  which  can  be  pressed  so  as  to  make  a  noise. 

(2)  An  electric  signal  writing  on  a  rapidly  moving  surfai  e. 

(3)  A  second  key  which  the  subject  will  release  as  sunn  as  he  hears  the  imise  of 
the  first  key  and  so  break  the  current. 

The  recording  surface  may  he  a  drum,  a  pendulum  myograph,  or  a  spring  myograph, 
such  as  the  'shooter'  of  du  Bois-Reymond.  If  the  sensory  impression  is  to  be  from 
the  skin,  the  current  may  be  made  to  pass  through  the  primary  coil  of  an  inductorium 
and  wires  be  taken  from  the  second  coil  to  some  part  of  the  surface  of  the  skin.  In 
this  ease  the  signal  may  be  started  by  opening  the  circuit,  and  the  subject  of  the  experi- 
ment will  respond  by  closing  the  circuit  by  means  of  a  spring  key  directly  be  feels 


MO  PHYSIOLOGY 

tin-  shook  caused  by  the  break  of  the  primary  circuit.  If  the  reaction  period  is  to  be 
determined  for  sight,  a  white  piece  of  paper  may  be  placed  on  an  electro-magnet  in  the 
primary  circuil  and  the  person  will  respond  directly  lie-  sees  this  move.  Many  other 
instruments  have  been  devised  for  the  same  purpose. 

The  average  reaction  limes  obtained  with  the  different  senses  arc  as 

follows: 

Electrical 
Sighl  Hearing.  Stimulation  of  Skin. 

0-186   to  0-222    see.  0-115   to  0-182    see.  0-117    to  0-201    see. 

The  t w ci  figures  given  for  each  ease  are  the  extremes  obtained  in  different 
series  of  observations. 

The  times  vary  according  to  the  condition  of  the  person  that  is  the  subject 
of  the  experiment.  They  are  lengthened  by  fatigue;  they  are  shortened 
up  to  a  certain  point  by  continued  practice.  Within  limits  also  they  are 
shortened   by  increase  of  the  strength  of  the  stimulus. 

DILEMMA.  When  the  subject  has  to  make  a  deliberate  choice  between 
the  parts  of  the  body  stimulated,  the  reaction  time  is  considerably  Longer. 
To  show  this,  the  wires  from  the  secondary  coil  are  connected  by  a  switch 
to  two  pairs  of  electrodes  which  are  applied,  one  to  the  right  and  one  to  the 
left  half  of  the  body.  It  is  agreed  beforehand  that  the  subject  shall  react 
only  to  stimulation,  say,  of  the  right  side.     The  switch  is  removed  from 

the  observation  of  the  subject  and  the  stimulus  is  applied  irregularly  t e 

side  or  to  the  other.  It  is  found  that  the  additional  neural  processes 
involved  in  determining  whether  the  stimulus  is  on  the  right  side,  and  there- 
fore should  be  followed  up  as  agreed,  adds  considerably  to  the  length  of  the 
reaction  time  (on  an  average  -006  sec).  It  is  possible  to  complicate  the 
dilemma  to  almost  any  extent.  Thus  the  experiment  may  be  so  arranged 
that  either  a  red  or  a  white  disc  appears  and  the  subject  lias  to  react  with 
the  right  hand  to  the  red  disc  and  with  the  left  hand  to  the  white  disc.  In 
such  an  experiment  the  reaction  time  was  found  to  be  be  0-131  sec.  longer  than 
the  simple  reaction  time.  A  still  more  complex  process  would  be  involved 
in  the  experiment  in  which  a  word  was  spoken,  and  the  subject  had  to  speak 
some  other  word  which  had  some  association  with  the  word  which  formed  the 
stimulus,  e.g.  horse — mammal  :  paper  pen,  &c  In  such  an  experiment 
the   reaction   time  was  found  to  be  as  long  as  0-7  to  IKS  sec. 

We  see  that  the  recording  of  the  time  of  occurrence  of  any  physical  event 
can.  occur  only  after  a  certain  lost  time,  which  represents  the  observer's 
reaction  time  for  the  stimulus  in  question.  This  applies  however  only 
to  movements  carried  out  in  response  to  single  stimuli  or  to  stimuli  repeated 
at  irregular  intervals.  When  the  stimuli  are  rhythmic  the  lost  time  applies 
only  to  the  first  one  or  two  of  the  stimuli.  The  observer  or  subject  is 
conscious  of  the  interval  elapsing  between  the  physical  event  and  his  react  ion. 
and  anticipates  the  later  stimuli  so  that  his  reaction  becomes  synchronous 
with  the  stimulus.  This  synchronism  of  stimulus  and  reaction  characterises 
all  rhythmic  movements,  such  as  dancing  or  the  playing  of  an  orchestra  in 
time  with  tin'  beat  of  the  conductor's  baton. 


SECTION   Will 

THE    NUTRITIVE    AND   VASCULAR    ARRANGEMENT 
OF   THE   CENTRAL   NERVOUS   SYSTEM 

The  brain  and  spinal  cord  arc  enclosed  within  three  membranes  or  meninges, 
named  from  without  inwards,  the  dura  mater,  the  arachnoid  membrane] 
and  the  pia  mater.  The  dura  mater  consists  of  a  strong  fibrous  membrane, 
smooth  and  lined  with  endothelial  cells  on  its  inner  surface.  In  the  head 
its  outer  surface  is  closely  attached  to  the  bones  forming  the  cranium,  of 
which  it  represents  the  periosteum.  Strong  fibrous  partitions  are  sent  from 
the  dura  mater  into  the  cavity  of  the  cranium  to  support  the  chief  parts 
of  the  brain.  One  of  these,  the  falx  cerebri,  supports  the  two  cerebral  hemi- 
spheres ;  a  second,  the  tentorium  cerebelli,  forms  a  horizontal  division  between 
the  cerebral  hemispheres  and  the  cerebrum;  and  a  smaller  one.  the  falx 
cerebelli,  passes  ,i  short  distance  inwards  between  the  cerebellar  hemispheres. 
In  the  spinal  canal  the  bones  have  their  own  periosteum,  and  the  dura  mater, 
which  is  closely  attached  round  the  margins  of  the  magnus,  forms  a  loose 
sheath  round  the  spinal  cord,  being  slung  up  in  the  vertebral  canal  by  the 
tubular  prolongations  which  it  sends  along  each  nerve  root  to  form  the  outer 
sheath  of  the  nerve.  The  dura  mater  in  the  cranium  may  be  separated 
with  greater  or  less  difficulty  into  two  layers,  and  between  these  two  layers 
are  found  the  venous  sinuses,  which  receive  the  whole  of  the  blood  returned 
from  the  brain.  These  venous  sinuses  are  angular  clefts,  the  chief  of  which 
lie  along  the  attached  margin  of  the  falx  cerebri  and  the  tentorium  cerebelli. 
Most  of  the  blood  leaves  the  skull  by  the  internal  jugular  veins.  In  the 
spinal  cord  the  place  of  these  venous  sinuses  is  taken  by  a  plexus  of  thin- 
walled  veins,  imbedded  in  fat,  lying  on  the  outside  of  the  dura.  Under  tin1 
dura  mater  we  find  the  subdural  space,  which  is  rather  potential  than  actual. 
It  can  be  regarded  as  a  large  lymph  space  and  any  contents  are  drained 
off  into  the  lymph  spaces  of  the  nerve  roots  and  adjoining  tissues. 

The  arachnoid  is  a  delicate  transparent  membrane  which  covers  I  he  whole 
of  the  brain  and  spinal  cord.  Superficially  it  presents  a  layer  of 
endothelial  cells  which  bound  the  subdural  space.  On  its  deep  surface  it  is 
connected  with  the  pia  mater  by  fine  fibres.  It  bridges  over  the  inequalities 
in  the  surface  of  the  brain  so  that  in  various  localities  a  space  is  left  which  is 
filled  with  cerebro-spinal  fluid  and  is  known  as  the  subarachnoid  space. 
In  certain  situations  it  sends  prolongations  into  the  fissures  of  the  brain. 
Thus  a  marked  expansion  passes  by  the  transverse  fissure  between  the 
cerebral  hemispheres  and  the  third  ventricle,  sending  prolongations  into  the 

461 


162  PHYSIOLOGY 

lateral  ventricles.  This  layer  of  connective  tissue  is  covered  on  one  surface 
by  the  ependyma  of  the  ventricles,  on  the  other  surface  by  the  ependyma 
forming  the  roof  of  the  third  ventricle.  It  carries  a  rich  plexus  of  blood 
vessels  known  as  the  choroid  plexus,  and  the  ependyma  covering  the  vascular 
fringes  which  dip  into  the  cerebral  ventricles  consist  of  clear  columnar  or 
cubical  cells,  often  spoken  of  as  the  epithelium  of  the  choroid  plexus. 
Similar  vascular  fringes  are  found  in  the  roof  of  the  fourth  ventricle. 

The  pia  mater  is  a  layer  of  connective  tissue  which  serves  to  carry  the 
blood-supply  to  the  whole  surface  of  the  brain.  It  is  closely  applied  to  the 
surface  and  follows  all  the  irregularities  of  the  latter,  dipping  down  into  the 
various  fissures  and  crevices  on  the  brain.  In  the  spinal  canal  the  pia  mater 
sends  out  a  series  of  processes  on  each  side  of  the  spinal  cord,  the  ligamentum 
denticulatum,  the  outer  extremities  of  which  are  attached  to  the  dura 
mater  and  serve  to  sling  the  spinal  cord  in  its  dural  sheath. 

The  brain  is  richly  supplied  with  blood.  Its  chief  supply  is  derived  from 
the  two  carotids  and  the  two  vertebral  arteries.  The  vertebrals  unite  on 
the  lower  surface  of  the  bulb  to  form  the  basilar  artery,  which  divides  again 
at  the  anterior  extremity  of  the  pons  varolii  into  two  branches  which  unite 
with  the  two  carotid  arteries  to  form  the  circle  of  Willis,  so  that  the  pressure 
in  this  arterial  circle  can  be  maintained  indifferently  by  any  three  out  of  the 
four  arteries  by  which  it  is  supplied.  From  these  vessels  three  main  arteries, 
the  anterior,  middle  and  posterior  cerebral,  pass  up  to  supply  the  correspond- 
ing regions  of  the  outer  surface  of  the  brain,  while  the  inner  parts  of  the 
brain,  e.g.  the  corpus  striatum,  optic  thalamus,  &c,  are  supplied  from 
arteries  arising  from  the  circle  of  Willis  and  passing  straight  into  the  sub- 
stance of  the  brain.  The  connection  between  the  vascular  supply  of  the 
different  parts  of  the  brain  is  slight  and  effected  only  by  the  capillaries  ; 
hence  obstruction  of  any  one  vessel,  such  as  the  middle  cerebral,  perma- 
nently cuts  off  the  blood  supply  to  the  greater  part  of  the  area  supplied  'by 
it  and  the  result  is  death  and  softening  of  the  brain  substance.  The  arteries 
supplying  the  surface  of  the  brain  divide  up  into  arterioles  and  capillaries 
within  the  pia  mater,  and  the  capillaries  run  into  the  brain  substance  sur- 
rounded by  a  so-called  lymphatic  sheath,  which  apparently  communicates 
with  the  subarachnoid  space. 

In  certain  cases  of  disease  these  perivascular  sheaths  may  be  found  to 
contain  leucocytes  often  filled  with  products  of  disintegration  of  the  nervous 
tissues. 

THE   CEREBRO-SPINAL   FLUID 

The  subarachnoid  space  contains  a  thin  transparent  colourless  fluid, 
known  as  the  cerebro-spinal  fluid.  In  composition  this  fluid  resembles 
blood  plasma  minus  its  protein  constituents.  It  contains  a  mere  trace  of 
coagulable  proteins  but  it  has  the  same  molecular  concentration  as  the  blood 
plasnia  and  its  salts  are  identical  with  those  of  the  blood  plasma.  It  also 
contains  other  diffusible  constituents  of  blood  plasma,  e.g.  small  traces  of 
sugar  and  of  urea.     It  may  be  collected  by  introducing  a  cannula  through  the 


THE  CENTRAL  NERVOl  JS  SYSTEM  463 

atlanto-occipital  membrane  into  the  ample  subarachnoid  space  lying  over 
the  fourth  ventricle.  Another  method  is  to  introduce  a  glass  cannula  through 
a  slit  in  the  sheath  of  a  nerve  root  up  into  the  subarachnoid  cavity  of  the 
spinal  canal.  In  man  it  may  be  obtained  in  small  quantifies  for  examination 
by  introducing  a  hollow  needle  directly  into  the  spinal  canal  in  the  lumbar 
region  between  the  laminae  of  the  vertebrae.  On  introducing  a  cannula 
into  the  subarachnoid  space,  the  fluid  may  spurt  out,  showing  that  it  is  under 
a,  certain  pressure  (about  100  mm.  H20).  After  the  first  rush  the  fluid  begins 
to  drop  away,  at  first  rapidly,  but  more  slowly  with  lapse  of  time.  If 
the  fluid  be  allowed  to  drain  off  for  some  hours,  signs  of  interference  with  the 
functions  of  the  central  nervous  system  are  evinced.  The  cerebrospinal 
fluid  appears  to  be  formed  chiefly  in  the  neighbourhood  of  the  choroid  plexus. 
Although  its  composition  would  suggest  that  it  was  merely  a  transudation 
from  the  blood,  the  amount  formed  does  not  seem  to  run  parallel  with  the 
pressure  in  the  capillaries  of  the  brain.  Moreover,  it  has  been  shown  by 
Dixon  and  Halliburton  that  a  considerable  increase  in  the  flow  of  cerebro- 
spinal fluid  may  be  brought  about  by  injecting  an  extract  of  the  choroid 
plexus  itself.  It  has  therefore  been  concluded  that  this  fluid  is  really  a 
secretion  by  the  modified  ependyma  cells  covering  the  fringes  of  the  choroid 
plexus. 

Although  the  method  of  formation  of  i\iv  cerebro-spinal  fluid  is  still  not 
clear,  there  is  no  question  that  its  removal  from  the  subarachnoid  space  is 
brought  about  by  simple  physical  factors.  The  subarachnoid  space  com- 
municates with  the  ventricles  by  means  of  openings  in  the  roof  of  the  fourth 
ventricle.  The  pressure  of  the  fluid  is  ordinarily  about  equal  to  the  pressure 
in  the  venous  sinuses  of  the  cranium.  If  salt  solution  be  injected  into  t lie 
subarachnoid  space,  it  escapes  with  extreme  ease,  and  it  is  found  that  its 
channel  of  escape  is  into  the  veins  and  especially  into  the  venous  sinuses  of 
the  dura  mater.  Its  removal  by  these  sinuses  is  facilitated  by  the  existence 
of  peculiar  structures,  known  as  the  Pacchionian  bodies.  Each  of  these 
bodies  is  a  bulbous  protrusion  of  the  arachnoid  membrane  into  a  blood 
sinus.  It  remains  connected  with  the  arachnoid  by  a  narrow  pedicle, 
through  which  a  continuation  of  the  sub-arachnoid  space  is  prolonged  into 
the  interior  of  the  sinus.  It  is  therefore  a  little  sac  of  arachnoid  membrane 
separated  from  the  blood  stream  only  by  an  invagination  of  the  endothelium 
lining  the  sinus.  Filtration  of  the  cerebro-spinal  fluid  will  occur  into  the 
venous  sinuses  whenever  (he  pressure  of  the  fluid  rises  above  that  ol  the 
blood  in  the  sinus.  The  fluid  can  also  escape,  but  with  greater  difficulty, 
along  the  sheaths  of  the  spinal  nerve  roots,  by  which  it  will  pass  into  the 
lymphatics  outside  the  spinal  canal. 

THE    NUTRITION    OF    THE    BRAIN 

The  grey  matter  of  the  brain  is  very  richly  supplied  with  blood 
vessels.  Any  interference  with  the  blood  flow  through  the  brain  rapidly 
checks   the  functions   of   the  central   nervous   system  in  consequence  of 


Kil  PHYSIOLOGY 

deprivation  of  oxygen.  Although  so  susceptible  to  slighl  deprivation 
(il  oxygenil  doesnotseem  thai  the  brain  tissues  have  a  verj  rapid  gaseous 
metabolism ;  thai  is.  they  need  oxygen  supply  at  high  tension  bu1  do 
mil  deprive  the  blood  ol  any  very  large  amount  of  the  oxygen  which  il  con- 
tains.    Nor  does  it  seem  probable  thai   the  brain  requires  a  large  supply 

of  I I  material.     It  must  be  remembered  thai   in  all  parts  of  the  brain 

a  peri-vascular  lymphatic  intervenes  between  the  capillary  and  the  brain 
tissue.  Since  these  'lymphatics'  communicate  with  the  subarachnoid 
space,  they  must  contain  a  fluid  which  differs  little  if  at  all  from  the  compo- 
sition of  the  cerebrospinal  fluid  obtained  from  the  subarachnoid  space.  'I  tie 
iniiiieiit  fluid  of  the  brain  is  therefore  practically  salt  solution  with  a  trace 
of  sugar  and  possibly  minute  traces  of  amino  acids. 

Our  study  of  the  events  which  accompany  the  propagation  of  a  nervous 
impulse  down  a  nerve  fibre  has  prepared  us  for  the  conclusion  that  very  little 
energy  is  involved  in  ordinary  nerve  activity.  It  is  true  that  extreme  fatigue 
causes  changes  in  the  Nissl  granules  of  the  nerve  cells  and  is  therefore  asso- 
ciated with  the  using  up  of  some  material  constituent.  But  even  though 
material  changes  in  the  nerve  cells  and  in  the  synapses  may  be  larger  in 
amount  than  those  in  nerve  fibres,  they  arc  probably  not  to  be  compared 
in  extent  wit  h  those  taking  place  in  a  cunt  railing  muscle  or  in  an  active  liver 


THE   CEREBRAL  CIRCULATION 

In  all  higher  animals  the  brain  is  enclosed  in  a  rigid  ca-  e  formed  by  the 
bony  cranium.  In  the  child,  before  the  crania!  vault  is  fully  ossified,  pari 
of  this  vault  consists  of  membrane,  known  as  the  anterior  fontanelle.  It 
is  easy  to  see  that  the  fontanelle  pulsates  with  each  beart-beal  as  well 
as  with  rise  of  venous  pressure,  such  as  that  produced  during  strong  expira- 
tory efforts.  -When  ossification  is  complete,  such  alterations  in  the  volume 
of  the  cranial  i  ontents  are  impossible.  And  vet  the  pressure  in  the  arteries 
within  the  cranium  must  be  still  pulsatile,  the  rise  of  pressure  a1  each  heart- 
beat must  make  the  arteries  expand,  hut  room  for  this  expansion  has  to 
be  found  by  contraction  of  some  other  part  of  the  cranial  contents.  We 
find  that  each  arterial  beat  is  associated  with  a  corresponding  expulsion 
of  some  of  the  contents  of  the  veins  and  a  contraction  of  these  vessels.  If, 
lor  instance,  a  cannula  be  introduced  through  the  occipital  bom'  into  the 
torcular  Herophili,  the  venou  blood  is  -ecu  to  pulsate  and  to  be  pressed  ou1 
with  each  beat  of  the  heart.  II  there  is  a  rise  of  arterial  pressure,  although 
the  arteries  may  expand  somewhat  at  the  expense  of  the  veins,  there  can  be 
no  dilatation  of  the  whole  organ.  The  only  effect  of  the  rise  oi  pressure 
will  be  to  cause  an  increased  pressure  fall  in  the  cranial  vascular  system,  and 
therefore  augmented  velocity  of  flow  through  the  system.  A  prolonged  rise 
of  pressure  may  cause  a  certain  amount  of  dilatation  of  the  vessels,  but  only 
at  the.  expense  of  the  cerebrospinal  fluid.  Since  this  is  only  small  in  amount, 
any  expansion  of  the  brain  due  to  vascular  causes  must  be  very  limited. 

BRAIN  PRESSURE.     II  bv  means  of  a  trephine  an  opening  be  made  into 


THE   CENTKAL  NERVOUS  SYSTEM  465 

the  cranial  vault,  the  brain  bulges  into  the  opening.  By  screwing  a  tube 
covered  with  a  membrane  into  the  trephine  opening,  we  can  find  the  pressure 
necessary  to  force  the  brain  back  to  its  previous  position.  This  is  known 
as  the  brain  pressure,  and  is  approximately  equal,  as  might  be  expected,  to  the 
cerebro-spinal  pressure  and  to  the  pressure  in  the  venous  sinuses.  It  is 
closely  dependent  on  the  latter.  Forced  expiratory  efforts,  such  as  may 
occur  in  the  convulsions  of  strychnine  poisoning,  may  raise  the  pressure  from 
30  to  50  mm.  Hg.  In  the  vertical  position  in  man,  the  pressure  may  be 
slightly  negative  in  consequence  of  the  tendency  of  the  venous  blood  to  run 
downwards  towards  the  heart. 

REGULATION   OF   THE    BLOOD  SUPPLY   TO    THE    BRAIN 

Xo  satisfactory  evidence  has  been  brought  forward  of  the  existence  of 
vaso-motor  nerves  controlling  the  calibre  of  the  cerebral  blood  vessels.  Nor 
indeed  are  such  nerves  necessary.  The  brain,  as  the  master  tissue  of  the 
body,  controls  through  the  medullary  centres  the  circulation  through  all 
other  parts  of  the  body.  It  is  therefore  able  to  regulate  the  blood  supply 
through  its  arteries  by  allowing  less  or  more  blood  to  pass  through  other  parts 
of  the  body.  For  the  exercise  of  its  normal  functions  it  requires  a  certain 
blood  supply,  which  again  will  depend  simply  on  the  pressure  in  the  carotid 
arteries  and  circle  of  Willis.  If  this  pressure  fails,  the  functions  of  the 
brain  are  affected  and  loss  of  consciousness  rapidly  ensues.  This  is  what 
occurs  when  a  person  who  is  weak  from  long  illness  faints  on  suddenly  getting 
up  from  bed.  In  the  normal  individual  the  change  in  the  circulation  with 
alteration  of  bodily  position,  which  would  be  produced  by  the  action  of 
gravity,  is  at  once  counteracted  through  the  vaso-motor  system.  The 
(splanchnic  area  is  contracted  or  dilated  according  to  the  necessities  of  the  case, 
but  the  pressure  in  the  carotid  and  the  circulation  of  the  brain  remains  unal- 
tered. Even  when  the  heart  in  consequence  of  disease  is  scarcely  able  to  carry 
on  the  circulation,  the  arterial  pressure  undergoes  little  or  no  alteration. 
Any  other  tissue  of  the  body,  even  the  heart  itself,  may  suffer,  but  the  brain 
at  all  costs  must  receive  its  proper  supply  of  blood. 


30 


SECTION  XIX 

THE   VISCERAL   OR    AUTONOMIC    NERVOUS    SYSTEM 

In  the  medulla  oblongata  it  is  easy  to  differentiate  the  central  grey  matter 
connected  with  the  peripheral  nerves  into  two  categories,  viz.  splanchnic 
and  somatic.  Each  of  these  two  sets  of  nerves  jrossesses  both  afferent  and 
efferent  fibres.  Gaskell  has  suggested  that  the  same  arrangement  would  hold 
for  any  typical  segmental  nerve,  which  would  therefore  have  four  roots,  viz. 
two  somatic — the  motor  and  sensory  roots  distributed  to  the  skin  and 
skeletal  muscles — and  two  splanchnic  roots,  also  motor  and  sensory,  and 
composed  of  small  fibres  distributed  to  the  viscera  or  structures  which  are 
visceral  in  origin  (e.g.  developed  from  the  branchial  arches).  In  the  medulla 
the  somatic  efferent  fibres,  such  as  the  sixth  and  twelfth  nerves,  arise  from  the 
column  of  large  cells  lying  in  the  floor  of  the  fourth  ventricle  close  to  the 
middle  line.  The  splanchnic  fibres,  e.g.  those  of  the  facial  and  vagoglosso- 
pharyngeal nerves,  arise  from  a  column  of  cells — the  nucleus  ambiguus  and 
facial  nucleus,  lying  more  laterally  and  deeper,  below  the  surface  of  the 
ventricle.  The  motor  root  of  the  fifth  would  also  belong  to  the  same  system. 
In  the  spinal  cord  the  visceral  fibres  arise  in  the  cells  of  the  lateral  horn.  i.e. 
from  a  situation  corresponding  to  the  splanchnic  motor  nuclei  of  the  pons 
and  medulla.  Whereas  however  the  splanchnic  afferent  nerves,  such  as  the 
glossopharyngeal,  and  perhaps  the  sensory  nucleus  of  the  fifth,  form  a  well- 
marked  splanchnic  system  of  nuclei  in  the  medulla,  in  the  cord  the  afferent 
fibres  from  the  viscera  pass  in  with  the  other  afferent  somatic  fibres,  and  their 
immediate  connections  in  the  cord  are  as  yet  unknown. 

The  autonomic  system  of  nerves  include,  the  sympathetic  system 
(properly  so  called)  and  some  of  the  cranial  and  sacral  nerves.  The  sym- 
pathetic system  (Fig.  237;  is  composed  of  a  chain  of  ganglia  lying  each  side 
of  the  vertebral  column,  there  being  as  a  rule  one  ganglion  to  each  spinal 
nerve  root.  In  the  cervical  region  these  ganglia  are  condensed  into  two, 
the  superior  and  inferior  cervical  ganglia,  united  by  the  cervical  sympa- 
thetic trunk  ;  and  the  upper  three  or  four  thoracic  ganglia  on  each  side  are 
condensed  to  form  the  '  stellate  '  ganglion.  At  the  bottom  of  the  chain 
there  is  only  one  coccygeal  ganglion  for  the  coccygeal  vertebrae. 

In  the  abdomen  is  a  second  system  of  ganglia,  in  special  connection 
with  the  abdominal  viscera,  lying  in  front  of  the  aorta  and  surrounding  the 
origins  of  the  large  arteries  to  the  alimentary  canal.  These  are  the  semi- 
lunar or  solar  ganglia,  the  superior  mesenteric  and  the  inferior  mesenteric 
ganglia. 

466 


THE  AUTONOMIC  NERVOUS   SYSTEM 


467 


Sup  cerv.  g  .- 


inf  cerv.g.^ 


>  Head  &  Neck 


Abdominal 
Viscera 


Hypogastric  n     'ppJvmcn 


Fig.  237.  Diagrammatic  representation  of  the  distribution  of  the  sympathetic  system. 
The  black  lines  represent  the  medullated  pre-ganglionic  fibres,  such  as  those  making 
up  the  white  rami  communicantes,  while  the  post-ganglionic  fibres  are  printed  in  red. 
On  the  extreme  right  of  the  figure  is  indicated  the  general  distribution  of  the  white  rami 
arising  from  the  several  nerve  roots,  while  the  double  brackets  point  to  the  nerve 
roots  making  up  the  limb  plexuses.  H,  heart  :  s.  stomach  ;  i.  small  intestine  ;  c,  colon  ; 
B.  bladder. 


468  PHYSIOLOGY 

In  the  organs  themselves  we  find  a  third  system  of  ganglion  cells,  cither 
scattered  or  collected  to  form  small  ganglia.  These  isolated  ganglion  cells 
as  a  rule  have  no  connection  with  the  fibres  of  the  sympathetic  system,  but, 
as  we  shall  see  later,  lie  on  the  course  of  the  impulses  descending  by  other 
nerves  of  the  autonomic  system,  e.g.  the  vagus  or  the  pelvic  visceral  nerves. 
The  three  systems  of  ganglia  have  been  distinguished  as  the  lateral,  collateral, 
and  terminal  ganglia. 


Fig.  238.  Diagram  of  spinal  segment  with  its  nerve 
roots,  somatic  and  visceral.  (G.  D.  Thane.; 
(The  visceral  roots  are  represented  in  red.) 

The  ganglia  of  the  sympathetic  chain  are  connected  with  all  the  spinal 
nerves,  just  after  they  have  given  off  their  posterior  divisions,  by  means  of  the 
rami  communicantes.  These  rami  communicantes  are  of  two  kinds  :  white 
rami  consisting  of  small  medullated  fibres,  and  grey  rami  composed  almost 
exclusively  of  non-medullated  nerves.  It  has  been  shown  by  Gaskell  that 
the  white  rami  are  formed  by  fibres  which  have  their  origin  in  the  spinal  cord 
and  perhaps  in  the  posterior  root  ganglia  ;  whereas  the  grey  rami  represent 
fibres  which,  arising  in  the  sympathetic  ganglia,  run  back  to  join  the  spinal 
nerves.  The  visceral  outflow  represented  by  the  white  rami  is  limited  to  a 
distinct  region  of  the  cord,  viz.  from  the  first  thoracic  to  the  third  or  fourth 
lumbar  nerve  roots  ;  whereas  the  grey  rami  pass  from  the  sympathetic 
to  all  the  spinal  nerve  roots.  It  is  found  by  experiment  that  stimulation  of  a 
limited  number  of  white  rami  produces  all  the  effects  that  can  be  evoked  by 
stimulation  of  the  grey  rami,  showing  that  the  impulses  leaving  the  cord  pass 
upwards  and  downwards  in  the  sympathetic  system  and  are  broken  some- 
where in  their  course,  being  transferred  to  a  fresh  relay  which,  by  means  of 
non-medullated  nerves,  carries  them  on  to  their  destination. 

Finally,  in  certain  organs  of  the  body  are  to  be  found  sheets  of  nerve 
structures,  including  both  ganglion  cells  and  fibres,  which  must  be  regarded 
as  local  nerve  centres,  capable  of  carrying  out  co-ordinated  acts  in  response 
to  stimuli,  independently  of  the  central  nervous  system.  It  seems  probable 
that  these  systems  are  to  be  regarded  as  analogous  rather  to  the  diffuse  neuro- 
fibrillar system  of  an  animal,  such  as  the  medusa,  than  to  the  synaptic  ner- 
vous structures  characteristic  of  the  central  nervous  system  of  vertebrates. 


THE  AUTONOMIC  NERVOUS  SYSTEM 


469 


In  the  latter  the  direction  and  effect  of  any  impulses  are  determined  by  the 
synapses  intervening  between  various  systems  of  neurons  and  allowing  the 
passage  of  the  impulse  only  in  one  direction.  This  law  of  forward  direction 
has  not  been  proved  to  hold  good  for  the  primitive  nerve  systems  ;  an 
impulse  apparently  spreads  equally  well  in  either  direction.  As  a  type  of  this 
peripheral  diffuse  nerve  system  may  be  cited  the  Auerbaeh/s  and  Meissner's 
plexuses  in  the  wall  of  alimentary  canal.  How  far  we  are  to  regard  the 
nerve  nets  in  other  viscera,  such  as  the  heart  and  the  bladder,  as  conforming 
to  this  type  is  still  a  moot  point,  and  will  be  discussed  in  dealing  with  the 
origin  of  the  heart  beat. 


Posc'root-, 

Ant/  root 


Made-up  '  spinal  nerve  ' 


-Pre -ganglionic  fibre 


-  -Symp.  gangl 


Post-gangliomc  fibre 


Fig.  230.  Diagram  (after  LanoLET)  to  show  the  manner  in  which  a  spinal  nerve  is 
completed  by  the.  entry  of  a  grey  ramus,  containing  fibres  derived  from  cells  in 
the  sympathetic  chain. 

p.pr.d,  posterior  primary  division.     (The  post -ganglionic  fibres  are  represented  red.) 


The  relationships  of  the  white  and  grey  rami  are  strikingly  illustrated 
in  the  case  of  the  pilomotor  systems  of  nerves.  These  in  the  cat  arise  from 
the  cord  by  the  anterior  roots  from  the  fourth  thoracic  to  the  third  lumbar 
inclusive.  Passing  by  the  white  rami  to  the  sympathetic  system,  they 
travel  upwards  and  downwards  and  end  by  arborisations  in  the  various 
ganglia  of  the  main  chain.  From  the  cells  of  each  ganglion  a  fresh  relay  i  ti 
fibres  starts,  which  runs  as  a  bundle  of  non-medullated  nerves  (the  grey 
ramus)  to  the  corresponding  spinal  nerve,  with  which  it  is  distributed  to 
its  peripheral  destination.  Each  grey  ramus  causes  erection  of  the  hairs 
above  one  vertebra,  whereas  stimulation  of  one  white  ramus  causes  erection 
over  three  or  four  vertebrae,  showing  a  distribution  of  the  fibres  of  the  white 
ramus  to  the  cells  in  several  successive  ganglia. 

These  pilomotor  fibres  in  the  cat  have  the  following  distribution  : 
( 1 )  For  the  head  and  upper  part  of  the  neck  the  fibres  arise  by  the  fourth 


170  PHYSIOLOGY 

to  the  seventh  thoracic  anterior  roots,  and  have  their  cell  stations  in  the 
superior  cervical  ganglion.  They  travel  as  small  medulla  ted  nerve  fibres 
from  the  white  rami  up  the  sympathetic  chain,  through  the  stellate  ganglion 
and  ansa  Vieussenii  and  up  the  cervical  sympathetic. 

(2)  The  next  set  of  nerve  fibres  have  their  cell  station  in  the  stellate 
ganglion.  The  white  rami  arise  from  the  fifth  to  the  eighth  thoracic  nerves, 
while  the  grey  rami  pass  to  the  nerve  roots  from  the  third  cervical  nerve 
to  the  fourth  thoracic  nerve. 

(3)  The  remaining  nerves,  supplying  all  the  rest  of  the  body  and  tail,  arise 
by  the  white  rami  from  the  seventh  thoracic  to  the  third  or  fourth  lumbar 
nerve,  and  are  distributed  as  grey  rami  to  all  the  spinal  nerves  below 
the  fourth  thoracic. 

We  thus  see  that,  in  speaking  of  the  functions  of  a  spinal  nerve  root,  we 
must  clearly  distinguish  whether  we  mean  the  root  as  it  arises  from  the 
spinal  cord,  in  which  case  its  visceral  functions  will  include  those  of  its  white 
ramus,  or  whether  we  mean  the  made-up  or  complete  spinal  nerve  after  it  has 
received  its  grey  ramus  (Fig.  239).  In  the  latter  case  the  visceral  functions 
of  the  root  will  be  more  restricted  than  in  the  former  case,  and  will  have  a 
different  distribution.  In  stimulating  the  nerve  roots  in  the  spinal  canal 
it  is  sometimes  possible,  by  weak  stimuli,  to  display  the  functions  of  the 
corresponding  white  ramus,  and  then  by  increasing  the  stimidus  to  get 
superadded  the  effects  due  to  the  excitation  of  the  grey  ramus  in  the  made-up 
nerve,  in  consequence  of  the  spread  of  current. 

"  When,  for  example,  the  eleventh  thoracic  anterior  roots  are  stimulated  in  the 
spinal  canal  with  weak  shocks,  a  fairly  long  strip  of  hairs  in  the  lumbar  region  will 
be  erected,  the  maximum  movement  of  the  hairs  being  near  the  middle  of  the  strip. 
This  marks  the  area  of  distribution  of  the  pilomotor  nerves  given  by  the  eleventh  thoracic 
nerve  to  the  sympathetic.  If  then  the  strength  of  the  shock  be  increased  to  a  certain 
point,  the  hairs  in  the  long  strip  will  of  course  be  erected  as  before,  but  in  addition 
there  will  be  energetic  erection  of  hairs  in  a  short  strip  a  little  distance  above  the  long 
strip,  and  separated  from  it  by  a  quiescent  region.  This  short  strip  is  the  same  as  that 
affected  by  stimulating  the  grey  ramus  or  the  dorsal  cutaneous  branch  of  the  eleventh 
thoracic  nerve.  It  marks  the  area  of  distribution  of  the  pilomotor  fibres  received 
by  the  spinal  nerve  from  the  sympathetic."     (Langley.) 

We  may  now  indicate  briefly  the  main  course  and  functions  of  the  fibres 
of  the  sympathetic  system. 

(1)  The  head  and  neck  are  supplied  by  fibres  leaving  the  spinal  cord 
by  the  first  five  dorsal  nerves  (chiefly  by  the  second  and  third).  They  all 
have  their  cell  station  in  the  superior  cervical  ganglion.     They  convey  : 

Vaso-constrictor  impulses  to  the  blood  vessels. 
Dilator  fibres  to  the  pupil. 

Secretory  fibres  to  the  salivary  glands  and  sweat  glands. 
Vaso-dilator  fibres  to  the  lower  lip  and  pharynx  (?). 

(2)  The  thoracic  viscera  (heart  and  lungs)  are  supplied  by  the  same  five 
nerve  roots.  The  cell  station  of  these  fibres  is  however  situated  in  the 
stellate  ganglion.     They  convey  : 

Accelerator  or  augmentor  impulses  to  the  heart. 


THE   AUTONOMIC  NERVOUS  SYSTEM 


471 


(3)  The  abdominal  viscera  receive  fibres  from  the  lower  six  dorsal  nerves 
and  the  tipper  three  or  four  lumbar.  Most  of  these  fibres  run  through  the 
sympathetic  chain  without  making  any  connection  with  the  ganglia,  and 
have  their  cell  stations  in  the  collateral  ganglia  of  the  solar  plexus,  the  semi- 
lunar and  superior  mesenteric  ganglia.  On  their  way  to  these  ganglia  t  hex- 
form  the  greater  and  lesser  splanchnic  nerves.     Their  functions  are  : 

Vaso-constrictor  for  stomach  and  small  intestine,  kidney,  and  spleen. 

Probably  vaso-dilator  for  the  same  viscera. 

Inhibitory  for  both  muscular  coats  of  stomach  and  small  intestine. 

Motor  for  ileocolic  sphincter. 

(1)  The  pelvic  viscera  are  supplied  by  the  lower  dorsal  and  upper  three 

or  four  lumbar  nerve  roots.     These  fibres  also  pass  by  the  main  chain  to 

4  * Spinal  cord 


Sympathetic  chain 


-  -  Soiar  ganqlian 


Fig.  24H.     Figure  (after  Lw.i  ey)  to  show  the  probable  mode  of  connection 
of  the  fibres  <if  the  splanchnic  nerve  with  nerve-cells. 

a.  usual  type,  all  the  h'lires  passing  through  the  lateral  chain  to  end 
in  the  collateral  ganglia  of  the  solar  plexus  :  B.  alternative  condition,  in 
which  a  small  minority  of  the  fibres  have  their  cell-stations  in  the  sym- 
pathetic chain.   The  pre-ganglionic  fibres  are  black,  the  post-ganglionic  red. 

make  connections  with  the  cells,  chiefly  in  the  inferior  mesenteric  ganglia. 
They  convey  : 

Vaso-constrictor  impulses  to  pelvic  viscera. 

Inhibitory  fibres  to  colon  (both  coats). 

Motor  and  also  inhibitory  fibres  to  bladder. 

Motor  fibres  to  retractor  penis. 

.Motor  and  inhibitory  fibres  to  uterus  and  vagina. 

(5)  The  fore  limb  receives  nerves  from  the  white  rami  of  the  fourth 
to  the  tenth  thoracic  nerves.  All  those  fibres  are  connected  with  cells  in  the 
stellate  ganglion.  '  They  convey  : 

Vaso-constrictor  impulses  to  the  blood  vessels. 
Secretory  nerves  to  the  sweat  glands. 

(6)  The  hind  limb  is  supplied  by  the  neive  roots  from  the  eleventh 
thoracic  to  the  third  lumbar  inclusive.     The  cell  stations  of  these  fibres 


472  PHYSIOLOGY 

are  situated  in  the  sixth  and  seventh  lumbar  and  first  sacral  ganglia.  They 
convey : 

Vasoconstrictor  impulses. 

Secretory  nerves  to  the  sweat  glands. 

Every  fibre  of  the  sympathetic  system  is  thus  in  some  point  of  its  course 
interrupted  by  a  nerve  cell,  and  Langley  has  shown  that  this  is  the  only  cell- 
break  in  the  fibre.  This  applies  not  only  to  the  sympathetic  fibres  hut  also 
to  the  fibres  of  the  other  visceral  nerves.  Each  fibre  therefore  can  be  re- 
garded as  made  up  of  two  sections — a  pre-gangl ionic  fibre  arising  in  the 
central  nervous  system  and  passing  down  to  a  ganglion  as  a  fine  medul- 
lated  nerve  fibre,  and  a  post-ganglionic  fibre  arising  in  this  ganglion 
and  continued  generally  as  a  non-medullated  fibre  to  its  peripheral  dis- 
tribution. 

This  transference  from  one  system  to  another  involves  the  passage  across 
a  synapse  and  a  nerve  cell.  The  situation  of  this  nerve  cell  may  be  easily 
revealed  by  utilising  the  action  of  nicotine,  first  studied  by  Langley.  If 
nicotine  be  applied  to  a  sympathetic  ganglion,  it  first  stimulates  and  then 
paralyses  any  junction  between  axon  termination  and  nerve  cell  which  may 
lie  in  the  ganglion.  Intravenous  injection  of  nicotine  therefore  causes  a 
primary  general  excitation  of  all  visceral  ganglion  cells.  There  is  an  enor- 
mous rise  of  blood  pressure,  which  may  be  accompanied  by  other  sympathetic 
effects,  such  as  dilatation  of  the  pupil,  secretion  of  saliva,  erection  of  the 
hairs,  and  so  on.  This  rise  rapidly  passes  off.  and  it  is  then  found  impossible 
to  evoke  any  reflex  visceral  effects  or  any  contraction,  e.g.  of  the  blood  vessels, 
by  stimulation  of  the  spinal  cord  ;  the  passage  of  the  impulses  is  blocked  in 
every  one  of  the  visceral  ganglia.  By  observing  the  effects  of  stimulation  of 
a  nerve  before  it  enters  a  ganglion  and  then  painting  the  ganglion  with  nico- 
tine and  again  trying  the  effects  of  excitation,  it  is  easy  to  determine  whether 
the  nerve  fibres  which  were  excited  in  the  first  case  form  any  connections 
with  the  nerve  cells  of  the  ganglion.  In  the  strength  in  which  it  is  usually 
applied  nicotine  is  without  effect  on  nerve  fibres. 

THE   CRANIAL    AUTONOMIC   FIBRES 

In  the  course  of  development  the  greater  part  of  the  fibres  of  the  facial 
nerve  have  lost  their  special  visceral  functions  and  have  the  aspect  and 
functions  of  ordinary  somatic  fibres.  Visceral  fibres  are  contained  in  the 
following  cranial  nerves — the  third,  seventh,  ninth,  tenth,  and  eleventh. 

Third  nerve.  The  visceral  fibres  of  this  nerve  pass  to  the  ciliary  ganglion 
in  the  orbit  where  they  end  ;  the  postganglionic  fibres  from  this  ganglion 
form  the  short  ciliary  nerves  which  innervate  the  sphincter  pupillae  and  the 
ciliary  muscles. 

Seventh  nerve.  The  autonomic  fibres  of  the  facial  arise  from  the  medulla 
in  the  intermediate  nerve  of  Wrisberg.  which  is  practically  the  anterior  con- 
tinuation of  the  ninth,  tenth,  and  eleventh  nerves.  From  the  seventh  nerve 
is  derived  the  chorda  tvmpani  nerve,  which  supplies  vaso-dilator  nerves 


THE   AUTONOMIC   NERVOUS   SYSTEM  473 

to  the  tongue,  the  submaxillary  and  sublingual  glands,  and  secretory  fibres 
to  these  glands. 

The  cell  stations  of  these  nerves  lie  peripherally,  those  of  the  sublingual 
gland  in  the  so-called  submaxillary  ganglion  ;  those  of  the  submaxillary 
gland  in  the  hilus  of  this  organ.  It  is  probable  that  the  seventh  sends  also 
pre-ganglionic  visceral  fibres  to  the  spheno-palatine  ganglion,  whence  a  fresh 
relay  of  fibres — post-ganglionic — run  with  the  branches  of  the  fifth  nerve, 
to  supply  secretory  fibres  and  possibly  vaso-dilator  fibres  to  the  mucous 
membrane  of  the  riose,  soft  palate,  and  upper  part  of  the  pharynx.  The 
glossopharyngeal  or  ninth  nerve  sends  fibres,  which  evoke  secretion  as  well  as 
vaso-dilatation  in  the  parotid  gland,  via,  the  otic  ganglion.  Probably  also 
dilator  fibres  leave  this  nerve  to  supply  vessels  at  the  back  of  the  tongue. 

THE  VAGUS 
The  efferent  visceral  fibres  of  the  tenth  and  eleventh  nerves  arise  in  the 
same  column  of  cells  as  the  two  nerves  just  considered.  Most  of  the  fibres 
run  in  the  vagus.  They  include  motor  fibres  to  the  oesophagus,  stomach,  and 
small  intestines  as  far  as  the  ileocolic  sphincter  ;  inhibitory  fibres  to  the 
heart ;  motor  fibres  to  the  unstriated  muscles  of  the  bronchi  ;  and  secretory 
fibres  to  the  gastric  glands.  The  cell  stations  of  these  fibres  are  apparently 
situated  peripherally,  the  jugular  ganglion  and  the  ganglion  of  the  trunk 
of  the  vagus  being  in  all  likelihood  responsible  only  for  the  afferent  fibres  in 
this  nerve.  Nicotine  therefore  abolishes  any  effect  of  stimulating  the  vagus 
in  the  neck,  though  inhibition  of  the  heart  can  still  be  produced  on  excitation 
of  the  post-ganglionic  fibres  arising  from  the  cells  in  the  sinus  venosus. 

SACRAL    AUTONOMIC   FIBRES 

These  all  run  in  the  pelvic  visceral  nerve,  also  called  nervus  erigens. 
This  nerve  is  connected  with  a  collection  of  ganglia  lying  in  the  hypogastric 
plexus  at  the  base  of  the  bladder.     It  has  the  following  functions  : 

Dilator  to  vessels  of  the  penis  (hence  its  name  of  nervus  erigens). 

Motor  to  bladder,  colon,  and  rectum. 

Inhibitory  to  sphincter  muscle  of  bladder. 

Inhibitory  to  retractor  penis. 

It  will  be  observed  that  in  many  cases  the  viscera  get  their  nerve-supply 
from  both  sets  of  visceral  nerves,  and  that  in  such  cases  the  two  sets  of 
nerves  are  antagomstic  in  function.  It  is  impossible  however  to  draw  a 
sharp  line  between  the  functions  of  the  two  sets,  since  the  same  nerve  may  be 
motor  for  one  set  of  muscular  fibres  and  inhibitory  for  another  set  in  the 
same  viscus.  Thus  the  colonic  branches  of  the  inferior  mesenteric  ganglion 
are  motor  (constrictor)  for  the  blood  vessels  and  inhibitory  for  the  muscular 
walls  of  the  colon.  While  the  sympathetic  nerve  supply  is  inhibitory  for 
nearly  the  whole  intestinal  muscles,  it  produces  strong  contraction  of  the 
band  of  muscle  forming  the  ileocolic  sphincter.  In  the  bladder  there 
is  no  doubt  that  the  sympathetic  supply  includes  both  inhibitory  and 
motor  fibres,  the  predominating  effect  on  excitation  of  the  nerve  varying 
from  one  species  of  animal  to  another. 


474  PHYSIOLOGY 

FUNCTIONS   OF   THE    SYMPATHETIC    AND    PERIPHERAL 
GANGLIA 

These  ganglia  consist  of  a  mass  of  nerve  cells  embedded  in  connective 
tissue,  each  cell  being  surrounded  by  a  special  capsule  of  endothelial  cells. 
The  nerve  cells,  though  in  section  resembling  those  in  a  posterior  root 
ganglion,  differ  from  these  in  being  multipolar,  each  cell  probably  possessing 
one  axon  and  several  dendrites.  The  dendrites  end  in  little  arborisations 
round  adjacent  cells. 

Since  the  main  nervous  system  is  characterised  by  the  possession  of 
nerve  cells,  it  was  formerly  thought  that  any  collection  of  nerve  cells  must 
partake  of  the  co-ordinating  and  reflex  functions  of  the  central  nervous 
system,  i.e.  must  act  as  local  nervous  centres.  All  efforts  have  failed  how- 
ever to  prove  the  existence  of  such  a  function,  and  we  must  conclude  that  the 
sole  use  of  these  ganglia  is  to  serve  as  distributing  centres.  We  may  assume 
that  one  pre-ganglionic  fibre  divides,  and  the  branches  arborise  round  several 
cells  (Fig.  240),  whence  new  fibres  arise  to  carry  the  impulse  to  the  periphery 
— an  impulse  in  the  case  of  which  there  is  no  need  for  any  minute  localisation. 
Indeed  the  essential  part  of  a  nerve  centre  is  not  the  nerve  cells  at  all, 
but  the  presence  of  a  complex  tangle  of  fibres,  rendering  possible  the  passage 
of  imjDulses  in  all  directions,  the  passage  of  an  individual  impulse  being 
limited  by  reason  of  the  varying  strength  of  the  impulse  and  the  varying 
resistance  of  the  many  possible  tracts.  In  many  invertebrata  the  nervous 
system  consists  of  a  punctated  material  composed  of  a  dense  interlacement  of 
fibrils,  while  the  cells  lie  outside  the  centres  and  have  one  thick  process 
dipping  into  the  nervous  mass,  from  which  process  both  axon  and  dendrites 
arise.  In  this  case,  as  we  have  seen,  extirpation  of  the  cell  bodies  does  not 
destroy  the  capacity  of  the  remaining  fibrillar  substance  to  act  as  a  reflex 
centre.  Such  a  complex  of  fibres  is  found  in  mammals  in  the  plexuses  of 
Auerbach  and  Meissner,  which  act  as  local  nerve  centres  for  the  intestine. 
But  all  such  mechanism  is  wanting  in  the  sympathetic  ganglia,  which  con- 
tain neither  association  fibres  between  different  cells  of  a  ganglion  nor  com- 
missural fibres  between  the  cells  of  adjacent  ganglia.  All  the  fibres  in  a 
sympathetic  ganglion  have  either  entered  it  from  the  white  rami  or  are 
destined  to  leave  it  as  fibres  of  grey  rami. 

Several  reflexes  formerly  described  in  jieripheral  ganglia,  as,  e.g.  the 
'  submaxillary  '  ganglion,  have  been  proved  to  be  fallacious.  There  is 
however  a  certain  group  of  phenomena  which  can  be  elicited  in  sympathetic 
ganglia,  and  which  have  been  termed  by  Langley  and  Anderson  pseudo- 
reflexes  or,  better,  axon  reflexes.  If.  for  instance,  we  divide  all  the  nerves 
going  to  the  inferior  mesenteric  ganglion,  leaving  the  bladder  connected 
with  the  inferior  mesenteric  ganglion  only  by  the  hypogastric  nerves,  and 
then  after  dividing  the  left  nerve  stimulate  its  central  end,  we  obtain  a 
contraction  of  the  right  half  of  the  bladder.  This  effect  is  abolished  by 
painting  the  inferior  mesenteric  ganglion  with  nicotine,  showing  that  the 
activity  of  the  cells  of  this  ganglion  is  involved  in  the  process.     It  has  been 


THE   AUTONOMIC    NERVOUS   SYSTEM 


475 


shown  however  by  Langlev  and  Anderson  that  this  is  not  a  true  reflex,  but 
is  rather  analogous  to  Kiihne's  gracilis  experiment  (cf.  p.  255).  A  pre- 
ganglionic fibre  arriving  at  the  inferior  mesenteric  ganglion  branches,  one 
branch  ending  round  the  cells  of  the  ganglion,  while  the  other  branch  passes 
down  in  the  left  hypogastric  nerve  to  a  cell  situated  near  the  base  of  the 
bladder  (Fig.  24 1 ).     When  therefore  we  stimulate  this  nerve  we  are  stimula- 

Sp  cord 


Post -ganglionic  fibre 


Pre -ganglionic  fibre 
Hypogastric  nerves 


I'ii;.  241.     Diagram  to  illustrate  Langley  and  Anderson's  explanation  cf  the  hypo- 
gastric reflex  as  an  axon  reflex. 
The  division  of  the  axon  when'  the  propagation  or  '  reflexion  '  takes  place  is  at  X. 

ling  a  pre-ganglionic  fibre,  and  the  excitation  spreads  up  to  the  point  of 
junction  of  the  two  branches  and  then  down  the  other  branch  to  excite  the 
cell  in  the  inferior  mesenteric  ganglion.  We  thus  obtain  an  apparent  motor 
reflex  by  stimulation  of  a  nerve  which  is  itself  motor.  Similar  pseudo- 
reflexes  can  be  obtained  along  the  abdominal  chain  on  the  pilomotor  nerves. 
But  furnish  no  grounds  for  ascribing  the  property  of  reflex  centres  to  peri- 
pheral ganglia.  On  the.  other  hand,  these  axon  reflexes  are  very  similar  to 
the  spread  of  the  excitatory  process  which  occurs  in  the  diffuse  nerve  network 
of  an  animal  such  as  the  medusa.  Irreciprocity  of  conduction  would  seem 
therefore  to  be  the  most  useful  criterion  of  a  true  reflex. 


INHIBITION    IN    PERIPHERAL    GANGLIA 

The.  existence  of  ganglion  cells  in  the  course  of  the  nerves  to  visceral  muscles  has 
often  been  supposed  to  account  for  certain  peculiarities  in  the  innervation  of  visceral, 
as  compared  with  skeletal,  muscle.  Chief  among  the  differences  between  these  two 
kinds  of  muscles  is  the  frequency  with  which  inhibition  may  be  brought  about  in  visceral 
muscle  by  stimulation  of  peripheral  efferent  nerves.  In  skeletal  muscle  inhibition  is 
known  only  as  the  result  of  alteration  of  the  activity  of  the  motor  centres  from  which 
it  is  supplied.  It  has  therefore  been  thought  that  the  peripheral  ganglia  of  visceral 
muscle  play  the  part  of  the  motor  spinal  centres  of  skeletal  muscle,  and  that  when 
we  excite  an  inhibitory  nerve,  say  to  the  intestine,  we  are  interfering  with  and  diminishing 


476  PHYSIOLOGY 

a  tonic  state  of  activity  which  has  its  seat  in  a  peripheral  ganglion  cell  connected  with 
the  visceral  muscle. 

This  view,  which  was  first  put  forward  by  Claude  Bernard,  has  been  specially  defended 
by  Dastre  and  Morat.  These  observers  point  out  that  vaso-dilator  action  diminishes 
or  disappears  as  nerve  strands  are  stimulated  more  and  more  peripherally,  and  con- 
clude that  the  vaso-dilator  fibres  run  to  the  sympathetic  ganglion  and  inhibit  their 
tonic  action.  The  untenability  of  this  view  has  been  demonstrated  by  Langley.  Thus 
the  chorda  tympani  fibres  run  to  a  local  nerve  '  centre  '  in  the  hilum  of  the  submaxillary 
gland.  On  Bernard's  theory  stimulation  of  the  fibres  peripherally  to  the  centre  should 
cause  contraction  of  the  arteries  ;  but  it  is  found  that,  after  paralysis  of  the  ganglion 
by  nicotine,  stimulation  of  the  post -ganglionic  fibres  causes  dilatation,  so  that  the 
nerve  fibres  given  off  from  the  local  centre  are  not  vaso -constrictor  but  vaso-dilator. 
Moreover  it  can  be  shown  that  the  sympathetic  fibres  which  do  cause  constriction 
make  no  connection  with  the  cells  in  the  hilum  of  the  gland,  but  run  on  the  walls  of 
the  arteries  to  their  distribution.  These  fibres  are  connected,  not  with  cells  of  the 
submaxillary  ganglion  (the  local  nerve  centre),  but  with  cells  in  the  superior  cervical 
ganglion. 

We  must  conclude  that  the  inhibitory  nerves  in  these  visceral  structures  exert 
their  influence  directly  on  the  peripheral  tissue,  and  not  by  a  diminution  of  activity 
i  if  a  tonieally  acting  peripheral  centre. 

AFFERENT   FIBRES    AND   THE    AUTONOMIC   SYSTEM 
(Referred  Pain) 

The  supply  of  afferent  fibres  to  the  viscera  is  very  small  in  proportion 
to  the  supply  to  the  outer  surfaces  of  the  body.  According  to  Langley,  in  a 
visceral  nerve,  such  as  the  hypogastric,  only  about  one-tenth  of  the  medul- 
lated  fibres  are  afferent,  and  the  proportion  of  afferent  fibres  in  the  splanchnic 
nerves  is  probably  not  very  different  from  this.  At  the  two  ends  of  the 
alimentary  canal,  i.e.  at  the  mouth  and  anus,  the  afferent  visceral  fibres 
become  of  more  importance,  since  through  their  means  co-operative  somatic, 
reflexes  have  to  be  excited  as  well  as  the  simple  visceral  reflexes.  Thus  in  the 
pelvic  visceral  nerve  about  one-third  of  the  fibres  are  afferent,  and  the  vagi 
contain  a  large  number  of  afferent  fibres  from  the  lungs  as  well  as  from  the 
other  viscera  innervated  by  it. 

According  to  Dogiel,  afferent  visceral  fibres  arise  from  sensory  cells  of  the  sympathetic 
ganglia  and,  passing  in  to  the  posterior  spinal  ganglia,  divide  and  form  pericellular 
endings  round  a  special  type  of  posterior  root  cells,  the  axon  from  which  divides  again 
into  a  number  of  branches  winch  end  in  connection  with  typical  unipolar  cells.  Thus, 
according  to  this  observer,  a  few  afferent  sympathetic  fibres  can  stimulate  a  considerable 
number  of  posterior  root  cells.  Langley  however  has  not  been  able  to  obtain  any 
experimental  confirmation  of  the  origin  of  branching  afferent  fibres  from  cells  of  the 
sympathetic  system. 

It  is  probable  that  the  afferent  fibres  of  the  visceral  nerves  arise,  like 
those  of  the  somatic  system,  from  ganglion  cells  of  the  posterior  spinal 
ganglia.  Every  white  ramus  contains  afferent  fibres,  stimulation  of  which 
may  evoke  a  rise  of  blood  pressure  as  well  as  movements  of  the  skeletal 
muscles.  In  spite  of  the  supply  of  afferent  fibres  to  the  viscera,  most  of  these 
organs  are  very  insensitive  to  ordinary  stimulation  such  as  handling  or  cut- 
ting.    In  operations  on  man  for  resection  of  the  gut,  if  the  abdominal  cavity 


THE  AUTONOMIC  NEKVOUS  SYSTEM  477 

be  opened  under  local  or  general  anaesthesia,  subsequent  cutting  and 
suturing  of  the  gut  may  be  conducted  without  any  anaesthetic  and  with- 
out causing  any  pain  to  the  patient.  On  the  other  hand,  impulses  may 
arise  in  the  afferent  nerve-endings  of  the  viscera,  as  a  result  of  disease  or 
certain  forms  of  stimulation,  e.g.  stretching  or  compression,  which  may 
reach  consciousness  and  give  rise  to  the  sensation  of  pain.  This  pain  is 
not  localised  in  the  viscera,  but  is  referred  to  certain  parts  of  the  surface 
of  the  body.  When  the  afferent  autonomic  fibres  of  a  nerve  are  the  seat  of 
pain,  the  primary  referred  pain  is  in  the  area  of  the  cutaneous  somatic  fibres 
of  the  nerve.  It  has  been  shown  by  Mackenzie  and  by  Head  that  visceral 
disease  may  cause  hyper-sensitivity  of  the  corresponding  areas  of  the  skin, 
and  a  method  has  been  elaborated  by  these  observers  for  utilising  this 
referred  pain  or  skin  tenderness  as  a  means  of  localising  the  site  of  the 
disease. 


CHAPTER  VIII 

THE  SENSE   ORGANS 

PAGES 

Pakt  1. — Introduction           ...........  478 

Past  2.— Vision 486 

Part  3. — Hearing         ............  595 

Part  4. — Speech  and  voice   ...........  Iil8 

Part  5. — Cutaneous  sensations      ..........  627 

Part  Ij. — Taste  and  smell     ...........  640 

Part  7. — Movement  and  position  sense           ........  647 

Part  S. — Labyrinth  sense     ...........  652 

PART  I 

INTRODUCTION 

The  ability  to  originate  sensations  is  common  to  almost  all  parts  of  the 
body.  Thus  the  muscles,  joints  and  viscera  send  nerve  impulses  to  the 
brain,  which  record  their  well-being  and  activities.  We  can  classify 
the  sense  organs  into  two  main  groups,  those  which  belong  to  the  common 
sensibility  of  the  body,  and  those  which  form  the  special  senses.  The  char- 
acteristics of  the  former  are  (1)  that  they  rarely  send  impulses,  other  than 
those  of  pain,  which  pass  the  threshold  of  consciousness ;  (2)  that  they  play 
a  very  large  part  in  the  initiation  of  the  numerous  reflex  actions  ;  (3)  that 
when  their  impulses  do  reach  consciousness  they  lack  definition.  The 
characteristics  of  the  special  senses  on  the  other  hand  are  (I)  that  they  very 
frequently  send  impulses  which  reach  consciousness ;  (2)  that  the  con- 
nection between  the  stimulus  and  the  resulting  response  on  the  part  of  the 
individual  (as  expressed  by  movements  of  limbs,  etc.)  is  usually  not  of  a  reflex 
nature  ;  (3)  that  the  information  supplied  to  consciousness  is  very  definite 
both  as  to  quality  and  intensity. 

The  indefiniteness  of  the  connection  between  stimulus  and  response  causes 
us  to  depend  almost  entirely  on  introspection  in  our  study  of  the  sense- 
organs.  But  introspection  as  a  method  of  research  has  grave  disadvantages, 
for  we  cannot  measure  our  sensations  in  terms  of  physical  units.  We  cannot 
sav  how  red  a  rose  is  or  how  nice  it  smells.  Neither  can  we  compare  the 
intensity  of  a  beam  of  light  when  we  feel  its  warmth  on  our  skin  with  the 
strength  of  the  stimulus  which  we  receive  when  it  enters  our  eye.  Still 
less  can  we  judge  accurately  of  the  sensations  evoked  in  other  individuals 
or   animals   when   we    apply    stimuli  to  them.     Because  of  this  difficulty 

478 


THE  SENSE  ORGANS  479 

of  measuring  sensations  two  methods  of  investigation  have  been  developed  ■ 
which  to  a  great  extent  avoid  it,  namely  the  method  of  threshold  values  and 
the  method  of  comparisons. 

In  the  method  of  threshold  values  gradually  increasing  stimuli  are  applied 
to  the  sense  organ  under  investigation,  until  a  sensation  is  just  perceived. 
Thus  increasing  weights  are  applied  to  the  skin  until  their  pressure  is  felt,  or 
a  light  of  increasing  intensity  is  presented  to  the  eye  until  its  presence  is  seen. 
Such  threshold  values  give  definite  information  concerning  the  sense  organ 
to  which  they  refer,  and  allow  us  to  compare  the  same  effects  in  one  and  the 
same  sense  organ  under  different  conditions,  and  also  in  different  individuals. 

In  the  method  of  comparisons  two  separate  stimuli  are  applied,  and 
one  or  both  are  varied  until  the  sensations  caused  by  them  are  equal.  Thus 
a  ray  of  yellow  light  may  be  compared  with  a  ray  mixed  from  red  and  green 
light,  and  the  intensities  of  the  two  adjusted  until  the  sensations  caused  by 
both  are  similar.  Both  these  methods  give  concordant  results  if  care  be 
taken  to  make  the  conditions  standard,  and  both  are  for  this  reason  largely 
used  for  studying  the  sense  organs. 

A  careful  study  of  these  organs  is  necessary  and  important  because  it  is 
onty  through  their  agency  that  we  derive  information  about  ourselves,  one 
another,  and  the  world  in  which  we  live.  The  limitations  of  our  sense  organs 
there  fore  restrict  our  knowledge  of  the  many  transformations  of  energy  that 
are  going  on  around  us,  except  in  so  far  as  we  are  able  to  devise  means  of 
extending  them  artificially.  Thus  our  knowledge  of  the  existence  of  ultra- 
violet light  began  only  with  the  discovery  of  photography.  Wireless  waves 
circulated  through  the  ether  around  unknown  to  us  before  the  invention  of 
the  coherer. 

CLASSIFICATION  OF  SENSE  ORGANS.  Sense  organs  differ  in  their 
anatomical  position  and  structure  and  also  according  to  the  nature  of  the 
stimulus  to  which  they  react  and  the  kind  of  sensation  which  they  cause. 
Any  of  these  differences  might  be  used  as  a  basis  of  classification,  but 
the  latter  is  found  to  be  the  best. 

Structure.  Kind  of  Sensation. 

,    Touch  | 

cm  •  I    Pain  I    _    ,. 

Skin    ...  .....    Heat  Feeling 

V  Cold 

|    Light  | 

_  I    Colour  c-  ,  ^ 

Eye "I    sv..™  -  Sl8ht 


v  Distance      ' 

f  Tone  \ 

Ear     .  .  .  .  .         .  .  .     J    Harmony    \  Hearing 

(_  Position      J 

f   Acid 
Tongue         .......  Sweet  .  Taste 

(   Bitter  1 

Nose   ........  Smell 

Stimuli  adequate  for  one  sense  organ  are  found  to  be  inadequate  for 


480  PHYSIOLOGY 

■another.     Thus  sound  applied  to  the  ear  is  adequate  but  to  the  eye  is  not. 

The  sense  organs  ajjpear  to  be  elaborated  from  a  very  simple  type,  and 
the  higher  they  are  developmentally  the  more  is  one  kind  of  stimulus  adequate 
and  the  less  are  all  others. 

Thus  the  end  organs  in  the  cornea  react  alike  by  a  sensation  of  pain  to 
touch,  electricity,  heat,  inflammation,  &c,  while  the  ear  reacts  to  sound 
waves  only.  This  specific  property  of  the  end  organs  is  also  attended  by  an 
increase  in  the  strength  of  response  to  the  chosen  stimulus.  Thus  the  retina 
of  the  eye  can  be  stimulated  mechanically  and  electrically,  but  has  its  greatest 
sensitiveness  to  light.  It  is  estimated  that  the  eye  is  30,000  times  as 
sensitive  to  light  as  any  instrument  that  has  been  so  far  constructed.  This 
specialisation  of  the 'end  organs  makes  the  information  which  we"  obtain 
from  them  more  detailed  and  complete,  but  at  the  same  time  sets  a  limitation 
to  the  range  of  stimulus  to  which  each  can  respond.  Thus  a  pain  end  organ 
can  react  alike  to  heat  rays,  visible  rays  and  ultra-violet  rays,  while  the  retina 
of  the  eye  responds  to  visible  rays  only. 

THE  LAW  OF  SPECIFIC  IRRITABILITY.  A  very  little  consideration 
suffices  to  show  that  there  is  no  resemblance  between  a  sensation  and  the 
stimulus,  and  that  one  and  the  same  physical  event  applied  to  different 
sense  organs  will  evoke  absolutely  distinct  sensations  ;  whils  different  modes 
of  stimuli  applied  to  one  sense  organ  will  always  evoke  the  same  sensation. 
Thus  if  light  falls  on  the  retina  it  causes  a  sensation  of  light.  If  the  same 
radiant  energy,  consisting  of  transverse  vibrations  in  the  ether,  be  allowed 
to  fall  on  the  skin,  it  either  produces  no  sensation  at  all  or,  if  concentrated 
by  means  of  a  burning-glass,  may  give  rise  to  a  sensation  of  warmth,  heat, 
or  pain.  If  we  take  a  tuning-fork  which  is  vibrating  100  times  per  second 
and  apply  it  to  the  surface  of  the  skin,  we  get  simply  a  sensation  of  vibration, 
i.e.  a  series  of  tactile  impressions  repeated  at  rapid  intervals.  If  the  same 
tuning-fork  be  applied  to  the  head,  its  vibrations  are  imparted  to  the  bones 
of  the  skull  and  thence  to  the  auditory  nerve  endings  and  arouse  in  our 
consciousness  a  tone  sensation  of  a  certain  note.  The  same  thing  happens 
if  the  vibrations  of  the  tuning-fork  are  conducted  by  the  ear  to  the  auditory 
nerve  endings  in  the  ordinary  way  through  the  external  and  middle  ear. 
On  the  other  hand,  a  sensation  of  light  may  be  aroused  not  only  by  the 
incidence  of  radiant  energy  of  a  certain  wave  length  on  the  retina,  but  also 
by  electrical  or  mechanical  stimulation  of  the  retina.  If  the  eye  be  turned 
inwards  and  the  finger  be  pressed  on  the  eye  through  the  outer  canthus  of 
the  lids,  a  sensation  of  light  is  aroused  and  we  see  a  coloured  circle  which  we 
refer  to  some  spot  lying  to  the  nasal  side  of  the  eye  stimulated.  The  character 
of  the  sensation  bears  therefore  no  resemblance  to  the  physical  events  by 
which  the  sensation  is  evoked,  but  depends  entirely  on  the  nature  of  the 
sense  organ  which  is  stimulated.  A  sensation  of  lighf  may  be  produced  by 
any  stimulation  of  the  retina,  or  of  the  optic  nerve,  or  of  the  terminations 
of  the  optic  nerve  in  the  brain.  In  the  same  way  stimulation  of  an  auditory 
nerve  or  its  intracranial  endings  gives  rise  to  sensations  of  sound. 

Where  the  question  has  been  investigated  it  has  not  been  found  possible 


THE  SENSE   ORGANS  481 

to  evoke  different  qualities  of  sensation  by  different  modes  of  stimulation 
of  nerve  fibres,  and  it  has  therefore  been  concluded  that  the  quality  of  any 
sensation  depends  simply  and  solely  on  the  termination  of  these  nerves  in 
the  central  nervous  system,  and  that  where  sensations  of  different  quality 
are  produced  there  must  be  also  difference  of  nerve  fibres.  This  idea  was 
formulated  by  Miiller,  and  is  often  alluded  to  as  Midler's  '  law  of  specific 
irritability.'  The  law  states  that  every  sensory  nerve  reacts  to  one  form  of 
.stimulus  and  gives  rise  to  one  form  of  sensation  only,  though  if  under  abnor- 
mal conditions  it  be  excited  by  other  forms  of  stimuli,  the  sensation  evoked 
will  still  be  the  same. 

Although  the  different  forms  of  sensation  must  be  regarded  as  dependent 
on  the  integrity  of  the  brain,  and  of  its  connections  with  the  peripheral 
sense  organs,  sensations  are  not  referred  to  the  brain,  but  are  localised  as 
proceeding  from  some  part  of  the  body  or  from  some  region  outside  of  the 
body.  Thus  the  sensation  of  taste  is  always  localised  in  the  mouth  ; 
sensation  of  touch  at  the  skin  or  surface  of  the  body  ;  while  the  sensations 
of  hearing  and  of  sight  are  '  projected,'  i.e.  are  interpreted  as  coming  from 
the  environment  outside  ourselves.  Even  the  organic  sensations  of  posture 
or  fatigue  are  referred  to  the  peripheral  reacting  parts  of  the  body  and  not 
to  the  central  nervous  system.  A  sensation  therefore  cannot  be  interpreted 
as  a  reproduction  of  external  events,  but  as  a  symbol  of  these  events  evoked 
by  stimulation  of  the  sense  organs  of  the  body. 

CONSCIOUSNESS.  How  the  physiological  excitatory  process  in  nerve 
fibres,  with  its  concomitant  chemical  and  electrical  phenomena,  is  able  on 
arrival  at  the  brain  to  excite  a  conscious  sensation  we  are  unable  to  decidej 
or  even  to  discuss,  since  we  are  dealing  here  with  processes  of  two  different 
orders.  We  should  not  arrive  any  nearer  to  the  solution  of  this  riddle  if 
we  were  able  to  follow  out  the  whole  of  the  events  occurring  in  the  body  as 
the  result  of  the  application  of  any  given  stimulus  to  its  surface.  We  might 
under  these  circumstances  be  able  to  predict  with  certainty  the  behaviour 
of  any  animal,  if  we  knew  its  past  history  and  the  comparative  resistance  of 
every  path  in  its  central  nervous  system  which  might  possibly  be  traversed 
by  any  given  nerve  impulse.  Such  knowledge  would  be  purely  objective, 
and  could  not  be  used  to  explain  the  '  epiphenomenon  '  of  consciousness. 
One  might  in  fact  imagine  a  machine  which  would  react  like  a  living  animal, 
but  would  be  perfectly  devoid  of  self-consciousness,  and  we  should  be  unable 
in  such  a  case  to  decide  whether  consciousness  were  or  were  not  present. 
Each  one  of  us  only  knows  consciousness  as  it  exists  in  himself. 

It  is  indeed  impossible  by  a  purely  intuitive  study  of  sensations  to  arrive 
at  any  correct  idea  of  their  origin  or  of  the  factors  concerned  in  their  produc- 
tion. No  sensation  is  the  immediate  and  sole  jiroduct  of  a  stimulus  applied 
to  the  peripheral  end  of  a  nerve  fibre,  but  the  simplest  sensation  involves 
a  judgment,  i.e.  complex  neural  activities  which  are  the  resultant  of  innumer- 
able past  and  present  streams  of  nervous  impulses  aroused  by  peripheral 
events  and  poured  into  the  central  nervous  system.  It  is  important  there- 
fore not  to  regard  a  sensation  as  in  any  way  constituting  an  elementarv 

31 


482  PHYSIOLOGY 

unit,  by  the  aggregation  of  a  number  of  which  a  conscious  state  is  produced. 
As  we  have  seen,  the  primitive  function  of  the  whole  nervous  system  is 
reaction.  The  neural  life  of  an  animal  is  composed' of  a  series  of  reactions, 
some  simple,  some  complex,  and  becoming  ever  more  complicated  as  we 
ascend  the  animal  scale.  The  first  reactions  of  a  baby,  for  instance,  will 
be  those  by  which  it,  procures  nourishment  and  satisfies  a  need.  The  earliest 
event  in  its  dawning  consciousness  will  be,  not  a  sensation  of  sweetness  or 
of  colour,  but  that  of  a  thing  which  can  satisfy  its  needs.  It  will  have  had 
to  try  many  gustatory  experiments  before,  out  of  the  sum  of  its  material 
experiences,  it  will  be  able  to  choose  a  number  of  like  factors  which  can 
he  grouped  together  as  '  sweet.'  Judgment  of  quality  of  sensation  involves 
a  power  of  abstraction  and  of  classifying  similar  elements  in  different  neural 
events  or  reactions  and  the  referring  of  these  elements  to  the  external  world. 
It  is  very  difficult  however  to  divest,  ourselves  off  the  mental  standpoint 
reached  as  the  result  of  many  years'  continual  trials,  successes  and  failures, 
and  constant  care  has  to  he  exercised  if  we  are  not  to  fall  into  the  common 
conception  of  the  ego,  the  personality  or  soul,  as  a  sort  of  sentient  god  sit  t  bug 
somewhere  in  the  brain  or,  as  Descartes  suggested,  in  the  pineal  gland,  and 
receiving  by  means  of  one  part  or  other  of  his  servile  material  brain  a  blue 
sensation  from  the  eyes,  or  an  auditory  impression,  or  a  tactile  impression, 
and  then,  if  he  feels  so  inclined .  j  uessing  the  stop  in  a  pyramidal  cell  to  let  out 
a  voluntary  motor  response.  An  elementary  unit  in  psychical  life,  as  in 
neural  life,  must,  be  a  complete  reaction.  It  is  from  the  reaction  and  not 
from  the  sensation  that  a  constructive  psychology  will  have  to  be  built  up. 
RELATIONSHIP  BETWEEN  STIMULUS  AND  SENSATION.  Although 
the  sensation  is  not  a  reproduction  of  the  stimulus,  it  is  a  symbol  of  the 
stimulus,  and  can  be  used  to  inform  us  of  events  occurring  in  the  world 
around.  Like  stimuli,  falling  on  the  same  end-organ,  always  evoke  like 
sensations,  other  conditions  being  equal.  An  orderly  sequence  of 
sensations  may  therefore  be  interpreted  as  indicating  a  corresponding 
orderly  sequence  of  physical  occurrences  in  the  world  around  us.  Since 
our  sensations  are  merely  symbols  of  the  physical  conditions  which  give  rise 
to  them,  it  is  important  to  inquire  how  far  they  correspond  quantitatively  to 
differences  in  the  energy  of  the  afferent  stimuli,  i.e.  how  alterations  in  the 
strength  of  stimulus  will  affect  the  intensity  of  the  resulting  sensation. 
Whatever  form  of  stimulus  be  applied  and  whatever  sense  organs  be  affected, 
a  certain  minimum  intensity  of  stimulus  is  necessary  for  it  to  be  effective, 
i.e.  to  produce  a  minimum  sensation.  This  strength,  which  varies  with 
different  sense  organs,  is  spoken  of  as  the  '  liminal  intensity,'  or  '  threshold 
value  '  of  stimulus  or  sensation  respectively.  As  the  strength  of  the  stimulus 
is  increased  above  this  minimal  amount  the  resulting  sensation  also  increases. 
The  change  in  intensity  of  sensation  does  not  however  continue  indefinitely. 
When  the  stimulus  is  increased  to  a  certain  amount  the  resultant  sensation 
becomes  maximal,  and  a  further  increase  in  the  stimulus  evokes  no  further 
increase  in  sensation.  In  fact  fatigue  of  the  sense  organs  or  recipient 
centres  of  the  brain  rapidly  sets  in,  so  that  the  sensation  diminishes  even 


THE  SENSE  ORGANS  483 

with  increasing  strength  of  stimulus.  In  each  sense  organ  we  can  measure 
the  amount  of  energy  which  must  be  applied  to  it  in  order  to  evoke  a  minimum 
sensation.  This  figure  varies  considerably  with  the  physiological  condition 
of  the  animal.  In  dealing  with  reflexes  we  have  seen  that  the  motor  result 
of  stimulation  of  a  receptor  organ  varies  in  the  same  manner.  Thus  a  mini- 
mal stimulus  is  more  effective  if  repeated  a  few  times  at  definite  intervals 
(summation  of  stimulus)  :  the  stimulus  which  is  subminimal  may  become 
minimal  and  effective  as  a  result  of  repetition. 

Another  factor  which  intervenes  is  that  known  as  '  adaptation  ' — a 
process  associated  to  a  certain  extent  with  the  phenomenon  of  fatigue. 
Adaptation  is  best  studied  in  the  case  of  the  eye.  Here  the  dark-adapted 
eve.  i.e.  one  that  has  been  kept  from  lighf  for  half  an  hour,  will  react,  and 
give  a  visual  sensation,  to  a  strength  of  stimulus  which  is  only  one-fiftieth 
of  the  minimal  stimulus  required  to  evoke  sensation  in  the  eye  (hat  has  been 
lately  exposed  to  light. 

Another  phenomenon  which  may  alter  t  he  strength  of  the  liminal  intensity 
of  stimulus  is  that,  known  as  '  contrast,'  A  finger  plunged  into  mercury 
feels  a  ring  of  constriction  at  the  level  of  the  surface  of  the  mercury,  i.e. 
where  there  is  a  contrast  between  the  pressure  of  the  mercury  and  the 
absence  of  pressure  as  the  finger  emerges  into  the  air. 

The  strength  of  the  effective  stimulus  depends  also  on  tin'  number  of 
nerve-endings  simultaneously  excited.  Thus  when  dealing  with  tactile 
sensations,  or  sensations  of  pressure,  in  determining  the  minimal  stimulus, 
we  must  take  into  account  the  area  stimulated,  and  we  express  the  stimulus 
just  sufficient  to  produce  a  threshold  sensation,  as  'weight  per  square  milli- 
metre of  surface.'  Moreover  the  rapid  '  fatigability  '  or  adaptation  of  all 
sense  organs  makes  the  rate  at  which  the  stimulus  is  applied  of  considerable 
importance. 

WEBER'S  LAW.  It  is  an  interesting  question  how  far  the  strength  of 
sensation  may  be  regarded  as  an  index  to  the  strength  of  stimulus.  Although 
it  is  easy  to  measure  in  absolute  terms  the  intensity  of  a  stimulus,  i.e  of  a, 
purely  physical  process,  there  is  no  means  by  which  we  can  express  in  abso- 
lute measure  the  strength  of  a  sensation.  We  cannot  even  compare  the 
strengths  of  two  sensations  differing  in  quality  or  modality  ;  and  although 
we  can  say  that  such  and  such  a  light  is  stronger  than  another  light,  it  is 
impossible  to  say  that  the  sensation  resulting  from  the  stronger  is  t\\", 
three,  or  more  times  that  of  the  weaker.  In  measuring  the  effect  on  sensa- 
t  ion  of  increasing  the  stimulus  we  are  therefore  reduced  to  using  the  smallest 
appreciable  increase  of  sensation  as  our  unit  of  sensation.  The  question  as 
to  the  relation  between  the  intensity  of  stimulus  and  the  intensity  of  sensa- 
tion resolves  itself  into  an  inquiry  as  to  what  increase  in  a  given  stimulus 
is  necessary  in  order  that  it  may  evoke  an  appreciable  increase  in  sensation. 
Weber's  law  states  that  the  increase  of  stimulus  which  is  necessary  to  produce 
an  appreciable  increase  in  sensation  must  always  bear  the  same  ratio  to  the 
whole  stimulus.  Thus  if  we  found  that  we  could  just  distinguish  the  differ- 
ence between  a  weight  of  10  oz.  and  a  weight  of  9  oz.,  it  would  not  be  sufficient 


484 


PHYSIOLOGY 


to  add  one  ounce  to  a  weight  <>i  10  lb.  in  order  to  produce  ;i  distinct  difference 
in  sensation.  In  the  latter  case  we  should  not  be  able  to  appreciate  any 
difference  until  we  had  added  a  pound,  i.e.  one-tenth  of  the  whole  stimulus 
to  the  weight.  We  can  distinguish  between  10  oz.  and  11  oz.,  or  between 
10  lb.  and  11  lb.,  but  not  between  10  lb.  and  10  lb.  1  oz. 

Several  methods  have  been  proposed  for  testing  the  limits  of  the  applica- 
bility of  this  law.     Of  these  the  most  important  are  : 

(1)  The  method  of  minimal  difference. 

(2)  The  method  of  average  error. 

In  the  first  method  we  find  by  trial  how  much  a  given  stimulus  must  be 
increased  in  order  to  evoke  an  appreciable  increase  of  sensation,  and  this 
determination  is  made  for  a  number  of  stimuli  of  different  intensity.  In 
the  second  method  it  is  sought  to  find  a  strength  of  stimulus  which  is  just 
equal  to  another  stimulus  of  given  intensity.  It  will  be  found  that  errors 
will  be  made  on  both  sides,  and  the  average  error  is  taken  as  representing 
the  minimum  difference,  which  is  just  sufficient  to  cause  a  distinct  difference 
of  sensation. 

In  all  sense  organs  Weber's  law  is  applicable  only  between  limits  which 
vary  with  each  sense  organ,  and  it  does  not  hold  either  for  very  weak  or  for 
very  strong  stimuli.  Within  these  limits  the  ratio  which  an  increase  of 
stimulus  must  bear  to  the  whole  stimulus  in  order  to  produce  an  increase  of 
sensation  may  be  given  approximately  as  follows  for  the  different  sense 
organs  : 

When  weights  are  placed  on  corresponding  points  of  two  sides  of  the 
body,  e.q.  on  the  two  hands,  we  can  appreciate  differences  of  about  one- 
third  ;  if  the  contrast  be  successive,  i.e.  if  the  weights  be  placed  on  the  same 
spot  in  succession,  we  can  appreciate  differences  between  one-fourteenth 
and  one-thirtieth.  The  range  over  which  this  amount  of  accuracy  is  attained 
extends  from  50  to  1000  grammes.     In  judging  of  weights  with  the  help  of 


Fig.   242.     Diagram  to  show  relationship  between  stimulus  and  sensation. 

movement  (the  method  one  ordinarily  adopts)  the  limit  of  accuracy  is  about 
one-twentieth  ;  for  sounds  the  appreciation  of  difference  amounts  to  about 
one-ninth,     The  organ  which  is  most  susceptible  to  slight  changes  of  intensity 


THE  SENSE  ORGANS  485 

is  the  eye  ;  by  this  organ  we  can  appreciate  differences  of  one  one-hundredth 
to  one  one-hundred-and-sixty-seventh  in  the  total  illumination. 

FECHNER'S  LAW  gives  the  result  of  an  attempt  to  state  Weber's  law 
in  mathematical  terms.  It  states  that  the  sensation  varies  as  the  natural 
logarithm  of  the  stimulus.  This  relationship  is  shown  diagrammatical]}-  in 
Fig.  242. 

In  view  of  the  fact  however  that  Weber's  law  holds  good  only  between  certain 
limits,  not  much  practical  value  can  be  attached  to  such  a  mathematical  expression. 
Moreover  Pechner's  calculation  is  based  on  the  unprovable  and  unjustifiable  assump- 
tion that,  within  the  limits  of  applicability  of  Weber's  law,  the  smallest  appreciable 
increase  in  sensation  is  always  the  same,  i.e.  that  the  increased  sensation  which  is  evoked 
by  the  addition  of  6  grammes  to  a  weight  of  100  grammes  is  identical  with  the  increased 
sensation  called  forth  by  adding  60  grammes  to  an  initial  weight  of  1000  grammes. 
Such  an  assumption  does  not,  as  a  matter  of  fact,  agree  with  our  own  experience ;  and 
it  is  probably  premature  here,  as  in  many  other  departments  of  biology,  to  attempt 
to  include  the  complex  of  variable  phenomena  presented  by  animal  functions  within 
the  Procrustean  bed  of  a  mathematical  formula. 


PART  II 


VISION 
By  H.  Hartridge. 

Section  1. — Properties  of  light,  colour,  and  the  spectrum 
2. — Orbital  cavity  and  its  contents    . 
3. — Eyeball,  its  histology.     Pupil  reflex 
4.     Nutrition  and  protection  of  the  eyeball 
5. — Optical  media  of  eye,  and  accommodation     . 
6. — ( Iptical  properties  and  defects  of  the  eye 
7. — Retina,  its- histology  and  physiology     . 
8. — Response  to  light  and  colour 
9, — Subjective  phenomena  of  vision  . 
10.-   Defects  of  vision,  and  their  detection    . 
]  1 . — Duplex  theory  and  hypotheses  of  colour  vision 
12. — Binocular  and  stereoscopic  vision 


PAGES 
48U 
4fl3 
500 
514 
'519 
529 
540 
555 
563 
577 
5s3 
588 


SECTION   I 
PHYSICAL    PROPERTIES    OF    LIGHT 

Light  is  a  form  of  energy,  and  consists  of  electro-magnetic  waves  which  travel  with 
greal  velocity  through  the  ether.  Since  we  receive  light  from  the  stars,  we  conclude 
that  the  ether  permeates  the  whole  of  space.  We  know  also  from  electrical  experi- 
ments that  the.  ether  also  permeates  matter.  Wo  might  expect  therefore  that  light 
would  freely  pass  through  matter,  or  in  other  words  that  all  matter  would  be  trans- 
|i.i  n-nt.  This  is  not  the  case  however,  because  most  forms  of  matter  have  the  property 
of  absorbing  light  energy ;  and  therefore  the  jiroperty  of  transparency  is  relatively 
rare. 

LIGHT  IS  A  FORM  OF  WAVE  MOTION.  Because  of  this,  one  of  its  char- 
acteristic properties  is  amplitude.  But  since  this  depends  on  the  amount  of  light 
energy  present,  it  is  equivalent  to  what  is  known  as  intensity.  The  other  characteristic 
property  of  wave  motion  is  wavelength.  In  the  case  of  ordinary  light  it  is  found  by 
experiment  that  a  whole  gamut  of  waves  varying  greatly  in  length  is  present.  Those 
falling  between  certain  limits  are  able  to  stimulate  the  eye,  and  are  therefore  called 
visual  rays.  These  limits  are  slightly  less  than  8000  Angstrom  units*  for  the  longer 
limit  and  4000  A.U.  for  the  shorter.  Rays  whose  wavelength  falls  outside  these  limits 
are  invisible  to  the  eye,  and  are  called  infra-red  rays  when  they  are  too  long,  and 
ultra-violet  when  they  are  too  short.  Since  the  infra-red  rays  are  able  to  stimulate 
the  sensory  end  organs  of  the  skin,  which  respond  to  heat,  they  are  also  called  heat 
rays  ;  while  the  ultra-violet  rays  from  their  ability  to  perform  certain  chemical  re- 
actions, and  notably  those  used  in  photography,  are  called  actinic  rays.  There  is 
however  no  sharp  line  of  demarcation  between  the  three  groups,  which  the  use  of 
these  terms  might  be  thought  to  imply. 

THE  SPECTRUM.  It  is  possible  by  suitable  apparatus  to  cause  the  constituent 
rays  in  a  beam  of  light  to  arrange  themselves  according  to  their  wavelength.  When 
thus  arranged  they  are  said  to  form  a  spectrum.  The  apparatus  is  therefore  called 
a  spectroscope.     The  visible  lays  thus  arranged  are  seen  as  a  coloured  band  which  has 

*  An  Angstrom  unit  =  one  ten-millionth  of  a  millimeter. 
486 


PHYSICAL  PROPERTIES   OF  LIGHT  487 

the  following  appearance.  Visibility  usually  begins  at  about  8000-7800  A.U.,  the 
rays  of  longest  wavelength  being  red.  As  the  wavelength  becomes  shorter  the  colour 
gradually  changes  to  orange,  the  transition  being  at  6500  A.U.  nearly.  From  orange 
the  colour  changes  to  yellow,  at  6000  A.U.  nearly.  From  yellow  to  green  at  5500  A.U., 
to  blue-green  at  5000  A.U.,  to  blue  at  4500  A.U.,  and  to  violet  at  4000  A.U.  The 
violet  extends  to  3800  A.U.,  where  visibility  ceases.  The  spectrum  exhibits  therefore 
a  gradual  change  of  colour  with  wavelength.  Above  the  red  is  the  invisible  region 
ocoupied  by  the  infra-red  or  heat  rays,  and  below  the  violet  (he  invisible  ultra-violet 
or  actinic  rays,  as  explained  above. 

Tlie  colours  of  tin"  spectrum  have  important  properties  which  form  the  foundation 
of  the  science  of  colour  mixture.  If  the  spectrum  produced  from  white  light  is  caused 
tn  fold  up  again,  it  is  found  that  white  light  is  reformed.  But  white  light  is  produced 
if  certain  pairs  of  colours  only  are  caused  to  combine  in  the  correct  proportion.  Thus 
red  (0562  A.U.)  and  blue-green  (4921  A.U.)  when  mixed  correctly  form  white  light, 
so  also  do  yellow  (5636  A.U.)  and  violet  (4330  A.U.).  Such  pairs  are  called  comple- 
ments y  colours.  But  sir.ee  there  is  in  the  spectrum  a  gradual  transition  from  one 
colour  to  the  next,  so  there  are  between  red  and  yellow  an  infinite  number  of  rays 
of  different  wavelength,  each  of  which  has  its  complementary  colour,  between  blue- 
green  and  violet.  If  therefore  from  white  light  we  remove  one  of  a  pair  of  complemen- 
tary colours  the  other  member  of  the  pair  will  be  left  unneutralised,  and  the  light  there 
fore  becomes  tinted  with  its  colour.  Green  rays  do  not  possess  a  complementary  in 
the  spectrum  ;  but  it  is  found  by  experiment  that,  by  combining  red  ami  violet  to  form 
purple,  the  required  colour  may  be  produced.  If  we  include  purple  with  the  spectral 
colours,  we  can  imagine  these  colours  to  form  a  closed  ring.  Each  colour  will  then  have 
its  complementary  opposite  to  it. 

THE  SPECTRUM  COLOURS  have  another  important  property,  for  if  red  and 
yellow  are  caused  to  combine,  they  are  found  to  produce  orange,  the  intermediate  colour. 
If  red  and  green  arc  mixed,  then  again  the  intermediate  colour,  yellow,  may  be  produced. 
It  is  found  that  by  vary  ing  tin-  intensities  of  the  two  components,  it  is  possible  to  produce 
orange,  or  yellow-green,  or  in  fact  any  other  intermediate  colour  at  will.  Careful 
experiment  slums  that  the  intermediate  colour  thus  formed  is  no  mere  approximation 
but  an  exact  match.  If  red  and  green  are  thus  able  to  combine  to  form  the  intermediate 
colour,  while  led  and  blue  green  an  complementaries  producing  white  by  their  mixture, 
the  question  arises  as  to  the  elicit  produced  by  mixing  red  with  a  colour  intermediate 
between  green  and  blue  green.  Experiment  shows  that  a  range  of  colours  is  produced 
containing  an  amount  of  white  light,  which  varies  with  the  intensities  and  wavelengths 
i't  (he  combining  colours.  Colours  diluted  with  white  light  are  spoken  of  as  unsaturated. 
In  order  that  the  colours  produced  by  a  mixture  of  red  and  green  rays  shall  be  fully 
saturated,  and  thus  be  able  to  match  the  colours  of  the  spectrum  exactly,  the  green 
must  not  be  shorter  in  wavelength  than  5400  A.U.  Similar  phenomena  are  to  be  found 
at  the  oilier  end  of  the  spectrum  ;  green  and  violet,  when  mixed  in  various  proportions, 
form  colours  which  match  the  intermediate  spectral  colours.  With  red,  green  and  violet, 
it  is  therefore  possible  to  match  the  whole  spectrum.  But  since  red  and  violet,  when 
mixed,  form  the  intermediate  purples,  with  the  three  coloured  rays  it  is  possible  to 
imitate  the  whole  range  of  colours.  Now  the  purple  formed  from  red  and  violet  is,  as  we 
have  seen,  the  complementary  colour  to  green  ;  by  means  of  these  three  colours  it  is 
thus  possible  to  produce  white  light.  It  should  therefore  be  possible  to  match 
an  unsaturated  colour  as  easily  as  a  saturated  one.  Experiment,  shows  thai  such  is 
l  he  case.  The  third  property  beside  colour  and  saturation,  is  intensity,  which  depends 
on  the  amplitude  of  the  waves.  The  intensity  of  the  mixture  formed  by  red,  green 
and  violet,  can  therefore  be  readily  adjusted  by  varying  the  intensity  of  each  of  the 
three  component  rays.  We  may  summarise  the  above  facts  by  stating  that  by  varying 
the  intensities  of  the  red,  green  and  violet  rays  it  is  possible  to  match  every  shade  and 
colour.  This  statement  has  been  put  to  the  test  by  Maxwell,  Abney  and  ol  her  observers, 
and  has  been  found  to  hold  good  in  all  cases  but  one,  spectral  blue  being  slightly  more 


488  PHYSIOLOGY 

saturated  than  the  mixture  of  green  and  violet.  In  describing  the  complementary 
pairs  of  colours,  we  have  mentioned  that  if  the  spectral  colours  are  placed  in  a  closed 
ring,  complementary  pairs  are  found  to  be  opposite  to  one  another.  If  now  the 
three  fundamental  colours  are  placed  at  equal  intervals  round  the  ring,  we  may 
regard  white  as  occupying  the  centre,  because  it  is  equidistant  from  the  three  fundamen- 
tals, and  at  the  same  time  lies  on  the  diameter  between  the  various  colours  and  their 
complementaries.  If  the  other  spectral  colours  are  arranged  in  position  relatively 
to  the  three  fundamentals,  they  form  a  figure  that  in  shape  resembles  a  triangle  more 
closely  than  it  does  a  ring.  This  is  due  to  the  facts  already  mentioned  (1)  with  regard 
to  flic  exact  matching  of  the  spectral  colours  between  red  and  green,  by  mixtures  of 
those  two  fundamental  colours :  (2)  with  regard  to  the  approximate  matching  of  the 
region  between  green  and  violet  by  the  mixtures  of  those  colours,  and  (3)  with  regard  to 
the  exact  matching  of  mauves  and  purples  by  mixtures  of  red  and  violet.  The  colour 
triangle  which  is  shown  in  figure  243  therefore  has  a  purely  experimental  basis,  and 
lias  no  association  whatever  with  theories  of  vision. 


sooo 

BLUB  GRCEM 


KED    saoo 


Fig.  243.     Colour  triangle. 
The  black  hue  shows  the  shape  of  the  curve  along  which  the  different  rays  of 
the  spectrum  fall  for  white  to  occupy  the  central  position. 

THE  OPTICAL  PROPERTIES  OF  MATTER 

Since  matter  is  permeated  by  the  ether,  we  should  expect  matter  to  be  transparent 
to  light.  We  find  however  that  all  matter  absorbs  light  to  a  greater  or  less  extent; 
even  substances  that  are  called  transparent,  like  glass  and  water,  absorb  strongly  when 
in  sufficient  thickness.  Beside  substances  which  may  be  classed  as  transparent 
or  opaque,  there  is  a  large  class  of  bodies  which  reflect  light.  When  the  body  presents 
a  smooth  surface  to  the  fight  rays,  the  reflected  ray  forms  a  compact  bundle,  and  the 
surface  is  therefore  said  to  reflect  light.  If  on  the  other  hand  the  surface  presented 
to  the  light  rays  is  rough,  the  light  bundle  is  split  up  into  a  number  of  separate  units 
which  scatter  diffusely  in  every  direction.  Such  a  surface  is  therefore  said  to  diffuse  or 
scatter  light.  If  light  is  incident  on  matter,  there  are  thus  four  different  processes  t  ha  t 
may  occur,  viz.  the  light  maybe  partiallyabsorbed.it  maybe  partially  transmitted, 
it  may  In-  partially  reflected  and  lastly  it  may  be  partially  scattered.  In  the  great 
majority  of  cases,  all  these  processes  take  place  to  a  certain  extent,  and  are  found  to  affect 
the  different  parts  of  the  spectrum  differently.  For  example,  while  the  colours  of  short 
wavelength  are  absorbed,  those  of  long  wavelength  may  be  almost  completely  reflected. 
(A  polished  copper  surface  is  found  to  have  these  properties.)  Another  example  would 
be  a  substance  which  while   absorbing  colours  of  long  wavelength,  scatters  almost 


PHYSICAL  PROPERTIES   OP  LIGHT  489 

completely  all  colours  which  belong  to  the  other  end  of  the  spectrum.  (Basic  acetate 
of  copper,  i.e.  verdigris,  has  this  property. )  Lastly  t  he  case  of  a  fluid  may  be,  given  which 
absorbs  colours  in  the  middle  of  the  spectrum,  while  it  transmits  freely  those  at  the 
ends.  The  light  transmitted  is  therefore  violet  in  colour,  (as  the  appearance  of  a  solution 
of  potassium  permanganate  or  methyl  violet  shows.)  Colour  is  thus  due  in  every  case 
to  some  difference  in  the  behaviour  of  the  substance  towards  the  various  rays  of  the 
spectrum.  In  order  to  complete  the  description  of  colour  formation,  two  other  methods 
should  be  described  by  which  colour  may  be  produced,  namely  fluorescence  and  pJios- 
phorescence.  The  former  term  is  applied  when  a  substance  absorbs  light  of  one  colour, 
and  at  the  same  time  emits  light  of  another.  The  latter  is  applied  when  a  substance 
emits  light   for  an  appreciable  time  after  the  exciting  light  stimulus  has  ceased. 

LIGHT  SOURCES  fall  into  two  classes,  those  which  emit,  radiant  energy  because 
of  the  high  temperature  to  which  they  have  been  raised,  and  those  which  are  excited  in 
other  ways.  The  light  from  the  former  class  as  a  rule  consists  of  rays  of  all  wavelengths, 
IK  an  the  longest  heat  rays  to  the  shortest  ultra-violet.  The  light  from  the  latter 
class  on  the  other  hand,  is  frequently  found  to  consist  of  rays  corresponding  to  char- 
acteristic regions  of  the  spectrum.  The  mercury  vapour  lamp  may  be  mentioned  as 
an  example  of  the  latter  typo  of  light  source,  which  has  come  into  general  use.  If 
the  \  ir-i I >!< -  spectra  obtained  from  a  few  light  sources  of  the  first  type  are  carefully 
measured,  it  is  found  that  although  rays  of  all  wavelength  are  present,  there  are  con- 
siderable  variations  in  the  intensities  of  the  different  rays.  This  causes  variation  not 
only  in  the  colour  of  the  light  as  a  whole,  but  also  affects  the  colour  of  objects  and  the 
case  with  which  the  eye  can  judge  vol. airs.  This  variation  in  the  distribution  of  intensity 
in  the  spectrum  is  found  to  be  accompanied  by  corresponding  changes  in  the  infra- 
red ami  ultra-violet.  For  equal  visual  intensity,  as  the  temperature  of  the  source  is 
increased,  the  greater  is  the  amount  of  ultra-violet  light  and  the  less  is  the  infra-red. 
Moreover  as  the  temperature  is  raised,  the  w  hiter,  and  therefore  the  more  like  daylight, 
does  t In-  light  become.     Measurements  of  the  energy  present  in  different  parts  of  the 


HEAT  VISUAL  ACTINIC 

PlO.  244.     Curves  shewing  relative  energy  and  luminosity  of  different  regions  of 
the  spectrum. 

spectrum  show  that  much  the  greater  part  of  the  energy  is  present  in  the  infra-red. 
These  heat  rays  play  no  useful  part  in  vision,  and  may  in  fact  do  harm  ;  the  greater 
part  of  the  energy  is  thus  wasted,  and  for  this  reason  the  efficiency  of  this  class  of 
light  source  is  very  low.  Since  raising  the  temperature  of  the  light  source  causes  the 
light  to  approximate  more  closely  to  daylight  and  at  the  same  time  reduces  the 
relative  amount  of  the  infra-red  rays,  it  effects  considerable  advantage  because  it 
increases  efficiency. 

THE  ENERGY  IN  THE  SPECTRUM  is  present  in  greatest  amount  at  the  red 
end,  and  least  at  the  violet.  In  spite  of  this  the  part  of  the  spectrum  with  the  greatest 
luminosity  to  the  eye  is  the  yellow.  The  values  obtained  by  Abney  are  shown  in 
figure  244. 

DIFFRACTION    AND    REFRACTION.     Beside  the  properties  of  light  that  have 


400  PHYSIOLOGY 

been  already  considered,  namely,  the  relationship  between  actinic,  visual,  and 
heat  rays,  and  the  effects  of  colour  mixture,  there  are  others  of  importance 
to  vision.  (1)  The  property  of  travelling  in  straight  lines;  (2) '  of  suffering 
refraction;  (3)  of  causing  chemical  change.  The  first  property  can  be  easily  demon- 
strated by  investigating  shadow  formation.  But  it  should  be  noted  that  straight  line 
propagation  is  only  approximate,  for  it  can  be  shown  that  at  the  edge  of  a  light  ray 
there  may  be  considerable  deviation.  This  effect  is  called  diffraction,  and  will  lie  con 
sidered  in  greater  detail  later.  The  second  property,  namely  that  of  suffering  refraction, 
is  found  to  take  place  whenever  light  travels  from  a.  medium  of  one  optical  density 
(refractive  index)  into  that  of  another.  Briefly,  refract  ion  consists  of  a  deviation  of 
the  light  rays  towards  the  normal  to  the  surface,  when  entering  a  denser  medium,  and 
away  from  the  normal  on  entering  a  lighter.  Rays  of  long  wavelength  tend  to  keep 
their  original  direction  more  than  those  of  short  wavelength.  Red  rays  are  therefore 
less  refracted  than  orange  rays,  and  orange  less  than  yellow,  and  so  on  according  to 
wavelength.  It  is  in  this  way  that  the  spectrum  is  formed  in  the  special  apparatus 
for  experiments  on  colour  mixture  referred  to  above.  But  the  most  important  effect 
of  refraction,  from  the  point  of  view  of  vision,  is  the  formation  of  an  image  by  a  lens. 
This  action  may  be  briefly  explained  by  considering  what  will  happen  to  a  beam  o! 
light,  when  it  encounters  a  mass  of  high  optical  density  having  a  convex  Bpherical 
surface.  Since  the  rays  on  entering  are  deviated  towards  the  norma]  to  the  surface, 
it  is  clear  that  rays  that  have  entered  near  the  edge  of  the  lens  will  he  bent  towards  one 
another,  and  will  therefore  approach  as  they  travel  through  the  lens  substance,  till 
they  ultimately  meet  at  the  loins  u  ith  all  the  other  rays  that  have  entered  the  lens  from 
tin-  same  source  as  themselves.  Hut  if  there  he  a  number  of  different  sources,  then  the 
rays  from  each  are  found  to  form  their  own  focus,  af  a  position  that  may  be  determined 
either  by  experiment  or  by  the  rules  of  geometry.  The  positions  of  the  different  foci 
are  found  to  bear  the  same  relationship  to  one  another  as  (hose  of  the  original  sources, 
or  iii  other  words  an  image  is  produced.  This  important  subject  will  he  found  referred 
to  again  in  greater  detail  in  section  5. 

PHOTO-CHEMICAL  CHANGE,  which  is  the  third  property  of  light  mentioned 
above,  is  well  illustrated  by  photography.  The  most  important  principle  of  light  action 
is  that  light,  to  cause  chemical  change,  must,  be  absorbed  (Draper's  law).  For  example, 
an  ordinary  photographic  plate  which  is  found  to  be  opaque  to  blue  violet  and  ultra 
violet  rays,  and  to  be  transparent  to  the  rcsl  of  the  visible  spectrum,  is  therefore  sensitive 
to  the  former  rays  but  inactive  to  the  latter.  Further  by  colouring  the  plate  by  a 
dye  which  absorbs  nil,  yellow  and  green,  it  is  possible  lo  make  the  plate  react  to  these 
rays.  Draper's  law  is  therefore  obeyed.  Chemical  reactions  caused  by  light  are  of 
many  types,  but  ma\  he  divided  into  reversible  and  irreversible.  The  former  type 
of  reaction  occurs  only  so  long  as  the  light  acts  (the  change  from  CO  to  oxyluemoglobin 
may  be  given  as  an  example),  while  the  latter  type  remains  in  the  final  state  that  has 
been  reached  (the  changes  in  a  photographic  plate  may  be  given  as  an  example).  There 
is  further  another  and  more  complicated  type  which,  when  once  started  by  an  incident 
beam  of  light,  goes  on  automatically  with  an  evolution  of  energy  until  the  reaction  is 
completed.  These  effects  of  light  are  probably  of  great  importance  in  connection  with 
vision  and  will  therefore  receive  further  consideration  later. 

THE  MECHANISM  OF  VISION 

The  organ  of  vision  makes  use  of  the  properties  of  light  which  have  been  above  de- 
scribed,and  we  may  briefly  consider  the  form  that  such  an  organ  would  take.  Tocom- 
mence  with,  there  must  be  some  method  of  causing  light  to  stimulate  the  end  of  a  nerve. 
I  me  possible  scheme  would  be  to  connect  the  nerve  to  a  modified  taste  bud,  which  had 

been  selected  for  its  sensitiveness  to  the  presence  of  a  chemical  substance  called  A.  If 
this  substance  A  is  formed  when  light  acts  on  another  substance  B,  so  long  as  light  is  in- 
cident A  is  being  formed  and  the  end  "I  thenerve  is  being  stimulated.  With  cessation  of 
the  light  however  B  is  reformed  from  A,  and  the  stimulus  to  the  nerve  at  once  ceases.  The 


PHYSICAL  PROPERTIES  OF  LIGHT  491 

mechanism  must  now  be  further  elaborated  in  order  to  permit  of  the  separate  apprecia- 
tion of  at  least  three  different  fundamental  colours.  Two  courses  are  open  to  us : 
we  may  either  provide  three  chemical  reactions  instead  of  one,  each  of  which  responds 
to  light  of  one  fundamental  colour,  and  may  assume  that  the  end  organ  is  able  ac- 
curately to  determine  the  amount  of  each  of  the  three  breakdown  products  present;  or 
we  may  provide  three  times  the  original  number  of  nerves  and  end  organs  and  place 
them  behind  colour  niters,  similar  to  those  used  in  three-colour  photography.  Which- 
ever method  be  adopted,  we  should  rind  we  had  added  considerably  to  the  complexity 
of  the  sensitive  apparatus.  Such  an  apparatus  by  itself  would  form  a  very  inefficient 
organ  of  vision  because  it  would  record  only  the  average  quality  of  the  light  which  fell 
on  it.  Some  additional  mechanism  is  required  by  which  the  direction  from  which  the 
light  rays  come  may  be  inferred.  Probably  the  simplest  method  would  be  to  place 
each  end  organ  at  the  bottom  end  of  a  narrow  box,  the  top  end  of  which  is  open  while 
the  sides  are  covered  w  ith  a  black  material  in  order  to  prevent  reflections.  By  arranging 
these  boxes  radially  in  relation  to  a  common  centre,  the  apparatus  would  be  capable  of 
'localising  the  direction  of  a  light  source.  (This  is  roughly  the  arrangement  found  in 
the  faceted  eyes  of  insects.)  (See  Fig.  251a.)  Although  such  a  visual  organ  can 
be  astonishingly  efficient  (one  need  only  mention  the  case  of  certain  dragon-flies,  in 
which  the  faceted  elements  number  12,000  to  17,000),  yet  there  can  be  no  question  that 
the  use  of  some  sort  of  optical  system  which  could  produce  a  focussed  image  of  external 
objects  en  flic  sensitive  surface  or  retina  would  be  better  still.  The  employment  for 
this  purpose  of  a  mass  of  high  refractive  index  with  a  spherical  anterior  surface  at  once 
suggests  itself.  Certain  complications  are  however  introduced  at  the  same  time, 
namely  the  necessity  of  changing  the  focus  or  accommodating  for  images  at  different 
distances,  and  of  automatically  controlling  this  mechanism  in  order  that  no  mental 
effort  may  be  required  for  focussing.  In  order  that  such  an  apparatus  may  be  employed 
with  light  of  different  intensity,  it  is  necessary  to  be  able  to  control  the  amount  of  light 
allowed  to  reach  the  sensitive  surface.  This  could  be  effected  by  introducing  a  senii- 
opaque  screen  such  as  the  nictating  membrane  of  the  bird;  a  better  plan  would  be 
h'iwe\  ei'  to  employ  an  opaque  screen  with  an  aperture  of  adjustable  size  in  it,  because,  as 
will  be  shown  later, by  this  means  we  can  reduce  flu-  effects  of  chromatic  and  other aber 
rations.  Since  the  rays  which  pass  through  the  centre  of  the  refracting  body,  or  lens. 
pass  through  undeviated  and  therefore  with  the  least  amount  of  aberration,  the  best 
pi  ice  for  the  aperture  would  be  immediately  opposite  the  centre  of  the  lens,  and  for 
Bimilar  reasoning  its  best  shape  is  found  to  be  circular.  The  diameter  of  this  aperture 
must  be  automatically  adjustable,  according  to  the  intensity  of  the  illumination  falling 
on  the  sensitive  surface  of  the  eye,  in  order  that  its  action  may  be  independent  of  mental 
effort.  We  may  now  conveniently  consider  for  a  moment  the  utility  of  such  an  organ 
of  vision  to  its  owner.  In  the  first  place  he  will  be  able  to  recognise  the  presence  of 
objects  sending  light  of  different  intensity  and  colour  into  his  organ  of  vision.  Move- 
ment on  their  put.  relative  to  himself,  will  be  at  once  perceived,  because-  of  change 
in  the  size  and  position  of  tin-  area  of  the  retina  which  is  receiving  stimulation.  Owing 
further  to  the  way  that  their  images  either  intercept,  or  are  intercepted  by,  the  images 
of  other  objects  near  them,  he  will  be  able  to  infer  their  relative  position  in  space, 
and  the  distance  at  which  they  are  placed  from  him.  This  estimate  will  however  be 
very  vague,  and  therefore  the  judgment  of  size  will  be  equally  uncertain.  In  the  second 
place  we  must  assume  that  the  whole  of  the  retina,  which  we  have  described,  is  equally 
sensitive  everywhere,  and  that  further  the  image  formed  on  it  by  the  lens  system  is 
equally  sharp  throughout.  There  will  thus  be  a  very  complicated  picture  of  external 
objects  presented  to  the  consciousness  of  its  owner,  and  it  will  be  correspondingly  difficult 
for  him  to  concentrate  his  attention  on  some  particular  pari  of  the  visual  field  to  the 
partial  exclusion  of  the  rest.  His  organ  of  vision  therefore  requires  two  further  improve 
ments,  one  to  increase  the  effioiency  of  the  appreciation  of  distance,  the  other  to 
increase  his  power  of  concentration,  The  first  might  be  obtained  bygreatlj  increasing 
the  ensithcness  of  the  mechanism  of  accommodation,  since  thefocui  i   altered  i ling 


492  PHYSIOLOGY 

to  the  distance  at  which  an  object  is  placed.  Such  a  me1  hod  would  be  found  ineffective 
except  for  relatively  near  objects  however,  because  of  the  small  change  of  focus  which 
is  involved.  A  superior  method  would  be  to  endow  a  particular  part  of  the  retina  with 
increased  sensitiveness,  next  to  provide  two  complete  organs  of  vision  instead  of  one, 
both  capable  of  rotation  in  all  directions,  and  then  to  mount  them  as  far  apart  as 
possible,  so  that  as  they  are  turned  relatively  to  one  another,  in  order  to  view  near  or 
distant  objects,  the  amount  of  such  relative  deviation  may  be  estimated  and  so  a  means 
be  provided  of  appreciating  distance.  But  the  provision  of  increased  sensitiveness  in  a 
particular  part  of  the  retina  also  tends  to  diminish  the  disturbing  effects  of  the  rest  and 
therefore  improves  at  the  same  time  the  power  of  concentrating  the  attention  on  a 
particular  object.  This  in  its  turn  greatly  simplifies  the  task  of  producing  the  lens  system, 
which  forms  the  image  of  external  objects,  since  only  a  part  of  the  image  is  required 
to  have  the  maximum  sharpness,  namely  that  corresponding  to  the  most  sensitive 
region  of  the  retina,  this  part  being  always  used  whenever  an  object  of  particular 
interest  is  being  examined.  In  order  to  employ  a  simple  lens  system  to  the  greatest 
advantage,  that  part  of  tin-  image  should  be  used  which  lies  immediately  in  front  of  I  lie 
axis  of  the  lens  :  for  it  is  here  that  the  best  definition  is  found.  The  most  sensitive  part 
of  the  retina  should  be  placed  therefore  in  this  position.  It  remains  to  describe  a  further 
improvement  which  may  be  effected  in  the  perception  of  distance,  when  a  pair  of  eyes 
are  used  which  move  in  co-ordination.  Suppose,  for  example,  that  there  are  two  objects 
one  more  distant  than  the  other,  which  appear  to  the  right  eye  to  lie  in  line.  Then  to 
the  left  eye  the  more  distant  one  will  appear  to  lie  to  the  left  of  the  other.  There  is 
thus  a   relative   displacement  of   the  two  images   of   the  objects,  which  will   be  found 

to  increase  as  the  distance  between  the  objects  increases.     If  tl bjects  do  not  appear 

in  line  to  either  of  the  eyes,  it  will  still  be  found  that  there  is  a  constant  difference  between 
the  positions  of  the  two  images  formed  on  the  retinse.  If  there  be  a  suitable  mechan- 
ism for  estimating  the  amount  of  this  displacement,  there  is  at  once  provided  a 
very  accurate  method  of  judging  distance.  One  form  which  this  mechanism  could  take 
will  be  considered  later. 

In  the  development  of  a  hypothetical  organ  of  vision,  which  has  been  traced  above 
from  a  simple  and  inefficient  to  an  elaborate  and.  improved  type,  we  have  seen  that  each 
modification  had  to  be  introduced  in  order  to  make  use  of  the  application  of  some  well- 
known  physical  property;  not  once  has  the  impossibility  of  obtaining  some  obvious 
beneficial  feature  to  be  faced.  The  eye  as  we  find  it  in  man  is  almost  identical  with 
this  organ  which  we  have  developed  as  it  were  from  first  principles.  The  eye  therefore 
provides  an  excellent  example  of  the  efficiency  with  which  evolution  has  been  controlled 
by  natural  laws,  and  of  the  small  extent  to  which  the  limitations  of  the  materials  avail- 
able have  prevented  the  introduction  of  desirable  features. 


SECTION  II 

EYE    MOVEMENTS 

ANATOMY    OF    THE    ORBIT 

The  eyeball  and  its  accessory  structures  lie  in  the  bony  orbital  cavity, 
Burrounded  and  padded  by  a  mass  of  semiliquid  fat.  The  cavity  is  pierced 
by  several  apertures,  through  which  pass  various  vessels  and  nerves.  The 
optic  nerve  enters  through  an  aperture  of  its  own,  the  optic  foramen,  together 
with  the  ophthalmic  artery.  Most  of  the  other  nerves  and  vessels  concerned 
with  vision  pass  through  the  sphenoidal  fissure.  These  are  the  3rd, 
4th  and  6th  motor  nerves  which  innervate  the  muscles  controlling  eye 
movement,  sensory  branches  of  the  upper  division  of  the  5th  nerve, 
connected  with  the  cornea,  conjunctiva,  lids,  etc.,  and  the  ophthalmic 
veins.  In  order  to  allow  the  eye  free  movement  the  surrounding  structures 
form  with  it  a  ball-and-socket  joint.  The  joint  cavity  is  formed  by  a  pouch- 
shaped  structure  called  the  capsule  of  Tenon.  This  pouch  surrounds  the 
posterior  four-fifths  of  the  eyeball,  in  fact  its  folded  margin  touches  the 
ocular  conjunctiva.  The  pouch  is  made  of  a  tough  smooth  membrane,  and 
contains  synovial  fluid  so  as  to  allow  the  eye  the  greatest  freedom 
of  movement.  Since  the  six  muscles  which  cause  the  eye  movements  arc 
attached  to  the  bony  wall  of  the  orbit  behind  and  to  the  front  portion  of 
the  globe  in  front,  it  is  clear  that  the  tendons  of  the  muscles  must  pierce 
the  capsule.  This  is  done  in  a  very  admirable  maimer,  so  as  to  allow  free 
movement  and  at  the  same  time  to  prevent  escape  of  synovial  fluid.  Moreover 
the  edges  of  the  apertures,  through  which  the  tendons  enter,  form  strong, 
Imnds  which  are  attached  to  the  bony  walls  of  the  orbit.  These  bands  act 
as  check  ligaments,  preventing  excessive  movement  on  the  part  of  the 
muscles.  Tenon's  capsule  contains  numerous  smooth  muscle  fibres  which 
are  innervated  by  sympathetic  nerves  from  the  cavernous  plexus,  via,  the 
ciliary  (lenticular)  ganglion  and  the  long  ciliary  nerves.  Stimulation  of  the 
nerves  described  causes  contraction  of  these  muscle  fibres,  protrusion  of  the 
eyes  and  rise  of  intraocular  pressure.  But  the  most  important  function  of 
these  fibres  is  that  by  their  tone  they  prevent  the  eye  from  being  dragged 
back  into  the  socket  by  the  contraction  of  the  external  muscles.  One  of  the 
explanations  of  the  protrusion  of  the  eyes  in  exophthalmic  goitre  is  given 
to  he  the  stimulation  of  the  sympathetic  nerves  in  the  neck  by  the  local 
pressure  of  the  thyroid  tumour,  and  it  is  said  that  removal  of  the  superior 
cervical  ganglion  relieves  the  condition. 

With  regard  to  the  position  of  the  centre  of  rotation  of  the  eye  it  might 

493 


494 


PHYSIOLOGY 


be  though!  that,  since  the  eye  forms  a  ball  and  socket  joint,  1  he  centre  of  rota 
tion  would  be  at  the  geometrical  centre  of  the  eyeball.  Careful  measuremenl 
shows  that  such  is  very  nearly  the  case.  The  amount  of  rotation  of  the  eyes 
is  considerable,  being  1S8  degrees  in  a  horizontal,  and  80  degrees  in  a  vertical 
plane.  If  the  sphericity  of  the  globe  of  the  eye  is  destroyed  through  disease. 
myopia  for  example,  then  it-  is  found  that  rotation  is  impaired. 

ANATOMY    AND    FUNCTION    OF    THE    EXTERNAL    MUSCLES    OF 
THE    EYEBALL 

The  six  external  ocular  muscles  produce  cotati if  the  eyeball ;  four  are 

called  recti  and  two  oblique.  The  recti  arise  from  a  fibrous  ring  attached 
to  the  margin  of  the  optic  foramen,  and  pass  forward  to  meel  the 
eyeball  at  its  equator,  where  they  form  tendons.  These  having  passed 
through  Tenon's  capsule  are  attached  to  the  sclera  about  ti  mm.  behind  the 
corneal  margin.  From  the  positions  they  occupy  they  are  called  superior, 
inferior,  external  and  internal.  When  they  contract  they  will  cause  upward, 
downward,  outward  and  inward  rotation  of  the  eyeball  respectively. 
In  the  case  of  the  first  two  muscles  there  is  a  turning  movement 
inwards  at  the  same  time;  this  is  due  to  the  muscle  attachment 
round  the  optic  foramen  being  on  the  inner  side  of  the  back  of  the  orbit, 
since  the  muscles  can  cause  rotation  only  in  the  directions  which  their  tendons 
take.  Tn  addition  to  the  above  movements,  and  for  the  same  reasons,  there 
is  a  very  small  amount  of  rotation  of  the  eye  about  the  visual  (antero-posterior) 
axis  in  the  case  of  the  superior  and  inferior  recti,  the  directions  in  both  cases 


FR.ONT      VIEW 


Fig.  245.    The  anatomical  position  of  the  external  muscles  in  respect  to  the  eyeball. 

being  obvious  from  the  directions  of  the  pull  of  the  muscles.  Figures 
245  and  246  show  the  above  diagrammatically.  The  two  oblique  muscles, 
the  superior  and  inferior,  are  both  smaller  than  the  recti.  The  former  arises 
near  the  optic  foramen,  and  passes  forward  to  the  upper  and  inner  side  of  the 
orbit,  forming  on  its  way  a  round  tendon.  It  here  passes  through  a  narrow 
fibrous  ring,  and  then  turns  downwards  and  backwards  under  the  superior 


EYE  MOVEMENTS  495 

rectus  and  becomes  attached  to  the  eyeball.  The  inferior  arises  from  the 
nasal  side  of  the  orbit,  just  within  its  lower  margin.  It  passes  outwards 
and  backwards  beneath  the  inferior  oblique  to  become  attached  to  the 
eyeball  nearly  opposite  to  the  attachment  of  the  superior  oblique.  On  con- 
traction of  the  superior  oblique  the  upper  side  of  the  eye  is  rotated  towards 
the  nose  ;  at  the  same  time  the  pupil  is  directed  slightly  downwards  and  out- 


OBLIQUE 


fir  sent 


(IV  n)«J 


shewing  the  directions  in   which  the  different  external  eye 
inn    iles  i  ■iili'  the  eyeball. 

wards.  The  inferior  oblique  alsocauses  rotation  about  the  visual  axes,  but 
in  the  opposite  direction ;  i1  at  tin'  same  time  produces  upward  and  mil  ward 
movement  of  the  pupil.  The  function  of  these  two  small  muscles  appears  to 
be  to  prevent  the  eyes  from  rotating  about  their  visual  axes,  and  in  particular 
to  prevent  the  rotation  inwards  which  is  associated  with  the  contraction 
of  the  superior  and  inferior  recti.  For  this  purpose  the  superior  rectus  is 
associated  with  the  inferior  oblique  and  vice  versa.  In  this  action  theoblique 
muscles  appear  to  be  very  efficienl  :  for  if  the  eye  is  first  fatigued  by  looking 
at  a  brilliant  line  ot  light,  e.g.  a  long  straight  electric  lamp  filament,  and  is 
then  directed  upwards  or  downwards  at  a  white  surface,  the  after  image  thus 
produced  is  always  found  to  keep  its  vertical  direction. 

On  tilting  the  head  suddenly  about  a  transverse  axis,  it  is  found  that  the 
eyes  rotate  in  the  opposite  direction,  so  that  in  fact  the  image  formed  on 
the  retina  shall  still  keep  in  the  same  apparent  meridian.  This  rotation 
is  called  compensatory,  and   is  largely  effected  by  the  oblique  muscles. 

CO-ORDINATED    MOVEMENTS    OF   THE    EYES 

The  notable  feature  of  the  eye  movements  is  the  close  association  which 
exists  between  the  muscles  of  the  two  eyes.  For  so  perfectly  has  this  mechan- 
ism been  developed  that  the  eyes  are  able  to  glance  rapidly  from  place  to  place 
without  there  being  any  obvious  doubling  of  the  images.  The  eye  movements 
are  therefore  of  such  a  kind  that  the  image  of  an  object  conveys  a  single 
impression  to  consciousness.  But  objects  vary  in  the  distance  at  which 
they  are  placed  and  therefore,  beside  movements  of  the  eyes  in  which  the 
visual  axes  remain  parallel,  there  are  also  movements  in  which  there  is 
a  certain  amount  of  convergence.     In  the  latter  case  there  is  usually  some 


496 


PHYSIOLOGY 


associated  accommodation  of  the  lens  for  near  objects,  and  at  the  same  time 
some  contraction  of  the  pupil.  By  experiments  in  which  prisms  are  placed  in 
front  of  the  eyes,  thus  calling  for  convergence  or  divergence  without  accommo- 
dation, and  by  others  in  which  lenses  are  placed  there  instead,  thus  requiring 
accommodation  without  change  in  the  angle  between  the  axes,  it  can  readily 
be  shown  that  the  association  between  the  functions  of  accommodation  and 
convergence  is  not  very  rigid.  The  co-ordinated  deviations  of  the  eyes  appear 
to  be  much  more  closely  connected.  Thus  Donders  found  co-ordinated 
deviations  both  in  the  newly  born  and  in  congenital  blindness.  This  is 
probably  due  to  the  close  anatomical  relationship  which  exists  between  the 
nerve  centres  of  the  muscles  on  the  two  sides.  This  relationship  may  be 
explained  with  the  help  of  Figure  247,  which  shows  roughly  the  relative 
positions  of  the  various  nerve  centres  in  the  central  part  of  the  Sylvian 
grey  matter  at  the  level  of  the  quadrigeminal  bodies. 


PUPIL 
ACCOMMODATION 

LEVATOR.  PALP 


Fig.  l'47.     Diagram  to  shew  relationships  of  different  parts  of  oeulo-motor  nuclei, 
and  tlie  principle  connections  between  them. 

It  will  be  seen  that  the  third  or  oculo-motor  nerve  supjmes  all  the  external 
eye  muscles  except  three,  viz. :  Tenon's  capsule,  which  is  supplied  by  the  sym- 
pathetic ;  the  superior  oblique,  which  is  supplied  by  the  fourth  or  trochlear 
nerve ;  and  the  external  rectus,  which  is  supjjlied  by  the  sixth  or  abducent 
nerve.  Further,  while  most  of  its  nuclei  supply  muscles  on  the  same  side, 
two  are  found  to  go  to  muscles  on  the  opposite  side,  namely  the  internal  and 
inferior  recti.  Another  eye  muscle  also  has  a  crossed  connection,  namely 
the  superior  oblique  (4th  nerve).  Of  the  many  bundles  of  association  fibres 
which  connect  these  different  nuclei,  the  following  may  be  mentioned  as 
being  of  special  importance: — (1)  From  the  external  rectus  of  one  side 
through  the  posterior  longitudinal  fasciculus  to  the  internal  rectus  of  the 
other  ;  thus  allowing  conjugate  deviation  of  the  eyes.  (2)  Between  the 
nuclei  of  the  pupil  sphincter,  of  the  mechanism  for  accommodation,  and  of  the 


EYE  MOVEMENTS  497 

internal  rectus  ;  thus  co-ordinating  the  adjustments  required  for  near  vision, 
namely  convergence,  accommodation  for  near  objects,  and  reduced  pupil 
diameter.  (3)  Between  the  superior  recti  muscles  of  the  two  eyes;  thus 
causing  symmetrical  upward  deviation.  (4)  Between  the  inferior  recti  of 
the  two  eyes  for  similar  reasons.  (5)  Between  the  superior  oblique  of  one 
eye  and  the  inferior  oblique  of  the  other  ;  thus  permitting  conjugate  rotation 
of  the  eyes..  (6)  Between  the  superior  rectus  and  the  inferior  oblique  of 
the  same  eye  ;  thus  permitting  the  deviation  caused  by  the  one  to  be 
corrected  by  the  other.  (7)  Between  the  inferior  rectus  and  the  superior 
oblique  of  the  same  eye  for  a  similar  reason.  (8)  Between  the  nucleus  of 
the  superior  rectus  and  that  of  the  levator  palpebral  of  the  same  eye.  This 
association  permits  simultaneous  raising  of  the  eyelid  with  the  upward 
deviation  of  the  eyes,  thus  preventing  any  restriction  of  vision. 

Besides  these  connections  between  the  muscles  producing  like  or  associ- 
ated action  there  are  others  equally  important  between  the  brain  and  these 
centres,  namely  those  which  connect  antagonistic  muscles.  Sherrington 
showed  that,  as  the  muscle  on  one  side  of  a  limb  contracts,  its  antagonist 
at  the  same  time  relaxes,  so  as  to  allow  the  movement  to  take  place  smoothly 
and  without  waste  of  energy.  This  is  called  'reciprocal  innervation.'  The 
eye  muscles  show  the  phenomenon  very  well.  If  the  right  frontal  cortex 
be  stimulated,  the  eyes  perform  co-ordinate  deviation  to  the  left.  If  now  all 
the  muscles  of  the  right  eye  are  divided  except  the  external  rectus,  it  is  found 
that  this  eye  still  moves  in  coordination  as  far  as  the  middle  line,  through 
the  relaxation  of  the  external  rectus  muscle. 

The  orbicularis  palpebrarum  is  also  supplied  by  the  3rd  nerve,  for  in 
lesions  of  its  nucleus  paralysis  of  this  muscle  is  found.  The  fibres  innervating 
it  probably  travel  all   the  way  with  the  7th  nerve. 

CAUSES    AND    DIAGNOSIS    OF    STRABISMUS 

'Squint  or  strabismus  may  be  caused  by  a  number  of  conditions:  (1)  by  congenita] 
abnormality  ;  (2)  by  interference  with  the  proper  rotation  of  the  eyeball ;  (3)  by  injury  to 
one  of  the  external  eye  muscles  ;  (4)  by  injury  to  or  stimulation  of  one  of  the  nerves  sup- 
plying these  muscles  ;  (5)  by  the  presence  of  certain  errors  of  refraction.  With  regard  to 
nerve  injury  the  following  description  may  be  given.  Injury  to  the  third  nerve  causes  (a.) 
drooping  of  the  upper  lid  owing  to  paralysis  of  the  levator  palpebrse ;  (ft)  external 
strabismus  from  paralysis  of  the  upper,  inner  and  lower  recti  and  the  unopposed  action 
of  the  external  rectus;  (c)  rotation  of  the  eye  about  its  visual  axis  from  paralysis  of 
tli.-  superior  oblique  and  therefore  unopposed  action  of  tin-  inferior;  (ii)  dilatation  ,,| 
the  pupil  from  paralysis  of  its  sphincter  and  tin-  unopposed  action  of  the  dilator  fibres 
which  are  innervated  by  the  sympathetic;  (e)  loss  of  the  power  of  accommodation 
from  paralysis  of  the  ciliary  muscle  ;  (/)  exophthalmos  or  protrusion  of  the  eye,  caused 
by  the  paralysis  of  so  many  of  its  muscles  and  the  unopposed  action  of  the  smooth 
muscle  fibres  in  Tenon's  capsule.  Owing  to  the  fact  that  for  a  considerable  portion 
of  its  course  the  3rd  nerve  lies  beside  the  4th,  5th  and  6th  nerves,  there  is  usually 
also  some  associated  symptoms  of  paralysis  in  the  structures  which  these  nerves  supply. 
Injury  to  the  4th  nerve  causes  paralysis  of  the  superior  oblique,  which  shows  itself 
by  defective  movements  in  a  downward  and  outward  direction.  Injury  to  the  6th 
nerve  causes  internal  strabismus  owing  to  paralysis  of  the  external  rectus.  This  fre- 
quently occurs  when  tumours,  haemorrhage  or  injuries  involve  the  base  of  the  brain. 

32 


198  PHYSIOLOGY 

Experimental  st inm la.< i< >n  <>f  these  nerves  causes  (lie  ei inverse  ell'eels  In  paralysis,  whioh 
therefore  'I"  no!   require  specific  description. 

When  strabismus  due  to  the  complete  paralysis  of  one  of  the  recti  is  present,  there 
is  not  as  a  rule  any  difficulty  in  ascertaining  which  muscle  is  ahVcted.  When  however 
nne  of  the  oblique  muscles  is  paralysed  or  when  the  paralysis  is  only  partial,  there  may 
be  some  difficulty  in  diagnosing  the  exact  condition.  It  is  found  however  thai  l hen 
is  a  simple  method  by  which  the  affected  muscle  may  lie  found.  This  depends  on  the 
principle  that,  if  t  he  eyes  are  rotated  in  that  direct  ion  which  requires  complete  contract  ion 
of  the  affected  muscle,  the  strabismus  will  be  found  to  get  worse,  owing  to  the 
failure  of  that  muscle  being  made,  more  pronounced  ;  if  on  the  other  hand  the  eyes  are 
turned  in  the.  opposite  direction,  the  injured  muscle  is  relaxed  and  the  strabismus 
vanishes.  The  following  example  will  slum  the  »a\  the  method  is  used  i  a  man  com- 
plains of  double  vision  following  an  injury  to  the  eyes  ;  by  directing  the  gaze  in  different 
direct  inns  it  is  found  that  the  double  vision  increases  in  amount  as  the  eyes  are  turned 
to  the  right.  The  injured  muscle  must  therefore  be  clearly  a.  dextro-rnfatnr,  that  is, 
the  external  rectus  of  the  right  eye,  or  the  internal   rectus  of  the  left.     Fig.  248  will 


& 


L.INF.R,. 


L.S.O.  r.s.o: 

DOWN 


Fig.  24S.  Showing  the  direction  in  which  paralysis  affecting  the  different  eye 
muscles  produces  diplopia  and  the  relative  positions  occupied  by  the  true 
and  false  images  (Hartridge).  Black  shows  image  of  right  eye.  white  shows 
image  of  left  eye.  The  false  image  is  always  the  one  placed  furthest  from  the 
centre.  • 

be  found  of  assistance,  because  the  arrows  which  show  the  directions  in  which  the  diplo- 
pia increases,  point  to  the  names  of  the  muscles  the  injury  of  which  will  set  up  the 
condition  which  is  found  to  exist.  Experience  shows  that  the  injured  eye  is  always 
that,  to  which  the  more  deviated  image  belongs,  and  this  fact  may  be  readily  ascertained 
by  placing  in  front  of  the  right  eye  a  slip  of  coloured  glass.  If  the  coloured  image  is 
found  to  be  the  one  that  is  the  more  deviated,  then  it  is  the  right  eye  that  is  involved 
in  the  injury,  and  therefore  in  the  case  that  we  have  been  considering,  the  right  external 
rectus  is  the  injured  muscle.  Conversely  if  the  uncoloured  image  is  found  to  be  the 
more  deviated,  then  the  injured  muscle  was  the  left  internal  rectus.  In  fact  it  is  found 
in  every  case  that  the  injured  muscle  is  the  one  which  would  give  by  its  contraction 
that,  position  to  the  more  deviated  image  which  it  is  actually  found  to  occupy. 


EYE  MOVEMENTS  499 

TREATMENT  OF  STRABISMUS.  This  consists  either  in  the  use  of  suitable 
prismatic  spectacles  which  will  cause  a  recombination  of  the  double  images,  or  in 
operative  measures.  In  the  latter,  either  the  tendon  of  the  paralysed  muscle  is  shorl 
rued,  or  that  of  its  antagonist  is  lengthened,  or  better  still  a  combination  of  both 
methods  of  treatment.  Lastly  there  is  a  type  of  strabismus  which  is  found  to  accom- 
pany the  refractive  errors  which  cause  long  and  short  sight.  This  type  of  strabismus, 
which  is  called  concomitant,  is  eliminated  by  correcting  the  refractive  error.  (This 
important  subject  will  be  referred  to  again  later  on  page  537.) 


SECTION  III 

THE    STRUCTURE    OF    THE    EYEBALL 

The  eyeball  is  a  sphere,  about  20  mm.  in  diameter.  It  lies  near  the  front 
of  the  orbital  cavity  protected  by  the  eyelids.  The  greater  part  of  its 
external  surface  is  formed  by  a  firm  white  membrane  called  the  sclera.  In 
front  this  is  replaced  by  a  transparent  structure  called  the  cornea.  This 
hasa  greater  curvature  than  the  rest  of  the  eye,  the  radius  of  its  surface  being 
about  8  mm.     Attached  to  the  eyeball  behind  and  slightly  to  the  inner 


Fig.  249.     Transverse  section  through  equator  of  left  eye  seen  from  above. 

side  is  the  optic  nerve,  the  function  of  which  is  to  convey  to  the  brain  the  light 
impressions  received  by  the  eye.  Attached  to  it  also,  about  6  mm.  from  the 
corneal  margin,  are  the  tendons  of  four  of  the  ocular  muscles,  as  described 
in  Section  II.  The  sclerotic  is  fined  within  by  a  highly  vascidar  and  deeply 
pigmented  coat  called  the  choroid.  In  front  this  coat  has  a  circular  aperture, 
in  relationship  with  which  the  choroid  becomes  modified  into  several  impor- 
tant structures,  namely  the  iris,  ciliary  muscles  and  ciliary  glands.     Spread 

500 


THE  STRUCTURE   OF  THE  EYEBALL 


£01 


out  within  the  hollow  cup  formed  by  the  sclera  and  choroid  is  a  soft  delicate 
membrane  of  nervous  tissue,  the  retina,  which  is  connected  with  the  optic 
nerve.  The  spherical  cavity  thus  formed  is  entirely  filled  by  three  trans- 
parent structures,  the  lens,  the  aqueous  humour  and  the  vitreous  humour. 
The  lens  is  a  biconvex  body  of  higli  refractive  index,  which  is  situated 
symmetrically  behind  the  opening  in  the  iris,  being  held  in  place  by  the 
suspensory  ligaments.  The  aqueous  is  the  fluid  which  fills  the  cavity  in  front 
of  the  lens,  while  the  semi-solid  vitreous  fills  the  cavity  behind  it.  The  eye 
is  therefore  a  solid  orgaii  having  considerable  rigidity. 

DEVELOPMENT  OF  THE  EYE.  The  period  at  which  the  development  of  (he 
eye  commences  in  the  embryo  follows  rapidly  after  the  invagination  of  the  epiblast 
to  form  the  central  nervous  system,  namely  at  about  the  first  week  in  the  human 
foetus.  It  shows  itself  by  a  bulging  outward  of  a  pair  of  buds  from  the  nervous  layer 
towards  the  sides  of  the  head.  During  its  advance  each  bud  becomes  folded  on 
itself  to  form  a  hollow  cup  which  remains  in  connection  with  the  central  nervous 
system  through  a  hollow  tube,  the  future  optic  nerve.  As  the  optic  cup  approaches, 
the  epiblast  becomes  thickened,  and  this  portion  sinks  inwards  till  it  comes  to  lie  in 
the  mouth  of  the  optic  cup.  The  epiblast  now  becomes  folded  over  it,  and  the  edges 
coalesce,  leaving  the  thickened  mass  as  a  nearly  spherical  body  (the  future  crystalline 


go"  MOUTH 

Piq.  250.     Diagram  to  show  the  different  stages  in  the  development  of  the  o.\e. 


502  PHYSIOLOGY 

lens)  af  the  mouth  of  the  optic  cup.  The  two  layers  of  the  optic  cup  now  become 
contiguous,  and  the  outer  develops  pigment,  while  the  inner  increases  greatly  in  the 
complexity  of  its  structure  to  form  the  adult  retina.  Through  a  special  cleft  in  the 
optic  cup  (the  choroidal  cleft)  enters  a  bud  of  mesoderm  to  form  the  vitreous  body. 
This  carries  with  it  blood  vessels  which  form  the  central  artery  of  the  retina  and  those 
which  nourish  the  lens  and  iris  during  their  development,  namely  the  hyaloid  artery 
and  its  branches.  These  vessels  are  accompanied  by  corresponding  veins.  During 
these  changes  tin-  mesoblast  surrounding  the  optic  cup  has  condensed  to  form  the  highly 
vascular  choroid  and  outside  it  the  dense  and  hard  sclera.  The  latter  becomes  at  the 
same  time  transparent  in  front  to  form  the  cornea.  Behind  the  cornea  a  cleft-like 
aperture  appears  which  develops  into  the  anterior  chamber,  and  thus  separates  the 
cornea  from  the  iris.  The  anterior  chamber  becomes  lined  by  endothelium,  and  is  filled 
with  fluid,  the  aqueous  humour.  The  iris  thus  becomes  composed  of  three  layers  :  (1 )  the 
posterior  pigmented  layer  which  is  the  continuation  of  the  retina;  (2)  the  iris  tissue 
propei  developed  from  mesoderm,  and  containing  the  two  muscle  layers  and  elastic 
tissue  ;  (3)  the  anterior  layer  of  endothelial  cells.  The  iris  is  thus  at  first  a  continuous 
sheet  of  tissue,  but  its  structure  is  thinner  at  the  part  corresponding  with  the  pupil, 
thus  forming  the  pupillary  membrane.  This  disappears  shortly  before  birth.  The 
ocular  muscles  are  formed  from  the  mesoderm  in  a  similar  way  to  other  muscles. 
The  lids  form  as  two  buds  growing  out  from  the  epiblast;  they  advance  till  they 
meet  and  then  fuse  together,  to  reopen  again  about  the  time  of  birth.  The 
nervous  layer  appears  to  take  a  very  important  part  in  tin-  development  of 
the  eye.  and  this  is  borne  out  by  experiment ;  for  if  the  outgrowing  optic  cup  be  diverted 
during  its  advance  to  the  epiblast  towards  some  other  part  of  the  embryo,  it  is  found 
that  a  normal  organ  of  vision  develops  in  this  new  and  entirely  abnormal  situation. 

COMPARATIVE  ANATOMY  OF  THE  EYE.  The  types  of  light-receiving 
organ  in  the  animal  kingdom  make  an  elaborate  study  because  of  the  variety  of 
form   that  is  met  with.     We  may  however  effect  an  approximate  classification, 

The  most  primitive  type  of  all  light  organs  consists  of  a  single  pigmented  spindle- 
shaped  cell  such  as  is  found  in  the  epidermis  of  certain  amphibia  and  coelenterata  (see 
Fig.  251  A).  In  cases  where  the  creature  is  transparent,  the  end  organs  may  be  devel- 
oped in  connection  with  the  nervous  system.  The  functions  of  such  organs  may  be 
to  inform  their  possessor  if  a  part  is  exposed  to  light,  and  therefore  also  liable  to  be 
noticed  and  attacked  by  passing  enemies.  In  the  next  type  of  light  organ,  a  number 
of  such  cells  are  grouped  together,  often  to  form  a  hollow  cup  in  the  epidermis,  as  shown 
at  B.  These  cups  retain  their  connection  with  the  nervous  system  by  means  of  an 
oplie  nerve.  This  type  of  organ  (B)  is  found  in  Platyhelminthes  and  in  the  mollusc 
Patella.  In  the  next  type  (C)  the  cup  becomes  deeper  and  its  mouth  small,  the  epidermis 
round  it  becoming  deeply  pigmented.  This  organ  therefore  functions  like  a  pinhole 
camera,  allowing  its  possessor  to  observe  a  rough  image  of  external  objects  ;  it  should 
be  noticed  however  that  this  image  formation  occurs  at  the  expense  of  brightness. 
This  type  ((')  is  found  in  most  annelida  and  in  the  mollusc  Nautilus.  The  next  type 
(D)  is  a  modification  of  the  last,  in  that  the  centre  of  the  optic  cup  is  filled  w  ith  a  spherical 
highly  retractile  body.  This  permits  a  larger  opening  to  be  used  for  the  admission  of 
light  without  at  the  same  time  causing  too  much  confusion  in  the  image.  This  is  the 
arrangement  met  with  in  the  mollusc  Helix  and  the  arthropod  Scorpio.  In  the  next 
type  of  light  organ  (E)  the  highly  retractile  lens  becomes  separated  from  contact  with 
the  retina,  and  the  space  between  is  filled  by  liquid  or  a  mass  of  transparent  cells  which 
form  a  vitreous  humour.  This  interval  between  the  lens  and  retina  allows  the  former 
to  produce  a  focussed  image  on  the  latter,  so  that  for  the  first  time  we  find  an  eye  having 
the  property  of  defining  external  objects.  This  type  of  eye  (E)  is  found  in  the 
eoelenterate  Charybdea  and  in  the  ocellus  of  insects.  In  the  mollusc  Sepia 
the  eye  is  further  improved  by  possessing  an  adjustable  iris.  The  eye  of  Pec  ten 
(F)  has  another  interesting  feature,  namely  that  the  optic  nerve  spreads  out  over,  and 


THE  STRUCTURE   OF  THE  EYEBALL 


503 


becomes  connected  with,  the  retina  on  the  side  nearest  to  the  lens,  an  arrangement 
similar  to  that  found  in  vertebrates.  The  insect  eye  (G),  which  is  also  found  in  Crus- 
tacea, is  arranged  on  an  entirely  different  plan.  It  may  be  regarded  as  being  formed 
by  packing  an  exceedingly  large  number  of  elongated  ocelli  together,  with  their  lenses 


Fig.  251.     Comparative  anatomy  of  the  eye. 
(A)  Single   cell   as  in   amphibia  and    coelenterata.     (B)  Mollusc   Patella.     (C) 
Mollusc  Nautilus.     (D)  Mollusc  Helix.      (E)  Ccelenterate  Charybdea  and  ocellus 
of  inserts.     (K)  Mollusc  Pecten.     (G)  compound  eye  of  insect. 

anterior  and  their  retinae  posterior,  to  form  a  solid  hemispherical  body.  If  is  this 
formation  from  a  number  of  separate  elements  which  gives  the  eye  of  the  insect  its 
faceted  appearance.  Exner  and  others  have  shown  that  the  refracting  media 
of  the  separate  elements  cannot  form  a  focusscd  image  on  the  sensitive  end  organ 
which  each  contains,  but  that  vision  must  consist  of  a  mosaic,  as  Johannes  Miiller  had 
suggested.  It  is  said  that  such  vision  is  well  adapted  to  observing  movement.  The 
eyes  of  vertebrates  may  be  considered  In  be  of  the  same  type  as  that  found  in  man,  for 

the  differences  that  are  met  with  chiefly  concern  detail,  except  as  regards  the  mechan 
ism  used  for  accommodation. 


504 


PHYSIOLOGY 


In  nnm,  as  we  shall  see  later,  this  is  accomplished  by  adjusting  the  power  of  the  lens. 
In  fish  the  eye,  which  is  normally  focussed  for  near  objects,  is  caused  to  focus  objects 
at  a  distance  by  movement  of  the  lens  closer  to  the  retina.  This  is  brought  about  by 
l  In-  contraction  of  a  muscle  called  the  retractor  lentis  (see  Fig.  252a).  In  snakes  the  eye 
,il  ivsl  is  also  far-sighted.  II  is  accommodated  for  near  vision  by  the  contraction  of  a 
circular  ring  of  muscle  which  compresses  the  eye  and  makes  tin-  lens  travel  forward 
(Fig.  252c).  In  birds  (he  eye  at  rest  is  long-sighted.  The  focussing  of  near  objects  is 
obtained  by  increasing  the  curvature  of  the  cornea.  This  is  caused  in  the  following 
manner.  Attached  t>>  the  inside  of  the  sclerotic,  which  forms  a  complete  bony  ring 
round  the  eye,  is  a  radially  arranged  muscle  (Crampton's  muscle).  (See  Fig.  252b.) 
The  other  end  of  this  muscle  is  attached  to  the  corneo-scleral  junction.  Therefore  when 
the  muscle  contracts  it  draws  the  periphery  of  the  cornea  backwards.  But  this  tends 
to  cause  an  increase  in  the  intraocular  tension,  since  the  total  volume  of  the  eye 
tends  to  be  decreased.  This  increased  tension  causes  a  bulging  of  those  external  eye 
structures  which  are    most  elastic,  namely  to  a    slight  extent  the   sclerotic  where  it 


Fio.  252.     The  methods  of  accommodation  used  in  fish,  birds  and  snakes. 

does  not  contain  bone,  but  to  a  much  greater  extent  the  front  of  the  cornea,  because 
of  its  thinness  and  greater  elasticity.  The  curvature  and  therefore  the  refracting  power 
of  the  cornea  very  greatly  increase,  thus  causing  light  rays  from  near  objects  to  be 
focussed  sharply  on  the  retina.  The  increase  in  the  distance  of  the  cornea  from  the 
retina  still  further  assists  this  process.  It  should  be  noted  that  Crampton's  muscle 
contains  voluntary  fibres  and  is  under  the  direct,  control  of  the  will.  This  probably 
serves  two  purposes:  it  allows  the  bird  to  rapidly  accommodate  as  it  swoops  towards 
the  ground,  and  at  the  same  time  it  may  assist  the  judgment  of  distance. 

In  describing  the  comparative  anatomy  of  the  visual  organs  it  should  be  remem- 
bered that  the  pineal  gland  is,  in  mammalia,  the  rudiment  of  one  of  a.  pair  of  median  eyes 
or  ocelli,  which  were  functional  in  the  vertebrate  ancestors. 


MINUTE  ANATOMY  OF  THE  EYE.  The  Cornea  forms  the  trans- 
parent anterior  convex  front  of  the  eye.  Its  curvature  has  a  radius  of 
nearly  8  mm.  and  a  diameter  of  11  mm.  Its  thickness  is  1*1  mm., 
and  is  composed  of  the  following  live  layers:  (1)  Stratified  epithelium 
continuous  with  that  covering  the  conjunctiva.  Superficially  the  cells 
are    nucleated    square!?,    deeply   the}'  are  nucleated   columnar  cells,  and 


THE  STRUCTURE  OF  THE  EYEBALL 


505 


the  layers  between  are  a  gradual  transition  from  one  type  to  the  other. 
(2)  The  anterior  elastic  lamina  of  Bowman.  This  is  not  true  elastic 
tissue,  but  a  layer  of  modified  substantia  propria.  (3)  Substantia  propria 
which  consists  of  a  special  type  of  fibrous  connective  tissue.  The  fibres 
are  arranged  in  parallel  rows  to  form  laminae,  and  the  lamina?  are  built 
one  above  the  other,  leaving  cell  spaces  or  lacunar  between.  The  fibres  of 
each  lamina  are  cemented  together  by  an  amorphous  substance  of  nearly 
the  same  optical  density  so  that  the  lamina?  form  one  homogeneous  structure. 
It  is  on  this  arrangement  that  the  transparency  of  the  cornea  depends. 
If  an  excised  eye  be  squeezed  so  as  to  produce  a  high  intraocular  tension, 
the  cornea  is  seen  to  become  partially  opaque.  This  is  caused  by  the 
tension  in  the  corneal  fibres  making  them  become  doubly-refracting  in  a 
similar  manner  to  that  set  up  by  the  contraction  in  a  striated  muscle  fibre. 
But  owing  to  this  double  refraction  the  laminae  of  the  cornea  cease  to 
form  one  homogeneous  structure,  and  therefore  opacity  is  the  result. 
Within  the  lacunae  are  to  be  found 
the  corneal  corpuscles,  which  are  flat- 
nucleated  star-shaped  cells.  (4)  The 
posterior  elastic  lamina  of  Descemet. 
This  is  a  clear  structureless  membrane 
which  splits  at  its  periphery  into  three 
layers.  The  first  enters  the  sclera,  the 
second  gives  attachment  to  the  ciliary 
muscle,  while  the  third  enters  the  iris 
as  the  ligamentum  pectinatum  and 
gives  attachment  to  it ;  the  intervals 
between  its  fibres  are  called  the  spaces 
of  Fontana.  (5)  A  layer  of  endothe- 
lium. This  consists  of  a  single  layer  of 
flat  nucleated  cells  which  line  the 
spaces  of  Fontana  and  the  anterior 
surface  of  the  iris. 

The  cornea  is  nourished  during 
health  by  a  How  through  the  cell  spaces 
of  lymph  which  comes  from  the  peri- 
pheral vessels.  During  its  development 
ami  when  diseased  it  is  supplied  by 
capillaries  which  run  in  from  its  edge. 
Its  sensory  nerve  supply  is  extremely 
rich,  but  pain  end  organs  alone  appear 
to  be  present. 

Histologically  the  sensory  nerve 
filaments  are  found  to  ramify  actually 
in  the  surface  layers  of  the  stratified 
epithelium,  a  condition  not  found,  in 
any  other  part  of  the  body.     This  ar- 


Nerve  supply  to  the  eyeball. 
(After  Fostee.) 
l.g,  lenticular  ganglion  with  its  three 
roots,  viz.  :  r.b,  radix  brevis  or  short 
root;  r.l,  radix  longus  or  lung  root; 
sym,  sympathetic  root;  V.  opth.  oph- 
thalmic division  of  V  nerve  j  ///  ocm, 
oculo-niotor  nerve ;  11,  optic  nerve  ; 
I.e.  long  ciliary  nerves;  s.r,  short  ciliary 
nerves. 


506  PHYSIOLOGY 

rangement  and  the  acute  painresponse,  which  even  t  he  smallest  foreign  body 
can  initiate,  obviously  has  for  its  object  the  protection  of  this  important 
surface  from  injury.  The  pain  impulses  are  conveyed  to  the  brain  either 
via  the  perichoroidal  nerve  plexus  and  the  long  ciliary  nerves  to  the  nasal 
branch  of  the  1st  division  of  the  5th  nerve,  or  from  the  plexus  by  the  short 
ciliary  nerves  to  the  ciliary  ganglion,  and  from  this  through  the  radix 
longa  to  the  nasal  nerve.  In  either  case  the  nerves  appeal  to  have  I  heir 
ci'll  station  in  the  Gasserian  ganglion. 

THE  SCLERA,  which  forms  the  tough  shell  of  the  eyeball,  consists  of 
three  layers :  (])  a.  thin  layer  of  endothelium  in  contact  with  the  capsule 
of  Tenon ;  (2)  numerous  interlacing  bundles  of  white  fibrous  connective 
tissue  ;  (3)  a  layer  of  flat  endothe'ial  cells  and  a  network  of  fine  pigmented 
connective  tissue  cells,  forming  the  lamina  fusca. 

Beside  the  optic  nerve  the  sclera  is  perforated  by  the  short  and  long 
ciliary  nerves  and  by  the  ciliary  arteries.  The  four  venas  vorticosae  leave 
it  at  the  equator.  At  the  corneo-scleral  junction  the  two  structures  are 
continuous.  A  space  is  left  however  which  forms  a  ring  round  the  cornea. 
This  is  called  the  canal  of  Schlemm ;  it  communicates  with  the  anterior 
chamber  through  the  spaces  of  Fontana  and  also  with  the  scleral  veins. 
The  presence  of  these  canals  renders  the  sclero-cornea  weak  and  therefore 
liable  to  be  ruptured  by  violence. 

THE  CHOROID  forms  the  vascular  and  pigmentary  lining  of  the  eye. 
It  intervenes'between  the  sclera  and  the  retina.  Histologically  it  consists 
of  three  layers:  (1)  the  lamina  sirpra-choroidea,  which  is  similar  in  its 
structure  to  the  lamina  fusca  of  the  sclera  :  (2)  the  lamina  propria  "which 
consists  of  connective  tissue,  richly  supplied  with  blood  vessels,  capillaries, 
veins,  and  nerves :  (3)  the  basilar  membrane  of  Bruch.  This  is  a  thin 
t  ransparent  structureless  layer  like  that  of  Descemet  in  the  cornea.  A  highly 
reflecting  surface,  called  the  Tapetuni,  is  present  in  certain  animals.  This 
is  formed  by  a  layer  of  iridescent  cells  in  the  lamina  propria. 

THE  CILIARY |  BODY  connects  the  choroid  to  the  iris.  It  consists 
of  three  parts  :  (1)  the  ciliary  muscle,  the  function  of  which  is  to  cause 
the  accommodation1  of  the  lens ;  (2)  the  ciliary  glands  which  secrete  the 
aqueous  humour ;  and  (3)  the  orbiculus  which  is  the  part  of  the  ciliary  body 
connecting  it  with  the  choroid.  The  ciliary  bodies  are  covered  by  a  thin 
pigmented  layer  which  is  a  continuation  of  the  retina.  This  also  covers 
the  posterior  surface  of  the  iris  and  ends  there. 

THE  IRIS  consists  of  three  layers  :  (1)  the  endothelium  continuous  with 
that  on  the  posterior  surface  of  the  cornea  :  (2)  the  stroma  of  the  iris,  which 
consists  of  connective  tissue  (especially  elastic  fibres),  two  thin  sheets  of 
muscle,  some  pigment  cells,  vessels  and  nerves;  (3)  the  pigmented  layer 
continuous  with  the  retina. 

It  should  be  noted  that  the  posterior  elastic  lamina  of  Descemet  in  the 
cornea,  after  its  division  into  three  parts,  forms  by  its  posterior  portion 
the  ligamentum  pectinatum  iridis,  by  which  the  iris  gains  attachment  to 
the  sclero-corneal  junction. 


THE  STRUCTURE  OF  THE  EYEBALL 


507 


THE  FUNCTIONS  OF  THE  IRIS.  The  iris  contains  two  layers  of 
unstriated  muscle  fibres,  the  anterior  which  is  circularly  arranged  so  that 
by  its  contraction  it  acts  as  a  sphincter,  while  the  posterior  is  arranged 
radially,  stretching  from  the  attachment  of  the  iris  to  the  rim  of  the  pupil 
so  that  by  its  contraction  it  causes  the  pupil  to  open.  Because  of  the 
numerous  pigment  cells  which  it  contains  the  iris  is  opaque  to 
light.  Contraction  of  the  pupil  thus  causes  the  following 
effects:  (1)  reduction  in  the  amount  of  light  entering  the  eye, 
so    that    an    image    of    less    intensity    is    formed    on    the    retina ;    (2) 


Cornea 


Sinus   venosus 


Conjunctiva         /£!$?> 


Rstma 


Fig.  2o4.     Section  through  anterior  part  of  eyeball  to  show  relations  of  iris  and 
ciliary  bodies  to  corneo-scleral  junction  and  lens. 

the  use  of  the  more  central  zones  of  the  lens  system  only.  The  advantage 
of  this  lies  in  the  fact  that,  as  will  be  described  later,  the  more  peripheral 
zones  suffer  from  errors  of  refraction  to  a  much  greater  degree  than  do  the 
central  ones:  the  contraction  of  the  pupil  therefore  improves  the  definition 
nl  Hie  image;  (:i)  an  increase  in  the  depth  of  focus  of  the  eye,  which  is 
of  great  value  for  near  vision.  The  way  t  hat  depth  of  focus  is  obtained  will 
be  described  later  (see  page  5'30). 

CONTRACTION  OF  THE  PUPIL  occurs  under  the  following  cir- 
cumstances : 

(1)  When  light  falls  on  the  retina.  This  movement,  which  is  known 
as  '  the  light  reflex,'  is  determined  by  a  contraction  of  the  sphincter  pupillse, 
together  with  a  relaxation  of  the  dilatator  muscle.  The  contraction  ensues 
within  a  period  of  004  to 0*05  sec.  after  the  moment  at  which  the  light  has 


508  PHYSIOLOGY 

access  to  the  retina,  and  attains  its  maximum  within  O'l  sec.  In  man  as 
well  as  in  other  animals  which  have  binocular  vision,  and  in  which  there 
is  a  partial  decussation  of  the  fibres  of  the  optic  nerves  in  the  optic  chiasma, 
the  reflex  is  bilateral,  i.e.  light  falling  into  one  eye  causes  simultaneous 
contraction  of  both  pupils.  In  the  higher  animals  this  reaction  of  the 
pupil  to  light  demands  the  integrity  of  the  nervous  paths  between  the  eye 
and  the  brain  ;  but  in  many  of  the  lower  animals,  e.g.  in  the  frog  and  eel, 
the  reflex  nervous  mechanism  is  aided  by  a  local  sensibility  of  the  iris  to 
light.  In  these  animals  the  contraction  of  the  pupil  in  response  to  illumi- 
nation takes  place  even  in  the  excised  eye,  and  seems  to  be  determined  by 
a  direct  stimulation  of  the  pigmented  contractile  fibres  of  the  sphincter 
pupillae  by  means  of  the  light. 

The  effect  of  light  on  the  pupil  varies  considerably  according  to  the 
condition  of  adaptation  of  the  eye.  The  dilatation  of  the  pupil  is  maximal 
when  the  eye  has  been  in  the  dark  for  some  time  and  may  amount  then 
to  7"3  to  8  mm.  In  one  experiment,  on  exposing  the  eye  to  a  feeble  light, 
e.g.  1'6  candles  at  a  moderate  distance,  the  pupil  diminished  in  size  to  6'3 
mm.  ;  with  an  illumination  of  50  to  100  candles  the  size  of  the  pupil  was 
37  mm.,  and  with  500  to  1000  candles,  3-3  mm.  This  effect  was  obtained 
by  a  rapid  change  in  the  illumination  of  the  eye.  When  the  change  in 
illumination  is  sufficiently  slow  no  alteration  of  the  pupil  takes  place,  and 
when  the  illumination,  which  has  at  first  caused  a  maximal  constriction 
of  the  pupil,  is  continued  the  pupil  gradually  relaxes  with  the  adaptation 
of  the  retina  to  fight.  This  relaxation  occurs  within  three  or  four  minutes 
after  exposure  to  light  has  taken  place.  The  same  influence  of  adaptation 
will  be  observed  if  two  individuals  are  brought  into  a  moderately  lighted 
room,  one  from  bright  daylight  and  the  other  from  a  dark  room.  The 
pupils  of  the  first  will  dilate  widely,  while  those  of  the  second  will  constrict 
to  their  maximum  extent.  In  each  case  the  change  will  pass  off  regularly, 
so  that  at  the  end  of  five  or  ten  minutes  there  will  be  no  difference  observable 
between  the  eyes  of  the  two  persons. 

(2)  When  vision  is  directed  to  a  near  object  the  functions  of  accommoda- 
tion of  the  lens  and  of  convergence  of  the  visual  axes  which  result,  are 
associated  with  contraction  of  the  pupil.  The  sharpness  of  vision  is  thereby 
improved  together  with  an  increase  in  the  depth  of  focus.  Results  are  very 
beneficial  for  the  close  examination  of  detail.  Since  it  is  possible  by  ex- 
periment to  cause  accommodation  without  convergence  and  vice  versa, 
we  may  ascertain  which  function  is  the  more  closely  associated  with 
the  pupil  mechanism.     The  evidence  appears  to  be  in  favour  of  convergence. 

(3)  In  sleep  the  pupils  are  always  contracted.  This  behaviour  may  enable 
us  to  distinguish  feigned  from  real  sleep.  This  contraction  of  the  pupils, 
in  spite  of  the  fact  that  no  light  is  entering  the  eyes,  has  been  held  to  be  caused 
by  association  with  the  upward  and  inward  direction  of  the  eye  axes  which 
was  said  to  be  found  in  sleep.  There  now  appears  to  be  irrefutable  evidence 
that  the  eyes  during  sleep  may  occupy  any  position;  another  explanation 
of  the  constricted  pupils  must  therefore  be  found. 


THE  STRUCTUKE  OF  THE  EYEBALL  509 

(1)  Contraction  of  the  pupils  is  a  marked  effect  of  certain  drugs  such  as 
Morphia  or  its  crude  extract  Opium ;  other  examples  are  Pilocarpine,  Mus- 
carine, Physostigmine  and  Cocaine.  The  parts  of  the  pupillo-rnotor  mechan- 
ism on  which  these  drugs  act  will  be  considered  later  (see  page  513). 

(5)  Constricted  pupils  are  also  met  with  in  excitable  conditions  of  the 
centra]  nervous  system,  and  therefore  during  the  induction  of 
chloroform  and  other  anaesthesia. 

(<>)  Small  pupils  which  do  not  react  to  light  are  also  met  with  in  injuries 
to  the  spinal  cord  which  involve  the  cervical  region.  The  explanation  of 
this  will  be  given  later  (see  page  511). 

(7)  Contracted  pupils  are  found  to  accompany  agon}-.  This  is  probably 
due  to  the  powerful  flow  of  efferent  impulses  which  leave  the  brain  in  this 
condition,  affecting  the  3rd  nerve  nucleus  which  controls  the  pupil. 

(8)  The  pupil  contracts  when  the  aqueous  is  allowed  to  escape 
from  the  anterior  chamber.  The  cause  of  this  is  said  to  be  the  dilatation 
of  the  vessels  of  the  iris,  owing  to  the  fall  of  the  surrounding  pressure. 

DILATATION  OF  THE  PUPIL  (1)  Occurs  on  removal  of  alight  stimulus 
from  the  eyes.  If  the  removal  be  complete  the  pupil  remains  dilated,  but 
if  there  be  any  light  at  all  the  pupil  gradually  contracts  again  as  the  eye 
becomes  dark  adapted. 

(2)  Occurs  on  accommodation  for  distant  vision  because  the  associated 
reflex  stimulation  of  the  pupilo-motor  centre  with  accommodation  is  no 
longer  called  into  play. 

(3)  Eeflex  dilatation  of  the  pupil  can  be  excited  by  the  stimulation  of 
any  sensi  iry-nerve.  This  may  be  due  to  some  of  the  afferent  impulses  reach- 
ing the  cilio-spinal  sympathetic  nerve  centre  in  the  cord. 

(1)  The  pupils  are  frequently  found  to  dilate  in  such  emotional  states  as 
fear,  anxiety,  exhaustion  and  dyspnoea,  and  also  at  the  moment  of  death. 

(5)  Dilatation  is  also  found  to  accompany  extreme  exhaustion  of  the 
central  nervous  system,  when  the  activity  of  all  nerve  centres  is  low, 
such  as  in  deep  chloroform  anaesthesia,  and  in  the  coma  produced  by 
alcohol  poisoning.  Many  other  drugs  such  as  atropine  and  homatropine 
cause  dilatation,  as  will  be  described  later. 

(6)  Dilated  pupils  inactive  to  light  are  found  in  injuries  of  the  3rd  nerve, 
or  its  nucleus. 

(7)  Dilated  pupils  are  also  found  when  the  intraocular  pressure  is  abnor- 
mally high,  as  in  glaucoma.  This  appears  to  be  due  to  constriction  of  the 
vessels  of  the  iris  owing  to  the  lygh  external  pressure  to  which  they  are 
.subjected. 

(8)  Dilated  pupils  inactive  to  light  are  found  in  compression  and  severe 
concussion  of  the  brain.  This  is  probably  due  to  the  abolition  of  the  normal 
nervous  impulses  to  the  muscles,  so  that  the  pupil  dilates  under  the 
influence  of  its  radial  elastic  fibres. 

(9)  Dilated  pupils  are  found  to  accompany  hyperactivity  of  the  supra- 
renal glands,  owing  to  the  presence  of  considerable  amounts  of  adrenaline 
in  the  blood.  This  occurs  for  example  in  oxygen  want,  dilated  pupils  being 
one  of  the  characteristic  signs  of  that  condition. 


510 


I'HYSIOUMJY 


INNERVATION    OF    THE    IRIS.     Before  the  work  of  Langley  and  Anderson 

on  the  iris  there  was  doubt  as  to  the  method  by  which  dilatation  was  brought  about  : 
some  thought  that  it  was  due  to  inhibition  of  the  sphincter,  thus  allowing  the  iris  to 
open  because'of  the  radial  clastic  fibres  which  it  contained  ;  others  that  it  was  due 
to  the  emptying  of  the  iris  of  blood  from  the  contraction  of  the  arterioles  following 
stimulation  of  the  sympathetic;  others  again  that  the  cause  was  the  longitudinal 
contraction  of  the  radial  arteries.  But  Langley  and  Anderson  showed  thai  a  radial 
strip  of  iris,  isolated  except  at  its  ciliary  attachment,  shortened  to  half  its  length 
when  the  cervical  sympathetic   was  stimulated.       It   has  been   found   further  thai 

local  stimulation  of  I  he  iris  near  its  periphery  causes  a  local  dilatation  of  the 
pupil,  and   that  cutting  the    sympathetic    causes  lasting  constriction    of  the  pupil. 


Km.  255.     Effect  on  iris  of  cat  of  local  stimulation. 
The  first  effect,  as  in  A,  is  to  cause  contraction  of  the  constrictor  pupillse  below 
the  electrodes,  and  this  is  succeeded  in  b  by  a  strong  localised  contraction  of  the 
radiating  fibres.     (Langley  and  Anderson.) 

Muring  these  experiments  they  proved  by  microscopic  examination  (hat  the  dilata- 
tion of  the  pupil  was  wholly  independent  of  the  contraction  of  the  blood  vessels  of 
the  iris,  and  that  draining  the  animal  of  blood  did  not  influence  the  contraction  of  the 
iris.  Later  it  was  proved  by  histological  technique  that  there  are  radial  muscle 
fibres  in  the  iris.  These  are  poorly  developed  in  mammals  but  are  well  marked  in  birds 
and  in  the  otter.  These  facts  together  prove  definitely  that  there  exists  a  dilator 
muscular  mechanism  in  the  iris. 

The.  sphincter  muscle  is  supplied  by  nerve  fibres  which  arise  from  the 
upper  portion  of  the  3rd  nerve  nucleus  in  the  ventral  part  of  the  Sylvian 
grey  matter  (see  Figure  247).  They  travel  down  in  the  nerve  as  far  as  the 
ciliary  (or  lenticular)  ganglion  which  is  situated  behind  the  eye  close  to  the 
optic  nerve.  Here  a  branch  from  the  nerve  enters  the  ganglion  to  anasto- 
mose with  its  nerve  cells.  These  nerve  cells  send  off  numerous  small  nerves 
called  the  short  ciliary  nerves  (Fig.  253)  which  enter  minute  apertures  in  the 
sclera  arranged  in  a  ring  round  the  optic  nerve.  Having  entered  the  peri- 
choroidal lymph  space  the  nerves  form  a  plexus  from  which  are  supplied  the 
local  blood  vessels,  the  ciliary  muscle  (thus  causing  accommodation)  and 


THE  STRUCTURE  OF  THE  EYEBALL  511 

the  sphincter  of  the  pupil.  The  dilator  muscle  of  the  iris  is  supplied  by 
nerve  fibres  which  originate  in  nuclei  situated  near  that  part  of  the.  3rd 
nerve  nucleus  which  supplies  the  sphincter  fibres ;  this  must  be  the  case 
in  order  to  explain  the  reciprocal  innervation  of  the  two  antagonistic  sets 
of  muscles.  From  these  nuclei  nerve  fibres  travel  down  the  cord  as  far 
as  the  8th  cervical  and  1st  dorsal  ventral  nerve  routs,  with  which  they  leave 
the  cord.  They  then  proceed  as  part  of  the  white  rami  communicantes  to 
the  superior  thoracic  ganglion,  and  thence  by  the  sympathetic  chain  to 
the  superior  cervical  ganglion,  with  the  cells  of  which  they  anastomose. 
From  these  nerve  cells  the  terminal  nerve  fibres  for  the  dilator  muscle  of  the 
iris  arise  ;  they  appear  to  travel  by  two  distinct  routes  :  (I)  from  the  superior 
cervical  ganglion  to  the  Gasserian  ganglion  of  the  5th  nerve  along  the  nasal 
branch  of  its  1st  division,  to  turn  off  with  the  two  long  ciliary  nerves  to  end 
l>v  entering  the  sclera  and  joining  the  perichoroidal  plexus,  and  thence  to 
the  dilator  muscle;  (2)  from  the  superior  cervical  ganglion  grey  rami  are  given 
off  which  travel  with  and  form  plexuses  on  the  various  branches  of  the  in- 
ternal carotid  artery.  One  of  these  is  the  cavernous  plexus  which  sends 
a  fine  branch  to  the  ciliary  ganglion.  From  here  the  fibres  travel  with  the 
short  ciliary  nerves  as  already  described. 

It  is  clear  therefore  that  the  short  ciliary  nerves  contain  both  pupil- 
constrictor  (3rd  nerve)  and  pupil  dilator  (sympathetic)  fibres,  so  that  when 
these  nerve  fibres  are  stimulated  electrically  both  the  sphincter  and  the  radial 
muscles  of  the  iris  will  contract.  But  the  sphincter  fibres  being  the  more 
powerful  will  overcome  the  others  and  therefore  cause  contraction  of  the 
pupil. 

The  nerve  paths  above  described  and  the  effects  on  the  pupil  which 
excitation  of  the  nerves  produces  have  been  ascertained  by  the  employment 
of  the  well-known  methods  of  cutting  the  nerves,  stimulating  the  cut  ends, 
and  also  by  following  the  tracts  marked  by  degeneration.  Thus  cutting 
the  sympathetic  anywhere  causes  contraction,  while  cutting  the  3rd  nerve 
produces  dilatation.  Stimulation  of  the  peripheral  cut  ends  causes  the 
opposite  effects.  The  course  of  the  dilator  impulses  down  the  cord  to  the 
cervico-dorsal  region  explains  the  contraction  of  the  pupil  which  sometimes 
accompanies  injuries  to  the  cervical  spine,  and  explains  the  origin  of  the  term 
cilio-spinal  centre. 

Since  the  dilatation  of  the  pupil  is  accompanied  by  contraction  of 
the  radial  fibres  on  the  one  hand,  and  inhibition  of  the  sphincter  fibres  on 
the  other,  and  vice  versa  when  contraction  takes  place,  it  would  seem 
almost  necessary  to  assume  that  there  is  some  system  of  reciprocal  innerva- 
tion, like  that  found  by  Sherrington  in  the  case  of  the  limbs.  Experimental 
evidence  would  point  to  such  being  the  case.  Thus  stimulation  of 
a  part  of  the  sensori-motor  area  of  the  brain  is  followed  by  dilatation 
of  the  pupil,  which  occurs  even  when  the  sympathetic  has  been 
cut.  Since  this  excludes  the  possibility  of  an  active  contraction  of  the  radial 
fibres  (their  nerve  supply  having  been  cut)  it  appears  to  prove  that  a 
reciprocal  inhibition  of  the  sphincter  has  been  produced.     The  existence 


512  THYSIOLOGY 

of  this  reciprocating  mechanism  must  greatly  increase  the  efficiency  with 
which  the  pupil  works. 

The  above  experiment  also  shows  that  there  is  a  connecting  nerve 
path  between  the  pupilo- motor  centre  and  the  cortex  of  the  brain.  The 
reaction  of  the  pupil  to  light  and  the  association  which  exists  between  pupil, 
accommodation  and  convergence  indicate  that  there  are  a  number  of  other 
important  connections  between  the  pupilo-motor  and  other  centres.  The 
more  important  of  these  will  be  therefore  traced. 

The  light  reflex  in  certain  animals  such  as  frog  ami  eel  is  assisted  by  a 
local  sensibility  of  the  iris  to  light,  while  in  birds  on  the  other  hand  it  is 
to  a  considerable  extent  under  voluntary  control  ;  but  in  man  and  in  most 
other  higher  vertebrates  the  control  is  involuntary  and  unconscious,  the  size  of  the 
pupil  being  determined  by  tin-  intensity  of  t ho  light  which  is  reaching  the  retina.  Thus 
in  bright  light  the  pupil  may  be  less  than  0-6  mm.  in  diameter,  while  in  the  dark  it  may 
In  luger  than  10  mm.;  such  achange  will  cause  the  intensity  of  the  light  with  the 
pupil  contracted  to  be  nearly  one  two-hundredth  part  of  the  intensity  when  the  pupil 
is  dilated.  This  indicates  an  extraordinary  range  of  variation  in  the  length  of  the 
sphincter  muscle  fibres.  The  reaction  of  the  pupil  to  light  varies  with  the  rate  at  which 
change  of  intensity  occurs.  When  the  alteration  is  sudden  the  amount  of  contraction 
was  found  by  Haycraft  to  be  equal  to  the  logarithm  of  the  intensity  of  the  light.  When 
however  the  alteration  is  so  gradual  that  the  retina  can  become  adapted  to  the  change 
as  it  proceeds,  then  little  or  no  change  in  the  size  of  the  pupil  occurs.  The  function 
of  the  pupil  appears  rather  to  protect  the  retina  from  any  sudden  change  of  intensity, 
than  to  control  the  actual  intensity  of  the  light.  With  regard  to  the  reflex  an  the 
connection  of  the  iris  with  the  pupillo-motor  centre  has  already  been  described.  The 
connections  of  the  retina  with  this  centre  appear  to  traverse  the  following  course, 
Starting  from  the  retina  on  one  side  the  impulses  travel  up  the  optic  nerve  as  far  as  the 
chiasma,  where  they  travel  on  without  decussating,  and  end  by  anastomosing  with  nerve 
cells  in  the  anterior  corpora  quadrigemina.  These  nerve  cells  correspond  with  second 
order  neurons  and  proceed  to  the  pupillo-motor  centres  of  both  sides.  It  is  found  by 
experiment  in  monkeys  that  dividing  the  chiasma  in  the  middle  line  docs  not  stop  either 
the  pupil  reflex  in  the  eye  stimulated  or  in  the  other  eye.  This  shows  that  the  nerves 
concerned  with  the  pupil  reflex  go  to  the  anterior  corpora  quadrigemina  of  the  same 
side,  and  that  the  consensual  reflex  is  due  to  the  fibres  from  each  anterior  corpus  quad- 
rigeininum  supplying  the  pupillo-motor  centres  of  both  sides.  The  appreciation  of  ligl  1 1  I  ly 
the  retina  is  exceedingly  rapid,  whereas  the  response  of  the  pupil  to  light  action  is  very 
delayed.  This  is  due  in  part  to  the  fact  that  the  muscles  of  the  iris  arc  composed  of 
involuntary,  smooth  fibres.  There  is  however  a  pathological  condition  called  Hippus,  in 
which  the  pupil  alternately  expands  and  contracts  at  a  rate  that  would  be  impossible  if 
the  attempt  were  made  to  produce  this  effect  by  alternately  exposing  the  eye  to  light. 
This  proves  that  the  muscle  fibres  can  react  more  quickly  and  therefore  that  there  is 
somewhere  in  the  reflex  arc  a  delay  action  mechanism.  The  object  of  this  mechanism 
would  appear  to  be  to  render  the  pupil  stable  and  to  prevent  'hunting.'  When  this 
mechanism  is  diseased  Hippus  results. 

The  accommodation  reflex  has  been  already  considered.  The  close  anatomical 
association  of  the  3rd  nerve  centres  for  pupil  sphincter,  accommodation  and  convergence 
by  the  internal  recti  is  shown  in  Figure  247.  When  volitional  impulses  therefore 
come  down  via  the  frontal  lobes  of  the  cerebral  hemispheres,  they  are  conveyed  to  this 
group  of  centres,  and  the  associated  reflex  results. 

ARGYLL  -  ROBERTSON  PUPIL.  The  diagnosis  of  interference 
with  the  pupillo-motor  reflex  is  of  considerable  practical  import- 
ance,   because    these    paths    appear    to    be  particularly    sensitive    to 


THE  STRUCTURE  OK  T1IK   EYEBALL 


513 


the  presence  of  certain  specific  toxins  in  the  blood.  The  com- 
monest type  is  one  in  which  there  is  contraction  of  the  pupil  on 
accommodation,  but  little  or  no  reaction  to  the  stimulus  of  the  retina  by 
light.  This  condition  of  the  pupil  is  called  the  Argyll-Robertson  pupil. 
The  seat  of  the  injury  appears  to  be  either  in  the  fibres  travelling  from 
the  retinae  to  the  anterior  corpus  quadrigeminum  or  those  coming  from 
these  centres  ami  travelling  to  the  3rd  nerve  nucleus. 

ACTION  OF  DRUGS.    The  following  Table  shows  the  action  of  certain 
drugs  on  the  pupil  : — 


Table  to  show  Action  of  Drugs  on  Pupil. 


Name  of  Drug 

Pupils 

Action. 

Morphia          .  ) 

Opium    .          .   J 

"Small 

Stimulate  3rd  nerve  nucleus. 

Pilocarpine      .   \ 
Physostigminc. 
Eserine            .   1 

Stimulate  3rd  nerve  endings  in  sphincter  pupillsa. 

( 'hloroform       .    ) 
Ether     .          .  ) 

Atropine          .  1 
Homatropine  .  j 

" 

At    first    act   like   morphia.       In    larger   doses   cause 
paralysis  and  therefore  large   pupils. 

Large 

Paralyse  3rd  nerve  endings  in  sphincter  pupillse. 

Adrenalin        .  } 
Cocaine           .  J 

Stimulate  the  sympathetic  nerve  endings  in  the   radial 
muscle  fibres. 

Curare    .          .  ) 

Nicotine           .  j 

Small  or     By  paralysing  the  synapses  in  the  ciliary  or  superior  eer- 
Large           vieal  ganglia  if  painted  on  them. 

SECTION  IV 

THE    NOURISHMENT    AND    PROTECTION    OF    THE 
EYE 

ANATOMY  OF  THE  LIDS.  Closing  the  orbit  in  front  and  in  close  relation- 
ship to  the  eyes  are  the  lids  or  palpebrse.  The  upper,  which  is  the  larger  and 
the  more  movable,  is  provided  with  a  special  muscle,  the  levator  palpebras 
superioris.  This  is  supplied  by  a  branch  of  the  oculo-motor  (3rd)  nerve.  The 
two  lids  meet  at  an  angle  on  both  sides,  forming  the  inner  and  outer  canthi. 
They  are  stiffened  by  two  plates  of  dense  fibrous  tissue, parallel  to  their  edges, 
which  are  called  tarsi.  Near  these  and  embedded  in  the  substance  of  the 
lids  are  two  sets  of  glands,  the  Meibomian  glands  and  those  of  Moll.  These 
secrete  a  greasy  material  which  spreads  over  the  lids.  Superficial  to  these 
structures  but  under  the  skin  is  a  ring  of  smooth  muscle  fibres  which  is 
common  to  both  lids,  the  orbicularis  palpebrarum,  innervated  by  the  7th 
nerve.  Its  contraction  closes  the  lids.  Lining  the  inner  surfaces  of  the  eye- 
lids is  a  thin  layer  of  mucous  membrane,  the  conjunctiva,  which  is  reflected 
on  to  the  front  of  the  eye,  and  is  continuous  over  the  cornea  as  the  anterior 
epithelial  layer. 

CLOSURE  OF  THE  LIDS  occurs:  (1)  during  sleep;  (2)  if  a  very 
luight  light  enters  the  eyes;  (3)  by  the  sudden  approach  of  some  foreign 
body  ;  (4)  by  contact  of  a  foreigii  body  with  the  lashes  ;  (5)  by  irritation 
of  the  cornea  or  conjunctiva;  (6)  in  sneezing;  (7)  in  order  to  renew  the 
fluid  film  on  the  cornea  and  conjunctiva.  The  reflex  closure  of  the  lids  is 
therefore  a  very  important  function  in  affording  protection  to  the  eyes.  The 
reflex  apparently  can  be  initiated  by  the  stimulation  of  any  of  the  branches 
of  the  ophthalmic  (1st)  division  of  the  5th  (trigeminal)  nerve.  From  the 
nucleus  of  this  nerve  in  the  pons  Varolii  fresh  fibres  take  the  impulses,  it 
is  believed,  to  the  upper  part  of  the  facial  nuclei  of  both  sides  (7th  nerve), 
and  from  these  to  the  orbicularis  palpebrarum.  This  reflex  is  one  of  the 
last  to  be  abolished  by  anaesthetics  and  is  therefore  used  as  a  convenient  test. 
It  is  called  the  corneal  reflex. 

The  conjunctivae  and  the  cornea  are  kept  in  a  moist  condition  by  the 
tears,  which  are  secreted  by  the  lachrymal  gland,  situated  in  the  upper  and 
outer  part  of  the  orbit.  This  is  a  small  acino-tubular  gland,  in  microscopic 
structure  similar  to  the  parotid.  Its  secretion  issues  through  several  ducts, 
the  mucous  linings  of  which  are  continuous  with  that  of  the  conjunctiva. 
Normally  the  secretion  is  just  sufficient  lo  keep  the  surfaces  of  the  lids  and 

514 


NOURISHMENT   AND    PROTECTION   OF   THE   EYE 


515 

Under 


cornea  moist,  the  evaporation  keeping  pace  with  the  production. 
certain  circumstances  there  is  excess,  and  tears  are  produced. 

TEAR  FLUIDconsists  chemically  of  an  aqueous  solution  oi  sodium  chloride 
and  carbonate  containing  mucus,  albumen  and  debris.  It  is  found  to  have 
a  bactericidal  power  which  is  lost  if  the  fluid  is  boiled.  Its  functions  are 
to  keep  the  surfaces  of  the  conjunctiva  and  cornea  moist,  and  to  remove 
foreign  bodies  and  organisms.  The  secretion  of  tears  is  increased  (1)  by- 
irritants  and  foreign  bodies   coming  in  contact  with  the  cornea,  conjunc- 


FlG.  250.     Diagram  to  show  origin  and  fate  of  tear  fluid. 


tiva  or  lids  ;  (2)  by  irritation  of  the  nasal  mucous  membrane  ;  (3)  by  power- 
ful illumination  of  the  eyes ;  (4)  By  the  incidence  on  the  eye  of  infra-red 
(heat)  and  ultra-violet  (actinic)  rays;  (5)  under  the  influence  of  emotion. 
When  excessive  tear  formation  occurs  the  fluid  either  escapes  over  the 
front  of  the  lids,  or  is  drained  away  through  the  lachrymal  duct  into 
the  nasal  sinus.  Three  theories  have  been  advanced  to  explain  the 
latter:  (I)  syphoning,  owing  to  the  mouths  of  the  ducts  being  at  a 
higher  level  than  their  exit  into  the  nose ;  (2)  capillarity,  owing  to  the  tendency 
of  the  liquid  to  flow  into  the  ducts  through  surface  tension ;  (3)  active 
removal  by  the  act  of  blinking.  It  is  not  at  the  present  time  definitely  known 
how  this  occurs.  Some  say  that  on  closing  the  eye  the  internal  palpebral 
ligament  tends  to  be  pulled  on,  and  that  this  dilates  and  fills  the  lachrymal 
sac  ;  others  that  the  sac  fills  automatically  through  having  been  previously 
emptied  by  the  contraction  of  Horner's  muscle.  It  is  possible  that  both 
processes  occur. 

The  eyes  of  some  fish  and  nearly  all  birds  are  provided  with  a  nictitating  membrane, 
a  semi-transparent  shutter  which  can  be  brought  over  the  surface  of  the  cornea. 
In  the  fish  its  possible  function  is  to  prevent  the  irritation  of  fine  sand  particles  when 
swimming  in  rough  water,  without  at  the  same  time  disturbing  vision,  [n  the  case 
of  the  bird  n  might  be  used  (1)  to  moisten  tin-  cornea  during  flight  without  interrupting 


,16 


PHYSIO  LUCY 


vision:  (•_')  to  reduce  the  light  intensity  when  flying  a(  high  altitudes  or  when  travelling 
towards  the  sun;  (3)  to  reduce  the  irritation  caused  by  ultra-violet  orinfra-red  rays 
which  are  present  in  excessive  amount  at   high  altitudes. 


NUTRITION    OF    THE    EYE 
The  eyeball  is  richly  supplied  with  blood  vessels,  which  form  numerous 
anastomoses.     Among  these  may  be  mentioned  the  arteries  of  the  optic 

nerve  sheath,  the  long  and 
short  posterior  ciliary  arteries, 
the  anterior  ciliary  arteries 
which  are  branches  from  the 
muscular  vessels,  and  the  con- 
junctival arteries.  These  pierce 
the  sclera  to  ramify  freely  in 
the  choroid  and  the  ciliary 
bodies.  The  iris  is  supplied 
by  two  concentric  vessels,  the 
circulus  major  and  the  circu- 
lus  minor.  Between  the  two 
pass  a  number  of  radial  fibres. 
The  retina,  as  will  be  shown 
later,  has  a  separate  blood 
supply  through  the  central 
artery  of  the  optic  nerve. 
Other  structures,  notably  the 
transparent  optical  media  of 
the  eye,  have  no  direct  blood 
supply  and  therefore  depend 
on  the  flow  of  lymph  from 
neighbouring  structures  for 
their  nutrition.  This  fluid  is 
formed  principally  by  the  cili- 
ary bodies,  and  is  called  aque- 
ous   humour. 

AQUEOUS  HUMOUR.  The 
chemical  composition  of  this 
fluid  is  water  containing  salts, 
traces  of  albumin  and  glob- 
ulin, and  a  reducing  sugar; 
it  is  probably  freely  oxy- 
genated. This  fluid  after 
secretion  leaves  the  eye  in  one  of  three  ways.  (1)  By  travelling 
through  the  pupil  into  the  anterior  chamber  of  the  eye  and  then  through 
the  spaces  of  Fontana  at  the  edges  of  the  iris  (the  so-called  filtration  angle) 
into  the  canal  of  Schlemm  and  thus  into  the  ciliary  veins.  (2)  Through  the 
crypts  in  the  anterior  surface  of  the  iris  into  the  veins  of  that  structure. 


Fig.  -■')'.     Diagram  to  show  the    blood  supply 
of  the  eyeball.     Arteries  'lined,'  veins  'black.' 


NOURISHMENT  AND   PROTECTION  OF  THE  EYE        51? 

(3)  Between  the  suspensory  ligaments  of  the  lens,  to  the  anterior  surface  of  the 
vitreous,  then  down  the  hyaloid  canal  to  the  papilla  of  the  optic  nerve,  and 
thus  out  via  the  lymphatics  of  the  nerve  sheath  or  the  retinal  vessels.  But 
whatever  the  fate  of  the  liquid  may  be,  it  is  clear  that  the  amount  secreted 
must  be  the  same  as  that  which  leaves,  because  otherwise  there  would  be 
a  variation  in  the  intraocular  pressure.  Insufficient  pressure  will  tend  to 
disturb  the  correct  relationship  between  the  internal  structures  of  the  eye, 
and  at  the  same  time  will  prevent  the  proper  action  of  the  ciliary  muscle  in 
causing  accommodation,  because  the  suspensory  ligaments  of  the  lens  will 
already  be  relaxed.  Too  great  a  pressure  on  the  other  hand  will  interfere 
with  the  proper  blood  supply  to  eye,  and  will  prevent  accommodation 
because  the  tension  in  the  choroid  will  be  too  great  for  the  ciliary  muscles 


I'm.  L'.jS.     Diagram  sin 


origin  and  fate  of  aqueous  humour. 


to  overcome  (see  page  52C>).  It  is  therefore  important  that  there  should 
be  a  proper  control  of  the  intraocular  pressure.  Experiments  by  Starling 
and  Henderson  in  which  the  intraocular  pressure  was  determined  by  a 
null  method  showed  that  such  a  mechanism  exists,  because  as  the  arterial 
pressure  increased,  so  also  did  that  in  the  eyeball. 

Whereas  the  arterial  pressure  varied  between  70  and  180  mm.  (by  a 
difference  of  110  mm.)  the  intraocular  pressure  was  found  to  vary  between 
23  and  40  mm.  (that  is  by  17  mm.  only).  The  change  in  intraocular  pressure 
is  therefore  less  than  one-sixth  that  taking  place  in  the  blood  ;  the  control 
mechanism  would  therefore  appear  to  have  very  considerable  efficiency. 

GLAUCOMA.  The  normal  intraocular  pressure  in  man  is  found  to  be 
between  25  and  30  mm.  of  mercury.  The  tension  thus  set  up  in  the  walls 
of  the  eyeball  is  principally  borne  by  the  sclera ;  to  some  extent  however 
assistance  is  rendered  by  the  choroid  owing  to  its  elasticity,  and  by  Tenon  s 
capsule  owing  to  the  tonic  contraction  of  its  smooth  muscle  fibres  (inner  vafri  I 
by  the  sympathetic). 

In  abnormal  conditions  the  efferent  channels  may  become  closed,  either 
from  pressure  of  the  lens  on  the  iris  (as  in  hypermetropia),oi  from  the  presence 


518 


PHYSIOLOGY 


of  epithelial  debris  in  the  anterior  chamber.  The  int  radicular  pressure  under 
these,  circumstances  becomes  very  high,  the  disease  being  known  as  glaucoma. 
The  principal  symptoms  of  glaucoma  are  pain  and  impaired  vision. 
The  chief  diagnostic  signs  are  a  stone-hard  eyeball,  sluggish  rather  dilated 
pupils,  and  the  retina  when  examined  through  the  ophthalmoscope  is  found 
to  show  cupping  of  the  optic  disc,  and  vessels  which  an-  thin  and  show  pulsa 


FlG.  259.     Arrangement   of  apparatus   for   measurement   of  intraocular  pressure. 

(Henderson  and  Starling.) 

c,  is  a  piston-recorder  for  recording  graphically  the  changes  in  pressure. 

tion.  In  treating  glaucoma  operative  measures  to  lower  the  pressure 
should  be  taken  immediately,  because  the  high  pressure  interferes  with 
the  proper  blood  supply  to  the  eye.  Since  all  hypermetropes  (persons  with 
long  sight)  have  a  tendency  to  suffer  from  glaucoma,  care  should  be  taken 
against  giving  drugs  such  as  atropine  which  cause  dilatation  of  the  pupil, 
since  this  increases  the  resistance  to  the  escape  of  fluid  at  the  filtration  angle, 
and  therefore  predisposes  to  an  attack  of  glaucoma. 

MALNUTRITION  OF  THE   EYE  shows  itself  in  many  ways  :    (1)  as  phlyctenular 

conjunctivitis  in  young  children  ;  (2)  as  myopia  in  school  children  in  whom  the  sclera 
being  ill-nourished  is  unable  to  withstand  the  intraocular  pressure,  so  that  the  sphericity 
of  the  eyeball  is  destroyed;  (3)  as  night  blindness  in  middle  age,  the  rod  elements  of 
the  retina  being  affected  ;  (4)  as  cataract  in  old  age.  In  this  condition  the  nutrition 
of  the  crystalline  lens  is  impaired,  and  as  a  result  it  loses  its  normal  transparency.  The 
opacity  develops  sometimes  at  the  centre  (nuclear),  sometimes  in  the  cortex.  The  condi- 
tion is  treated  by  removing  the  lens   (extraction   of  cataract). 


SECTION  V 

THE    OPTICAL    SYSTEM    OF    THE    EYE 

The  optical  system  of  the  eye  consists  of  those  structures  which  together 
locus  an  image  of  external  objects  on  the  retina.  In  the  mammalian 
eye  bhere  are  four  concerned :  the  cornea, the" aqueous  humour,  the  crystalline 
lens  and  the  vitreous  humour.  The  histology  of  the  cornea  has  already  been 
considered.  The  aqueous  humour  is  a  structureless  liquid.  The  vitreous 
humour  consists  of  anastomosing  trabecule  of  collaginous  material,  the 
interstices  of  which  are  filled  by  a  slowly  circulating  fluid  similar  to  aqueous 
humour.  The  vitreous  is  enclosed  in  the  hyaloid  membrane,  and  through 
the  middle  of  it  runs  the  hyaloid  artery  during  foetal  life,  which  goes  from 
the  central  artery  of  the  retina  to  the  posterior  surface  of  the  lens. 

THE  CRYSTALLINE  LENS  is  a  biconvex  transparent  elastic 
body,  enclosed  in  an  elastic  membrane  called  the  capsule.  To  the 
periphery  of  the  capsule  are  attached  the  suspensory  ligaments 
of  the  lens,  which  are  formed  by  the  anterior  radial  fibres  of  the 
thickened  portion  of  fchehyaloid  membrane  (the  zonula  of  Zinn).     Between 


-    5/nus  venosus 


Conjunctiva 


Retma 
Fig.  260,     Sectii 


through  anterior  part  of  eyeball  to  show    mode  of  suspi 
of  lens.     (After  Mkrkki.  and  Ku.i  n 


520 


PHYSIOLOGY 


the  suspensory  ligaments  are  shallow  pockets  into  which  the  ciliary  processes 
fit  closely.  In  this  way  the  lens  is  held  firmly  in  position,  while  at  the  same 
time  by  the  movement  of  the  ciliary  processes  under  the  action  of  the  ciliary 
muscle,  traction  can  be  applied  to  the  suspensory  ligaments,  thus  effecting  the 
change  in  curvature  of  the  lens,  which  will  be  shown  later  to  be  necessary 
for  accommodation. 

Histologically  the  lens  is  composed  of  a  number  of  radially  arranged  fibres 
each  of  which  is  a  modified  epithelial  cell.  These  fibres  are  arranged  in 
concentric  layers,  the  more  peripheral  being  soft,  nucleated  and  of  low 
refractive  index,  while  the  central  form  a  dense  non-nucleated  mass  of  high 
refractive  index,  the  fibrous  layers  between  having  an  intermediate  structure 
and  index. 

REFRACTION  BY  THE  CRYSTALLINE  LENS.  Refraction  occurs 
whenever  light  passes  from  a  medium  of  one  optical  density  into  another. 
It  is  due  to  the  fact  that  the  waves  of  which  the  beam  of  light  is  com- 
posed travel  more  slowly  in  a  dense  medium,  than  they  do  in  one  of  less 
density.  Some  of  the  effects  which  this  produces  are  shown  in  the  diagram 
below. 


Fig.  261.     Diagram  .showing  refraction  of  light. 

(A)  By  an  inclined  surface,  (B)  by  a  lens,  (C)  by  a  plate  of  greater  density  at 
its  lower  end  than  at  its  upper,  (D)  by  a  plate  of  greater  density  at.  its  centre  than 
at  its  edges.  (E)  by  a  lens  of  greater  density  at  its  centre  than  at  its  edges. 

At  A  plane  waves  are  seen  entering  a  dense  medium  at  an  angle.  At 
B  the  medium  is  lens  shaped.  At  C  the  medium  has  a  plane  surface  but 
has  a  greater  density  on  the  right  than  on  the  left.  At  D  the  medium 
has  a  plane,  surface  but  a  greater  density  at  its  centre  than  at  its  edges. 
At  E  the  medium  is  lens  shaped  as  at  B,  and  also  varies  in  density  as  at  D. 
The  very  great  refracting  power  of  such  a  structure  is  well  shown.    Since 


THE   OPTICAL  SYSTEM   OF  THE  EYE  521 

this  is  the  arrangement  found  in  the  lens  of  the  eye,  the  power  of 
refraction  is  very  much  greater  than  an  ordinary  lens  would  possess  of  the 
same  curvature  as  the  lens  and  the  same  refractive  index  as  the  average 
density  of  its  substance.  The  optical  properties  of  the  lens  are  therefore 
unique,  and  it  is  interesting  to  find  the  same  chemical  substance  in  the  lens 
of  different  morphological  groups  of  animals.  This  would  point  to  the 
substance  with  the  required  optical  properties  being  somewhat  rare.  To 
show  the  effect  which  the  increasing  density  of  the  lens  produces,  the  refrac- 
tive indices  of  its  parts  may  be  compared  with  its  equivalent  R.I.  (that  is 
the  refractive  index  of  a  glass  lens  of  the  same  size,  shape  and  focal  length). 
The  refractive  index  of  the  periphery  of  the  lens  is  1-37,  and  that  of  the  central 
nucleus  1 -41 ,  the  mean  being  about  1  -39.  But  the  equivalent  density  of  the 
lens  is  found  to  be  1  '42,  that  is,  greater  by  -03  than  the  mean  refractive  index 
of  its  substance.  The  lens  lies  in  contact  with  twTo  transparent  media 
both  of  which  have  an  approximate  refractive  index  of  1'34.  The  power 
of  the  lens  if  its  composition  was  uniform  would  therefore  be  proportional  to 
the  difference  between  its  own  mean  R.I.  (1-39)  and  that  of  its  surroundings 
(1"34),  that  is  to  0-05.  Owing  to  its  peculiar  structure  its  equivalent  R.I.  is 
1-42,  and  therefore  its  power  is  proportional  to  the  difference  between 
that  and  1-34,  that  is  to  0-08.  Owing  to  its  structure  the  lens  has 
therefore  increased  in  power  in  the  ratio  of  0-08  to  0"05.  Now  since  the  range 
of  accommodation  depends,  other  things  being  equal,  on  the  power  of  the 
lens,  we  see  that  the  peculiar  structure  of  the  lens  has  nearly  doubled  its 
range.  The  graduation  in  the  densities  of  the  different  layers  of  the  lens 
has  a  further  advantage  which  will  be  described  later,  in  that  it  reduces 
the  spherical  aberration  of  the  eye  as  a  whole  (see  page  531 )  and  also  reduces 
the  amount  of  scattered  light  within  the  eyeball. 

THE    OPTICAL    CONSTANTS    OF    THE    EYE.     In    the    case    of  the 
crystalline  lens,  two  methods  are  available  for  the  determination  of  the  radii 


observers  Ere 


Fig.  262.  Diagram  to  show  a  method  of  determining  the  curvature  of  the  anterior 
surface  of  the  cornea.  The  images  of  the  lamps  A  and  B  are  caused  to  coin- 
cide by  shifting  the  position  of  the  double  image  prism.  The  greater  the 
curvature  of  tin-  cornea  the  closermust  the  double  image  [irism  be  to  the  eye. 

of  curvature  of  the  anterior  and  posterior  surfaces,  namely  measurements 
mi  the  excised  lens,  either  in  the  air  or  preferably  suspended  in  a  fluid  oJ 


522  PHYSIOLOGY 

known  optical  properties,  or  by  estimating  the  apparent  size  of  the  images 
of  an  object  which  are  formed  by  reflection  at  its  surfaces.  In  order  that 
the  latter  method  shall  succeed,  a  device  must  be  employed  for  eliminating 
the  effect  of  chance  movements  of  the  eye  while  under  observation.  This 
was  first  done  by  Thomas  Young,  by  employing  a  method  used  in  astronomy 
namely  that  of  doubling  the  image  to  be  measured  and  then  adjusting  t  In* 
lower  edge  of  one  image  to  be  in  coincidence  with  the  upper  edge  of  the 
other.  If  the  eye  moved  (luring  the  determinations,  both  image.-,  moved 
together  and  therefore  difficulties  in  adjustment  were  avoided.  Jn  the  case 
of  the  cornea  this  method  is  alone  available  because  only  in  the  living  state 
is  the  true  curvature  preserved.  In  the  case  of  the  lens  the  determinations 
are  complicated  by  the  fact  that  the  refraction  of  the  cornea  has  to  be  allowed 
for.  Further,  the  images  that  are  seen  are  neither  bright  nor  sharply  defined  ; 
but  in  spite  of  this  considerable  accuracy  is  attainable.  The  following 
are  the   approximate  values  given  by  these  methods. 

Radius  of  cornea  ........  .8  mm. 

Radius  of  lens,  anterior  surface  ......  .10  mm. 

Radius  of  lens,  posterior  surface  .  .  .  .  .  .    i>  mm. 

THE  REFRACTIVE  INDICES  (optical  densities)  of  the  eye  media 
are  determined  on  the  excised  eye  by  means  of  the  Abbe  refractometer.  It 
is  found  that  the  cornea  and  aqueous  are  so  nearly  alike  that  for  all  practical 
purposes  they  may  be  regarded  as  one,  particularly  as  the  posterior  corneal 
surface  has  nearly  the  same  centre  as  the  anterior.  The  refractive  indices 
may  therefore  be  given  as  follows: — ■ 

Refractive  index'of  cornea  and  vitreous        .....  1-34  ■ 

Refractive  index  of  lens  (equivalent)    .....  .  I  "42 

Refractive  index  of  aqueous  humour    .....  .1  -.'!.'i 

THE  APPLICATION  OF  GAUSS'  THEOREM.  In  addition  to  the 
above  data  we  require  to  know  the  distance  between  the  principal 
surfaces;  these  are  found  to  be: — 

Distance  from  cornea  to  anterior  lens  surface  ....       3-6  mm. 
Distance  from  cornea  to  posterior  lens  surface  .  .  .       7-6  mm. 

Distance  from  cornea  to  the  retina  .....     220  mm. 

These  values  being  known  it  is  possible  by  calculation  to  determine  the 
path  of  any  ray  through  the  eye.  The  problem  is  however  made  very  much 
simpler  by  the  application  of  Gauss'  theorem,  which  may  be  briefly  stated 
as  follows.  Any  system  of  spherical  optical  surfaces,  the  centres  of  which 
lie  along  a  straight  line,  possesses  six  cardinal  points,  namely — two  principal 
points  h  and  h',  two  nodal  points  K'andK',andtwTo  focal  points,  the  anterior 
</>  and  the  posterior  <$>' .  It  is  found  that  these  have  certain  properties  which 
may  be  summarised  as  follows  : — 

An  object  placed  at  the  first  principal  point  is  found  after  refraction 
to  be  at  the  second.  Further,  the  image  and  its  object  are  found  to  be  of  the 
same  size.  A  ray  passing  through  the  first  nodal  point  on  its  way  into 
the  system  appears  to  come  from  the  other  on  its  way  out,  hut  its  direction 


THE  OPTICAL  SYSTEM  OF  THE  EYE 


523 


is  still  parallel  to  the  path  which  it  travelled  initially.  A  ray  passing  through 
either  focus  leaves  the  lens  system  on  the  other  side  parallel  to  the  axis.  It 
is  further  found  that  the  distances  between  some  of  these  points  are  equal, 
for  example  : — </>h  =  K'4>'  and  h'<£'  =  <£K.  Also  hh'  =  KK'.  The 
positions  of  these  cardinal  points  has  been  determined  in  the  case  of  the 
eye  with  considerable  accuracy  ;  the  following  approximate  values  may  be 
given  : — 


Distance  from  front   of  cornea  to  first  principal  point        h 
to  second  principal  poinl    h' 


to  first  nodal  point 
to  second  nodal   poinl 
to  anterior  focus 
to  posterior  focus 
to  retina. 


K 

K' 


1  -7  mm. 
2-0  mm. 

7-0  mm. 

7-3  nun. 
136  mm. 
22'6  mm. 

22'6  mm. 


The  position  of  these  points  being  determined,  the  direction  of  the  rays 
of  light  through  the  eye  can  be  easily  obtained,  and  is  shown  diagrammatically 
in  Fig.  263. 


Fig.  263.     The  optical  system  of  the  eye  shown  diagrammatically, 
H  and  H'  principal  points.     K  and  K'  nodal  points.     </>  and  0'  anterior  and 
posterior  foci. 

It  is  of  some  interest  to  know  the  relative  part  taken  by  the  various 
refractive  media  of  the  eye  in  the  formation  of  the  image.  By  far  the 
greater  part  is  performed  by  the  cornea.  The  following  values  in  mm. 
and  dioptres  may  be  given  : — 

Mm,  Dioptres. 

.24  ..  42 

.44  ..  23 

.    15-5  ..  65 


Focal  length  of  the  cornea   . 
of  the  lens 
of  the  whole  eye 


When  opacities  form  in  the  lens  (cataract)  this  structure  "is 
removed  by  operation.  It  is  then  found  that  a  lens  of  approximately 
23  dioptres  has  to  be  worn  by  the  patient  in  order  that  he  may 
see  distinctly.  When  the  eye  is  placed  under  water  the  refraction  <>l  the 
cornea  is  necessarily  abolished  because  water  has  approximate]}'  the  same 
refractive  index.  Underthese  conditions  the  eye  becomes  too  long  sighted 
for  distinct  vision.     The  eye  of  the  fish  has  met  this  difficulty  by  the  provision 


524  PHYSIOLOGY 

of  a  small,  nearly  spherical  lens  of  very  great  density.  In  the  fish  therefore 
the  lens  takes  the  principal  part  in  the  refraction  of  the  ilight  so  as 
to  form  an  image. 

REDUCED  EYE.  It  is  an  interesting  fad  that,  owing  to  the  closeness 
of  the  principal  and  nodal  points  to  one  another,  it  is  possible  to  imagine  the 
media  of  the  eye  replaced  by  a  single  optical  surface  without  introducing 
any  appreciable  error.  To  this  system  is  given  the  title  '  reduced  eye.' 
Its  constants  are  given  in  the  following  Table:  — 

Radius  of  surface             .          .          .          .          .          .          .  ">        in  in. 

Position  of  principal  point     ......  .        215     mm. 

Position  of  nodal  point            .          .          .          .          .          .  .        71     mm. 

Position  of  retina            .          .          .          .          .          .          .  22  C    mm. 

Refractive  index    .          .          .          .          .          .   •                 .  .1  '33  mm. 

Focal  length           ........  .      15'5    mm. 

THE    ACCOMMODATION    OF    THE    EYE 

The  above  description  has  been  made  on  the  supposition  that  the  rays 
entering  the  eye  consist  of  parallel  bundles,  or  in  other  words  that  the  objects 
seen  are  at  an  infinite  distance  from  the  eye.  But  during  near  vision  such 
is  by  no  means  the  case.  If  there  were  no  means  of  varying  the  focus  of 
the  eye  it  would  not  be  possible  for  divergent  rays  (those  coming  from  near 
objects)  to  be  brought  to  a  focus  on  the  retina.  The  mechanism  for  varying 
the  focus  of  the  eye  is  called  the  accommodation. 

THE  THEORIES  OF  ACCOMMODATION.  Of  these  three  are  of  historic  interest 
only.  (1)  That  during  accommodation  the  cornea  increases  in  curvature  (similar 
to  the  bird's  eye).  This  was  disproved  by  Thomas  Young  who  placed  his  eye  under 
water,  replaced  the  corneal  refraction  by  a  convex  lens,  and  then  found  the  amplitude 
of  accommodation  unaffected.  (2)  That  the  eye  elongates  in  near  vision,  thus  causing 
the  rays  from  near  objects  to  focus  on  the  retina  (similar  to  the  arrangement  in  the  mollusc 


Fig.  204      Methods  by  which  accommodation  of  the  refraction  of  the  eye  for  objects 

at  different  distances  could  be  effected. 
(A)  By  lengthening  the  eyeball.     (B)  By  increasing  curvature  of  cornea. 
(C)  By  moving  lens  forward.     (D)  By  increasing  curvature  of  lens. 

Pecten).  This  also  Thomas  Young  disproved  by  placing  two  iron  rings  which  could  be 
clamped  together,  one  in  front  of  and  one  behind  the  eyeball.  Having  very  prominent  eyes 
he  could  do  this  if  the  eye  being  tested  were  rotated  strongly  inwards.  The  phosphene 
caused  by  the  pressure  of  the  posterior  ring, which  extended  to  the  fovea,  did  not  change 
in  appearance  during  accommodation.  He  thus  found  no  evidence  for  an  elongation 
of  the  eye  during  accommodation.  (3)  That  the  lens  during  near  vision  advances 
towards  the  cornea  (similar  to  the  mechanism  in  the  fish's  eye).  This  view  was 
disproved  Ijv  Tscherning,  who  calculated  that  the  lens  would  have  to  advance 
nearly  10mm.  in  order  to  give  the  lull  amplitude  found  for  the  eye,  whereas  the  anterior 


THE   OPTICAL  SYSTEM   OK  THE    EYE 


525 


chamber  of  the  eye  is,  as  we  have  seen,  approximately,  --6  mm.  only.  This  brings  us  to 
the  two  modem  theories,  that  of  Hehnholtz  and  Tscheming.  The  theory  of  the  former 
(which  is  the  one  most  generally  accepted)  supposes  that  the  lens  when  removed  from 
the  eye  is  strongly  convex  and  is  accommodated  for  near  vision.  When  in  the  eye 
however,  it  is  caused  to  become  flatter  through  the  traction  of  the  zonula  of  Zinn  (suspen- 
sory ligaments)  on  the  edges  of  its  capsule,  and  is  therefore  focussed  for  distance.  But 
when  the  ciliary  muscle  contracts,  it  removes  the  tension  on  the  zonula  and  therefore 
allows  the  lens  to  return  by  its  elasticity  to  its  more  spherical  form.  Before  describ- 
ing the  rival  theory  it  would  be  well  to  examine  the  principal  evidence  on  which 
Helmholtz'  theory  has  been  based.  During  near  vision  measurement  by  means  of 
the  ophthalmometer  shows  that  the  anterior  surface  of  the  lens  advances  slightly  and 
becomes  at  the  centre  of  much  greater  curvature  (10  mm.  radius  for  distant  vision,  to 
fi  mm.  for  near).  There  can  thus  be  no  question  that  tin-  change  in  the  curvature 
nt  the  lens  is  responsible  for  accommodation.     The  posterior  surface  is  found  to  change 


Fig.  265.      Diagram  to  show  the  changes  in  the  position  and  shape  of  the  eye  structures 
ilurirc<  accommodation.     Thin  line  at  rest  ;  thick  line  during  accommodation. 

but  little  ;  almost  the  whole  range  is  therefore  produced  by  the  anterior  surface.     The 
i  bangee  found  to  occur  in  the  lens  may  therefore  be  summarised  as  follows: — 

Distance  Near 

Radius  of  anterior  surface          .          .          .          .          .10  . .  6 

Radius  of  posterior  surface         .          .          .          .          .6  .  .  5-5 

Thickness  of  lens       .          .          .          .          .          .          .3-0  .  .  4 

Focus  of  lens  in  mm.         ......     44  30 

Focus  of  lens  in  dioptres            .          .          .          .          .23  . .  33 

If  the  lens  in  near  vision  becomes  more  spherical  owing  to  the  relaxation  of  the 
zonula,  as  Helmholtz  supposed,  we  should  expect  a  lens  removed  from  the  eye  to  be 
more  spherical  still,  that  is  in  a  state  of  strong  accommodation.  Tscheming  stated  that 
the  changes  in  the  curvature  of  the  lens  are  much  more  complex  than  those  given  above. 
During  accommodation  not  only  is  there,  he  says,  an  increase  in  the  curvature  near  the 
centre  of  the  lens,  but  at  the  same  time  a  decrease  in  the  curvature  at  the  periphery. 
This  view  he  supported  by  quoting  the  careful  measurements  which  Young  made  by 
means  of  his  optometer,  and  which  have  been  confirmed  by  other  observers.  There 
is  found  to  be  a  zone  about  1-4  mm.  from  the  centre  of  the  lens  where  the  curva- 
ture does  not  change  appreciably.  Inside  this  zone  the  curvature  increases  during 
accommodation,  whereas  outside  the  lens  becomes  flatter. 

Tscheming  supposed  that  these  changes  of  curvature  are  produced  by  increase  in  the 
tension  of  the  zonula  during  accommodation,  in  other  words  exactly  the  opposite  action 
to  that  which  Helmholtz  supposed  to  occur.  This  question  as  to  whether  contraction 
of  the  zonula  is  associated  with  near  or  distant  vision  can  therefore  be  used  as  a  criterion 
between    tin-    rival    theories.      Experiments    have    shown    that    tin-    choroid    moves 


526  PHYSIOLOGY 

forward  during  accommodation  in  both  man  and  animals;  further,  Hess  has  shown  that, 
when  lull  accommodation  has  been  performed,  the  lens  is  only  loosely  supported,  so  that 
gravity  can  act  on  it  and  cause  it  to  sink  slightly  in  relationship  to  the  other  eye  struc- 
tures. These  i-ITeets  appeal-  to  he  definitely  in  favour  of  Helmholtz'  theory,  and  against 
that  of  Tscherning.  The  way  in  which  the  contraction  of  the  ciliary  muscles  causes 
slackening  of  die  zonula  may  therefore  be  given  with  some  degree  of  confidence  on 
Helmholtz'  theory. 

THE  MECHANISM  OF  ACCOMMODATION.  The  ciliary  muscle  con- 
sists of  two  separate  sets  of  unstriated  muscle  fibres,  the  more  superficial 
set  of  radial  or  longitudinal  fibres,  the  deeper  of  bundles  of  radial  fibres. 
The  former  take  their  origin  from  the  sclero-corneal  junction,  and  are  attached 
to  the  anterior  part  of  the  choroid  coat  behind  the  ciliary  processes.  When 
these  fibres  contract,  they  draw  the  choroid  forward  and  inward,  the 
ciliary  processes  tending  to  occupy  a  smaller  circle.  The  circular 
fibres  lie  in  the  substance  of  the  base  of  the  ciliary  processes  so  that, 
when  they  contract,  they  cause  the  apices  of  the  processes  to  come 
together.  In  addition  to  these  two  sets  of  fibres  a  third  set  has  been 
described  as  meridional.  These  are  however  part  of  the  radio-longitudinal 
set  from  which  there  does  not  appear  to  be  much  object  in  differentiating 
them.  The  ciliary  muscles  therefore  have  a  common  action,  causing  the 
ciliary  processes  to  form  a  smaller  circle.  The  zonula  of  Zinn,  or  sus- 
pensory ligament,  is  formed  of  a  large  number  of  very  fine  fibres  which 
run  from  the  ciliary  processes  to  the  capsule  of  the  lens.  Further  those 
which  arise  posteriorly  are  attached  anteriorly  and  vice  versa.  When  the 
ciliary  muscle  is  in  a  state  of  rest,  the  tension  in  the  choroid  set  up 
by  the  intraocular  pressure  causes  the  ciliary  processes  to  be  pulled 
in  an  outward  and  backward  direction  and  therefore  puts  tension  on  the  lens 
capsule  through  the  zonula.  The  lens  therefore  tends  to  be  flattened  and 
accommodated  for  distance.  On  stimulating  the  ciliary  muscle  the  tension 
in  the  choroid  is  opposed  and  the  ciliary  processes  approximated.  The 
zonula  thus  becomes  slack,  and  the  tension  of  the  lens  capsule  decreases, 
allowing  the  lens  to  take  up  its  more  natural  spherical  shape,  and  thus  to 
focus  the  rays  from  nearer  objects. 


Fig.  266.     Accommodation   in   the   cat's  eye.     R,   distance  ;     a.   for  near  vision. 
(After  Beer.) 
Two   needles   have  been  passed  through  the  edge    uf   cornea  into   the  ciliary 
bodies,  to  show  forward  movement  of  the  hitter  during  accommodation. 


THE   OPTICAL  SYSTEM   OF  THE   EYE  527 

INNERVATION  OF  MECHANISM  OF  ACCOMMODATION.  The  ciliary 
muscle  is  innervated  through  the  3rd  nerve,  its  nucleus  being  situated  near 
the  mid  line  under  those  of  the  pupils.  Owing  to  the  close  association 
of  the  nuclei  on  the  two  sides  it  is  impossible  to  cause  accommodation  of 
the  eyes  separately.  From  these  nuclei  the  fibres  travel  down  with  the  rest 
of  the  nerve  through  the  outer  wall  of  the  cavernous  sinus,  and  when  they 
reach  the  orbital  cavity  are  given  off  to  the  ciliary  (lenticular)  ganglia,  where 
they  anastomose  with  nerve  cells  the  processes  of  which  then  proceed  through 
the  short  ciliary  nerves  to  the  eyeball. 

The  position  of  the  higher  centres  connected  with  the  nuclei  concerned 
in  accommodation  are  not  definitely  known  ;  it  is  believed  that  theycomefrom 
the  occipital  cortex.  But  since  it  is  possible  to  carry  out  willed  changes  of 
Eocus  as  well  as  subconscious  ones,  there  must  be  connections  with  other 
parts  of  the  brain  as  well. 

THE  AMPLITUDE  OF  ACCOMMODATION  in  the  emmetropic  (normal)  eye  is 
measured  by  ascertaining  the  nearest  point  from  the  eye  at  which  perfect  vision  can 
be  obtained.  Since  it  is  possible  that  the  eyes,  when  examined  separately,  can  focus 
nearer  objects  than  they  can  when  used  together  (owing  to  the  limitation  in  the  power 
of  convergence),  one  of  the  eyes  should  be  closed  when  making  the  determination.  In 
the  ametropic  (abnormal)  eye  it  is  necessary  to  determine  the  far  jxiint  as  well  as  the 
near,  since  the  former  is  not  at  infinity  as  it  is  in  the  emmetropic  eye.  But  other  diffi- 
culties are  encountered,  because  in  the  case  of  hypermetropic  (long-sighted)  eyes  an 
object  placed  at  infinity  still  requires  some  accommodation  in  order  to  focus  it.  Lastly 
there  comes  the  personal  equation  of  the  patient,  because  it  is  found  that  even  when 
apparent  Ly  fully  relaxed,  the  instillation  of  atropine  usually  causes  some  further  relaxa- 
tion of  the  accommodation  ;  so  in  the  same  way  the  instillation  of  eserine  is  usually 
Followed  by  a  definite  increase  in  the  accommodative  effort  over  that  which  can  be 
voluntarily  exerted.  To  obtain  the  maximum  amplitude  of  the  accommodation  these 
drugs  should  therefore  be  used.  Where  a  comparative  and  relatively  inaccurate  value 
is  alone  required  they  may  be  omitted.  Of  the  many  methods  that  may  be  employed 
probably  the  simplest  is  by  the  use  of  the  set  of  trial  lenses,  which  vary  in  their  curvature 
by  small  uniform  amounts  from  strongly  convex  (plus)  to  strongly  concave  (minus). 
Tin-  test  object  consists  of  a  pin  placed  vertically  in  a  board  at  any  fixed  distance  from 
i he  eye.  a  white  surface  being  arranged  behind  it.  A  pair  of  spectacles  to  hold  the  trial 
lenses  arc  placed  before  the  eyes,  and  in  them  are  inserted  two  metal  plates  witl  two 
vertical  slits  in  them,  so  that  each  eye  in  turn  may  look  at  the  test  object  through  the 
slits  in  the  plate  opposite  it.  To  determine  the  near  point,  minus  (concave)  lenses  of 
gradually  increasing  power  are  placed  before  one  of  the  eyes,  the  other  being  closed, 
until  one  is  found  that  just  causes  the  image  of  the  pin  to  appear  double.  The  power 
of  the  next  weaker  lens  is  therefore  taken  to  be  the  correct  one.  To  determine  the  far 
point,  plus  (convex)  lenses  of  increasing  power  are  tried  in  a  similar  manner,  and  that 
one  taken  which  just  does  not  cause  appreciable  doubling.  The  difference  between  the 
]  >ower  of  the  two  lenses  found  in  this  way  gives  in  dioptres  the  value  of  the  amplitude  of 
the  aeeonmioil.il  ion.  ( 'are  should  be  specially  taken  to  see  that  the  value  found  for  the 
concave  lens  has  the  minus  sign  placed  in  front  of  it.  Thus  if  it  was  found  that  the 
far  point  was  reached  by  the  use  of  a  convex  lens  of  2-2S  dioptres,  and  that  the  near- 
point  required  a  concave  one  of  7-5  D.,  then  the  amplitude  is  not  5-25  D.  but  9-75  D. 
Careful  measurements  made  in  the  above  manner  show  that  there  is  for  different 
ages  a.n  average  amount  of  accommodation.  In  youth  the  amplitude  is  large,  but  h 
decreases  uniformly  to  old  age.  and  this  decrease  is  called  presbyopia  (old-sight).  The 
amplitude  found  as  a,  rule  at  different  ages  is  approximately  constant  and  is  given  in  the 
Table  below. 


528  PHYSIOLOGY 

Age  iii  years.  Accomi lotion  in  dloptffea. 

10 13-8 


15 

20 
25 
30 
35 
4(1 
45 
50 
55 
fin 


12-6 

1 I  -5 
10-2 
8-9 

7-:< 
5-8 
3-7 

2-11 
[•3 
11 


This  gradual  reduction  in  the  amplitude  oi  the  accommodation  is  caused  by  the 
hardening  of  tin-  crystalline  lens,  which  with  the  advance  of  years  robs  it  of  the  elasticity 
of  youth.     As  a  rule  the  change  goes  on  unheeded  till  the  time  comes  when  the  near 

point  of  vision  has  receded  so  far  from  the  eye  that  the  I k  lias  to  be  held  at  a  distance, 

in  order  to  be  focussed  clearly.  Then  it  is  found  that  the  print,  particularly  if  it  is  fine, 
becomes  unreadable,  and  convex  glasses  have  to  be  worn.  It  is  at  that  time  that 
presbyopia  may  be  said  to  begin,  usually  at  an  age  of  45  to  50,  in  emmetropia.  In 
hypermetropia,  presbyopia  shows  itself  earlier  than  normal,  and  in  myopia  (short-sight) 
later.  The  reason  for  these  differences  will  be  described  later  when  dealing  with  these 
conditions. 

The  mechanism  of  accommodation  is  affected  in  a  number  of  pathological  con- 
ditions ;  the  principal  ones  will  be  given.  Paralysis  of  the  ciliary  muscles  frequently 
occurs  after  diphtheria  and  influenza:  it  is  probably  due  to  bacterial  toxins 
circulating  in  the  blood.  The  paralysis  usually  disappears  during  convalescence.  Loss 
of  accommodation  is  frequently  one  of  the  first  symptoms  of  glaucoma:  in  this  case  the 
cause  is  the  abnormally  high  intraocular  pressure,  since  that  will  cause  so  great  an 
increase  in  the  normal  tension  of  the  choroid  that  the  ciliary  muscles  have  not  sufficient 
power  to  draw  the  edges  of  the  choroid  and  ciliary  bodies  into  a  circle  of  smaller  radius, 
and  thus  to  allow  the  lens  to  accommodate.  Apparent  diminution  of  the  amplitude  of 
accommodation  combined  with  apparent  myopia  (short-sight)  occurs  in  patients  who 
have  spasm  of  the  ciliary  muscles.  This  is  found  in  two  types  of  cases,  children  with 
eye-strain,  and  women  with  hysteria.  In  both  the  employment  of  atropine  yields  the 
normal  amplitude  and  at  the  same  time  removes  the  apparent  myopia,  thus  indicating 
the  cause  of  the  trouble.  Occasionally  the  amplitude  of  accommodation  is  different 
in  the  two  eyes,  and  is  accompanied  by  unequal  pupils.  Such  a  condition  may  follow 
an  accident  or  be  caused  by  specific  toxins. 

THE  EFFECT  OF  DRUGS  on  the  accommodation  has  already  been  alluded  to. 
In  ophthalmic  practice  three  are  used  in  order  to  paralyse  the  ciliary  muscle,  namely 
atropine  (one- half  per  cent,  solution),  homatropine  (2  per  cent.)  and  scopolamine  (one- 
fifth  per  cent.).  One  of  these  drugs  is  placed  within  the  conjunctival  sac,  and  from  here 
it  slowly  travels  by  an  at  present  unknown  route  to  the  ciliary  and  iris  muscles,  both  of 
which  are  paralysed.  This  fact  is  of  the  greatest  importance,  for  if  this  path  did  not 
exist  the  use  of  these  valuable  drugs  would  hardly  be  possible.  Contraction  of  the 
ciliary  muscles  and  of  the  sphincter  pupilhe  is  caused  by  the  three  drugs  eserine. 
pilocarpine  and  physostigmine,  One  of  these  is  often  used  to  counteract  the  effects 
of  the  atropine  group. 


SECTION  VI 

THE    REFRACTION    OF    THE    EYE 

Since  the  eye  forms  an  imago  of  external  objects  by  means  of  its  refracting 
media,  it  is  found  to  have  properties  and  to  sutler  from  defects  similar  to 
those  met  with  in  the  case  of  other  optical  systems.  We  may  therefore 
treat  the  eye  as  if  it  were  an  optical  instrument  and  estimate  its  efficiency 
from  that  point  of  view.  In  the  first  place  therefore  we  must  consider  what 
kind  of  an  image  it  would  form  if  it  were  a  perfect  lens  system,  suffering  from 
no  kind  of  aberration.  Our  experience  of  other  lens  systems,  well- 
nigh  perfect,  has  shown  us  that  the  image  of  a  distant  point  source  of  light 
is  nut  a  mathematical  point,  as  geometrical  optics  would  have  us  believe, 
but  is  on  the  contrary  a  definite  pattern  of  quite  considerable  size,  the  shape 
and  dimensions  of  which  can  cither  be  calculated  from  the  conditions,  or 
may  be  seen,  measured  and  photographed  by  appropriate  means.  The 
formation  of  this  pattern  is  flue  not  to  any  defect  of  the  lens,  but  to  tin- 
fact  that  light  is  a  form  of  wave  motion,  which  exhibits  a  property  called 
diffraction. 

DIFFRACTION  OF  LIGHT.  When  a  broad  wave  of  light  surges  through 
the  other  from  a  distant  source  of  light,  its  front  travels  straight  and  inflexible 
under  the  influence  of  certain  well-known  laws.  These  in  popular  language 
lest  rain  the  tendency  of  a  portion  of  the  wave  front  to  deviate,  because  of 
.in  equal  efi'ort  of  a  neighbouring  portion  of  the  wave  front  to  do  the  same 
thing,  only  in  (lie  opposite  direction.  At  the  edges  of  the  wave  on  the  other 
hand  there  is  no  neighbouring  portion  from  which  to  obtain  support,  and 
therefore  these  edge  portions  tend  to  spread  sideways  more  and  more  from 
the  main  wave.  A  narrow  ray  of  light  therefore  after  passing  through  the 
pupil  of  an  optical  system,  will  show  this  phenomenon  to  such  a  marked  extent, 
that  only  a  small  portion  of  the  total  amount  of  light  will  actually  reach 
the  goal  defined  by  the  original  wave  front.  The  smaller  the  pupil  and 
I  herefore  the  narrower  the  beam  of  light,  the  greater  the  amount  of  spreading 
that  we  should  expect  to  find.  And  experiment  shows  that  this  is  the  case. 
Further,  we  should  suppose  that  in  the  case  of  any  one  beam  the  more  spread- 
ing would  occur  the  further  the  ray  has  to  travel.  This  also  is  found  to 
be  the  case.  Lastly  if  waves  of  different  wavelength  were  tried,  we  would 
expect  a  short  wave  to  suffer  more  than  a  long,  because  to  the  short  wave  the 
distance  travelled  would  seem  relatively  greater.  And  so  it  is.  We  can 
therefore  summarise  the  above  by  saying  that  the  size  of  the  diffraction 
pattern  formed  by  any  lens  system  varies  directly  as  the  focal  length  ol  the 
system  anil  the   wavelength  of   the  light,  and  inversely  as  the  diameter  of 

529  34 


530  PHYSIOLOGY 

the  pupil  "through  winch  the  lighl  passes.  In  the  caseoJ  any  lens  system 
such  as  the  eve  in  which  the  pupil  is  circular,  experimenl  and  calculation 
are  agreed  thai  the  image  of  a  point  source  consists  of  a  series  of  concentric 
rings  of  light,  having  a  bright  spot  at  their  centre.  The  diameter  of  this 
spot  in  the  case  of  the  eve  is  found  to  be  0'0]  mm.  with  a  pupil  of  '1  mm. 
diameter.  No  matter  how  perfect  the  eye  be  as  an  optical  instrument,  diffrac- 
tion sets  a  limit  in  this  way  to  the  perfection  of  the  image  that  can  be  formed. 
This  should  not  however  be  thought  of  as  a  defect  but  as  a  property,  since 
it  is  caused  by  the  nature  of  light  itself.  In  the  consideration  of  the  principal 
optical  errors  of  the  normal  eve  we  have  to  decide  in  each  case  not  only 
to  what  extent  the  defect  is  present,  but  whether  the  defect  produces  any 
noticeable  change  in  the  diffraction  pattern  which  may  affect  definition. 

DEPTH  OF  FOCUS,  like  diffraction,  is  a  property  of  a  lens  system  and  not  an 
aberration.  Its  origin  may  be  explained  as  follows: — Suppose  objects  100  metres 
awaj  lo  be  forming  sharp  images  on  the  retina,  then  objects  at  200  metres  will  form 
images  which  come  to  a  focus  slightly  in  front  of  the  retina,  and  objects  at  f>0  luetics 
images  that  are  slightly  behind.  If  however  the  focussing  paints  arc  only  a  short 
distance  In  front  of  or  behind  the  retina,  the  image  of  a  distant  point  which  fell  on  a 
single  .one  would  still  do  so  because  the  cone  has  a  certain  diameter,  although  its  distance 
from  the  eye  hail  been  altered.  Depth  of  focus  in  the  ease  of  the  eye  is  the  greatest 
distance  through  which  a  point  can  be  moved,  and  still  produce  an  image  which  tall., 
exactly  on  a  cone  without  spreading  at  all  on  to  neighbouring  ones.  For  example, 
in  the  above  case  the  distance  moved  was  from  lit K >  to  oil  metres,  that  is.  the  depth  of 
torus  was  150  metres.  Now  it  is  found  in  the  case  of  any  lens  system  that  depth  varies 
with  the  aperture  of  the  pupil.  Thus  in  the  case  of  the  eye  the  following  values  are 
obtained. 

Pupil  diameter,  Dspthat  infinity.  Depth  at  25  cms. 

1  mm.  From  inf.  to  S    metres  ....         3-2     cm. 

2  ..  ..  „     16                        ....          Mi  ., 

3  „  ..  „     24         ..             ....         II  .. 

4  „  .          .              ..  ,.     32         ..              ....            -8  „ 

We  see  therefore  that  not  only  does  depth  decrease  as  the  aperture  of  the  pupil 

increases,  but  that  it  also  decreases  as  the  mean  distance  of  the  objects  from  the  eye 
decreases.  Thus  with  a  pupil  of  3  mm.  the  eye  if  focusscd  sharply  on  objects  24  metres 
away,  would  also  be  in  focus  for  objects  at  infinity  and  also  for  objects  at  12  metres. 
Depth  of  focus  is  therefore  considerable  at  this  distance.  But  if  the  eye  is  working  at 
the  ordinary  reading  distance  (25  cm.)  depth  would  be  IT  cm.  only.  At  a  pupil  diameter 
of  1  mm.  depth  would  be  increased  threefold,  and  therefore  the  closure  of  the  pupil, 
which  accompanies  accommodation  and  convergence  for  near  objects,  has  the  valuable 
property  of  increasing  the  depth  of  focus  at  the  same  time. 

CHROMATIC  ABERRATION  OF  THE  EYF.  It  was  shown  in  Section  1 
that  white  light  consists  of  a  number  of  rays  of  different  wavelength. 
and  that  the  short  rays  on  refraction  are  more  bent  than  the  long. 
When  therefore  white  light  is  incident  on  a  lens,  the  rays  of  short 
wavelength  come  to  a  focus  in  front  of  those  of  longer  wavelength.  This 
difference  of  focus  for  rays  of  different  colour  is  called  chromatic  difference 
of  focus.  Experiment  show's  that,  when  such  a  series  of  foci  are  formed 
by  the  eye,  the  accommodation  is  so  adjusted  that  the  rays  of  greatest 
intensity  (usually  yellow  rays)  form  the  most  sharply  focussed  image,  and 
the  colours  of  longer  and   shorter  focus  form  blurred  discs  of  light  of 


THE   REFRACTION  .  OF  THE   EYE  531 

relatively  low  intensity  on  top  of  this.  Under  these  conditions  it  is  found 
that  quite  well  defined  images  are  produced.  Tims,  with  a  pupil  of  2  mm. 
diameter,  approximately  70  per  cent,  of  the  light  falls  in  an  area  of 
0*005  mm.  diameter.  Further  it  may  be  shown  that  a  lens  system  such  as 
the  eye,  which  suffers  from  chromatic  alienation,  produces  an  image  that 
is  only  just  appreciably  worse  than  one  that  is  perfectly  corrected,  when 
the  effects  of  diffraction  are  taken  into  account  in  both" cases.  Bui  since  the 
effects  of  chromatic  aberration  increase  as  the  pupil  enlarges,  while  those 
caused  by  diffraction  decrease,  it  is  clear  that  the  larger  the  pupil  the  more 
does  chromatic  alienation  tend  to  spoil  definition.  But  as  this  is  accom- 
panied by  decrease  in  diffraction,  the  two  changes  taken  together  have  the 
cll'cct  of  leaving  the  actual  definition  practically  unchanged.  This  important 
conclusion  will  be  referred  to  again  more  fully  in  the  last  section. 
Beside  effects  on  definition,  chromatic  aberration  causes  small  bright 
points  of  light  on  a  dark  ground  to  form  images  which  are  largely 
composed  of  yellow  rays,  and  on  the  other  hand  small  black  objects 
on  a  bright  ground  to  be  purple  in  colour-.  The  reason  for  these  colours 
being  unnoticed  in  ordinary  circumstances  is  due  to  the  recognition  by 
the  eve  of  the  presence  of  the  complementary  colour  which  forms  a  fringe 
round  the  central  point. 

SPHERICAL  ABERRATION  OF  THE  EYE.  The  employment  of 
spherical  surfaces  to  bound  optical  media  leads  to  a  difference  in  the 
position  of  the  foci  of  rays  that  have  passed  through  the  centre  of 
the  lens  anil  those  that  have  passed  through  the  more  peripheral  parts. 
The  latter  usually  form  a  locus  nearest  to  the  lens,.  Since  the  eye  is 
bounded  by  nearly  spherical  curves  it  has  keen  assumed  thai  this  aberra- 
tion must  be  present  in  this  organ.  It  should  be  remembered  however 
that   the  crystalline   lens   has  a   structure  quite  different    to   that    found   in 

the  lens  systems  of  optical  instruments.     For  the  presenc I  a,  graduation 

of  optical  density,  culminating  in  a  nucleus  of  relative  great  curvature,  causes- 
rays  passing  through  the  centre  of  the  eye  to  be  refracted  to  a  greater 
extent  than  more  peripheral  rays,  or  in  other  words  exactly  the  opposite 
effect  to  that  produced  by  spherical  alienation.  .Measurements  on  the  eyes 
of  different  individuals  therefore  show  the  presence  both  of  small  amounts 
of  under  correction  (when  the  correcting  effect  of  the  lens  nucleus  has  not 
1  cm  enough)  and  also  actually  of  over  correction  (when  the  lens  nucleus 
has  had  too  big  an  effect).  In  quite  a  number  of  cases  the  amount 
of  spherical  aberration  is  negligible  even  with  pupils  of  4  mm.  diameter-. 
With  larger  pupils  there  is  probably  a  certain  amount  of  under  correction, 
but  this  again  is  less  than  would  be  found  in  the  case  of  spherical  surfaces 
because  the  more  peripheral  parts  of  the  cornea  are  flattened  and  therefore 
refract  less  (as  Gullstrand  has  shown).  We  may  say  therefore  that  in  every- 
day life  the  effects  of  spherical  aberration  are  altogel  ber  negligible,  compared 
with  those  of  diffraction  and  chromatic  aberration. 


PHYSIOLOGY 

PERIPHERAL    ABERRATIONS    OF    THE    EYE. 

So  far  the  definition  of  an  image  lying  on  the  principal  axis  of  the 
lens  has  alone  been  considered.  When  this  is  not  the  case  other  conditions 
are  encountered  which  introduce  less  favourable  conditions.  In  the  first 
place  the  rays  that  form  images  on  the  peripheral  parts  of  the  retina  make 
considerable  angles  with  the  surfaces  of  the  eye  media.  This  will  cause 
chromatic  difference  of  magnification,  since  blue  rays  will  be  more  bent 
and  will  therefore  form  smaller  images  than  red  rays.  It  will  also  introduce 
'  comma,'  that  is,  the  effect  due  to  disobedience  of  the  sine  condition.  It 
is  seen  at  once  therefore  that  the  image  formation  by  the  periphery  of 
the  eye  is  altogether  more  imperfect  than  it  is  at  the  centre. 
The  presence  of  the  nucleus  of  the  lens  still  further  impairs  the  marginal 
definition.  In  fact  we  may  say  that  in  the  eye,  as  in  the. microscope  objective, 
the  marginal  images  have  been  sacrificed  in  order  thereby  to  improve  the 
central  ones.  That  this  has  been  a  very  valuable  policy  will  be  shown  later. 
1 1  will  be  shown  in  the  next  section  that  the  most  sensitive  region  of 
the  retina  is  not  exactly  in  correspondence  with  the  optical  axis  of  the  lens 
system  of  the  eye,  being  displaced  approximately  0-5  mm.  to  the  temporal 
side.  We  must  therefore  consider  briefly  to  what  extent  the  peripheral 
aberrations  of  which  we  have  just  spoken  will  interfere  with  the  definition. 

THE  SINE  CONDITION  (COMMA).  This  aberration  is  found  to  show  itself  in 
optical  instruments  by  a  difference  in  the  position  of  the  various  parts  of  the  image 
produced  by  the  separate  zones  of  the  lens.  Instead  of  rays  from  a  point  source 
coming  to  a  focus  at  one  and  the  same  point,  they  are  found  to  form  a  fine 
line  in  comma,  the  tail  of  which  points  towards  the  optical  axis.  If  the  optica] 
system  obeys  a  rule  called  the  sine  condition,  comma  is  corrected.  The  eye  appears 
to  obey  this  condition  exactly,  and  therefore  so  far  as  comma  is  concerned  the  dis- 
placement of  the  fovea  to  one  side  of  the  optical  axis  is  no  disadvantage. 

CHROMATIC  DIFFERENCE  OF  MAGNIFICATION,  like  chromatic  difference 
i if  focus,  is  caused  by  the  unequal  refraction  of  light  rays  of  different  wave- 
length. But  since  on  refraction  violet  rays  are  more  bent  than  red  rays,  their 
foci  form  not  only  at  different  distances  from  the  cornea,  bat  also  at  different  angles 
with  the  optical  axis.  It  follows  from  this  that  objects,  subtending  a  consider- 
able angle  at  the  eye,  produce  images  which  are  smaller  for  violet  rays  than  they 
are  for  yellow  rays,  while  those  for  red  rays  are  larger  still.  Images  produced  by  rays 
of  different  wavelength  therefore  vary  in  size.  Since  that  part  of  the  retina  which 
possesses  the  best  vision  (the  fovea)  is  situated  to  one  side  of  the  optical  axis,  all  images 
formed  on  it  must  suffer  from  this  error.  Far  from  this  being  a  disadvantage  however,  if 
is  surprising  to  find  that  there  is  because  of  this  an  actual  diminution  of  the  effects  of 
chromatic  aberration,  ami  thai  the  displacement  is  therefore  a  wholly  beneficial  one. 
That  this  is  probably  the  explanation  of  the  development  of  the  most  sensitive  part 
of  the  retina  at  this  point  hardly  requires  indication. 

RADIAL  ASTIGMATISM  must,  according  to  optical  theory,  be  present  in  the 
image,  formed  on  the  fovea.  Experiment  shows  however  that  its  effects  can  be  to  a, 
considerable  extent  neutralised  by  positive  axial  astigmatism  such  as  is  found  in  the 
eye  of  emmetropes.  The  presence  of  this  aberration  may  therefore  be  ignored  so  far 
as  the  fovea  is  concerned. 

STRUCTURE  OF  FOVEAL  IMAGE  may  be  determined  approximately  by  con- 
sidering in  turn  the  effects  of  different  aberrations  on  the  light  rays  which  enter  the 
eye,     For  this  purpose  the  only  errors  of  importance  a.re  chromatic  differences  of  focus 


THE  REFRACTION   OF  THE   EfE  533 

and  magnification.  In  addition  however  we  must,  take  into  account  the  very  important 
effects  of  diffraction.  The  final  results  of  such  a  calculation  show  that 
the  images  of  rays  of  different  wavelength  overlap  one  another.  At  the 
centre  of  the  image  is  seen  the  sharp  yellow  focus  of  the  highest  intensity. 
Eccentric  to  it  and  overlapping  one  another  are  seen  the  diffuse  red  and  green 
foci,  which  are  of  much  less  intensity.  Where  these  overlap  they  produce  a 
compound  yellow  according  to  the  rules  of  colour  mixture.  Further  outwards  is 
the  still  more  diffuse  image  of  the  bine  rays,  which  is  of  almost  negligible  intensity. 
It  is  seen  therefore  that  the  centre  of  the  image  is  entirely  occupied  by  the  sharp  and 
intense  focus  of  the  yellow  rays.  Not  only  are  these  rays  the  brightest  in  the  spec- 
trum* but  they  are  also  those  nearest  to  white  light  in  their  physiological  properties. 
It  is  because  of  this  structure  of  the  image  that  the  acuity  of  vision  is  so  great  at  the 
fovea. 

PERIPHERAL  IMAGES  have,  as  stated  above,  been  to  a  considerable  extent  sacri- 
ficed,  so  far  as  their  definition  is  concerned,  in  order  to  obtain  the  best  possible  conditions 
at  the  fovea.  We  find  therefore  at  the  periphery,  images  that  in  no  way  compare 
with  those  formed  near  the  optical  axis  of  the  eye.  Even  here  however  there  is 
evidence  (bat  the  eve  lias  been  designed  to  give  the  best  results  obtainable.  The  two 
aberrations  which  must  concern  us  other  than  those  already  mentioned  are  curvature 
uf  tin-  field  and  distorsion. 

CURVATURE  OF  THE  FIELD  is  found  in  all  positive  lens  systems  of  simple 
formula.  Since  the  photographic  plate  is  Hat  it  is  one  of  the  principal  errors  to  be 
corrected  in  the  photographic  lens.  In  the  eve  on  the  contrary  the  effects  of  the 
aberration  have  been  avoided  not  by  correcting  the  lens  system  but  by  curving  the 
sensitive  surface  to  correspond.  Calculation  shows  that,  for  correction,  the  radius  of 
the  surface  of  the  retina  should  be  somewhat  shorter  than  the  equivalent  focal  length  of 
the  lens  system.  Hut  we  know  that  the  radius  of  the  retina  is  approximately  10  mm.. 
while  tin'  focal  length  of  the  eye  is  15-5  mm.  The  required  conditions  therefore  appear 
to  ha  ve  been  fulfilled. 

DISTORSION  shows  itself  in  photography  by  a  curving  of  lines  which  are  known 
by  experience  to  lie  straight.  But  this  straightening,  which  can  be  readily  effected  by 
suitably  designing  the  lens  system  and  by  using  a  flat  plate,  is  found  to  be  accompanied 
by  a  change  in  the  size  of  an  image,  according  as  it  is  formed  at  the  centre  or  the  edge 
o!  the  plate.  Hut  such  a  change  in  size  would  be  most  disadvantageous  in  the  case 
nf  the  eye.  Iierause  not  only  would  the  apparent  size  of  objects  vary,  according  as  their 
images   fell  mi    the  centre  or  tile   periphery  of  the   retina,   but  also   the   perception   ot 

perspective,  which, as  we  shall  see  later,  depends  mi  the  correct  estimation  of  the  differ- 
ences between  the  position  of  near  and  distant  objects,  would  lie  seriously  inter- 
fered with.  In  the  eye  it  is  very  much  mure  important  that  images  should 
keep  the  same  size,  than  that  distortion  should  be  corrected  by  optical  means.  In  order 
that  images  shall  be  constant  in  size,  the  retina  must  be  curved  to  approximately 
1  hr  sa  me  extent  as  is  required  for  the  correction  of  curvature  of  field.  We  see  therefore 
t  ha  i  l  lie  shape  of  the  retina  has  a  very  important  effect  on  peripheral  vision,  and  further 
that,  so  far  as  we  are  able  to  judge,  the  best  shape  has  been  adopted. 

OTHER  OPTICAL  DEFECTS.  The  analogy  between  the  eye  and  the  photo- 
graphic camera  shows  that  there  are  a  number  of  other  defects  from  which  the  eye 
may  suffer;  these  are  (1)  the  presence  within  the  eyeball  of  light  scattered  from  one 
part  of  the  retina,  to  another  (equivalent  to  shiny  bellows  in  the  camera)  :  (2)  the 
spreading  of  the  image  formed  on  one  part  of  the  retina  to  neighbouring  portions 
(equivalent  to  halation)  ;  (3)  the  illumination  of  the  retina  by  light  internally  reflected 
at  the  different  optical  surfaces  (known  in  photography  as  flare)  ;  (4)  the  exposure 
of  parts  of  the  retina  close  to  those  receiving  the  image  because  of  imperfection  in  the 
optical  system   (called  irradiation). 

Scattered  Light.  In  describing  the  histology  of  the  retina  it  will  be  shown  how 
generously  tin-  layer  ot  cells  lying  immediately  under  the  sensitive  layer  of  mils  and 


v;i  PHYSIOLOGY 

cones  is  supplied  with  pigmenl  ;  the  objeot  of  these  is  clearly  to  absorb  scattered  light. 
In  spile  of  this  however  we  find  considerable  amounts  of  light  being  reflected  baok 
,  ii,,  by  the  retina  ;  in  fad  ii  is  this  ligh.1  thai  enables  us  to  see  the  retinal  nerves 
and  vessels  through  the  ophthalmoscope  (sec  page  554).  The  spherical  shape  of  the 
eyeball  will  cause  the  greater  pari  of  this  reflected  lighl  to  travel  towards  the  front  of 
the  rye  and  to  fall  on  an  insensitive  layer  of  iris  or  retina  anterior  to  the  ora  serrata. 
From  here  it  will  be  reflected  again  on  to  the  retina,  bul  with  such  reduced  intensity 
as  not  to  cause  stimulation.  Light  reaching  the  anterior  pari  of  the  retina  through 
the  | in | ii  I  would  after  reflection  tend  to  travel  towards  the  posterior  pari  of  the  retina, 
thai  is  the  part  most  sensitive  to  light.  The  intensity  of  these  peripheral  rays  is  how- 
ever diminished  in  a   number  of  ways:    firstly   by  the  eyebrows,  cheeks  and  nose; 

econdbj  by  the  eye-lashes  when  the  lids  are  approximated,  as  they  are  when  looking 
towards  a  bright  light  ;  thirdly  by  the  relative  smallness  of  the  pupil  for  oblique  rays 
(the  pupil  being  a  slit  shaped  instead  of  a  circular  opening  for  such  rays).  The  effect 
of  scattered  light  in  the  eye  is  therefore  eliminated  in  tins  way.  It  should  be  noted 
thai  in  certain  animals,  which  have  very  acute  night  vision,  the  pigment  cells  of  the 
choroid  at   the  posterior  pole  of  the  eye  are  iridescent,  and   form  a  highly  reflecting 

urface  behind  the  retina,  which  is  called  the  tape1  turn.  The  object  of  this  would  seem 
to  he  to  increase  the  stimulus  of  a  given  intensity  of  light,  bul  the  presence  of  this 
reflecting  layer  must  increase  tin-  amount  of  scattered  light  in  the  eye,  and  would 
therefore  appear  to  he  of  disadvantage  in  day  vision. 

Halation.  This  is  caused  in  the  camera  by  the  image  that  has  formed  on  the  plate 
Inn  i."  idler  ird  back  again  on  to  the  plate  from  the  internal  surface  of  the  glass.  This 
is  not  apparent  in  the  photographic  film,  because  owing  to  the  thinness  of  the  gelatin 
film  flic  reflected  image  falls  back  on  to  the  same  part  of  the  plate  again.  In  the  case 
of  the  retina  the  reflecting  layer  must  lie  exceedingly  close  to  the  sensitive  layer,  if 
indeed  tin-  two  are  not  identical:  halation  in  the  eye  would  therefore  appear  to  be 
negligible  in  amount. 

Flare.  The  amount  of  light  reflected  by  the  surface  bounding  two  optical  media 
increases  as  the  difference  between  their  refractive  indices  increases,  and  also  with 
the  angle  which  the  light  makes  with  the  surface.  Therefore,  other  things  being  equal, 
I  he  mailer  the  angle  of  incidence  and  the  more  nearly  the  refractive  indices  are  identi- 
cal, the  less  the  amount  of  flare  will  he.  In  the  eye  the  lens  system  is  as  i  I  were  immersed 
in  a  medium  of  almost  the  same  refractive  index  as  itself :  and  furl  her  even  that  differ- 
ence is  reduced  by  (he  fact  that  the  actual  refractive  index  of  the  crystalline  lens  is 
very  much  less  than  its  equivalent  R.I.  owing  to  its  peculiar  structure.  Flare  in  the 
eye   must    therefore   be  quite  inconsidera ble   in  amount. 

Irradiation.  That  this  phenomenon  is  present  in  the  eye'may  he  shown  directly 
by  experiment.  If  for  example  an  electric  light  filament  be  looked  at  before  and  after 
(he  switching  on  of  the  current,  the  increase  in  thickness  on  illumination  is  obvious. 
Its  cause  appear-  to  be  imperfect  definition,  spreading  of  the  lighl  from  one  retinal 
element  to  its  neighbours,  or  .spreading  of  the  nerve  impulse  cither  at  the  retina  or 
even  in  (he  brain  itself. 

ABNORMAL  REFRACTION  OF  THE  EYE 
It  would  almost  ho  anticipated  that  such  a  complicated  organ  as 
the  eye  would  he  found  to  show  individual  abnormalities.  A  further  con- 
sideration would  probably  suggest  to  us  that,  considering  the  smallness  of  the 
change  that  is  necessary  in  any  one  of  the  optical  media  in  order  completely  to 
destroy  definition,  if  is  nothing  short  of  astonisbing  that  abnormality  of  refrac- 
tion is  relatively  so  uncommon.  In  the  newly  born  the  eye  is  almosl  always 
long-sighted  (hypermetropic)  :  this  is  due  to  the  eyeball  being  too  small  for 
the  optical  system  which  it  contains  ;  the  image  formed  by  the  latter  is  there- 
fore  focussed  behind  the  retina.     As  age  advances  the  eyeball  grows  until 


THE   REFRACTION   OF  THE   EYE  535 

the  point  is  reached  at  which  the  eye  is  emmetropic  (normal).  It'  however 
the  child  is  allowed  to  use  its  eyes  too  much  for  near  work,  the  eyeball 
goes  on  increasing  in  size  until  it  has  overshot  the  mark  and  has  thus  caused 
the  eye  to  become  short-sighted  (myopic).  There  would  appear  to  be 
some  kind  of  automatic  control,  which  causes  the  eye  to  grow  till  it 
is  in  adjustment  with  the  conditions  most  frequently  encountered.  This 
hypothesis  is  confirmed  by  the  fact  that  if  a  child  which  is  beginning  to 
develop  short-sight  is  prevented  from  using  near  vision  for  a  year  or  two, 
the  development  of  short-sight  stops.  The  importance  of  the  early  detection 
of  the  onset  of  short-sight  therefore  cannot  be  too  strongly  urged. 

THE  METHODS   OF   DIAGNOSIS.     The  Setection  (.tennis  of  refraction  in  the 

,i\  be  effected  in  various  ways,  each  of  which  is  said  to  possess  advantage.     Some 

of  these  have  come  into  such  general  use  that  they  may  be  briefly  considered  as  an 
introduction  to  the  description  of  the  more  important  types  of  error  which  thej  are  used 
to  investigate. 

THE  DETERMINATION  OF  THE  VISUAL  ACUITY.  It  lias  been  found  by 
experiment  that  persons  with  normal  sight  can  distinguish  between  objects  when  the 
angle  separating  them  is  not  much  less  than  One  minute.  Test  type  lias  therefore 
been  prepared  in  which  the  letters  are  composed  ol  lines  which  subtend  this  angle  at 
the  eye.  when  the  type  is  placed  at  a  standard  distance  of  six  metres.  Persons  who 
are  aide  to  read  the  type  at  this  distance  arc  said  to  have  normal  vision.  Above  these 
standard  letters  are  placed  a  series  of  larger  letters,  which  al  two,  three  or  four 
times  the  standard  distance  would  subtend  the  standard  angle.  A  person  with  reduced 
acuity  might  be  able  to  read  at  six  metres  the  type  that  should  he  read  at  sixty.  He 
therefore  has  vision  which  is  one-tenth  th"  normal.  Such  a  person  might  have 
long-sight,. short  sight  or  astigmatism :  to  determine  which  is  present  a  pair  of  spectacles 
is  placed  before  his  eves  into  which  can  be  inserted  any  two  of  a  la  ice  selection  of  glasses 
of  different  power,  which  are  known  as  (rial  lenses.  These  are  tried  in  turn  ill  an  orderly 
manner  until  some  are  found  which  allow  the  man  to  read  the  standard  type  at  the  stan- 
dard distance.  His  visual  acuity  is  now  at  the  normal  and  the  strength  and  shape  of 
the  glasses  in  front  of  his  eyes  is  carefully  noted,  so  that  others  of  the  same  power  may 
in  fitted  I"  spectacles  tor  him  to  wear.  If  the  glasses  are  found  to  he  convex  (plus). 
then  lie  was  suffering  from  long-sight  (hypermetrqpia),  and  if  com -a  ve  (minus)  from  short - 
ii 'lii  (myopia).  But  if  on  the  other  hand  cylindrical  lenses  had  to  be  used,  then  be 
had   astigmatism,  cither  alone  or  in   conjunction   with   long-  or  short-sight. 

THE  METHOD  OF  RETINOSCOPY.  Such  a  method  as  that  just  described 
could  only  succeed  if  the  person  tested  were  an  intelligent  adult,  because  we  depend 
entirely  on  his  giving  the  correct  answer  when  wc  ask,  if  the  substitution  of  a  different 
lens  to  the  one  we  have  already  placed  before  him  makes  vision  better  or  worse.  With 
a  child  such  a  method  could  never  succeed.  Another  method  is  therefore  practised, 
which  has  the  great  advantage  of  being  independent  of  the  patient;  in  fact  for  the 
purpose  of  the  test  he  might  be  blind.  This  method  consists  in  throwing  into  each  of 
his  eyes  in  turn,  a  beam  of  light  reflected  off  a  plane  mirror,  in  the  centre  of  which  is 
a  hole,  through  which  the  doctor  looks.  When  1 1  it ■  beam  of  light  is  directed  into  the 
patient's  eye  the  doctor  sir.,  a  pink  reflected  beam  of  light  coming  to  him  through 
the  patient's  pupil.  As  the  mirror  is  gently  tilted,  SO  as  to  throw  the  beam  slightly 
upwards  and  slightly  downwards,  so  the  pink  beam  appears  to  move  up  and  down 
behind  the  patient's  pupil.  If  it  moves  down  as  the  mirror  is  tilted  down  the  move- 
ment is  said  to  be  WITH  the  mirror,  and  the  patient  is  hypermetropic,  requiring  plus 
spectacles.  If  on  the  other  hand  the  beam  mows  m:\i\si.  minus  spectacles  are 
required  since  the  patient  is  short  sighted.  By  placing  glasses  of  different  power  in 
front  of  his  eye  until  oneii  found  which  cau  es  I  Ik-  pink  beam  to  move  neither  with  nor 
i  the  mirror,  the  actual  power  for  the  spectacles  required  by  the  patient  i    .1  111 


536 


PHYSIOLOGY 


tinned.  It  should  be  carefully  noted  however  that,  since  the  doctor  is  standing  at 
about  a  meter  distance  from  the  eyes  of  his  patient,  plus  one  I)  must  be  subtracted  from 
the  power  of  any  glasses  that  are  found  to  be  necessary.  Thus  it  the  patient  was 
found  to  be  myopic  and  minus  7  D  spherical  lenses  were  required  to  neutralise  the 
movement  of  the  beam,  then  the  power  that  should  be  ordered  is  minus  8  l»  spherical. 
This  test  is  found  to  work  admirably  in  practice.  It  is  better  to  have  paralysed  the  pupil 
reflex  and  the  accommodation  of  the  patient  previous  to  the  test  by  the  use  of  atropine. 
but  some  say  that  this  is  unnecessary. 

OTHER  METHODS.  Of  other  methods  of  testing  vision  little  requires  to  be  said  : 
some  require  the  use  of  special  instruments  such  as  the  optometer  and  the  refractometer. 
Another  again  depends  on  the  determination  of  both  the  far  and  near  points.  This  is 
of  distinct  value  because  it  at  once  gives  the  amplitude  of  the  accommodation,  which 
is  an  important  determination.  Others  are  based  on  the  use  of  the  ophthalmoscope. 
But  none  of  these  methods  are  so  simple  or  accurate  as  the  method  of  retinoscopy 
described  ah  ive. 

STENOPEIC  APERTURE.  Often  in  practice  the  question  arises  as  to  whether 
low  visual  acxty  is  due  to  defect  in  the  optical  media  of  the  eye,  or  to  disease  of  the 
retina,.  This  question  can  be  readily  answered  by  placing  in  front  of  each  eye  in  turn 
a  metal  disc  in  which  has  been  drilled  a  one- third  millimeter  hole.  If  this  improves  acuity 
the  defect  is  not  ill  the  retina  ;  if  it  does  not  it  is.  This  test  should  lie  done  in  a  good 
light  because  of  the  small  amount  of  light  passed  by  the  hole.  A  hole  used  in  this  way 
is  called  a  stenopeic  aperture. 

HYPERMETROPIA  OR  LONG-SIGHT.  There  are  two  principal  varieties  of 
long  sight,  firstly  that  in  which  the  eyeball  is  too  small  and  too  short  for  the  normal 
optical  system,  secondly  that  in  which  the  eyeball  is  normal  hut  the  refracting  power 
of  the  lens  below  the  normal.  The  first  variety  is  found  in  childhood,  because  the  optical 
system  reaches  its  adult  size  much  earlier  than  does  the  eyeball.  In  the  majority  of 
children  the  eyeball  continues  to  grow  until  it  is  the  correct  size,  and  therefore  long-sight 
disappears.  In  a  certain  number  of  cases  this  does  not  happen  and  therefore  long-sight 
remains  through  life.  The  second  variety  is  found  in  old  age,  and  appears  to  be  due  to 
the  absorption  of  water  by  the  lens;  the  result  in  both  cases  being  that  the  rays  of 
light  from  distant  objects  are  brought  to  a  focus  beliind  the  retina,  and  therefore  in  order 
to  focus  them  the  accommodation  has  to  be  used  (see  Fig.  2f!7).      It  follows  from  this 


luo.  267.     Hypermetropic  eye. 
The  eyeball  is  too  short  and  therefore 
rays   from   a  distant   object    come    to   a 
focus  beyond  the  retina. 


Fiu.  2G8.     Myopic  eye. 
The  eyeball  is  too  long  and  therefore 
rays   from   a  distant   object    come   to   a 
focus  in  front  of  the  retina. 


THE   REFRACTION  OF  THE  EYE  537 

that  there  is  less  accommodation  remaining  for  the  focussing  of  near  objects,  and  there- 
ion- an  inability  to  see.  distinctly  at  relatively  short  distances  from  the  eye.  Thus  the 
use  of  the  term  Long-sight. 

Hypermetropia  in  adults  is  therefore  more  an  abnormality  than  a  disease ;  it  causes 
a  disposition  however  to  three  more  serious  conditions,  namely  glaucoma,  internal  strabis- 
mus and  eye-strain.  Glaucoma  has  already  been  described  (see  page  517) ;  it  is  due  to 
an  abnormal  rise  in  the  intraocular  pressure,  which  occurs  owing  to  the  free  escape  of 
the  aqueous  humour  at  the  filtration  angle  being  checked.  Now  in  hypermetropia  we 
have  seen  that  the  eyeball  is  too  small  for  its  optical  apparatus,  and  therefore  the  lens 
occupies  too  much  of  the  space  in  the  small  anterior  and  posterior  chambers.  This 
causes  the  ciliary  bodies  and  roots  of  the  iris  to  be  squeezed  and  greatly  reduces 
the  space  at  the  filtration  angle.  An  attack  of  glaucoma  is  therefore  more  liable  to 
occur  in  the  hypermetrope  than  in  a  person  with  normal  refraction. 

Internal  strabismus  is  caused  in  hypermetropia  by  the  accommodative  effort  that 
is  made  in  order  to  focus  an  image  on  the  retina,  because,  as  we  have  seen  above  (page 
497),  convergence  and  accommodation  are  associated  actions.  When  therefore  the  long 
sight  has  been  corrected  by  means  of  spectacles,  ami  the  accommodation  is  no  longer 
called  into  play  for  seeing  at  a  distance,  the  associated  convergence  no  longer  occurs 
and  the  strabismus  disappears. 

Eye-strain  is  caused  in  hypermetropia  by  the  continual  call  for  accommodation. 
Further,  this  must  occur  without  convergence,  for  otherwise  diplopia  (seeing  double) 
and  strabismus  develop  as  just  described.  A  special  strain  is  therefore  placed  not  only 
on  the  ciliary  muscles  but  also  on  the  external  eye  muscles.  This  state  of  affairs  \  el  A 
rapidly  causes  fatigue,  headaches  are  therefore  common. 

The  treatment  of  long-sight  consists  in  prescribing  suitable  convex  spectacles.  It 
should  be  noted  that  the  amount  of  long-sight  actually  present  is  shown  only  when  the 
accommodation  has  been  paralysed  by  atropine,  because  the  patient  has  grown  so  accus 
tomedtouse  his  accommodation  in  ordinary  vision  thai  he  is  unable  voluntarily  to  relax  it. 
There  is  a  certain  amount  of  spasm  of  the  accommodation.  Because  of  this  the  glasses  pre 
scribed  should  he  iess  strong  ai  first  than  the  full  correction  shown  to  be  necessary. 
These   may   lie  substituted   by  more  powerful  ones  later. 

MYOPIA  OR  SHORT-SIGHT.  In  this  condition  parallel  rays.  that,  is  those  coming 
from  distant  objects,  come  lo  a  focus  so  far  hi  front  of  the  retina,  that  the  image  appears 
blurred  (see  Pig.  268).  Myopia  may  be  caused  in  two  ways,  which  are  similar  to. 
hut  opposite  in  action  to  1 1  lose  that  cause  hypermetropia;  the  first  type  is  caused 
b\  the  eyeball  being  too  long,  and  the  second  by  the  refraction  of  the  lens  being  too 
high.  The  former,  which  is  (he  more  common,  usually  develops  in  youth,  particularly 
at  the  school  age  when  the  growth  of  (he  body  makes  special  demands  on  the  system, 
and  at  the  same  lime  feeding  is  usually  bad.  The  constant  use  of  the  eye  for  near  work 
causes  them  considerable  strain  which  they  are  unable  to  withstand  owing  to  their 
being  unable  to  compete  for  nourishment  with  the  rest  of  the  body.  The  choroid  and 
si  (era  t  herefore  become  thin,  are  no  longer  able  to  stand  the  tension  set  up  by  the  intra- 
ocular pressure,  and  therefore  expand,  causing  the  eyeball  to  become  larger  than  normal. 
and  taking  the  retina  beyond  the  focus  of  the  optical  system.  The  treatment 
of  myopia  is  therefore  not  only  the  wearing  of  spectacles,  but  the  absolute  prohibition 
of  near  work  or  close  study,  the  administration  of  extra-nourishing  food  and  an 
open-air  life  for  a  year  or  more.  If  these  steps  are  taken  at  once,  the  myopia,  may 
get  no  worse,  and  may  in  fact  get  better.  But  if  neglected  the  condition  will  almost 
certainly  get  worse.  As  myopia  is  a  disease,  particularly  liable  to  occur  at  the  school 
age,  schoolmasters  and  others  associating  with  children  should  be  on  the  look  out  for 
conditions  likely  to  cause  it,  such  as  bad  light,  bad  food  and  poor  ventilation,  and  tor 
its  presence  in  any  of  the  children.  Glasses  should  always  be  prescribed  and  care  taken 
that,  the  child   wears  them   constantly,   because  it   is  found   that    beside  assisting  good 

definition  and  relieving  eye  strain,  they  actually  tend  to  cheek  the  further  development 
of  the  trouble. 


538 


PHYSIOLOGY 


■yeball 

3ed    by 


Certain  complications  sometimes  attend  myopia;    these  are  divergent  strabismus' 
eye-strain,  and  spasm  of  the  accommodation. 

The  divergent  Btrabismus  lias  a  similar  origin  to  the  convergenl  strabismus  met 
with  in  nypermetropia,  namely  association  of  deviation  of  the  eye  axes  with  the  adjust 

ment  el  the  ac imodation.     Now-  since  in  the  normal  individual  the  relaxation  of  the 

aceommodal  ion  of  the  eye  is  associated 
with  parallel  axes  "1  the  eyes  (in  order 
in  look  at  distant  object!  ).  in  myopi  i 
the  disuse  oi  the  accommodation  for 
near  vision  causes  theeye  axes  to  re 
main  straight  and  therefore  produce 
the  effects  of  an  external  strabismus. 
The  use  of  glasses  introduces  again  the 
necessity  of  accommodation,  exactly  as 

if  the  eye  was   'mal,  and    therefore 

abolishes  the  strabismus.  In  the  ma 
jority  of  ease,  an  actual  strabismus 
does  not  develop,  but  there  is  never- 
theless a  strong  tendency  to  diplopia. 

especially    when    the    eyes    are     tired. 
The  eve-strain    which    frequently   ac- 
companies   in\ opia    proba bly    hai     it 
origin    in  the   effort  to    converge    the 

eye  axes  Without  at  (he  same  time 
calling  the  accommodation  into  play. 
Spasm  of  accommodation  fre- 
quently accompanies  myopia,  and  has 
the  effect  of  making  themyopia  seem 
greater  than  it  actually  is.  The  true 
state  of  affairs  is  at  once  found  when  atropine  is  used,  because  the  accommodation  is 
thus  abolished.    Sometimes  in  children  spasm  of  accommodation  occurs    without  any 

actual    il' 'mality  of   refraction.     Such  cases  should  he  treated  with  the  same  care 

as  those  that  are  already  developing  myopia. 

ASTIGMATISM.  The  condition  of  the  eye  called  astigmatism  is  one  ill  which 
parallel  rays  arc  not  brought  to  a  focus  in  a  single  plane,  but  in  a  number  of  different 
planes.  There  are  two  different  varieties  of  astigmatism.  In  the  first  or  irregular 
variety  the  separate  parts  of  one  meridian  of  the  eye  form  different  foci. 
This  is  found  to  occur  during  the  development  of  cataract  in  the  crystalline 
lens,  and  also  after  ulceration  of  the  cornea.  The  effects  of  this  form  of  astigmatism 
on  vision  vary  with  the  severity  of  the  condition  :  in  moderate  cases  a  frequent  pheno- 
menon is  the  formation  of  a  double  image  in  the  affected  eye.  Glasses  as  a  rule  do  not 
give  benefit.  In  severe  types  the  use  of  a  stenopeic  aperture  may  improve  definition. 
In  the  second  variety,  or  regular  astigmatism,  the  parts  of  any  one  meri- 
dian give  the  same-  focus,  but  the  different  meridians  have  different  foci. 
There  are  however  two  meridians  at  right  angles  to  one  another,  one  of 
which  has  the  longest  and  the  other  the  shortest  focus,  the  meridians 
in  between  showing  an  orderly  sequence  between  these  two  extreme  values. 
Thus  the  use  of  the  term  regular  astigmatism.  Two  types  of  patient  are  found  to 
Buffer  from  fins  condition,  those  who  have  inherited  and  those  who  have  acquired  it 
as  a  sequence  to  injury,  operation  or  disease.  The  effects  on  vision  are  varied,  but 
the  characteristic  features  ate  distortion  of  objects  looked  at,  and  indistinctness  of 
lines  in  one  direct  i. .n.  while  those  at  right  angles  are  quite  sharp.  Headaches,  eye-strain 
and  dimness  of  vision  are  very  common.  Many  types  arc  met  with  because  the  maximum 
anil  minimum  meridian  may  occupy  any  angle  so  long  as  they  arc  at  right  angles  to 
one  another,  and   they   may   have  any  degree  of  myopia   or   nypermetropia. 


Fig.  269.  The  asymmetry  of  tin- 
anil  kinking  of  the  optic  nerve  ca 
high   myopia. 


THE   REFRACTION   OF  THE   EYE 


539 


70.     Showing  the  shape  of  foci  at  different  position 


The  diagnosis  and  measurement  of  astigmatism  presents  no  difficulties.  Its  exist- 
ence  may  be  readily  proved  by  causing  the  patient  to  I > •< >  1^  at  a  figure  consisting  of  a 
.scries  of  lines  radiating  from  a  common  centre.  It  is  then  found  that  while  sunn'  of 
the  lines  are  sharp  those  a1  right  angles  are  indistinct.  This  test  also  slums  the  axes 
of  the  principal  meridians.  By  retinoscopy  (seepage535)  the  axes  and  the  antounts 
i  the  abnormality  in  those  axes  may  be  readily  determined.  The  treatment  con  d  I  ■ 
in  giving  spectacles  which  have  been  ground  on  one  side  to  a  cylindrical  surface.  The 
axis  of  this  cylinder  is  adjusted  to  correspond  with  one  of  the  principal  meridians  of 
the  eye  of  the  patient.  The  curve  given  to  the  cylinder  is  that  which  will  cause  th<- 
focus  of  the  meridian  with  which  it  corresponds  to  be  equal  to  the  focus  of  the  other 
meridian.  The  other  side  of  the  spectacle  lens  is  ground  to  that  spherical  surface 
which  will  make  the  eye  emmetropic  after  it    has   Keen  corrected   by  the  cylinder. 

ANISOMETROPIA.    Tin  last  abnormality  of  refraction,  which  we  have  to  consider, 
is  called   anisometropia;      It   simply   means  difference   between   the  refraction   of  the 

two  1-ytv.     The  effect  on  vision  is  very  slight,  since  it  is  found  that  as  a  rule eye 

docs  all  the  work  and  the  image  of  the  other,  which  is  necessarily  indistinct,  is  prevented 
from  reaching  consciousness.  The  result  in  course  of  time  is  that  the  unused  eye  loses 
to  a  considerable  extent  it  i  power  of  seeing  and  as  a  result  strabismus  develops.  Treat- 
ment consists  in  giving  glasses  w  hi  h  correct  each  eye  separately,  ami  then  instituting 
ci  es  for  the  poorer  eye.  in  on  lei'  to  improve  it--  vision.  The  results  of  this  treatment 
are  good. 


SECTION   VII 

HISTOLOGY    OF    THE    RETINA 

The  retina  is  a  delicate  membrane  lying  inside  the  choroid  coat  of  the  eye. 
Its  internal  surface  lies  in  contact  with  the  hyaloid  membrane  of  the  vitreous 
body.  It  is  thus  supported  on  both  sides.  The  retina  itself  consists  of 
two  layers,  tin'  outer  or  pigmented,  and  tin-  inner  or  nervous.  Whereas 
embryologies  11  v  the  retina  covers  the  whole  internal  surface  of  the  eye  includ- 
ing the  ciliary  processes  and  the  iris,  this  is  not  the  case  with  the  nervous 
layer,  because  this  stops  near  the  equator  of  the  eye  at  the  ora  serrata,  and 
is  here  replaced  by  a  layer  of  columnar  epithelium.  Opposite  the  pupil  a 
yellow  spot  is  seen  on  the  retina,  the  macula  lutea,  and  in  the  centre  of 
this  there  is  an  oval  depression,  the  fovea  centralis.  The  optic  nerve  enters 
the  eyeball  through  an  aperture  in  the  sclera  and  choroid,  and  then  passes 
through  the  posterior  surface  of  the  retina  to  spread  out  over  the  internal 
surface.  In  the  fovea  however  this  is  not  the  case,  for  the  depression  at 
this  point  is  caused  by  the  absence  of  nerve  fibres.  The  point  at  which 
the  optic  nerve  enters  the  eye  is  easily  recognised  from  inside  the  eyeball 
because  the  numerous  white  nerve  fibres,  as  they  bend  over  the  edge  of  the 
aperture  in  the  retina,  form  a  characteristic  white  mound  called  the  colliculus, 
at  the  centre  of  which  is  a  depressed  portion  called  the  optic  cup.  It  is  in 
the  centre  of  this  cup  that  the  central  artery  of  the  retina  and  the  cone 
s  ponding  vein  first  make  their  appearance.  These  have  the  important  func- 
tion of  nourishing  the  retina;  the  additional  blood  supply  through  the  inti- 
mate contact  between  the  retina  and  the  vascular  choroid,  althoughimportant, 
is  quite  insufficient  to  supply  the  needs  of  vision,  as  is  shown  by  the  immediate 
and  permanent  blindness  which  follows  blocking  of  the  central  artery  of  the 
retina. 

When  sections  of  the  retina  are  examined  under  the  microscope  it  is  found  that 
they  consist   of  (lie   following  layers  from  within   outwards: 

1.  Layer  of  nerve  fibres  and  vessels 

2.  Layer  of  ganglion  nerve  cells 

X  Inner  molecular  or  plexiform   layer  I      ,.        .         ,    ,  , 

r  •  DeveloiM-d  from  anterior  layer 

4.  Inner  nuclear  or  granular  layer  -  , .       ,. 

,      ,         ,  "I  optic  vesicle. 

5.  Outer  molecular  or  plexiform  layer 

fi.   Outer  nuclear  or  granular  layer  I 

7.  Layer  of  rods  and  cones  (bacillary   layer) 

8.  Layer  of  pigmented  epithelium       ..  •■       Developed  from  posterior  layer. 

540 


HISTOID  »<;V    OF  THE   RETIN  \ 


541 


In    order    to    understand  the  structure  of  these   layers,  it    is  necessary   to   keep 

the    lnt    in    mind    that    the   optic   nerve   and    cup    arc    outgrowths   of   pari    of   the 


EXTgRNAL 


GANCLICHIC    LAYfR 


STRATUM  QPTICUM 


■NJ£RHAL 

Fig.  271.    Diagram  of  transverse  tion  oi  retina. 

brain.  We  must  therefore  be  prepared  to  find  in  the  retina,  the  presence  of  all  those 
structures  winch  are  found  in  the  case  of  every  sensory  nerve  to  intervene 
between    the    sense    cell    and   the   brain   nucleus.     Be   it    taste-cell  or  touch-cell,  m- 

\    cell  of  any  cither  kind,  the  stimulus  is  conveyed  in  every  case  through  three 

sets  of  neurons  or  relays  before  it  reaches  the  brain.  We  must  therefore  expect  to 
find  m  the  retina  all  these  three  sets  of  neurons  represented. 

THE  NERVE  FIBRE  LAYER  (stratum  opticum)  consists  of  the  non -myelinated 
(noii-nicdullated)  axons  of  the  large  ganglion  cells  found  in  the  second  layer.  These 
axons  are  the  third  order  neurons  which  become  myelinated  after  tiny  have  passed  out 
of  the  eyeball  and  travel  bypaths  to  the  occipital  cortex  described  on  page  532. 
Beside  the  fibres  conveying  visual  impressions  there  are  others  which  belong  to  the 
pupillo-motor  reflex.  Others  again  bring  impulses  from  the- brain  to  the  retina;  their 
functions  will  be  considered  below. 

THE  GANGLION  NERVE  CELL  LAYER  consists  of  a  single  layer  of  large  oval 
cells.     These  are  nucleated  and  give  off  the  axons  which  we  have  already  described 


>42 


PHYSIOLOGY 


and  .'  bunch  of  dendi  iti  s  h  hich  ramify  with  others  in  thi  inner  molecular  layer.     <  Inly 

al   the  macula  is  more  than •  layer  of  ganglion  cells  presenl  ;  this  is  due  to  their  almost 

complete  absence  at  the  fovea.  The  macula  therefore  not  only  has  its  own  relays  but 
tlu.se  of  the  fovea  as  well. 

THE  INNER  MOLECULAR  LAYER  consists  of  a  felt-work  mad.-  up  by  the 
interlacing  dendrites  of  the  ganglion  cells  with  those  of  the  inner  nuclear  cells  or  second 
order  neurons.  There  are  also  the  dendrites  of  horizontal  cells  or  spongioblasts,  These 
possibly  serve  to  associate  the  impulses  from  different  parts  of  the  retina,  such  as  is 
supposed  to  occur  in  the  brain,  it  should  be  noted  that  they  appear  to  be  absent  in 
the  fovea  and  macula. 

THE  INNER  NUCLEAR  LAYER  largely  consists  of  bipolar  second  order  neuron 
cells.  There  are  however  also  present  the  nuclei  of  the  horizontal  cells,  and  also  the 
nuclei  of  similar  cells,  whose  dendrites  travel  in  the  outer  molecular  layer.  The  bipolar 
cells,  which  arc  fusiform  in  shape  and  nucleated,  ale  of  three  kinds  :  (a)  those  which 
connect  with  rods.  (6)  those  which  connect  with  cones,  and  (c)  giant  bipolars  which 
connect    with   either. 


the  different  cellular  structures  found  in  the  retina. 


THE  OUTER  MOLECULAR  LAYER  is  much  like  the  inner;  it  consists  of  the 
dendrites  of  the  second  order  neurons  and  the  first. 

THE  OUTER  NUCLEAR  LAYER  consists  of  the  cells  of  the  first  order  neurons 
or  the  granules  of  the  rods  and  cones.  The  cells  arc  nucleated,  somewhat  smallci  than 
the  dipolar  cells,  and  their  nuclei  are  striated.  They  give  off  two  processes,  one  of  which 
forms  dendrites  in  the  fifth  layer,  the  other  connects  with  either  a  rod  or  cone  as  the  case 
may   be. 

THE  BACILLARY  LAYER  of  rods  and  cones  is  separated  from  the  previous  layer 
by  the  externa]  limiting  membrane.  Both  rods  and  cones  consist  of  an  outer  and  inner 
Limb,  the  forms  of  which  are  well  shown  in  Fig.  273.  It  will  he  seen  that  the  outer 
limlis  arc  striated,  the  cones  coarsely,  the  rods  finely.  Like  some  types  of  striated 
muscle  they  tend  after  hardening  to  break  up  into  discs.  The  inner  Limbs  of  both  rods 
and  cones  have  a  strong  affinity  for  dyes. 

THE  STRATUM  PIGMENTI  is  the  only  one  that  is  developed  from  the  external 
layer  of  the  embryonic  optic  cup.  The  epithelium  consists  of  a  single  layer  of  hexagonal 
nucleated  cells  containing  numerous  pigment  granules.     The  cells  send  fine  processes 


HISTOLOGY   OF   THE   RETINA 


543 


•h    they 


between  the  limbs  "I  the  mils.     The  bases  of  these  cells  are  firmly  attached  to  the 
choroid  and   thus  give  support   to  the  resl   of  the  retina. 

The    object     ■•!     these    cell    processes   and    the     pigment    granules    wl 
contain  would  appear  to  be  either  the  preven- 
tion of  an  image    formed    on    one  part    of  the 
retina   from  spreading  to  the    sensitive  elements 

of  surrounding  portions,  or  elsethe  protection  of 

these  elements  from  excessive  light  action.  But 
it  has  been  definitely  proved  that  the  cells 
themselves  have  another  and  important  func- 
tion to  perform,  namely  the  secretion  of  the 
pigment  called  visual  purple  (rhodopsin).  The 
important  functions  of  this  pigment  "ill  be 
described  later. 

It  should  be  noted  that  beside  the  struc- 
tures described  above,  which  have  the  func- 
tional activities  of  the  retina  to  perform,  there 
are  a  number  of  connective  tissue  elements 
which  form  the  retina  into  one  coherent  struc 
tine.  Since  the  retina  is  developed  from  an 
outgrowth  of  the  brain,  these  structures  are 
mi i I  1 1  iii  type  to  those  met  there;  we  there- 
fore find  neuroglia  and  also  long  cells  which 
extend  through  the  first  seven  layers  and  hold 
them  together,  namely  the  fibres  of  Miiller. 

THE  DEVELOPMENT  OF  THE  RETINA. 
The  complex  Series  of  layers  of  which  the 
retina  consists  are  developed  from  the  two  walls 
of  the  primitive  optic  cup,  which  grows  as  a 
hollow  laid  from  the  anterior  cerebral  vesicle  "I 
t!n  embryo.  At  first  the  tun  layers  are  of  the 
same  thicknees,  hut  the  outer  becomes  reduced 
t'i  a  single  layer  ol  flattened  cells;  which  become 
pigmi  nted,  forming  the  stratum  pigmenti.  The 
i  ini  i  layer  consists  at  first  of  a  single  layer  of 
elongated  nucleated  cells,  which  become  differ- 
entiated into  spongioblasts,  germinal  cells  and 
neuroblasts,  similar  to  those  found  in  the  de 
velopmont  of  the  spinal  cord.  The  spongioblasts  I 
form  the  inner  and  outer  limiting  membranes, 
and  a  groundwork  within  which  the  functional 
elements  develop.  The  germinal  cells  give  rise 
to  three  series  of  neuroblasts  in  all.     The   first 


Fig    Jt:>. 

I,  a  rod  :     1 1 .  a   ei 


of  mammalian 
retina  ;   h,  external   limiting  membrane. 
(It.  Gbeefe  ) 
set  are  much  larger  than  the  others,  and  become 

tin-  ganglion  cells  (these  appear  to  he  formed  by  mitotic  di\  ision).  The  next  two  '  l  ■ 
are  much  smaller,  and  become  the  first  and  second  nuclear  layer  (these  seem  to  be 
formed  by  amitotic  division).  Lastly  the  germinal  cells  themselves  become  trans- 
formed into  the  rods  and  cones.    The  molecular  layers  are  formed  of  the  arborisations 

of  the  processes  of  the  cells  between  which  they  lie.  The  innermost  layer  of  nerve 
fibres  is  formed  by  th  i  growth  of  long  processes  from  the  ganglion  cells,  which  make 
their   u:i\    from   the   retina   into  the   brain. 

THE  DIFFERENT  PARTS  OF  THE  RETINAslmw  marked  variation  in  detail. 
At  the  fovea  cones  alone  are  found;  each  of  these  connects  to  one  axon  only. 

Other  structural  differences  are  found  beside  (1)  absence  of  rods,  namely 
(J)  the   cones    are   longer,   more   highly   developed,  and    some   say    mure  rod  like  than 


&a 


I'l I ^  si< M,< m ;^ 


those  found  elsewhere.  Thej  an  very  cloaeTy  packed,  so  that  their  inner  limbs 
arc  seen  in  transverse  section  t>>  h;i \ >■  a  hexagonal  slu> ] ><■,  the  fiat  surfaces  being 
in  contact  with  those  Of  their  neighbours.  (3)  The  rows  of  nerve  cells  and 
ili  mlntes.  which  iii  the  rest,  of  the  retina  lie  approximately  in  line  with  the  rod 
or  cone  to  which  they  belong,  are  in  the  fovea  pressed  to  one  side,  in  a  direction  away 
from  the  centre.  In  this  way  a  cone  may  have  the  nerve  cells  to  which  it  is  connected 
placed  at  a  considerable  distance  away  in  the  surrounding  macula.  It  is  this  displace- 
ment of  the  nerve  fibres  and   their  cells  that  causes  the  fovea  to  appear  hollow.      The 


Fig.    274.     Section    through    half    the    fovea    centralis 
and    GOLDING    l'.IR!>.) 

purpose  of  this  physiological  arrangement  would  appear  to  be  without  question  the 
avoidance,  at  this  important  region  of  the  retina,  of  the  scattering  of  the  image  which 
passage  through  the  nerve  cell  layers  would  introduce.  (4)  The  fovea  unlike  the 
rest  of  the  retina  is  devoid  of  blood  vessels.  The  purpose  of  this  arrangement  would 
appear  to  be  similar  to  that  just  given.  (5)  Visualpurple  is  said  to  be  absent  from  the 
fovea,     This  would  appear  to  be  connected   with   the  absence  of  rods. 

Hound  the  fovea  is  a  ring  in  which  rods  and  cones  arc  present  in  almost  equal 
number.  In  still  more  peripheral  regions  cones  are  relatively  few,  and  several  rods 
connect   with  each  axon:   this   reduces   the   relative  number  of  nerves. 


CHANGES  IN  THE  RETINA  ON  EXPOSURE  TO  LIGHT 
A  light  stimulus  falling  on  the  retina  causes  a  number  of  changes  to  occur 
which  may  be  classed  as  structural,  physical,  chemical  and  physiological. 
STRUCTURAL  CHANGES  occur  on  exposure  of  the  eye  to  light : 
firstly,  movement  of  the  pigment  from  the  outer  epithelial  layer  into 
the  space  between  the  rods  and  cones,  secondly,  shortening  of  the 
cones  themselves.  These  changes  occur  only  when  the  connections  of  the 
eye  with  the  brain  are  intact.  The  rate  of  movement  appears  to  vary  with 
intensity,  and  violet  light  is  said  to  be  better  than  red.  It  is  interesting  to 
find  that  electrical  stimulation  of  the  optic  nerve  or  the  falling  of  light  on 
the  other  retina  to  that  of  the  eye  observed  also  causes  these  cone  move- 


HISTOLOGY   OF  THE   RETINA 


545 


i niMiis.  It  is  supposed  that  the  impulses  which  effecl  these  movements  i  ravel 
through  the  nerve  fibres  already  described  as  descending  from  the  brain  tothc 
retinae;  it  is  for  this  reason  that  Engelmann  called  these  fibres  '  retinomotor.' 

Others!  ructural  changes  that  arc  ton  ml,  by  histological  investigation,  to  follow  expo- 
sure of  the  retina  to  light,  arc  swelling  of  the  oufer  limits  of  the  rods,  and  the  disappear 
ance  of  chromatin  granules  from  the  ganglion  cells.  Both  these  changes  are  said  to 
occur  more  rapidly  under  the  action  of  rays  of  short  wavelength. 

PHYSICAL  CHANGES  are   also   bund   when   the   retina   is  stimulated 
by  light,  namely  an  electrical  response  somewhat  similar  to  the  current 
A  B. 


Fig.  275.     Sections  of  the  frog's  retina. 
\.  kept   in  the  dark;    n.  after  exposure  to  the  light,  showing  retraction  of  the 
cones,  and  protrusion  of  the  pigmented  epithelium  between  the  outer  limbs  of  the 
rods.     (Engelmanit.) 

"I  action  in  nerve.  Three  typical  curves  and  the  conditions  under 
which  they  were  obtained  are  shown  in  Fig.  276.  One  point  of  particular 
interest  should  be  noted,  namely  the  response  to  darkness.  The  complicated 
nature  of  these  curves  has  been  explained  on  the  supposition  that  there 
are  three  substances  present  in  the  retina  of  different  reaction  time.  It 
has  not  however  been  found  possible  to  identify  any  of  them.  The  difference 
in  the  electric  response  to  light  of  different  colour  and  intensity  has  been 
found  to  give  the  following  results.  With  light  of  any  one  colour  a  geometric 
;  ise  of  intensity  causes  an  arithmetic  increase  in  the  current.  With  coloured 
i  apparent  equal  intensity  yellow  rays  are  said  to  give  a  larger  current 
in  the  light  adapted  eye.  and  green  in  the  dark  adapted  eve.  It  is  interesting 
to  observe  that  the  current  commences  after  a  latent  period  which 
is  of  the  same  order  as  that  found  for  the  perception  of  light  by  the  eye 
This  and  other  facts  mentioned  above,  would  seem  to  point  to  the  currents 
observed  being  the  accompaniment  of  the  passage  of  the  nervous  impulses 
to  the  brain.  . 

CHEMICAL  CHANGES  in  the  retina  on  exposure  to  light  are  ol 
two  kinds,  firstly  a  tendency  of  the  retina  as  a  whole  to  become  acid 
in  reaction,  as  is  shown  in  the  change  in  its  behaviour  to  certain  stains, 
and  secondly  the  bleaching  of  two  pigments,  namely,  the  visual  purple  and 
fucsin,     With  regard  to  visual  purple  (or  rhodopsin)  a  large  number  of  facts 

35 


546 


PHYSIOLOGY 


have  beenmade  out.  In  tin'  lirsl  place  it  is  found  In  association  with  the 
rod  retinal  structures  only,  and  is  therefore  absenf  from  the  human  Eoven 
cenl  ralis.     It  is  bleached  on  exposure  to  light,  both  in  the  retina  and  also  in 

1. 


' 

. 

' 

; 

■ 

J^A       ^j 

Fig.  -7<i.     Electrical  variation  in  frog's  eye  as  reeorded  by  the  string  galvanometer. 
(Einthoven  and  Jolly.) 
I,  on  exposure  t"  a  single  (lash  :   II,  on  exposure  to  light  of  moderate  duration  : 
III.  effect  "ii  a  light  eye  of  momentary  darkening 

solution.  The  absorption  of  light  by  visual  purple  is  greatest  for  the  middle 
of  the  spectrum;  the  transmitted  colour  is  therefore  composed  principally 
of  red  and  violet  rays.  Small  variations  of  colour  are  found  however  in 
samples  obtained  from  different  animals ;  some  are  even  rose  pink  in 
colour.  In  the  second  place  the  most  potent  colours  in  producing 
bleaching  are  those  near  the  centre  of  the  spectrum,  that  is  the  rays 
which  are  most  strongly  absorbed.  This  pigment  therefore  obeys 
.Draper's  law,  which  states  that  those  rays  that  are  absorbed  are  those 
which  produce  chemical  change. 


HISTOLOOY    OF    INK    KKTIXA 


547 


It  will  he  shown  below  that  the  retina  when  adapted  for  vision  in 
dim  light  is  not  onlycolour-blind,  but  also  that  the  green  rays  of  the  spectrum 
appeal  to  have  to  it  the  maximum  luminosity.  It  will  be  also  shown  that 
the  rod  containing  parts  of  the  retina,  where  visual  purple  is  to  be  found, 
are  the  only  regions  that  react  to  light  of  low  intensity.  Moreover  the 
curve  which  represents  the.  rate  of  bleaching  of  visual  purple  by  rays 
of  different  colour  is  very  similar  in  shape  to  that,  which  shows  the 
visibility  of  lights  of  low  intensity,  as  shown  in  Fig.  '277.  The  obvious 
inference    is   that  visual  purple  is  the  pigment  concerned    with    twiligb.1 


^S\ 

^^     ± 

n^     s^ 

2               x!S 

■u                        x\ 

W_                               Ov- 

lt                            ^ 

-*                               ^S 

Z                                     \!^> 

-l                                                                          t^^v 

'                                                                   s     ^ 

S~"n 

"^•-^^ 

Xj: 

o  o— L_ — .— — .i ii —J — 

g 


Fig.  277.  Shows  the  similarity  between  the  curves  representing  the  rate  of  bleach- 
ing of  visual  purple  by  light  <>f  different  wavelength  ami  the  luminosity  curve 
of  twilight  vision. 

vision.  When  the  visual  purple  in  the  retina  has  been  bleached 
by  exposure  to  light,  there  follows  a  gradual  reformation  of  purple 
which  is  independent  of  nerve  connections,  but  occurs  only  so 
long  as  the  stratum  pigment]  is  in  contact  with  the  rod  epithelial  layer. 
If  we  suppose  that  the  product  formed  by  the  bleaching  of  the  visual 
purple  stimulates  the  rod  appa rates,  causing  it  to  send  impulses  to  the  1  rain, 
we  have  at  once  obtained  some  idea  of  tin1  mechanism  used  for  night  vision. 
This  we  may  briefly  describe  as  follows:  when  light  falls  on  the  retina 
i  ertain  rays,  particularly  those  near  the  middle  of  the  spectrum,  are  absorbed 
by  the.  visual  purple.  The  pigment  is  bleached  in  proportion  to 
the  light  absorbed,  forming  a  new  product :  this  acts  on  the  rods,  causing 
them  to  send  impulses  to  the  brain  which  continue  so  long  as  the  light  falls. 
When  the  light  stops  the  stimulating  product  is  no  longer  formed,  therefore 
the  stimulus  to  the  rods  ceases. 

It  is  stated  that  in  diseases  of  the  liver,  in  which  there  are  1  He  salts  circulating  in 
the  blood,  twilight  vision  is  found  to  be  impaired.  This  condition  is  ascribed  to  the 
solubility  of  visual  purple  in  bile  salts,  and  it  is  thought  that  tin-  removal  of  i  he  pig- 
ment from  the  retina  prevents  the  rod  apparatus  from  functioning. 


548  PHYSIOLOGY 

A  picture  formed  by  the  bleaching  of  1 1n •  visual  purple  iu  those 
parts  of  the  retina  which  correspond  to  the  high  lights  of  the  image 
formed  by  the  lens,  can  be  fixed,  much  like  a  photograph,  by  immersing 
the  retina  in  a  solution  of  alum.  Fuosin  is  the  pigment  found  in  the 
form  of  needles,  plates  or  prisms  in  the  processes  of  the  cells  of  the  stral  urn 
pigmenti  (the  outer  layer  of  the  retina).  The  object  of  tins  pigment  is 
apparently  to  absorb  light  which  might  tend  to  spread  from  those  retinal 
elements,  on  which  an  image  of  a  light  source  is  falling,  to  neighbouring  ones. 
Some  of  this  pigment  is  bleached  by  strong  light,  but  so  far  as  is  known 
tlic  break-down  products  have  no  visual  function  to  perform.  The  presence 
of  other  pigments  has  been  described  in  the  retina,  such  as  visual  yellow  and 
the  bright  pigment  granules  found  in  birds.  Their  presence  is  too  variable 
for  them  to  be  considered  to  take  any  essential  part  in  the  visual  mechanism. 

PHYSIOLOGICAL  CHANGES  produced  by  light  depend  greatly  on 
the  region  of  the  retina  on  which  they  fall,  since  this  may  contain  rods 
only,  cones  only,  both  rods  and  cones,  or  neither  rods  nor  cones.  The 
peripheral  parts  of  the  retina  contain  numerous  rods  and  very  few  cones. 
When  stimulated  by  light  of  low  intensity,  this  part  of  the  retina  is  found 
to  be  exceedingly  sensitive,  particularly  if  the  eyes  have  been  closed  or 
kept  in  the  dark  for  a  time.  Tests  with  light  of  low  intensity  and  of  different 
colour  shows  that  the  region  is  colour-blind,  but  that  rays  in  the  middle  of 
the  spectrum  are  more  readily  appreciated  than  others.  We  have  here 
well  developed  the  so-called  twilight  vision,  which  is  associated  with  the 
rod-visual  purple  mechanism  just  described.  Besides  being  very  sensitive 
to  light  of  low  intensity,  the  periphery  of  the  eye  is  particularly  perceptive 
of  light  of  low  intensity  and  short  duration.  This  part  of  the  retina  there- 
fore apj:>reciates  movement  at  night  very  readily.  Lastly,  owing  to  the  fact 
that  a  number  of  rods  connect  with  one  nerve  fibre  which  conveys  the 
impulses  to  the  brain,  the  periphery  of  the  eye  has  a  poor  perception  of 
detail. 

THE  FOVEA  CENTRALIS  is  found  to  contain  cones  only.  The  vision 
in  this  region  is  therefore  the  antithesis  of  that  found  in  the  periphery.  The 
appreciation  of  light  of  low  intensity  is  bad,  but  when  an  image  is  sufficiently 
bright  to  cause  stimulation,  its  colour  is  perceived.  When  light  is 
poor,  rapid  motion  is  not  so  well  observed  as  it  is  by  the  periphery. 
There  is  an  extraordinary  acuteness  at  perceiving  fine  detail.  This  is  due 
to  the  fact  that  the  cones  in  the  fovea  are  very  closely  packed,  so 
closely  that  they  become  flattened  where  they  touch  one  another 
and  thus  have  a  hexagonal  shape  in  transverse  section.  Further 
each  cone  is  connected  to  its  own  nerve  fibre,  so  that  no  cyphering  of  the 
impulses  can  occur  on  the  way  to  the  brain.  Experiments  on  visual  acuity 
definitely  show  that  the  fineness  of  the  detail,  which  the  eye  can  perceive 
at  the  foveal  region,  is  fully  as  great  as  that  which  we  should  expect 
to  find,  if  each  cone  acted  quite  independently  of  its  neighbours.  Parts  of 
the  retina  around  the  macula  lutea,  since  they  contain  both  rods  and 
cones,  possess  as  we  should  expect  both  the  power  to  perceive  colour  found 


HISTOLOGY   OF  THE   RETINA 


549 


at  the  fovea  and  the  ability  to  react  to  light  of  low  intensity  without  colour 
vision  which  is  possessed  by  the  periphery  of  the  retina.  The  presence  of 
rods  scattered  between  the  cones  naturally  impairs  to  some  extent  however 
the  appreciation  of  fine  detail.  At  the  white  papilla  where  the  optic  nerve 
enters  the  eye,  there  are  neither  rods  nor  cones,  and  therefore  as  we  should 
expect  this  region  is  quite  blind.     This  fact  can  be  readily  proved  by  looking 


Fro.  278.     Look  at  cross  with  right  eye,  hold  book  at  about  10  inches. 

with  the  right  eye  at  the  cross  in  Fig.  278.     If  now  the  book  be  held  about 
10  inches  from  the  eye  the  white  disc  will  be  found  to  disappear.  By  a  simple 
calculation  it  is  found  that  the  disc 
corresponds  with  the  papilla  of  the 
optic  nerve. 

THE  VISUAL  FIELDS.  Since 
the  appearance  of  an  external  object 
will  vary  to  a  considerable  extent 
according  to  the  region  of  the  retina 
on  which  its  image  falls,  it  is  a  mat- 
ter of  considerable  interest  to  deter- 
mine the  positions  at  which  the 
appearances  undergo  change.  This 
is  also  of  practical  value  because  the 
positions  are  found  to  be  affected  by 
disease.  The  determinations  are 
usually  made  by  means  of  an  instru- 
ment called  a  perimeter.  . 

This  will  beseen  from  Fig.  279  to  consist 
of  a  metal  arm  bent  to  the  segment  of  a 
circle.  This  is  so  mounted  in  relation- 
ship to  a  horizontal  bearing  that  the 
segment  always  has  its  centre   in  corre- 


PlO.  -  Tit.     Priestley  Smith's  perimeter. 


spondence  with  a  fixed  pointer  which  is  seen  on  the  left  of  the  diagram.  If  the  eye 
of  the  patient  is  placed  close  to  this  pointer  and  looks  towards  the  centre  of  the 
bearing,  the  degrees  marked  on  the  metal  segment  show  the  actual  angle  at  which  an 
index  is  .situated  in  relationship  to  the  eye  axis,  no  matter  what  meridian  the  metal 
Begment  may  lie  in.  The  index  mark  usually  consists  of  a  small  disc  2  mm.  diameter 
cither  of  white  or  of  coloured  pa  per,  according   to  whether  the  rod    or  cone  area  is   to 

be  determined. 


550  PHYSIOLOGY 

The  values  obtained  by  means  of  this  instrument  are  shown  in  Pig.280, 
which  give;  a  typical  curve  for  the  right  eye.  The  shaded  area  on  the 
Left  of  the  diagram  is  due  to  the  obstruction  of  the  eyebrow,  nose  and  cheek 
of  the  patient.  The  visual  field  on  the  outer  side  will  be  seen  to  extend 
actually  11  degrees  beyond  the  right  angle.  This  result,  which  at  first  sight 
appears  to  be  impossible,  is  in  fact  due  to  the  considerable  refraction  of  the 


Fig.  isO.     Field  of  vision  for  white  and  colours  of  a  normal  right  eye  as  obtained  by 
the  perimeter.     (Hyrtkidge.) 

light  rays  that  occurs  at  the  extreme  edge  of  the  cornea.  The  direction  of 
the  beam  of  light  entering  the  eye  under  these  circumstances  is  shown  in 
Fig.  281  X  below. 

It  will  be  observed  that  even  when  looking  straight  in  front,  a  man 
can  see  to  a  considerable  angle  behind  himself.  By  deviating  the  eyes  only 
slightly  to  either  side,  this  angle  can  be  increased  to  40  degrees  in  the  average 
case  as  shown  at  Fig.  281  Z.  This  ability  to  see  to  a  considerable  extent 
behind  him  is  due  to  the  narrowness  of  the  head  between  the 
frontal  processes  and  zygomatic  bones.  In  those  animals  in  which 
the  eyes  are  placed  on  the  sides  of  the  head,  and  the  visual  axes  are  diametri- 
cally opposite  to  one  another,  the  visual  fields  will  actually  overlap  a  short 
distance  from  the  head,  so  that  there  wall  be  no  direction  from  which  an 
enemy  can  attack  without  being  observed  (Fig.  281  Y). 


HISTOLOGY   OF  THE   RETINA 


551 


UTILITY  OF  PERIPHERAL  VISION.  The  high  visual  acuity  of  the  fovea  and 
the  great  facility  with  which  the  eyes  can  be  directed,  so  that  imagi  s  form  onthisregion, 
might  raise  the  question  as  to  the  utility  of  peripheral  vision.  This  question  may  be 
investigated  experimentally  by  placing  restricting  screens  in  front  of  the  eyes,  or  by 
ascertaining  the  experience  of  persons  who  are  suffering  from  blindness  in  the  periphery 
as  the  result  of  disease.  e.g.  retinitis  pigmentosa.  Both  methods  show  that  the  periphery 
is  of  great  value  in  directing  attention  to  outlying  obstacles.  Our  attention  being  excited 
we  direct  the  gaze  in  the  direction  indicated,  in  order  to  bring  into  action  the  greater 
power  of  analysis  of  the  fovea. 


'XTK  i% 


*-» 


I'm:.  281.      Diagram  '/,  shows  size  of  blind  zone  in  man.     (II  vrtridoe.)     Diagram 
\   shows  how  extremely  peripheral  rays  cuter  the  eye  and  reach  the  retina. 
i  lib  Y  shows  absence  of  blind  zone  in  certain  birds  and  animals. 

CENTRAL  CONNECTIONS  OF  THE  RETINA.  The  connecting  paths 
between  the  retina  and  the  brain  are  formed  by  the  optic  nerves.  At  first 
i  licse  are  hollow  tulles  to  which  tin-  optic  cups  are  attached.  After  the  retinal 
artery  has  Pound  its  way  through  the  cleft  in  the  optic  cups,  the  nerves  fold 
round  it  ami  become  solid,  and  through  their  substance  the  nerve  fibres  from 
the  ganglion  cells  of  the  retina  grow  toward  the  brain.  The  primitive  ground- 
work of  the  nerve  is  also  invaded  close  to  the  optic  cup  by  mesoblast  forming 
the  cribriform  plate  of  the  sclera.  Through  the  meshes  of  this  plate  the 
nerve  fibres  have  to  pass.  Traced  backwards  the  optic  nerves  leave  the  orbit 
through  the  optic  foramen  accompanied  by  the  ophthalmic  artery.  The 
optic  nerve  lias  sufficient  slack  in  order  to  permit  free  motion  to  the 
Having  entered  the  cranial  cavity  the  nerve  pierces  the  dura  mater,  and 
meets  its  fellow  from  t  he  other  eye  ;  with  this  it  connects,  forming  the  chiasma, 
and  the  fibres  partially  decussate.     The  fibres  thus  torn:  the  optic  tracts 


552 


I'HYSIOLOCY 


which  travel  round  under  the  crura  cerebri  and  then  divide  to  end  in  cells 
in  three  different  nuclei,  (a)  the  anterior  corpus  quadrigeminum, 
(/>)  the  external  geniculate  body  and  (c)  the  pulvinar.  The  optic  nerve 
contains  four  different  sets  of  fibres:  (1)  those  which  convey  visual  impressions 
to  the  brain;  (2)  those  going  to  the  pupillomotor  centres;  (3)  those  which 
come  down  from  the  brain  to  the  retina?,  the  so-called  retinomotor  fibres, 
which  may  have  trophic  fibres  associated  with  them;  (4)  nerves  travelling 
from  one  retina  to  the  other.  The  courses  of  these  separate  fibres  must  now 
be  traced. 

LEFT  RETINA  right  retina  (1)    From   each   retina   three 

separate  bundles  of  visual  fibres 
arise :  (a)  those  from  the  right 
halves  of  the  retinas,  which  join 
at  the  chiasma  and  travel  to 
the  brain  via  the  right  optic 
tracts ;  (b)  those  from  the  left 
halves  of  the  retinas  which  travel 
via  the  left  tracts  ;  and  (c)  those 
from  the  foveae  centrales  (in  man 
and  monkey  only)  which  partly 
travel  via  the  tract  of  their  own 
side  and.  partly  cross  to  that 
of  the  other.  The  right  optic 
tract  thus  contains  all  the  visual 
fibres  from  the  right  sides, 
and  half  those  from  the  centres 
of  the  two  retinae,  which  travel 
to  the  right  occipital  cortex 
through  the  pulvinar  and  exter- 
nal geniculate  body  of  that  side. 
The  left  tract  travels  to  the  left 
occipital  cortex  in  a  similar  man- 
ner. These  connections  are 
represented  diagrammatically  in  Fig.  282. 

(2)  The  pupillomotor  impulses  travel  up  without  crossing,  as  I  have 
already  described  on  page  510,  to  the  anterior  corpora  quadrigemina  (see  also 
Fig.  203  and  page  406). 

(3)  Nothing  is  I  believe  known  as  to  the  fate  of  these  so-called  retino- 
motor fibres  ;  some  of  them  may,  in  fact,  be  trophic  or  vaso- constrictor  fibres. 

(4)  The  function  of  these  inter-retinal  fibres  are  not  known  definitely. 
It  has  been  suggested  that  they  cause  changes  in  one  retina  wheD  light 
falls  on  the  other,  as  for  example  cone  movement.  It  has  also  been  sup- 
posed that  the  sympathetic  inflammation  which  occurs  in  one  eye  after 
certain  injuries  to  the  other,  is  due  to  impulses  which  have  travelled  via  these 
nerves ;  lastly  binocular  contrast  and  after  images  have  been  ascribed  to  them. 

It  is  of  practical  importance  to  be  able,  to  locate  an  injury  to  the  visual 


Fig.  282.  Diagram  showing  the  probable 
relations  between  the  parts  of  the  retinae 
and  the  visual  area  of  the  cortex.  (Schafer.) 


HISTOLOGY   OF  THE   RETINA 


553 


nerve  paths.  Injury  to  the  optic  nerves  causes  blindness  of  the  eye  to  which 
the  nerve  belongs,  and  stimulation  of  the  eye  by  light  will  not  then  elicit 
the  pupil  reflex.  Injury  to  the  optic  tract  causes  blindness  of  the  halves 
of  both  retinae  on  the  same  side  as  the  lesion,  that  is  to  say  blindness 
to  external  objects  on  the  opposite  side  to  the  injury.  It  is  interesting  to 
note  that,  whereas,  in  most  other  nerve  paths,  crossing  of  the  impulse  occurs 
from  one  side  to  the  other  as  it  travels  to  the  brain,  so  that  the  left  side 
of  the  brain  corresponds  to  the  right  side  of  the  body,  this  is  not  the  case 
with  the  optic  impulses.  These  are  already  crossed  by  the  optical  apparatus 
of  the  eye  and  therefore  crossing  of  the  impulses  is  rendered  unnecessary. 
Injury  to  the  optic  radiation  or  the  occipital  cortex  will  cause  blindness  of 
both  retina?  on  the  same  side,  but  will  not  affect  the  pupil  reflex,  because 
these  fibres  have  already  turned  aside  to  go  to  the  anterior  corpora  quad- 
rigemina.  Injury  of  the  middle  of  the  chiasma,  such  as  may  occur  in 
tumours  of  the  pituitary  body,  affects  the  nasal  halves  of  both  retinae  and 
produces  double  temporal  hemianopia. 

THE  OPHTHALMOSCOPE.  If  the  retina  of  a  patient  be  illuminated  by  causing 
a  beam  of  light  to  enter  the  pupil,  the  reflected  light  will  cause  the  interior  surface 
(■I  the  retina  to  be  visible.  In  order  to  see  the  image  distinctly  it  is  necessary  either 
that  both  the  eye  of  the  patient  and  also  that  of  the  observer  should  be  focussed  for 
infinity  (the  direct  method)  or  that  both  eyes  should  be  focussed  for  oneand  the  same 
intermediate  plane  (the  indirect  method).  The  former  has  many  disadvantages  which 
are  not  found  in  the  case  of  the  latter,  and  therefore  will  not  be  considered  further. 
The  indirect  method  is  carried  out  as  follows : — A  bright  source  of  light  having  been 
placed  behind  and  slightly  to  one  side  of  the  patient,  the  observer  standing  about  half 
a  meter  in  front  of  him  reflects  by  means  of  a  convex  mirror  an  image  of  the  light  into 
his  pupil.  At  the  centre  of  the  mirror  is  an  aperture  through  which  the  doctor  sees 
i  in  light  which  is  reflected  back  from  the  patient's  retina.  The  observer  now  holds  a 
bici  m  vex  lens  of  about  G  cm .  focal  length  about  8  em.  in  front  of  the  patient's  eye,  while  he 
si  ill  directs  the  beam  of  light  into  t  he  pupil  as  before.  The  image  of  the  retina,  which  would 
normally  be  focussed  by  the  lens  system  of  the  patient's  eye  at  infinity,  is  now  brought 
to  a  focus  by  the  convex  lens,  forming  what  is  called  an  aerial  image  (see  Pig.  283). 
It  is  this  image  that  the  observer  sees,  and  in  it  are  shown  all  the  particular  features 
of  the  vessels  and  nerves  of  the  patient's  retina.  Beside  its  very  great  utility  to  the  oculist, 
the  ophthalmoscope  is  a  very  valuable  instrument  to  the  physician,  for  retinal  vessels 
and  nerves  frequently  show  the  evidences  of  constitutional  disease,  which  are  of  great 
assistance  to  diagnosis,  ophthalmoscopes  are  usually  fitted  with  a  number  of  small 
lenses  of  graduated  power,  u  Inch  may  be  introduced  as  required  behind  the  mirror.  For 
the  indirect  method  they  are  seldom  required.  The  magnification  of  the  retina  given 
by  the  direct  method  is  usually  about  3.  while  that  provided  by  the  direct  is  12.  If 
a  higher  magnification  is  an  advantage  it  may  lie  obtained  by  using  a,  biconvex  lens  of 
longer  Focal  length  (saj   12  em.). 


I  h     M      Diagram  In  show    paths  of  rays  from  eye  of  patient  t"  doctor  when 
the  indirect  method  of  ophthalmoscopy  is  in  use.     (Habtkidqe.) 


m  i 


PHYSIOUMJY 


The  image  seen  in  the  ophthalmoscope  is  shown   in   Pig.  284. 

(  to  examining  the  back  of  the  eyeball  by  .either  of  these  methods,  the  must  prominent 
object  is  tin-  optic  disc-  or  optic  nerve-papilla,  which  marks  the  point  of  entrance  of  the 
optic  nerve.  It  is  seen  as  a  pale  oval  disc  surrounded  by  a  deep  red  background  (Fig. 
284).  From  the  middle  of  the  papilla  the  retinal  vessels  pass  into  the  eyeball,  and 
they  ate  seen  diverging  from  the  papilla  to  ramify  over  the  rest  of  the  retina.  The 
arteries  can  be  distinguished  from  the  veins  by  their  brighter  red  colour  as  well  as  by  the 
stronger  reflection  of  light  from  their  surfaces.  The  yellow  spot  is  very  difficult  to  see, 
except  in  atropinised  eyes,  since  it  comes  into  view  only  when  the  observed  eye  is  looking 
straight    into    the   ophthalmoscope.     Under  these  conditions  there  is  a  strong  Might 


/4 


Km.  2s4.  Ophthalmoscopic  view  of  fundus  of 
eye,  showing  the  optic  disc,  or  point  of  entry 
of  the  optic  nerve, with  the  retinal  vessels  branch- 
ing from  its  centre. 


a  X> 


Fig.    285.     Diagram     of    tin- 
path  of  the  rays  of  light  in 
the  formation   of  Purkinje's 
figures. 
v  represents  a  retinal  vessel. 

When  this  is  illuminated  from 

A,  a  shadow  is  formed  on  the 
hinder  layers  of  the  retina  at 
it'.  This  is  projected  along  a 
line  passing  through  the  optic 
axis,  and  appears  to  come  from 
a  point  ('/")  on  the  wall.  (In 
moving    the   light    from    a    to 

B,  the  image  of  the  vessel 
appears  to  move  from  a"  to  /,. 


reflex,'  and  the  pupil  contracts  up  to  a  pin-point,  unless  paralysed  by  means  of  atropine. 
In  order  to  see  the  blind-spot,  or  optic  disc,  the  observed  eye  must  he  directed  inwards  ; 
thus  if  A  is  looking  at  the  right  eye  of  B,  B  must  be  told  to  look  over  A's  light  shoulder. 

By  projecting  a  highly  concentrated  beam  of  light  on  to  the  side  of  the  eyeball, 
it  is  possible  to  cause  sufficient  light  to  pass  through  the  wall  that  the  retina  perceives 
the  stimulus.  When  that  is  the  case  it  is  found  that  the  retinal  arteries  and  veins  are 
seen  as  dark  images  on  a  bright  ground  (Purkinje's  figures).  By  moving  the  point  of 
illumination  and  then  measuring  the  apparent  shift  of  the  vessels  which  occurs,  it 
has  been  found  possible  to  estimate  the  depth  below  the  vessels  at  which  the  re- 
ceptive surface  of  the  retina  is  placed,  namely  -17  to  -30  mm.  Now  the  average 
distance  between  the  vessels  and  the  layer  of  rods  and  cones  is  found  to  be  -2  to  -3 
mm.  ;  it  must  therefore  be  the  layer  of  rods  and  cones  which  forms  the  sensitive 
layer.      The  directions  taken  by  the  light  rays  are  shown  in  Fig.  285. 

Another  method  of  viewing  the  vessels  in  one's  own  eye  is  to  look  through  a  small 
hole  in  a  met  il  plate  at  a  smooth  white  surface.  <  hi  oscillating  the  aperture  in  relation 
ship  with  the  pupil  about  once  a  second,  the  vessels  will  he  seen  as  shade  us  on  the  bright 
background. 


SECTION    VIII 

THE    RELATIONSHIP    BETWEEN    STIMULUS    AND 
SENSATION 

In  the  introduction  I  have  pointed  out  that,  since  we  are  unable  to  express 
our  sensations  in  terms  of  physical  units  (we  cannot  say,  for  example,  when 
one  source  is  twice  as  bright  as  another),  two  methods  of  investigation  are 
alone  available,  namely,  that  which,  involves  the  determination  of  threshold 
values,  and  that  which  depends  on  the  making  of  comparisons. 

In  order  that  a  source  of  light  shall  be  perceived,  the  image  which  is 
formed  on  the  retina  must  have  certain  properties.  In  the  first  place  it 
must  last  for  a  certain  finite  time,  for  if  it  be  of  shorter  duration  than  this 
it  will  not  be  perceived.  Secondly  it  must  be  larger  than  a  certain 
size  Thirdly  its  intensity  must  be  greater  than  a  certain  limiting 
quantity.  Fourthly  the  rays  which  it  emits  must  have  wavelengths 
which  lie  between  certain  limits  So  that  in  the  case  of  each  of 
these  four  properties  there  are  limiting  values  which  must  be 
exceeded ;  these  values  are  called  thresholds.  The  retina  has 
distributed  over  its  surface  two  different  types  of  sensitive  organ,  the 
cone  apparatus,  which  has  the  function  of  perceiving  colours  and  is 
used  in  day  vision,  and  the  rod-visual  purple  apparatus,  which  is  colour- 
blind but  verj'  sensitive  to  light  of  low  intensity  and  is  therefore  used  for 
twilight  vision.  Owing  to  the  fact  that  the  distribution  of  these  organs 
is  not  uniform,  we  have  to  state  the  part  of  the  retina  which  is  being  stimu- 
lated when  assigning  a  value  to  any  of  the  above-mentioned  thresholds.  For 
example,  the  threshold  for  intensity  may  be  that  which  just  actuates  the 
rods,  that  is  the  achromatic  limit,  or  that  which  is  sufficient  to  affect 
the  cones  and  therefore  causes  an  appreciation  of  colour.  Moreover 
the  value  of  any  one  threshold  is  to  a  considerable  extent  [controlled 
by  the  value  of  the  other  factors  which  1  have  mentioned;  for  example, 
tin-  time-  threshold  is  shinier  the  greater  the  size  and  intensity  of  the  light 
source.  The  exact  conditions  must  therefore  lie  carefully  stated  in  quoting 
the  value  of  a  threshold.  Lastly  we  must  consider  the  personal  equation 
of  the  observer,  and  also  the  state  of  his  vision,  for  both  are  affected  by 
constitution,  health,  fatigue,  &c,  to  an  important   extent. 

INTENSITY   THRESHOLD    FOR    LIGHT    (ACHROMATIC) 
II   a  spectrum  be  gradually  reduced   in  intensity,  it   loses  its  coloui  and 
finally  appears  to  the  eye  as  a  bright   band  which  has  its  greatest  lumi 
nosity  in  the  green  region  of  the  spectrum  and  gradually  fades  towards  both 

555 


556 


PHYSIOLOGY 


the  red  and  violet  ends.  Since  the  band  is  colourless,  any  one  part  mas- 
he  matched  by  any  cither  part  by  suitably  adjusting  the  intensities.  But 
compared  with  the  appearance  under  ordinary  intensity,  the  red  region 
of  the  spectrum  has  become  greatly  reduced  in  visibility,  while  the  blue  has 
become  relatively  brighter.  The  part  of  the  spectrum  with  maximum 
luminosity  is  found  to  be  the  yellow  when  the  intensity  is  high,  but  to  be 
the  green  \\  hen  it  is  low.  It  is  therefore  this  shifting  of  the  position  in  the 
spectrum  of  the  maximum  which  lias  caused  red  to  darken  and  blue  to 
become  lighter.  The  relative  forms  and  positions  of  the  luminosity  (apparent 
brightness)  curves  for  spectra  of  various  intensity  are  shown  in  Fig.  286. 


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Fig.  286.  Luminosity  curves  for  spectra,  of  different  intensity.  A  =  highest, 
H  =  lowest.  Abscissae  =  wavelengths,  ordinates  luminosities  (Konig). 
The  maximum  of  curve  for  light  of  high  intensity  is  seen  to  !«■  at  6100  A.l*. 
that  at  low  intensity  5150  A.U. 

If  the  spectrum  of  low  intensity  be  still  further  decreased,  a  point  will 
be  reached  at  which  the  different  parts  become  invisible  to  the  eye;  this 
will  occur  first  with  the  ends,  and  last  with  the  middle  (at  about  5271  A.U.). 
It  is  found  however  that  the  intensity  values  at  which  visibility  ceases 
decrease  the  longer  the  eye  is  kept  in  the  dark,  that  is  to  say  the  retina 
gradually  becomes  'dark  adapted.'  The  curves  obtained  for  different 
degrees  of  dark  adaptation  are  also  shown  in  Fig.  286. 

We  must  now  consider  the  effects  on  the  achromatic  threshold 
of  size  of  light  source,  duration  of  stimulus  and  part  of  retina  illuminated. 
With  regard  to  size,  experiment  shows  that  as  the  size  of  the 
source  decreases  so  the  intensity  at  which  extinction  occurs  increases,  in 
fact  that  the  area  of  the  source  multiplied  by  its  intensity  is  constant. 
With  regard  to  the  region  of  the  retina  that  is  stimulated,  it  is  found  that  the 


RELATIONSHIP   BETWEEN  STIMULUS    WD  SENSATION    557 

rod-visual  purple  apparatus  is  responsible  for  the  appreciation  of  the  light 
of  low  intensity  ;  it  is  therefore  found  in  all  parts  of  the  retina  other  than 
the  Eovea  centralis  from  which  rods  are  absent.  The  effect  of  time  of  stimulus 
will  be  considered  shortly. 


INTENSITY   THRESHOLD   FOR  COLOUR 

If  a  spectrum  of  low  intensity  which  appears  colourless  to  the  eye  be 
graduallyincreased  in  brightness,a  point  will  be  readied  at  which  the  colours 
begin  to  lie  recognisable,  first  yellow  and  green,  then  blue  and  lastly  red  and 
violet.  If  the  intensity  at  which  the  colour  just  vanishes  is  measured, 
the    curve    obtained    is   similar   to    that    shown    in    Fig.    287.       As     the 


s 


10  15         20         15        30        35        40        15        SO         S5 

!\\t  inction  of  colour  '  curve.     Abscissae = wavelengths;  ordinate 
sity  in  candle  feet  when  colour  just  vanishes.     (Aunev.) 


intensity  is  increased,  the  point  of  maximum  luminosity  gradually 
shifts  from  the  green  to  the  yellow.  As  a  coloured  object  is 
gradually  increased  in  intensity,  it  is  first  seen  without  colour,  but 
after  an  interval  the  colour  also  is  recognised ;  this  is  called  the  photo- 
chromatic  interval.  It  follows  from  what  we  have  said  that  the  interval 
is  greatest  for  colours  of  short  wavelength  (blue)  and  least  for  long  (red) 
(the  I'urkinje  phenomenon).  The  thresholds  for  light  and  colour  differ  in 
another  important  respect,  namely  that  whereas  that  of  light  varies  with  the 
degree  of  dark  adaptation,  that  of  colour  is  found  by  experiment  to  lie  nearl) 
constant.  With  regard  to  the  effect  of  area  of  light  source,  it  is  found  that 
the  same  type  of  relationship  exists  in  the  case  of  colour  as  for  light, 
namely,  that  as  the  area  is  decreased,  so  the  intensity  must  be  correspond- 
ingly increased.  The  area  and  intensity,  multiplied  together,  do  not  how c\  er 
equal  a  constant  as  they  do  in  the  case  of  light.  The  appreciation  of  colour 
is   associated    with   the  cones   and    is    therefore  most  highly  developed    at 


,vs 


PHYSIOLOGY 


the  fovea.  As  the  periphery  of  the  retinaB  is  approached  the  number  oi 
the  cones  very  rapidly  decreases,  and  we  should  therefore  expecl  to  Bnd  a 
1 1 n 1 1 1  in  the  size  of  the  visual  field  for  different  colours.  This  may  be  tested 
by  means  of  the  perimeter  (Fig.  279)  and  small  coloured  discs,  <>r  more 
accurately  by  suitable  apparatus  for  employing  spectral  colours.  By  these 
methods  it  is  found  that  the  colour  fields  are  smaller  than  those  for  light, 
hut  more  or  less  concentric  with  them  (Fig.  288).     The  actual  size  of  the 

fields  varies  with  (he  intensity 
and  size  of  the  test  light  source, 
or  object.  The  order  in  which 
the  colours  disappear  varies  some- 
what but  appears  to  be  usually 
as  follows-: — First  green,  then 
yellow,  then  red,  and  lastly  blue. 
The  determination  of  the  size  of 
the  colour  fields  is  a  technique  of 
considerable  practical  importance, 
because  they  are  found  to  be- 
come restricted  in  those  progres- 
sive lesions  of  the  optic  nerves 
which  may  finally  lead  to  total 
blindness,  and  also  in  inflamma- 
tory conditions  of  the  retina  and 
choroid.  Careful  examination  of 
the  apparent  limits  of  the  blind- 
spot  by  means  of  similar  appa- 
ratus was  found  by  Haycraft  to  show  that  there  is  a  similar  variation  in 
the  relative  sizes  of  the  fields  for  different  colours  (Fig.  288).  The  same 
phenomenon  is  also  found  round  the  Mind-spots  formed  in  the  retina  by 
disease. 


Fig.  288.     Limitation  of  colour  fields  round 
the  blind  spot.     (Havi  b  \kt.) 


SIZE   THRESHOLD   OR  VISUAL    ACUITY 

If  a  small  source  of  light  be  gradually  reduced  in  size,  a  point  is  soon 
reached  at  which  it  becomes  invisible.  If  it  is  a  coloured  source,  it  as  a  rule 
shows  a  well-marked  photochromatic  interval,  that  is,  it  first  loses  its  colour 
and  then  disappears  later.  If  the  intensity  of  the  source  is  very  great,  the 
size  has  to  be  greatly  reduced  before  it  becomes  invisible  :  it  is  because 
of  this  that  we  see  the  stars.  If  the  size  and  intensity  at  the  point  of  dis- 
appearance be  measured,  it  is  found  that  when  multiplied  together  they 
equal  a  constant,  so  that  as  in  the  case  of  the  light  threshold  the  determining 
factor  appears  to  be  the  amount  of  light  which  falls  on  the  retina.  In 
the  case  of  intermittent  illumination  a  similar  relationship  is  found. 

Visual  acuity  is  the  ability  to  see  as  separate  the  images  of  small  bright 
light-sourCes  of  any  shape  placed  very  close  together.  Experiment 
shows  that  the  distance  between  the  sources  must  be  increased  as  their 
distance  from  the  eye  is  increased.     In  other  words  that  the  angle  which 


RELATIONSHIP  BETWEEN  STIMULUS   AND   SENSATION    559 

(hey  make  at  the  eye  must  be  greater  than  a  certain  limiting  value.  The 
angle  usually  obtained  is  an  angle  of  one  minute,  and  on  this  I  lie  lettering 
used  in  practice  for  testing  the  visual  acuity  of  patients  is  based  (see 
page  535).  Persons  with  exceptionally  good  vision  are  able  to  see 
the  images  separated  when  the  angle  which  the  sources  make  at  thi- 
eve is  very  much  less  than  this,  namely  U I  seconds.  Assuming  that 
the  posterior  nodal  point  is  156  mm.  from  the  retina  (this  being  the 
distance  in  the  normal  eye,  see  page  523)  '2 !  seconds  corresponds  with  a 
distance  between  the  images  at  the  retina  of  "0018  mm.  The  diameter 
of  the  cones  is  between  "0020  and  'C030  mm.,  and  in  the  fovea  they  are 
very  closely  packed  so  as  to  present  a  hexagonal  section.  The  maximum 
visual  acuity  is  therefore  certainly  as  great  as  the  size  of  the  cones  would 
lead  us  to  suppose  possible. 

The  case  of  a  dark  spot  on  a  bright  ground  is  similar  to  the  case  just 
considered,  because  for  the  dark  spot  to  be  recognised  it  must  subtend 
at  the  eye  the  minimal  angle  mentioned  above.  Increasing  the  intensity 
of  the  ground  or  the  blackness  of  the  spot  will  make  a  very  small  difference. 
The  case  of  the  black  spot  is  therefore  very  different  to  that  of  the  white 
in  which  an  increase  in  the  intensity  is  sufficient  to  make  up  for  a  difference 
of  size. 

TIME   THRESHOLD 

In  considering  the  time  threshold  two  different  sets  of  conditions  require 
description,  firstly  the  minimum  time  during  which  a  given  stimulus  must- 
art  m  order  to  reach  consciousness,  and  secondly  the  minimum  rate  at  which 
a  series  of  stimuli  must  follow  one  another  in  order  to  give  a  uniform  impres 
sion  without  flicker.  Both  are  of  considerable  importance  since  the  first 
enters  such  problems  as  the  determination  of  the  length  of  time  during 
which  a  lighthouse  beam  should  be  caused  to  travel  in  a  given  direction, 
the  second  because  it  gives  a  reliable  method  of  comparing  the 
intensity  of  lights  of  different  colour.  Experimental  investigation  of  the 
first  type  of  time,  threshold  is  effected  by  measuring  the  length  of  stimulus 
necessary  to  cause  a  source  of  a  certain  intensity  to  affect  the  retina,  and 
it  is  found  that  the  lower  the  intensity  the  longer  must  the  image  fall  on  the 
retina.  But  if  the  eye  be  dark  adapted,  if  the  time  and  the  intensity 
values  be  multiplied  together,  then  within  limits  a  constant  is  obtained. 
On  the  other  hand,  in  the  light  adapted  eye,  the  value  is  found  to  vary 
somewhat,  but  is  sufficiently  constant  to  show  that,  the  relation  between 
intensity  and  time  is  approximately  the  same.  Within  limits  therefore  we 
find  that  at  the  threshold  the  total  amount  of  light  is  constant  whether  if 
be  of  high  intensity  for  a  very  short  period  of  time  or  of  low  intensity  for 
a  correspondingly  longer  one.  This  relationship  ceases  to  be  true  if  the  time 
of  stimulation  is  longer  than  about  one- tenth  of  a  second,  and  this  is  appar- 
ently due  to  the  fact  that  the  retinal  apparatus  reaches  a  steady  state  in 
about  one-quarter  of  a  second  in  the  dark  adapted  eye  (rod-visual  purple 
apparatus).    A  lighthouse  flash  should  therefore  be  visible  to  the  ej  e  for  t  his 


560  PHYSIOLOGY 

length  <>f  time  in  order  to  make  the  greatesl  impression  possible. 
For  coloured  lights  approximately  the  same  values  are  found,  pro- 
vided that  allowance  is  made  for  the  comparative  intensity  of  the  colour. 
Since  the  time  required  for  the  retina  to  reach  a  steady  state  is 
nearly  that  at  which  a  series  of  stimuli  must,  fall  on  the  retina  in  order  to 
produce  a  uniform  sensation,  for  intensities  near  the  threshold 
the  rale  at  which  flicker  disappears  is  one  stimulus  every  quarter 
oi  a  second.  But  it  is  found  that  as  the  intensity  rises  the  rate  must  be 
increased  in  order  to  abolish  flicker.  The  rule  which  most  nearly  expresses 
the  relation  appears  to  he  that  geometrical  increase  in  the  intensity  requires 
an  arithmetic  increase  in  the  rate.  Sherrington  showed  however  that  the 
results  are  affected  by  simultaneous  contrast..  This  phenomenon  of  flicker 
is.  as  I  have  said,  used  in  practice  for  measuring  the  intensities  of  light  sources. 
Two  methods  are  employed,  firstly  that  in  which  the  two  light  sources  to  be 
compared  are  measured  separately  for  the  intensity  at  which  flicker  ceases 
when  the  same  rate  of  stimulation  is  used  for  both;  and  secondly  that  in  which 
the  two  sources  are  caused  to  fall  alternately  on  the  eye,  and  are  adjusted 
in  intensity  until  flicker  ceases.  Of  the  two  methods  the  latter  is 
the  more  accurate.  The  value  of  these  methods  lies  in  the  fact  that 
they  measure  brightness  independently  of  colour.  The  shape  of  the  curves 
obtained  by  plotting  the  luminosity  of  different  parts  of  the  spectrum  has 
been  shown  in  Fig.  286. 

Lastly  we  have  to  consider  the  relationship  between  time  intensity  and 
apparent  brightness  in  the  case  of  an  intermittent  source,  the  rate  of  which 
is  sufficiently  great  to  avoid  flicker.  Experiment  shows  that  the  brightness 
increases  in  proportion  as  either  the  intensity  or  the  time  is  increased, 
and  further  that  equal  brightness  is  obtained  if  the  time  multiplied  by  the 
intensity  is  constant.  This  statement  is  true  of  both  the  cone  and  the  rod 
apparatus,  and  is  known  as  the  Talbot  Plateau  Law.  Use  is  made  of  this 
law  in  the  sector  method  of  controlling  intensity  (see  page  56-1)  because  the 
intensity  is  proportional  to  the  time  during  which  the  light  is  allowed  to 
pass  through,  which  is  in  its  turn  controlled  by  the  angle  between  the 
blades  of  the  sector. 

COLOUR   THRESHOLD 

On  testing  the  violet  end  with  a  photographic  process,  or  the  red  end 
by  a  thermopile,  it  can  readily  be  shown  that  the  spectrum  extends  at 
both  ends  far  beyond  the  visible  limit.  The  visible  limit  at  the  red 
end  under  the  most  favourable  conditions  has  been  found  to  be  8350  A.U., 
while  under  ordinary  circumstances  it  is  difficult  to  go  beyond  8000  A.U. 
Since  rays  beyond  this  reach  the  retina  in  considerable  amount,  the  limit 
cannot  be  caused  by  opacity  of  the  eye  media,  and  must  therefore  be  due 
to  an  actual  inability  on  the  part  of  the  retina  to  record  their  presence. 

Of  several  hypotheses  which  might  be  advanced  for  this  inability,  the 
most  probable  is  that  the  retinal  pigments  are  unable  to  absorb  rays  in  the 
infra-red  part  of  the  spectrum,  and  therefore  according  to  Draper's  law  such 


RELATIONSHIP  BETWEEN  STIMULUS  AND  SENSATION    561 

rays  cannot  produce  photochemical  change  and  cannot  be  perceived 
by  the  eye.  It  may  be  mentioned  in  this  connection  that  few  organic 
pigments  absorb  strongly  in  the  infra-red. 

The  limit  at  the  violet  end  islesseasy  to  determine  because  the  eye  media, 
in  common  with  a  large  number  of  other  bodies,  have  the  property  of  fluoies- 
cing  when  the  ultra-violet  rays  fall  on  them,  i.e.  they  convert  them 
into  rays  of  longer  wavelength  and  therefore  make  them  visible.  The 
resulting  impression  is  however  quite  different  because,  since  these  rays 
are  generated  in  the  eye  media  themselves,  they  are  spread  over  the  re- 
tina as  a  haze  without  there  being  any  proper  image  formation.  The  limit  of 
the  visibility  of  the  violet  end  of  the  spectrum  appears  to  be  at  about  3800 
A.U.,  while  the  portion  which  is  seen  because  of  the  fluorescence  which  it 
produces,  and  which  appears  a  pale  lavender,  ends  at  about  3200  A.U.  Since 
the  wavelength  of  the  extreme  red  rays  is  a  little  more  than  double  that  of 
the  extreme  violet,  the  eye  is  sensitive  to  a  little  over  an  octave.  The  range 
of  appreciation  of  the  eye  is  therefore  very  much  smaller  than  that  of  the  ear, 
which  is  about  10  octaves.  As  age  increases  the  eye  media  become 
yellow  in  colour:  this  change  particularly  affecting  the  lens,  the  violet 
end  of  the  spectrum  becomes  shortened  owing  to  absorption.  On 
removing  the  lens  of  the  eye  as  in  an  operation  for  cataract, 
the  sensitiveness  to  the  violet  end  of  the  spectrum  is  considerably 
increased.  It  would  therefore  seem  certain  that  the.  limitation  of  the 
spectrum  of  the  violet  end  is  largely  due  to  absorption  by  the  eye  media  and 
not  to  inappreciation  on  the  part  of  the  retina.  The  causes  of  the  limitation 
of  the  two  ends  of  the  spectrum  are  therefore  different. 

DIFFERENCE  THRESHOLDS 
Beside  the  thresholds  for  light,  colour,  time,  and  wavelength,  which 
we  have  considered  above  and  which  may  be  called  absolute  thresholds, 
there  are  certain  difference  thresholds  that  must  be  considered.  Thus,  for 
example,  a  certain  finite  difference  must  exist  between  the  intensities  of  two 
sources  of  light  of  the  same  colour  for  a  difference  between  them  to  be  appreci- 
ated by  the  eye.  There  are  four  principal  types  of  difference  threshold,  that 
of  intensity,  that  of  colour,  that  of  saturation,  and  that  of  size. 

Difference  Threshold  of  Intensity 
It  is  found  by  experiment  that  a  just  perceptible  difference  between  the 

intensities  of  two  surfaces  varies  with  the  mean  value  of  their  intensities. 
Thus  supposing  that  it  had  been  found  by  one  experiment  that  a  difference 
of  intensity  of  one  foot  candle  was  necessary  in  order  that  two  sources  should 
lie  just  distinguishable,  the  average  inteiisities  of  which  were  one  hundred 
foot  candles,  then  in  another  case  in  which  the  average  was  25  F.O.  the  least 
perceptible  difference  would  be  found  to  be  one-quarter  F.O  This  condition 
is  known  as  Weber"s  law.  It  appears  to  be  true  for  light  of  medium  intensity 
and  for  sources  not  separated  by  more  than  a  small  interval.  But  the  least 
perceptible  difference  is  found  by  most  observers  to  be  less  than  that  taken 
for  purposes  of  illustration  above,  namely  one-hundredth  part  of  the  mean 

36 


562  PHYSIOLOGY 

intensity ;  thus  Helrnholtz  found  it  to  be  a  |,';;tli,  other  observers  have 
obtained  even  higher  fractions.  It  is  interesting  to  find  that  the  results  are 
not  influenced  by  the  size  of  the  pupil. 

Difference  Threshold  of  Colour 
I  [  the  range  of  colours  exhibited  in  the  spectrum  be  carefully  examined)  it 
will  be  seen  that  there  are  certain  parts,  notably  at  the  red  and  violet  ends, 
at  which  the  change  of  colour  with  wavelength  is  a  very  gradual  one.  At 
ot  her  parts  on  the  contrary  1  he  change  of  hue  is  very  rapid,  the  yellow  region 
at  5800  A.U.  may  be  given  as  example.  If  therefore  we  determine  by  experi- 
ment what  difference  of  wavelength  is  just  perceivable  by  the  eye,  we  find 
that  it  varies  with  the  part  of  the  spectrum  under  observation.  We  may 
therefore  conveniently  express  the  difference  threshold  in  different  parts 
of  the  spectrum  in  the  form  of  a  curve,  as  in  Fig.  289.  In  persons  with  normal 
vision  the  total  number  of  different  hues  in  the  spectrum  is  calculated  to  be 
165.     In  persons  with  colour-blindness  the  number  is  greatly  reduced. 


Fig.  289.     Curve  showing  difference  threshold  for  colour  at  different  pints  of  the 
i  spectrum. 

7 Abscissa©  =  wavelengths.     Ordihates     =  difference    between    wavelengths    call- 
able of  being  discriminated.     (Steindler.) 

Tins  fact  has  been  applied  by  Edridge  Green  for  the  detection  of  colour- 
blindness ;  details  of  the  method  will  be  given  later.  It  should  be  pointed 
out  that,  since  in  this  method  the  spectrum  itself  is  presented  to  the 
observer  so  that  there  is  a  gradual  change  from  one  colour  to  the  next,  it 
is  the  threshold  of  rate  of  change  of  colour  that  is  determined,  and  not  differ- 
ence threshold  of  colour. 

Difference  Threshold  of  Saturation 

By  saturation  is  meant  the  amount  of  white  light  which  is  present  with 
and  is  therefore   diluting   a   colour.     The   threshold  would  appear  to   be 


RELATIONSHIP  BETWEEN  STIMULUS   AND  SENSATION    563 

of  the  same  crder  as  that  of  intensity  given  above,  namely,  that  a  differ- 
ence in  the  amount  of  white  light  diluting  a  colour  by  ,  ,!;7lth  of  the  total 
intensity  present  can  be  just  appreciated  by  the  eve. 

Difference  Threshold  of  Size 
If  two  objects  are  the  same  distance  from  the  eye,  and  are  close  to  one 
another  and  in  similar  positions,  a  difference  of  one-hundredth  the  mean  size 
ran  as  a  rule  be  appreciated.  If,  they  are  at  different  distances  from 
the  eye,  or  are  far  apart,  or  are  not  in  similar  position  {e.g.  one  perpendicular 
and  the  other  horizontal),  then  considerable  errors  may  occur. 

THE   METHOD   OF  COMPARISONS 

In  the  application  of  this  method  three  different  series  of  investigations 
have  been  carried  out.  (1)  To  determine  the  intensities  of  three  primary 
colours  which  when  mixed  together  will  match  the  different  spectral  colours 
or  white  light.  (2)  To  determine  the  intensities  and  wavelengths  of  the 
complementary  colours.  (3)  To  ascertain  the  intensities  and  wavelengths  of 
red  and  green  rays  which  when  mixed  together  match  a  pure  spectral  yellow. 

The  colour  box  in  some  form  or  other  is  used  for  these  tests.  Abney's 
apparatus  may  be  described  as  a  typical  example.  Light  from  an  arc  lamp 
is  focussed  on  to  the  slit  of  a  powerful  spectroscope,  which  consists  of  a  colli- 
mator, a  train  of  prisms  and  a  telescope.  The  spectrum  thus  produced  is 
caused  to  fall  on  three  slits,  one  of  which  corresponds  with  the  red,  another 
with  the  green,  and  the  third  with  the  blue.  The  light  having  passed  through 
the  slits  falls  on  a  lens  which  forms  an  image  of  the  prism  faces  on  a  screen. 
The  light  from  the  slits  thus  recombines  on  the  screen  to  produce  a  bright 
patch,  the  colour  of  which  alters  according  to  the  intensities  of  the  three 
components.  To  one  side  of  the  patch  a  second  patch  of  light  can  be  thrown ' 
from  the  arc  lamp,  and  this  also  may  be  varied  in  different  ways  according 
to  the  nature  of  the  experiment.  The  intensities  of  the  different  beams  could 
be  modified  by  altering  the  widths  of  the  slits ;  a  preferable  method  is 
to  employ  rotating  sectors,  the  angles  between  the  blades  of  which  can 
be  varied  at  will  (see  Fig.  290). 

COLOUR  MIXING  EXPERIMENTS  performed  with  this  apparatus 
give  results  that  have  already  been  briefly  considered  in  Section  I.  It  is 
found  that,  not  only  do  the  three  primary  colours  when  mixed  together  in- the 
right  proportions  form  a  white  light  that  is  indistinguishable  from  ordinary 
white  light,  but  they  can  also  be  made  to  match  the  whole  range 
of  colours  both  of  the  spectrum  and  of  pigments.  It  was  also  described  how 
that  certain  pairs  of  colours  when  mixed  in  the  right  proportions  are  able 
to  match  white,  and  that  these  pairs  are  called  complementary  colours. 
If  the  colours  that  are  mixed  are  further  apart  than  are  the  complementary 
colours,  then  the  mixed  colour  is  found  to  be  a  shade  of  purple  ;  but  if  nearer 
together  than  the  complementaries.  then  the'colour  formed  by  the  mixture 
corresponds  to  an  intermediate  part  of  the  spectrum.  Thus,  if  the  colours 
mixed  are  red  and  green,  the  intermediate  yellow  and  orange  portions  of  the 


564 


PHYSIOLOGY 


spectrum  can  l>c  matched.  As  a  rule  the  mixed  colour  is  not  so  pun' 
as  the  corresponding  spectral  colour,  being  less  saturated  (thai  is  diluted  with 
a  certain  amount  of  white  light).  The  mixture  of  red  and  green  is  an  excep- 
tion because  it  is  found  that  accurate  matches  with  spectral  yellow  can  be 


una 


.%  COHOCm 


VERTICAL   STOP 


SCREEN 


COIOLIK    WXTURt  PATCH  '       ^COHRWSOH  miTC  U6HT  , 


Fig.  290.    Colour  patch  apparatus  for  mixture  and  comparison  of  pure  spectra! 
colours.     (Abney.) 

made  if  the  green  component  be  not  shorter  in  wavelength  than  5400  A.U. 
These  facts  can  be  expressed  diagrammatically  in  the  form  of  a 
geometrical  figure,  the  colour  triangle,  in  which  the  three  fundamental 
colours  occupy  the  corners  and  white  the  centre  (see  Fig.  243). 
Matches  made  by  light  of  one  intensity  require  readjustment  if 
the  intensity  be  changed,  and  matches  made  by  one  observer  are 
different  to  those  made  by  another.  The  variation  with  intensity  is 
readily  explained  by  the  shifting  of  the  centre  of  the  luminosity  curve 
from  the  yellow  towards  the  green,  as  the  intensity  is  lowered. 
The  amount  of  red  required  in  a  match  will  become  increasingly  greater,  and 
that  of  the  blue  less,  as  the  intensity  is  lowered.  The  variation  with  the 
observer,  when  small,  is  explained  by  individual  peculiarity  in  the  pigmenta- 
tion of  the  eye  media  or  the  fovea  centralis ;  but  when  considerable,  by  abnor- 


RELATIONSHIP  BETWEEN  STIMULUS  AND  SENSATION    565 

mality  in  the  response  of  the  retina  to  colours.  Because  of  this  the  method 
of  colour  mixtures  forms  a  very  valuable  technique  for  the  investigation  of 
colour-blindness. 

THE  FLICKER  METHOD.  The  majority  of  observers  can  only 
obtain  consistent  measurements  of  intensity  with  the  above  method 
when  the  colours  of  the  two  patches  are  exactly  alike.  Thus  it 
is  difficult  to  adjust  a  green  light  to  be  of  equal  apparent  brightness 
(luminosity)  with  a  red  because  the  difference  in  colour  makes  the  judgment 
of  brightness  inaccurate.  Abney  found  that  in  his  own  case  practice 
greatly  increased  the  certainty  with  which  the  measurement  could  be 
made.  A  more  reliable  technique  is  given  by  the  flicker  method 
(see  page  559).  The  two  patches  are  viewed  through  a  rotating  sector, 
the  speed  of  rotation  of  which  can  be  controlled.  The'intensity  of  one  of  them 
is  now  adjusted  so  that,  when  the  speed  of  the  sector  is  altered,  both  commence 
to  show  and  to  cease  showing  flicker  at  the  same  time.  By  applying  this 
method  to  the  colour-mixing  apparatus  the  luminosity  of  the  different  parts 
of  the  spectrum  can  be  determined.  The  curves  obtained  at  different  lumino- 
sities have  already  been  given  in  Fig.  286.  Tested  by  this  method  different 
observers  show  individual  peculiarities,  which  amount  in  some  cases  to  a 
greatly  diminished  perception  of  a  certain  part  of  the  spectrum.  Some  of 
the  types  met  with  will  be  described  later. 


SECTION  IX 


THE)  SUBJECTIVE    PHENOMENA    OF    VISION 

By  '  subjective  *  we  mean  that  the  sensations  under  consideration  cannot 
be  directly  traced  to  the  stimulus  which  initiated  them.  Thus 
at  a  certain  rate,  intermittent  stimuli  presented  to  the  eye  form 
a  continuous  sensation,  so  that  flicker  appears  to  have  ceased.  But 
the  carrying  on  of  the  sensation  from  one  stimulus  to  the  next  is  performed 
by  some  part  of  the  visual  mechanism,  and  has  nothing  to  do  with  any  physi- 
cal peculiarity  of  the  light.  It  is  therefore  an  example  of  a  subjective 
phenomenon. 

ORDINARY     CONE    RESPONSE. 


ROD  RESPONSE 


Fig.  291.  Curve  representing  diagrammatically  the  sensations  aroused  when  the 
eye  has  been  stimulated  by  a  flash  of  light.  Intensity  of  sensation-vertical. 
Time-horizontal.     (Hartridoe.) 

THE  SENSATION  CURVE.  When  a  light 
stimulus  enters  the  eye  a  certain  period  of 
time  elapses  before  a  sensation  is  perceived. 
This  latent  period  may  be  compared  with  that 
which  occurs  between  the  stimulus  and  con- 
traction of  a  muscle.  After  its  commencement 
the  sensation  rapidly  rises  to  a  maximum  (see 
Fig.  291)  and  then  shows  several  rapid  fluctua- 
tions as  it  reaches  its  mean  value.  These 
fluctuations  are  called  Charpentier's  bands,  and 
are  well  seen  after  stimulating  the  eye  by 
means  of  the  flash  from  an  electric  spark. 
They  have  been  compared  to  the  oscillations 
which  occur  when  an  electric  current  is  passed 
down  a  telegraph  cable,  and  which  are  caused 
by  the  inductance  and  capacity  of  the  circuit. 
566 


Fig.  292.  Charpentier's  bands 
as  seen  when  a  disc  with  a 
narrow  radial  slit  is  rotated 
in  front  of  an  illuminated 
screen  about  once  a  second. 


THE  SUBJECTIVE  PHENOMENA  OF  VISION  567 

Similar  oscillations  occur  when  the  telegraph  circuit  is  broken  ;  these 
oscillations  also  have  been  witnessed  and  described  by  Bidwell  at  the 
end  of  the  primary  visual  response.  The  time  taken  for  the  sensa- 
tion to  reach  its  maximum  varies  from  0"16  to  007  sees.,  being  shorter 
the  greater  the  intensity  of  the  stimulus.  This  so  called  primary 
image  is  followed  under  certain  conditions  by  a  less  definite  and  less 
intense  image,  which  has  the  following  characteristics:  (1)  It  is  not 
seen  when  the  eye  is  light  adapted.  (2)  It  is  strongest  for  green  light,  and 
is  absent  for  red.  (3)  It  is  absent  from  the  fovea.  (4)  It  is  not  seen  by 
persons  suffering  from  night  blindness.  (5)  It  is  always  of  a  bluish  grey 
colour.  All  the  above  facts  fit  in  with  the  view  that,  whereas  the  primary 
response  corresponds  with  the  reaction  of  the  cones  to  the  stimulus,  the 
image  which  is  sometimes  seen  to  follow  belongs  to  the  rod  apparatus. 
THE  AFTER  IMAGE.  Following  these  responses  of  the  cone  and  rod 
end-organs  is  the  so-called  secondary  image,  which  certainly  concerns  the 
cones  and  may  concern  the  rods  as  well.  This  image  is  of  longer  duration 
than  those  already  considered,  and  it  is  of  much  lower  intensity.  It  has 
however  the  peculiarity  that,  so  long  as  it  lasts,  the  part  of  the  retina  affected 
gives  a  diminished  response  to  a  stimulus  of  the  same  type  as  that  which 
it  had  previously  received.  For  exampe,  if  the  first  stimulus  was  one  of 
white  light,  then  a  second  white  lighl  stimulus  falling  in  the  period  occupied 
by  t  he  after  image  of  the  first,  would  not  be  recorded  by  the  retina  with  the 
normal  intensity.  It  has  been  pointed  out  that  the  after  image  period  in 
some  ways  resembles  the  refractory  period  which  follows  the  activity  of 
muscle  and  nerve.  If  the  second  stimulus  occupies  a  larger  area  of  the 
retina  than  that  on  which  the  first  stimulus  fell,  the  first  area  stimulated 
appears  dark  on  the  bright  ground  corresponding  to  the  second  area.  If 
the  first  stimulus  is  coloured,  and  no  stimulus  follows,  the  secondary 
image  is  found  to  have  the  same  colour  ;  but  if  a  second  stimulus  of  the  same 
colour  falls  on  the  retina  during  the  secondary  image,  then  as  before  the 
area  first  stimulated  appears  dark  on  the  bright  area  occupied  by  the  second 
area.  If  on  the  other  hand  the  second  stimulus  he  one  of  white  light, 
the  sensation  received  is  one  of  the  complementary  colour,  the  reason  being 
that  the  red  constituents  of  the  white  light  are  partially  excluded 
by  the  after  image  of  the  first  stimulus,  but  not  so  the  other  spectral 
colours,  and  the  image  which  is  seen  is  therefore  a  blue-green  one.  Because 
of  these  peculiar  properties  the  after  image  is  said  to  have  two  phases  :  being 
called  positive  when  the  eye  receives  no  second  stimulus,  and  the  appearance 
(it  t  he  after  image  is  the  same  as  thai  of  the  first  stimulus  ;  and  being  called 
negative  when,  owing  to  the  incidence  of  a  second  stimulus,  the  after  image 
shows  the  opposite  intensity  or  colour  to  the  stimulus  which  originated  it 
Since  absence  of  the  second  stimulus  causes  the  after  image  to  be  positive 
and  the  presence  of  a  second  stimulus  makes  it  appear  negative,  we  should 
expect  a  second  stimulus  of  the  right  intensity  to  cause  the  after  image  to 
disappear  altogether,  since  it  would  stimulate  the  surrounding  retina  with 
the  same  intensity  as  does  the  after  image  of  the  first  stimulus.     Experiment 


068  PHYSIOLOGY 

shows  that  this  result  can  be  achieved.  Because  of  the  importance  of  these 
properties  of  the  after  image  we  may  with  advantage  recapitulate  as  follows  : 
— -As  a  result  of  a  stimulus  the  region  of  the  retina  affected  gives  a  response 
which  is  followed  by  a  second  or  after  image.  During  this  after  image 
this  area  is  incapable  of  reacting  with  the  normal  intensity  to  a  like 
stimulus,  but  shows  increased  excitability  to  a  stimulus  of  the  opposite 
kind.  For  example,  after  a  green  stimulus  the  retina  is  unable  to 
respond  fully  to  another  green  stimulus  unless  it  falls  either  before 
or  after  the  period  (if  the  after  image.  Therefore  if  during  that  period  a  white 
stimulus  be  caused  to  fall  on  the  retina,  it  will  cause  a  purple  sensation  (purple 
being  white  minus  green)  in  that  part  of  the  retina  first  stimulated.  The 
duration  of  the  after  image  is  variable,  but  is  found  to  correspond  roughly 
with  the  intensity  and  duration  of  the  stimulus.  Thus  after  a  few  seconds' 
exposure  to  a  bright  light  the  after  image  may  be  noticeable  for  two  or  three 
minutes,  its  intensity  waxing  and  waning  in  an  irregular  maimer.  Successive 
images  are  often  found  to  show  a  series  of  colours,  a  common  series  is  bluish- 
green,  violet,  rose,  and  finally  orange  or  green  ;  the  phenomenon  is  however 
very  variable.  The  colours  may  be  explained  by  assuming  a  difference  in 
the  rate  of  oscillation  for  the  after  images  of  the  different  colours.  For 
example  the  above  series  would  point  to  green  being  more  rapid  and  red  less 
rapid  than  blue. 

FLICKER  AND  VISUAL  PERSISTENCE.  A  study  of  the  character- 
istics of  the  sensation  curve  provides 
an  explanation  of  a  number  of  the 
subjective  phenomena  of  vision.  For 
example,  if  a  cardboard  disc  marked 
as  shown  in  Fig.  293  be  'caused 
to  rotate  slowly,  while  the  J  black 
and  white  sectors  are  readily  j  recog- 
nised, their  radial  margins  appear 
blurred.  This  blurring  is  due  to  the 
slow  rise  and  fall  of  the  primary  image 
of  the  sensation  curve.  If  the  speed 
be  increased,  a  point  is  reached  at 
which  the  disc  gives  an  unpleasant 
glittering  appearance  ;  this  would 
appear  to  be  due  to  one  stimulus  occurring  during  the  after  image  of  the 
previous  one  and  thus  becoming  suppressed,  but  being  followed  in  its  turn 
by  a  fresh  stimulus  which  is  caused  by  contrast  (see  later)  to  have  a  greatly 
increased  intensity.  If  the  rate  of  rotation  of  the  disc  be  still  further  increased, 
a  point  is  reached  at  which  a  stimulus  falls  during  the  primary  image  of 
the  previous  one.  The  persistence  of  the  primary  image  after  the  cessation 
of  the  stimulus  causes  the  stimuli  to  fuse  to  give  a  uniform  sensation  without 
flicker,  which  may  be  compared  to  the  complete  tetanus  of  a  muscle.  Since 
the  primary  response  is  more  abrupt  the  greater  the  intensity  of  the 
stimulus,  a  more  rapid  rate  of  rotation  is  required  to  produce  fusion  at  high 
intensities  than  at  low. 


THE  SUBJECTIVE  PHENOMENA   OF  VISION  569 

PERIODIC  STIMULI.  We  have  seen  that,  if  a  stimulus  falls  dur- 
ing the  after  image  of  a  previous  one,  its  character  is  altered.  If  the  two 
stimuli  are  similar  the  second  tends  to  be  suppressed,  but  if  dissimilar 
the  .second  appears  to  be  increased.  If  on  the  other  hand  the  second  stimulus 
falls  either  before  or  after  the  after  image,  it  appears  to  be  unaffected.  But 
the  experiments  on  flicker  show  us  more  than  this,  because  even  in  a  case 
where  a  second  stimulus  comes  before  the  after  image  of  the  first,  it  is  clear 
that  the  third  would  at  a  certain  speed  coincide  with  it  and  would  therefore 
be  modified.  Experiment  seems  to  show  no  evidence  for  such  an  effect, 
and  we  must  therefore  conclude  that  the  occurrence  of  the  second  stimulus 
in  some  way  inhibits  the  after  image  of  the  first,  so  that  its  effects  are  not 
apparent.  Further  evidence  for  this  view  is  to  be  obtained  from  continuous 
stimuli,  for  we  do  not  find  a  sudden  diminution  in  the  intensity  of  the  response 
a  moment  or  two  after  a  continuous  stimulus  has  begun,  such  as  we  should 
expect  if  the  after  image  of  the  commencement  of  stimulus  were  suddenly 
after  a  short  interval  to  assert  itself.  What  happens  to  these  suppressed 
after  images  ;  are  they  entirely  destroyed,  or  are  they  caused  to  accumulate 
until  the  end  of  the  stimulus  ?  The  evidence  appears  to  be  in  favour  of  the 
latter  view,  because  an  after  image  has  a  more  definite  character  the  longer 
the  stimulus.  Moreover  if  the  gaze  be  directed  towards  a  fixation  point,  and 
the  inclination  to  blink  be  rigidly  suppressed,  after  a  few  seconds  the  images 
of  objects  which  fall  on  the  periphery  of  the  retina  begin  to  appear  milky, 
particularly  in  the  shadows.  At  the  same  time  the  brightness  of  the  high 
lights  seems  to  be  reduced  so  that  it  approximates  more  and  more  closely 
with  the  milkiness  of  the  shadows.  When  this  stage  is  reached  objects  appear 
in  outline,  the  contours  being  produced  and  renewed  by  imperfect  fixation. 
If  fixation  can  be  retained  for  a  short  period,  it  will  be  found  that  the 
whole  field  becomes  blank  with  the  exception  of  the  fixation  mark.  If  this 
also  disappears  momentarily,  then  fixation  is  lost,  the  eye  makes  an  involun- 
tary movement  and  the  whole  field  immediately  fills  with  detail  again.  In 
this  experiment,  two  processes  seem  to  be  going  on  :  firstly,  in  the  shadows, 
the  disappearance  of  the  after  images  of  previous  impressions,  the  replace- 
ment of  the  visual  purple  previously  bleached,  and  possibly  also  the  recovery 
of  these  parts  of  the  retina  from  the  effects  of  previous  stimulation,  all  of 
which  will  increase  the  sensitiveness  of  the  retina  so  that  it  now  responds 
to  the  light  reflected  by  the  shadows ;  secondly,  in  the  high  lights,  the  accumu- 
lation of  after  images,  the  bleaching  of  the  visual  purple,  and  possibly  the 
effects  of  fatigue,  all  of  which  tend  to  reduce  the  intensity  of  the 
impression.  So  that  these  processes,  tending  to  increase  the  brightness 
in  the  shadows  and  to  decrease  that  of  the  high  lights,  finally  brings  them  to 
the  same  level.  In  these  processes  the  accumulation  and  removal  of  after 
images  would  appear  to  take  a  considerable  part.  The  conclusion  to  which 
we  are  forced  is  that  at  the  beginning  of  a  continuous  stimulus  the  after  images 
are  effectively  removed  until  such  time  as  the  stimulus  shall  cease,  when 
they  can  be  permitted  to  assert  themselves.  But  if  the  stimulus  be  pro- 
longed the  suppression  becomes  more  and  more  difficult,  imtil  the  accumula- 


570  PHYSIOLOGY 

tion  of  after  images  is  so  extensive'  that  they  begin  to  obtrude  more 
and  more  on  the  impression  conveyed  to  consciousness. 

FATE  OF  AFTER  IMAGES.  If  the  conclusion  drawn  from  the 
above  experiments  is  valid,  the  question  arises  as  to  the  apparent  unimpor- 
tance of  the  after  image  in  ordinary  vision.  The  answer  is  to  be  obtained 
from  experiments  like  the  following: — If  fixation  be  continued  until  the 
images  formed  on  the  retina  appear  in  outline  as  in  the  previous  experiments, 
and  the  gaze  be  then  quickly  turned  to  a  second  fixation  mark  placed  some 
distance  from  the  first,  it  is  found  that,  on  returning  to  the  first  mark, 
some  time  lias  to  elapse  before  the  appearance  in  outline  is  obtained 
again  ;  in  fact  the  time  taken  is  not  very  different  to  that  required  to  reach 
this  stage  at  the  beginning  of  a  new  experiment.  The  second  impression 
had  effected  an  almost  complete  removal  of  the  after  image  of  the 
first,  so  that  on  returning  to  the  first  again,  the  slate  had  as  it  were  been 
wiped  clean,  and  the  first  impression  therefore  acted  as  if  it  were  a  new  one. 
This  conclusion  is  entirely  in  agreement  with  our  previous  conclusions  with 
regard  to  the  after  image,  namely  that  it  corresponds  to  a  period  in  which 
a  stimulus,  similar  to  that  to  which  the  after  image  belongs,  is  inhibited, while 
that  of  a  different  kind  is  favoured.  If  therefore  during  fixation  the  gaze 
be  directed  elsewhere  momentarily,  the  after  image  that  had  been 
set  up  is  quenched  by  the  new  impression,  and  on  returning  the 
gaze  to  the  fixation  point  the  old  image  behaves  almost  like  a  new  one. 
The  non-intrusion  of  the  after  image  in  ordinary  vision  is  therefore  due  to 
a  considerable  extent  to  the  continual  and  rapid  replacement  of  one  impres- 
sion by  another,  by  the  shifting  of  the  gaze,  and  also  to  the  spreading  of  the 
accumulation  of  partially  effaced  after  images  more  or  less  uniformly  over 
the  retina.  It  has  been  suggested  that  impulses  may  be  originated  from  the 
external  eye  muscles  on  movement,  which  on  reaching  the  brain  assist  in 
the  removal  of  the  after  images  of  previous  stimulation. 

ADAPTATION.  If  the  eye  after  being  in  the  dark  is  rapidly 
removed  to  the  light,  at  first,  the  sight  is  confused  and  the  eye 
dazzled  in  spite  of  the  powerful  constriction  of  the  pupils.  The 
eve  however  very  quickly  becomes  accustomed  to  the  greater  in- 
tensity, or  as  we  say.  it  becomes  light  adapted.  In  a  similar  manner 
on  entering  the  dark  from  the  light  the  eve  can  at  first  see  nothing, 
but  by  degrees  it  becomes  accustomed  to  the  new  conditions  and  objects 
begin  to  be  recognised  ;  the  eye  has  therefore  become  dark  adapted.  In 
the  first  case  the  initial  light  stimulus  reduced  the  sensitiveness  of 
the  eye  to  light  to  such  an  extent  that  the  eye  ceased  to  react  to  an  excessive 
degree  as  it  had  done  at  first.  Dark  adaptation  appears  to  consist  of  two 
separate  processes  :  (1)  the  removal  of  after  images  from  the  cone  light- 
receiving  mechanism,  and  (2)  the  replacement  of  visual  purple  for  the  rod 
apparatus ;  the  former  predominating  at  high  intensities  and  the  latter  at 
low. 

FATIGUE  OF  THE  RETINA.  If  the  eye  has  been  exposed  to  a 
very   bright   light   for   a   considerable   time,    there   is  at    first    inability 


THE   SUBJECTIVE   PHENOMENA   OF  VISION  571 

to  see  with  the  dazzled  part  of  the  retina.  If  a  field  is  looked 
at,  a  black  spot  appears  to  lie  in  front  of  it ;  if  on  the  other 
hand  the  field  subsequently  looked  at  is  dark,  this  same  area  of  the 
retina  appears  to  be  filled  by  a  bright  haze.  If  the  dazzling  light  be 
restricted  to  one  colour,  there  is  an  inability  to  see  the  same  colour, 
if  of  lower  intensity,  immediately  afterwards.  The  power  to  see  other 
colours  is  apparently  quite  unaffected  ;  in  fact.  Burcli  stated  that  the 
complementarj  colour  actually  appears  to  be  more  vivid  than  usual. 
These  changes  are  similar  to  those  caused  by  after  images.  The  negative 
after  image  causes  diminished  appreciation  of  colours  similar  to  itself,  while 
the  positive  shows  itself  as  a  bright  image  similar  in  colour  to  the  original 
stimulus  when  a  dark  field  is  looked  at. 

SUCCESSIVE  CONTRAST.  Visual  impressions  are  affected  by  tin- 
previous  history  of  the  retina  ;  thus  after  the  eyes  have  been  directed 
towards  a  red  surface,  a  grey  surface  appears  to  be  tinted  green,  a  green 
surface  seems  a  more  vivid  colour  than  normal,  while  a  red  colour  is  relatively 
dull.  In  other  words,  after  stimulation  by  one  kind  of  source,  another  of  a 
similar  nature  is  inhibited,  while  that  of  a  different  nature  is  either  unaffected 
or  may  be  even  increased.  This  effect  is  called  successive  contrast.  Experi- 
ment shows  that  the  change  of  the  second  stimulus  is  such  that  it  favours 
the  colour  complementary  to  the  first  stimulus.  These  effects  are 
similar  to  those  already  described  under  adaptation  and  fatigue,  and  the 
causation  of  the  phenomenon  is  the  same  as  that  given  above,  being  due  to 
the  presence  of  an  after  image. 

SIMULTANEOUS  CONTRAST.  If  the  retina  is  stimulated  by  two 
separate  impressions,  any  differences  between  the  impressions  will  be 
found  to  be  accentuated.  Thus  if  a  small  grey  surface  be  placed  on 
a  white  ground,  the  grey  will  become  darker  and  to  a  less  extent 
the  white  ground  will  become  lighter.  If  now  the  same  grey  surface  be 
placed  on  a  dark  ground,  it  will  be  found  to  become  lighter  and  the  field 
darker.  The  nearer  the  surfaces  are  together  the  greater  are  the  effects 
of  contrast,  the  edges  shewing  the  effects  of  contrast  most.  In 
the  case  of  colours  similar  changes  take  place  ;  thus  two  similar' 
colours  of  different  intensity  placed  together  appear  to  be  more 
different;  two  colours  of  different  sat  mat  ion  change,  the  one  to 
greater,  the  other  to  less  saturation;  while  two  colours  of  different 
wavelength  appear  under  the  influence  of  contrast  to  sutler  ;.  varia 
fcion  towards  the  complementary  colour.  A  similar  change  is  observed  if 
contrast  is  occurring  between  a  colour  and  a  grey  surface  of  approximately 
the  same  intensity,  [or  we  find  that  the  grey  is  very  obviously  tinted  with 
a  colour  that  is  very  nearly  the  complementary  of  the  colour  in  question 
It  has  been  stated  that  the  light  which  reaches  the  eye  other  than  through 
the  pupil  (e.ij.  the  sclera)  and  which  is  coloured  an  orange-pink  in  consec  | 
of  its  partial  absorption  by  the  blood  pigment  in  the  capillaries,  is  re- 
sponsible lor  the  contrast  colours  not  being  strictly  complementarj  to 
those    which    produce    them.      It    is    also    found    that    separation    of    the 


572 


PHYSIOLOGY 


surfaces,  or  the  demarcation  of  the  junction  of  the  two  surfaces  by  means 
of  a  narrow  black  or  white  line,  or  even  the  existence  of  small  marks  or 
creases,  reduces  the  effects  of  contrast  to  a  considerable  extent. 

We  can  summarise  the  effects  of  simultaneous  contrast  in  the  following 
way  : — if  one  part  of  the  retina  is  being  stimulated,  the  part  surrounding  it 
not  only  tends  to  discourage  a  similar  stimulus  but  also  favours  one  of  a 
complementary  nature  (black  in  this  connection  being  considered  as  being 
complementary  to  white).  But  this  statement  is  similar  to  that  which  we 
have  already  made  with  regard  to  the  effects  of  the  after  image  on  the  same 
part  of  the  retina  which  has  received  stimulation.  Simultaneous  contrast 
would  therefore  appear  to  be  simply  an  extension  of  the  after  image  phenome- 
non into  a  region  of  the  retina  outside  the  confines  of  the  original  stimulus. 
Kxperirnent  shows  that  this  extension  does  not  go  far  from  the  excited  area, 
for  the  contrast  effects,  which  may  be  considerable  near  the  contour, 
rapidly  decrease  as  the  distance  from  the  contour  increases. 

BIDWELL  'S  EXPERIMENT.  If  a  short  white  light  stimulus  be  caused 
to  fall  during  the  after  image  period  of  a  previous  red  stimulus,  we 
should  exj>ect  the  white  fight  to  be  tinted  blue-green,  because  red  light 
is  suppressed  and  its  complementary  increased.  If  the  intensity  and  time 
intervals  are  carefully  chosen,  the  blue-green  sensation  may  be  made 
stronger  than  the  original  red  stimulus  to  which  it  owes  its  colour.  The 
persistence  of  vision  causes  this  blue-green  response  to  last  an  appreciable 
time,  and  therefore  if  another  red  stimulus  rapidly  succeeds  the  white  one 


Fig.    294.     Bidwell's    rotating    disc;    an    object    looked 
through  it  appears  in  complementary  colours. 


(the  one  which  is  coloured  blue-green)  it  will  tend  to  be  suppressed  from  con- 
sciousness.    But  the  white  stimulus  succeeding  this  second  red  one  will  be 


THE  SUBJECTIVE   PHENOMENA  OF  VISION 


573 


coloured  blue-green  by  its  after  image,  because  it  has  left  its  impression  on 
the  visual  mechanism,  although  that  impulse  has  not  been  conveyed  to 
consciousness.  If  therefore  a  series  of  such  red  and  white  impulses  be  caused 
to  fall  on  the  retina,  each  white  one  will  he  tinted  blue-green,  and  each 
red  one  will  be  suppressed,  the  result  being  that  the  complementary 
colour  is  alone  seen.  This  interesting  phenomenon  was  discovered  by 
Bidwell.  He  took  a  disc  of  tin  plate  about  8  inches  in  diameter,  and 
arranged  so  that  it  could  be  rotated  by  an  electric  motor  6  to  8  times  a  second. 
From  this  disc  a  sector  was  cut  of  approximately  60  degrees  ;  half  the 
remainder  was  covered  with  black  velvet  and  the  other  half  with  white 
paper.  Behind  the  disc  were  mounted  two  pieces  of  silk,  one  red,  the  other 
blue-green.  The  order  in  which  the  images  were  presented  to  the  eye  on 
rotation  of  the  disc  were  :  (1)  coloured  silks,  (2)  white  sector,  (3)  black  sector, 
and  so  on.  The  result  was  found  to  be  that  the  red  silk  appeared  pale  blue- 
green,  and  the  other  pink  ;  that  is  in  both  cases  the  complementary  colour 
was  alone  seen.  This  experiment  brings  out  very  clearly  the  fact  that  the 
after  image  process  is  entirely  subconscious.  The  following  observations 
confirm  this  conclusion. 

BURCH'S  EXPERIMENT. 
It  has  been  much  discussed  in 
the  past  whether  contrast  phe- 
nomena are  due  to  errors  of  judg- 
ment as  Helmholtz  supposed,  or 
due  to  physical  or  physiological 
changes  taking  place  in  the  retina 
or  in  the  conducting  paths  leading 
from  it  to  consciousness.  Burch 
disproved  Helmholtz'  view  by  the 
following  simple  experiment.  A 
box  (Fig.  295)  is  divided  into 
two  long  compartments,  a  b  and 
c  d.  At  a  the  com  part  mint  is 
closed  by  a  red  glass-plate  and 
at  e  by  a  blue  glass-plate.  Aper- 
tures are  provided  at  b  and  d  for 
the  observer's  eyes.  At  +  and  + 
two  small  grey  crosses  are  fixed 
about  the  middle  of  the  compart- 
ment on  sheets  of  transparent  glass.  On  looking  through  the  openings  b  and  d  and  run 
verging  the  eyeballs,  so  as  to  fix  the  line  «.  we  gel  a  fusion  more  or  Less  complete  of  the 
two  colours  red  and  blue,  so  that  the  background  appears  purple  ;  or  there  may  be  a 
struggle  between  the  colours,  at  one  time  blue,  at  another  red  predominating.  To 
the  judgment  however,  there  is  one  background  and  not  two,  and  therefore,  accord- 
ing to  the  theory  of  Helmholtz,  the  grey  crosses  should  by  contrast  both  acquire  H)< 
same  induced  colour,  which  would  be  complementary  for  purple.  But  it  is  found  that 
the  two  crosses  are  perfectly  distinct  in  colour,  that  which  is  seen  by  the  eye  again  I 
the  blue  ground  being  yellow,  while  that  on  the  red  ground  is  green,  showing  thai  thi 
phenomena  of  simultaneous  contrast  are  not  due  to  an  error  of  judgment. 

SHERRINGTON'S  EXPERIMENT.  The  same  fact.is  very  definitely  established 
by  the  following  experiment  devised  by  Sherrington.  The  disc  (Fig.  29fl)  present  t\\<> 
rings,  each  half-blue  and  half-black.     The  outer  ring  is  intensified  when  at  rest    by 


Purple 


Purple 


Yellow  Green       Purple 

Purple 
Fig.     295. 


574 


PHYSIOLOGY 


simultaneous  conl  ra 
i  be  luminosity  of  i  h 


Fig.  296. 


I.  1 1:<-  M. "Is  halt  lieing  seen  against  the  surrounding  yellow,  while 
■  blue  half  is  incieased  bj  the  effect  oi  the  surrounding  black.  In 
the  inner  ring  the  blue  half  is  dark- 
i'ihiI  l.\  contrast  with  the  surround 
ing  yellow,  while  the  black  half  is 
ii"*  evident  at  all.  If  the  disc  be 
rotated,  we  gel  two  concentric  rings 
on  an  apparently  homogeneous 
Beld.  Il  is  found  however  that 
the  outer  ring  flickers  long  after 
complete  fusion  has  taken  place  in 
the  inner  ring,  showing  that  the 
stimulation  of  the  retina  by  the 
outer  ring  is  increased  under  the 
influence  of  contrast. 


CAUSE  OF  AFTER  IMAGE. 
Sherrington  has  shown  that 
in  the  case  of  muscles  there 
is  what  is  called  reciprocal 
innervation.  Thus  stimula- 
tion of  the  cortex  which,  causes  the  contraction  of  one  muscle  also 
brings  about  a  corresponding  relaxation  of  its  antagonist,  in  order 
that  a  rapid  and  economical  motion  ma)'  take  place.  The  contraction  and 
corresponding  relaxation  are  therefore  analogous  to  the  response  of  one 
part  of  the  retina,  which  is  accompanied  by  an  inhibition  of  the  surrounding 
parts  of  the  retina  to  the  same  kind  of  stimulus  (simultaneous  contrast).  In 
a  similar  manner  the  inclination  to  extension  which  is  found  to  accompany 
the  prolonged  flexion  of  a  limb,  finds  its  analogy  in  the  phenomena  of  after 
images  and  adaptation  of  the  eye,  since  the  tendency  is  to  suppress  a  similar 
stimulus  in  the  part  of  the  retina  stimulated  and  to  encourage  its  comple- 
mentary. The  inference  to  be  drawn  from  these  analogies  is  that  the  after 
image  and  its  allied  phenomena  are  caused  by  changes  in  the  conducting 
paths  of  visual  impressions  which  are  similar  to  those  found  to  exist  in  paths 
belonging  to  the  motor  system.  What  the  nature  of  these  changes  in  the 
conducting  paths  may  be  is  at  the  present  time  undecided.  McDougall  has 
suggested  that  they  are  fatigue  effects  in  the  synapses  of  the  higher  conduct- 
ing paths.  If  this  view  is  correct  it  would  seem  difficult  to  explain  why  after 
images  and  contrast  phenomena  are  best  seen  with  a  rested  eye. 

UTILITY  OF  THE  AFTER  IMAGE.  We  have  seen  that  the 
effect  of  the  after  image  is  to  inhibit  the  possible  repetition  of  a 
similar  stimulus,  and  at  the  same  time  to  favour  the  reception  of  one 
of  a  different  nature.  The  process  is  therefore  one  which  favours  change, 
for  not  only  is  there  a  tendency  to  efface  an  old  impression  but  also  to  welcome 
a  new  one.  Such  effects  must  be  of  great  value  to  an  organ  such  as  the  eye 
the  function  of  which  is  to  a  considerable  extent,  in  everyday  life,  to  present 
to  consciousness  the  greatest  number  of  impressions  in  a  given  time.  For 
example,  by  measuring  the  time  taken  to  read  a  passage  in  which  almost 
every  word  was  of  importance,  it  was  found  that  on  an  average  eight  words  were 


THE  SUBJECTIVE   PHENOMENA  OK    VISION 


57:» 


read  in  each  second,  and  that  the  eight  w  ords  had  an  average  of  forty  lei  ters. 
It  is  clear  from  this  that  between  eight  and  forty  different  impressions  must 
be  presented  to  consciousness  in  each  second.  The  function  of  the  after 
image  in  preparing  the  retina  for  the  reception  of  new  impressions  would 
therefore  appeal  to  be  a  very  important  one.  The  effects  of  simultaneous 
contrast  are  equally  important  to  vision,  because  the  changes  produced 
by  it  are  such  that  the  images  falling  on  contiguous  portions  of  the 
retina  are  made  as  unlike  as  possible.  Not  only  are  the  intensity  and  colour 
of  adjacent  parts  of  the  image  made  more  definite  (this  process  being  compar- 
able to  the  effects  of  intensification  on  a  photograph),  but  the  blurring  at  the 
edges  of  contours  due  to  imperfections  in  the  image  formed  on  the  retina  are 
also  largely  eliminated  (this  comparing  with  retouching  in  photography). 
BINOCULAR  RIVALRY  must  be  briefly  referred  to  here  because  of 
the  similarity  which  it  shows  with  the  phenomena  described  above. 
If  for  any  reason  the  images  formed  on  the  retina  have 
dissimilar  contours,  rivalry  ensues,  first  one  image  and  then  the  other 
reaching  consciousness.  This  process  usually  occurs  independently  in  differ- 
ent parts  of  the  Held,  so  that  the  visual  impression  consists  of  a  patchwork 


LLFT 

LYE 

% 

//// 

y//, 

RIGHT     EYE 


STEREOSCOPE. 


Fir;.  29".  Diagram  to  show  how  the  binocular  combination  of 
two  dissimilar  images  produces  a  fluctuating  image  con- 
taining parts  of  both  of  them. 

of  the  two  image.-.  Seldom  if  ever  are  both  images  seen  in  the  same 
part  of  the  retina  at  the  same  time.  It  is  found  that  a  number  of 
factors  can  cause  one  image  totally  to  suppress  the  other  ;  these  are  interest, 
novelty,  and  brightness.  The  importance  of  this  suppression  can  be  apprecia 
ted  by  picturing  the  confusion  which  would  occur  if  two  different  images  were 
.simultaneously  presented  to  consciousness,  as  would  happen  in  animal:,  in 
which  different  images  are  formed  in  the  two  retinas  and  in  cases  of  strabismus 
in  man.  The  parallelism  between  this  process  and  those  which  we  have  already 
described  can  be  traced  by  regarding  for  one  moment  one  of  the  images  as 


576  PHYSIOLOGY 

the  primary  one.  This  causes  impulses  to  travel  to  the  visual  centres  un- 
affected at  first  by  the  effects  of  other  images,  but  these  tend  to  accumulate 
more  and  more  until  the  primary  image  is  overcome,  and  that  of  the  other 
eye  put  in  its  place.  But  this  image  in  time  suffers  in  the  same  way,  so  that 
the  images  alternate.  The  fact  that  a  new  image  can  suppress  an  old  is  due 
to  the  absence  of  after  images  in  the  first  and  their  presence  in  the  second. 
The  predominance  of  a  bright  image  can  be  explained  by  the  longer  time 
required  for  the  after  image  to  reach  such  a  level  as  shall  cause  suppression. 
The  preference  for  an  image  with  contours  would  seem  to  be  due  to  the  greater 
ease  with  which  the  after  image  may  be  removed  by  small  deflections  of 
gaze. 


SECTION  X 

ERRORS    OF    APPRECIATION 

Under  this  heading  we  include  all  types  of  abnormality  in  the  retinal 
apparatus  or  in  its  central  connections.  The  class  therefore  includes  cases 
in  which  the  image  formed  on  the  retina  is  in  every  way  normal,  and  those 
in  which  the  optical  defects  do  not  adequately  explain  the  whole  of  the  visual 
disability,  which  experiment  shows  to  be  present.  The  class  is  found  to 
include  cases  which  range  from  slight  impairment  to  complete  blindness. 

The  following  classification  may  be  used : — ■ 

Group  1.  Both  rod  and  cone  vision  are  affected,  and  there  is  thus 
both  night  blindness  and  total  colour  blindness. 

Group  2.  Rod  vision  is  either  affected  alone,  or  there  is  slight  defect  in 
cone  vision  as  well. 

Group  3.  Rod  vision  is  unaffected,  while  cone  vision  is  either  altogether 
absent  or  is  found  to  show  abnormality,  which  affects  certain  colours  only. 

Note  that  any  one  of  the  above  groups  may  be  found  to  affect  either  one 
or  both  eyes,  and  may  involve  the  whole  or  only  a  limited  part  of  the  retina. 

COMPLETE  BLINDNESS  (group  I)  may  affect  the  whole  of  one 
or  both  eyes,  or  may  occur  in  half  the  visual  fields  only.  It  may  be 
limited  to  irregular-shaped  islands  or  patches,  or  it  may  be  found 
associated  with  central  or  peripheral  vision.  The  shape  of  the  affected 
area  frequently  gives  a  direct  clue  to  tha  cause  of  the  condition.  The 
shape  is  best  determined  by  means  of  the  perimeter  (Fig.  279). 

(a)  The  whole  of  one  or  both  eyes  is  found  to  be  blind.  The  disease  may 
be  congenital  or  may  be  the  result  of  inflammation  affecting  the  posterior 
parts  of  the  eye  (ophthalmoscope  will  confirm).  Injury  involving  the  whole 
of  the  optic  nerve  trunk  will  also  cause  blindness  of  the  corresponding  eye. 

(b)  The  blindness  involves  the  right  or  left  halves  of  one  or  both  retinae 
only.  The  lesion  in  such  cases  involves  the  optic  tracts.  Tumours  are  the 
commonest  cause. 

(c)  The  blindness  is  limited  to  a  segment  of  the  retina  when  the  retinal 
vessels  are  affected  (e.g.  by  embolism).     The  ophthalmoscope  will  confirm. 

(d)  Blindness  which  affects  the  periphery  of  the  retina  only  is  due  either 
to  deficiency  of  blood  supply  (as  may  occur  in  glaucoma),  defective  blood 
(severe  anaemia),  or  the  presence  of  poisons  in  the  blood. 

(e)  If  blindness  affects  the  centre  of  the  retina  chiefly,  the  cause  is  prob- 
ably poisoning  by  either  tobacco,  alcohol,  or  both.  At  first  vision  is  impaired 
for  certain  colours  only,  but  the  blindness  quickly  becomes  complete  if  the 
absorption  of  the  poison  continues. 

•  577  37 


578  PHYSIOLOGY 

(/)  If  irregular  blind  islands  called  scotomata  an  Eound  in  the  visual 
fields,  the  cause  may  be  inflammation  of  the  choroid  or  of  the  retina  itself, 
or  the  detachment  of  the  retina  from  the  choroid. 

NIGHT    BLINDNESS  (group  2)  is  found  in  four  different  types  of  case. 

(a)  As  an  inherited  condition,  (b)  In  diseases  of  the  liver  in  which  bile 
salts  are  found^  to  circulate  in  the  blood,  since  these  dissolve  the  visual 
purple  out  of  the  retina  and  therefore  impair  rod  vision,  (c)  As  a  symptom 
of  insufficient  food,  (d)  In  disease  of  the  retina  or  choroid  (e.g.  retinitis 
pigmentosa).  In  the  last  two  cases  it  is  usual  to  find  colour  vision  affected 
to  some  extent. 

The  symptoms  of  night  blindness  are  well  described  by  the  name.  The 
eye  does  not  possess  the  power  of  becoming  fully  dark  adapted,  and  even 
a  moderate  degree  is  only  attained  after  a  prolonged  stay  in  the  dark.  A 
photochromatic  interval  is  not  found,  that  is  to  say,  when  the  intensity 
of  a  colour  is  reduced  it  does  not  pass  through  an  uncoloured  stage  (due  to 
the  rods).  Purkinje's  phenomenon  is  usually  poorly  developed  or  not  seen 
at  all.     There  is  no  cure  in  the  congenital  cases. 

COLOUR  BLINDNESS.  The  detection  of  this  condition  is  important 
because  of  the  use  of  coloured  signals  in  the  railway  and  marine  services.  The 
employees  of  such  services  should  be  tested  at  stated  frequent  intervals, 
because  colour  blindness  may  develop  (e.<j.  from  tobacco  or  alcohol  poison- 
ing) in  a  relatively  short  space  of  time. 

The  methods  of  testing  colour  blindness  fall  roughly  into  three 
classes:  (1)  those  of  historic  interest;  CI)  those  used  by  ophthal- 
mologists for  practical  tests;  (3)  those  used  lor  research.  Holmgren's 
wool  test  is  an  example  of  the  first  class.  It  consists  of  a  large  series  of 
coloured  worsteds,  the  number  of  different  shades  being  very  great.  In 
using  the  test  the  doctor  hands  to  the  patient  selected  skeins  which  have  been 
found  by  experience  to  give  difficulty  to  colour-blind  persons.  He  then 
instructs  the  patient  to  select  from  the  box  all  the  skeins  that  appear  to 
him  to  have  the  same  colour.  His  visual  defect  is  judged  by  the  mistakes 
which  he  makes.  Since  coloured  wools  readily  fade  and  get  dirty  in  use, 
slips  of  coloured  glass  or  beads.  &c,  have  been  used  in  a  similar  way.  These 
tests  are  however  no  longer  used,  because  it  is  found  that  colour-blind  persons 
may  be  able  to  pass  them  without  detection. 

Of  practical  tests  the  lantern  test  would  appear  to  yield  the  best  results, 
because'it  gives  a  close  imitation  of  a  signal  light  as  seen  at  different  distances 
and  under  various  atmospheric  conditions.  In  using  the  test,  the  doctor 
shows  the  patient  in  turn  a  series  of  different  coloured  lights,  and  in 
each  case  asks  him  to  state  what  he  sees.  If  he  makes  no  mistakes,  the  colours 
are  shown  through  modifying  glasses  which  give  the  effect  of  a  signal  when 
seen  through  mist,  fog,  rain,  &c,  and  the  answers  noted.  One  definitely 
wrong  answer  should  reject  the  patient,  particularly  if  red,  green,  or  white  be 
one  of  the  signals  misnamed.  Objections  have  been  raised  to  this  test,  because 
it  is  possible  for  a  man  ignorant  of  colour  names  to  be  failed  even  if  he  has 
normal  colour  vision.     The  objection  is  readily  met  however.     When  the 


ERRORS   OF   APPRECIATION 


;>79 


driver  of  a  train  sees  a  signal,  he  says  to  himself  "  that  is  a  green  signal  and 
therefore  my  train  may  proceed.''     But  supposing  all  the  time  it  were  a  red 


SIGNAL    OR£EN 


ed  in  practice  for  tin    detection 
(Edridck  Gbeen.) 


signal,  and  that  he  called  it  green  through  colour  ignorance,  that  man 
is  as  much  a  danger  to  the  community  as  if  he  in  fact  were  colour-blind.  No 
lest  can  he  too  searching,  and  no  borderline  case  should  ever  lie  passed;  the 
risk  is  too  serious. 


Of  tests  of  theoretical  importance  some  have  already  been  described,  namely  the 
measurement  of  the  thresholds  for  light  and  colour,  the  colour-mixing  apparatus  and 
the  nicker  method  of  photometry.  There  is  however  another  test  which  is  found 
to  give  valuable  information,  namely  the  spectroscope  test  of  Edridge  Green.  The 
instrument  consists  of  a  spectroscope  to  which  is  fitted  two  shutters,  one  of  which 
may  be  caused  to  obscure  the  spectrum  from  the  red  end  and  the  other  from  the  violet. 
The  patient  commences  the  test  by  placing  the  shutter  on  the  red  side  at  the  place 
where  lie  sees  the  red  begin.  The  doctor  notes  this  position  on  the  wavelength  scale 
of  the  shutter.  The  patient  is  then  told  to  move  the  other  shutter  until  it  reaches  the 
place  where  red  changes  to  orange.  This  wavelength  also  is  noted.  The  red  side 
shutter  is  now  moved  until  it  occupies  the  position  of  the  violet  side  shutter,  and  the 
violet  side  shutter  is  now  moved  until  a  difference  in  colour  at  the  two  sides  of  the 
spectral  area,  which  is  thus  isolated  is  just  not  able  to  be  seen.  The  wavelengths  are 
again  noted,  and  the  next  area  measured  off,  and  so  on  until  the  violet  end  of  the  pi 
tram  is  reached.  A  person  with  normal  vision  will  with  this  instrument  map  out 
between 20  and  30  distinct  areas.  Abnormal  vision  may  lie  shown  in  two  ways,  first!} 
by  the  ends  of  the  spectrum  being  found  in  abnormal  positions,  the  spectrum 
shortened  at  the  red  or  the  violet  or  both,  secondly  by  the  isolated  areas  being  too 
large  and  too  few,  and  thirdly  by  wrong  names  being  applied  to  some  of  them.  The 
value  of  the  method  is  considerable  because  it  shows  the  presei  ce  oi  >  I  threi 
of  defect,  those  due  to  blindness,  those  cawed  by  ignorance  of  colour  names,  and  those 
in  which  the  appreciation  of  colour  is  deficient. 


5K0  PHYSIOLOGY 

Cases  of  colour  blindness,  when  tested  by  the  above*  methods,  are 
found  to  show  every  possible  variation  between  complete  blindness 
and  slight  impairment  of  the  colour  sense.  Their  classification  is  as  a  rule 
complicated  by  the  fact  that  cases  are  usually  described  in  terms  of  one  of 
the  theories  of  colour  vision.  Most  varieties  of  colour  blindness  are  inheritei  I . 
and  are  commoner  in  men  than  in  women.  But  it  may  also  be  acquired, 
as  explained  above,  in  poisoning  by  alcohol  and  tobacco.  Cases  of  colour 
blindness  may  be  grouped  as  follows  : — 

1.  Cases  in  which  the  cone  mechanism  of  the  retina  is  not  functioning. 
The  patient  is  found  to  be  colour  and  day  blind,  red  is  not  seen  at  all,  while 
the  other  colours  are  seen  as  different  shades  of  grey.  Vision  at  night  is 
good,  vision  by  day  is  complicated  by  the  fact  that  the  patient  must  ;m1 
expose  his  eyes  to  a  bright  light,  for  otherwise  his  visual  purple  will 
become  bleached  and  his  rod  apparatus  therefore  cease  to  function.  Owing 
to  the  absence  of  rods  from  the  fovea,  this  part  of  the  retina  is  blind. 
Visual  acuity  is  low  therefore.  When  tested  by  the  flicker  method  his 
luminosity  curve  is  found  to  correspond  to  that  of  twilight  vision.  His 
condition  may  be  improved  by  using  neutral  tinted  glasses  fitted  with  a  sky 
shade. 

2.  Cases  in  which  the  cone  apparatus  is  apparently  normal,  that  is  to 
say,  there  is  no  avoidance  on  the  part  of  the  patient  of  strong  light,  no 
diminished  visual  acuity,  no  fovea]  blindness  and  no  inability  to  see  red 
light.  Yet  there  is  absolute  inability  to  recognize  all  colours,  any  one  pari 
of  the  spectrum  being  able  to  be  matched  by  any  other.  Tests  by  means 
of  the  flicker  method  show  a  luminosity  curve  which  corresponds  to  that 
of  day  vision.  It  would  seem  clear  that  the  retinal  apparatus  is  in  every 
way  normal ;  one  is  therefore  forced  to  the  conclusion  that  the  defect  concerns 
the  brain  centre  which  subserves  the  appreciation  of  colour.  This  view  is 
supported  by  the  fact  that,  between  this  extreme  type  a^td  normal  colour 
perception,  there  are  a  large  number  of  cases  which  show  various  grades 
of  defect.  Some,  for  example,  see  two  colours  at  the  ends  of  the  spectrum 
only,  the  intermediate  portion  being  a  neutral  colour ;  others  see  three  only, 
at  red,  green  and  blue,  and  so  on.  Since  in  all  these  cases  the  cones  are  appar- 
ently normal,  there  woidd  appear  to  be  a  parallel  with  cases  in  which  there 
is  no  trace  of  deafness,  and  yet  there  is  an  inability  to  appreciate  harmony 
or  to  tell  when  two  notes  are  in  tune.  In  both  types  of  cases  it  would  seem 
that  the  higher  centres  of  jjerception  and  appreciation  are  either  absent  or 
are  undeveloped.  As  might  be  anticipated  therefore,  instruction  and  practice 
at  colour  naming  and  colour  matching  benefit  a  certain  number  of  these 
cases,  so  that  it  is  sometimes  found  that  after  such  instruction  the  less  abnorma  1 
cases  are  not  readily  detected.  If  however  they  are  tested  in  a  poor  light, 
they  are  found  to  make  mistakes  which  a  person  with  normal  vision  would 
not  commit.  But  these  are  the  circumstances  under  which  signals  have 
frequently  to  be  recognised,  and  it  is  for  this  reason  that  the  lantern  test 
with  its  modifying"glasses  is  so  valuable. 

3.  Cases  in  which  certain  parts  of  the  spectrum  are  not  seen  at  all.     This 


ERRORS   OF  APPRECIATION  r„s| 

condition  frequently  affects  the  red  end  of  the  spectrum,  but  it  may  be  found 
in  other  parts.  The  principal  effects  to  be  noted  are  :  ( 1 )  an  abnormal  type 
of  luminosity  curve,  as  examined  by  means  of  the  flicker  method  :  (2)  the 
requirement  of  different  amounts  of  the  primary  colours  in  order  to  match 
a  given  spectral  colour,  as  compared  with  individuals  with  normal  vision  ; 
(3)  inability  to  recognise  the  normal  number  of  different  hues  in  the  pan 
of  the  spectrum  affected,  as  shown  by  the  spectroscope  test  ;  (1)  shortening 
of  the  spectrum,  if  either  of  the  ends  of  the  spectrum  is  affected.  The 
condition  would  appear  to  be  directly  traceable  to  abnormality  in  the  colour 
receiving  apparatus  of  which  the  cones  form  an  important  part.  These 
cases  therefore  show  quite  distinct  features  which  at  once  differentiate  them 
from  those  of  class  2.  For  in  that  class,  so  far  as  can  be  ascertained,  the  peri- 
pheral receiving  apparatus  is  normal,  and  the  error  lies  with  the  higher 
centres  in  which  the  resulting  nerve  impulses  are  interpreted.  A  typical 
example  of  a  case  belonging  to  class  3  will  now  be  described,  namely,  that 
in  which  there  is  shortening  at  the  red  end  of  the  spectrum.  The  flicker 
test  shows  that  the  luminosity  curve  for  different  parts  of  the  spectrum 
lias  its  maximum  in  the  green,  instead  of  in  the  yellow.  Further,  the  curve 
does  not  extend  so  far  into  the  red,  or  show  such  high  values  in  the  orange 
as  the  normal  curve.  This  curve  therefore  explains  the  apparent  shortening 
of  the  spectrum.  Colour  mixture  experiments  show  that  the  patient  can 
match  mixtures  of  green  and  blue  with  white  light.  When  required  to  match 
yellow,  he  uses  an  excessive  amount  of  red,  and  correspondingly  less 
green  than  the  normal  sighted ;  this  test  again  shows  the  deficiency  of 
the  red  sensation.  Tested  by  the  spectroscope  it  is  found  that,  beside  the 
shortening  at  the  red  end  of  the  spectrum,  there  is  also  an  inability  to  distin- 
guish the  normal  number  of  hues  at  the  green  and  yellow.  This  effect  is 
readily  explained,  because  the  difference  between  green  and  yellow  shades 
largely  depends  on  the  varying  extent  to  which  they  stimulate  the  red 
sensation.  When  the  red  sensation  is  absent,  it  is  clear  that  the  differen- 
tiation of  greens  and  yellows  must  suffer. 

EFFECT  OF  INTENSITY  ON  COLOUR  VISION.  It  is  well  known 
bhal  there  is  a  certain  range  of  intensity  over  which  the  appreciation  of 
colour  is  a  maximum,  and  that  at  high  and  low  intensities  appreciation 
is  diminished.  Thus  at  low  intensity  the  spectrum  will  appear  shortened 
at  both  red  and  violet  ends,  and  with  the  spectroscope  test  perhaps  In 
monochromatic  areas  will  be  mapped  out  instead  of  the  normal  20  to  30. 
At  high  intensity  on  the  other  hand,  the.  spectrum  appears  to  extend  further 
than  usual  at  both  red  and  violet  ends,  but  again  it  is  found  that  the  number 
of  apparently  monochromatic  areas  is  considerably  reduced.  In  the  one 
case  it  would  seem  that  the  impulses  received  by  the  brain  from  the  cone 
mechanism  are  so  feeble  that  appreciation  is  diminished,  and  in  the  second 
that  a  powerful  colour  stimulus  arouses  all  three  sensations  indifferenl  ly  and 
therefore  makes  the  differentiation  of  colour  difficult. 

PERIPHERAL    VISION.     Experiments  with  the   peri]  how   that 

there  is  under  ordinary  circumstances  a  reduced  appreeiation  ol  colour  in 


582  PHYSIOLOGY 

the  periphery  of  .the  retina.  Thus  in  an  annular  zone  round  the  macular 
region  there  is  red-green  blindness  but  full  appreciation  of  yellow  and  blue. 
Outside  this  area  coloured  objects  are  seen  in  different  shades  of  grey.  More 
careful  experiments  show  firstly,  that  there  is  no  hard  and  fast  line  limiting 
the  zones,  but  a  gradual  diminution  of  colour  perception  on  passing  in  any 
direction  from  the  centre  to  the  periphery;  and  secondly,  that  intensity  plays 
a  most  important  part,  an  increase  being  sufficient  to  effect  normal  colour 
perception  even  in  quite  peripheral  vision.  The  red-green  blindness 
found  at  one  intensity  might  be  due  either  to  an  absence  or  more  probably 
to  a  weakness  or  deficiency  of  cither  the  red  or  the  green  sensations,  or  to 
defective  appreciation  on  the  pari  of  the  higher  centres  in  the  brain.  In 
the  first  case  there  would  be  an  abnormal  shape  to  the  luminosity  curve,  such 
as  is  found,  in  fact,  in  red  or  green  blindness,  whereas  in  the  second  case  the 
luminosity  curve  would  be  similar  to  that  of  normal  vision.  Experiments 
aresiid  toshowthat  the  curse  is  normal,  and  therefore  the  cones  in  the  peri- 
phery must  be  in  every  way  normal,  a  supposition  which  is  borne  out  by  t  he 
correct  appreciation  of  colour  at  high  intensity.  Whythenit  may  be  asked  is 
colour  vision  reduced  at  the  periphery  if  the  cones  are  normal  ?  The  answer 
is,  1  think,  firstly  that  the  number  of  cones  is  greatly  diminished,  and  secondly 
that  the  effective  area  of  the  pupil  is  much  less  at  the  periphery  than  it  is  at 
the  centre  of  the  retina.  We  have  seen  in  a  previous  section  (1)  that  the 
threshold  necessary  for  the  appreciation  of  eolour  depends  on  the  size  of  the 
area  of  the  retina  which  is  receiving  stimulation.  The  larger  the  area  the 
lower  can  the  intensity  be.  Therefore  one  unit  of  intensity  falling  on 
ICO  cones  is  equivalent  to  100  units  falling  on  one  cone.  Now  consider 
the  relative  conditions  of  the  fovea  and  the  periphery  ;  at  the  fovea  let  us 
suppose  there  to  be  100  units  of  intensity  falling  on  100  cones,  then  at  the 
periphery  there  will  be  but  50  units  (because  the  effective  area  of  the  pupil 
is  less  owing  to  the  rays  entering  obliquely),  and  these  will  fall  on  perhaps 
two  cones  only.  Whereas  in  the  first  case  there  are  10,000  cone-units,  in  the 
second  there  are  Kin  cone-units  only,  and  it  is  therefore  to  be  expected  that 
appreciation  of  colour  would  be  decreased  in  the  same  way  as  it  is  at  the  fovea 
under  reduced  illumination.1  That  blue  is  perceived  at  a  greater  angle  than 
yellow  is  probably  due  to  the  greater  refraction  of  blue  than  yellow  rays  when 
they  strike  the  eye  surfaces  obliquely.  For  a  blue  ray  and  a  yellow  ray  to 
meet  on  the  retina,  the  angle  subtended  by  the  blue  must  be  5  per  cent,  larger 
than  that  of  the  yellow. 

1  The  above  explanation  dues  not  however  adequately  account  for  the  fact  that 
peripheral  vision  does  not  lose  its  colour  appreciation  for  blue  and  yellow  so  readily 
as  it  does  that  for  red  and  green.  The  phenomena  of  peripheral  vision  still  require 
further  investigation. 


SECTION    XI 
THEORIES    OF   COLOUR   VISION 

The  value  of  a  theory  60  science  is  as  much  due  to  the  fresh  lines  of  research  which 
it  indicates,  as  to  the  explanation  which  it  offers  of  the  already  ascertained  tacts.  The 
theories  of  vision  therefore  are  of  value  in  spite  of  the  fact  that  they  do  not  at  tin- 
present  time  offer  a  complete  account  of  the  retina  and  its  functions. 

THE  DUPLEX  THEORY  of  von  Kries  states  that  there  are  in  the  retina  two  entirely 
separate  mechanisms,  namely  that  used  for  twilight  vision  which  is  colour  blind,  and 
that  used  for  day  vision  which  responds  to  colour.  Tin-  view  that  the  rods  with  the  visual 
purple  supply  the  former  whereas  the  cones  provide  the  latter,  is  already  familiar 
because  it  has  been  made  the  basis  of  the  description  already  given  in  previous  section 
The  evidence  on  which  this  opinion  is  based  may  with  advantage  be  repeated  because 
of  its  importance. 

Twilight  vision  is  found  in  those  parts  of  the  retina  where  there  are  rods;  it  is  not 
found  therefore  at  the  fovea  centralis  (because  cones  alone  are  to  be  found  there),  if  a 
spectrum  be  examined  it  is  found  that  the  colour  with  the  greatest  luminosity  is  the 
green,  but  that  red  rays  are  not  seen  at  all.  The  form  of  the  luminosity  curve  is  identical 
with  the  bleaching  curve  of  visual  purple,  and  this  pigment  is  found  only  where  there 
are  rods.  The  visual  acuity  of  twilight  vision  is  low,  and  is  explained  by  the  fact 
that  many  rods  as  a  rule  send  their  impulses  through  one  and  the  same  nerve  fibre. 
In  addition  to  this  experimental  evidence,  there  is  the  statement  that  animals  (e.g. 
bats  and  hedgehogs)  and  birds  (e.g.  owls)  which  are  nocturnal  in  habit,  have  rods  in  their 
retinae  and  not  cones. 

Day  vision  is  found  most  highly  developed  in  the  fovea,  from  which  rods  an-  absent . 
Not  unly  arc  the  cones  at  the  lovea  placed  very  closely  together,  but  it  would  appear 
that  each  cone  connects  to  one  nerve  fibre  only;  in  this  way  the  high  visual  acuity  is 
explained.  Further  it  is  stated  that  animals  (e.g.  tortoises)  and  birds  (>.</■  hens)  which 
are  diurnal   in   habit,  have  cones  only  in   their  retina;. 

It  has  been  suggested  recently  that  the  following  modifications  should  lc  made 
in   the  duplicity  theory  of  von   Kries: — , 

1.  That  the  cones  do  in  certain  eases  function  to  some  extent  in  night  vision,  thus 
retaining  one  of  their  primitive  rod  characteristics,  from  which  on  morphological 
grounds  they  appear  to  have  been  developed. 

2.  That  the  fovea  contains  some  visual  purple,  being  necessary  in  order  that  the 
cones  may  function  in  night  vision  as  ahove,  or  possibly  for  the  green  sensation  of  day 
vision. 

.'!.   Thai   the  rods  play  sonic  part   in  day  vision,  adding  I  hen  response  to  tiiat  ot  the 

cones. 

These  modifications  of  the  duplicity  theory  concern  detail  more  than  thej  do  'I" 

basis  of  the  theory,  and  do  not  appear  to  detract  at  all  from  the  strength  of  its  posil 

So  that  so  far  as  the  relative  roles  of  the  rods  and  cones  are  concerned  there  would 
not  appear  to  be  any  room  for  speculation.  Such  is  not  the  ease  however  \\  ith  regard 
to  colour  vision,  because,  of  the   various  hypotheses  that    have   been  so  fir  advanced, 

none  have  been  found  to  otter  a  feasible  explanation  of  all  the  known  facts,  or  to  leave 
no  other  possible  alternative.  A  brief  account  of  the  mil  theories  may  be  given 
with  advantage. 

YOUNG'S   HYPOTHESIS  stales  that  thee  are  in  the  retina  three  differcnl  types 
583 


58 1 


IMIYSIOI.OUY 


of  cone,  each  being  so  made  as  to  respond  to  one  of  the  three  Fundamental  colours, 
namely  red,  green  and  violet.    The  impulses  from  these  cones  are  bo  combined  in  the 

brain  that  they  give  a  complete  picture  of  the  separate  coloured  images.  When  all 
three  types  of  cone  are  equally  stimulated,  a  Colourless  sensation  results.      Each  visual 

mil  may  therefore  be  regarded  as  consisting  of  three  cones,  one  of  which  responds 
to  each  of  the  fundamental  colours.  From  this  we  should  expect  that  the  limit  to  the 
acuteness  of  vision  would  be  reached  when  the  separation  of   the  images  on  the  retina 

is  not  less  than  the  diameter  of  such  a  unit.     But  the  diameter  of  the  foveal  c i 

approximately  0-0025  mm.,  and  therefore  that  of  a  unit  would  be  roughly  0-004  mm. 
Now  it  is  found  by  experiment  that  the  limit  to  the  acuteness  of  vision  is  reached  when 
the  retinal  images  are  separated  by  about  0-002.  It  is  therefore  clear  that  the  unit 
cannot  be  larger  than  one  cone,  and  that  in  consequence  each  cone  must  be  capabli 
of  responding  to  all  three  fundamental  colours.  In  consequence  of  this  Helmholtz 
made  the  suggestion  that  there  are  three  different  chemical  substances,  each  of  which 
undergoes  alteration  under  the  influence  of  one  of  the  three  fundamental  colours. 
The  breakdown  products  thus  formed  stimulate  the  cones  in  proportion  to  the  amount 
in  which  they  are  present,  their  function  in  this  respect  being  comparable  to  the  taste 
buds  of  the  tongue.  In  this  way  each  cone  can  respond  to  all  three  colours  and  also 
to  white  light,  and  therefore  the  requirements  of  visual  acuity  are  satistied.  As  to  what 
these  chemical  substances  are,  we  at  present  know  nothing  :  it  has  been  suggested  that 
the  substance  responsible  for  the  perception  of  blue  is  a  pigment  discovered  by  Kiihne 
called  visual  yellow,  and  visual  purple  might  from  its  absorption  curve  provide  the 
pigment  for  the  green,  but  at  present  we  have  no  evidence  for  this.  It  should  be  noted 
that  the  three  sensations  are  brighter  and  more  saturated  than  the  three  fundamental 
colours  with  which  they  may  be  said  to  correspond.  This  follows  from  the  researches 
of  Maxwell  and  Abney,  which  showed  that  each  of  the  fundamental  colours  stimulates 
to  some  extent  the  other  sensations  beside  its  own.  Thus  blue  light  stimulates  the 
green  and  red  sensations  to  a  certain  extent,  green  similarly  the  red  and  blue  sensations, 
but  red  the  green  slightly,  and  the  blue  not  at  all.  This  view  as  to  the  greater  saturation 
of  the  sensations  finds  some  confirmatory  evidence  from  the  increase  which  the  satura- 
tion of  a  colour  undergoes  after  the  eye  has  been  stimulated  by  its  complementary. 


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FlO.  -!)9.     The  red,  green  and  blue  sensation" curves  and  the  luminosity  curve  of 
white  light.     Luminosity  vertical  wavelengths  horizontal.     (Abney.) 


Having  thus  briefly  outlined  the  hypothesis  of  Young  and  Helmholtz. 
ship  with  the  results  of  experiment  may  receive  consideration. 


relation- 


THEORIES   OF  COLOUR  VISION  585 

1.  The  results  of  colour  mixture  are  all  adequately  explained.  Since  to  each  of 
the  fundamental  colours  there  is  a  corresponding  sensation,  and  since  mixtures  of  the 
fundamentals  can  produce  the  whole  range  of  colour,  it  follows  that  corresponding 
stimulation  of  the  sensations  and  their  resynthesis  in  the  brain  tits  in  with  the  facts. 

2.  The  various  classes  of  colour  blindness  which  show  abnormal  types  of  luminosity- 
curve,  abnormal  colour  mixture  values,  and  possibly  also  a  shortening  of  the  spectrum, 
are  readily  explained  by  supposing  one  of  the  sensations  to  he  defective  or  absent. 
For  example,  cases  which  show  a  shortening  of  the  red  end  of  the  spectrum  are  stated 
by  the  theory  to  have  a  deficient  red  sensation.  The  luminosity  curve  calculated  on 
this  basis  is  found  to  fit  closely  the  curve  found  by  experiment  in  these  cases  of  colour 
blindness.  The  hypothesis  would  appear  therefore  to  be  able  to  fully  explain  the 
various  cases  which  fall  in  this  class.  Certain  objections  have  however  been  advanced 
which  it  would  be  well  to  examine,  (a)  That  it  does  not  explain  why  the  red  blind  and 
the  green  blind  state  that  the  ends  of  the  spectrum  as  they  see  them  are  yellow  and 
blue,  whereas  it  w  ould  be  expected  that  they  would  say  green  and  blue  if  red  blind,  arid 
red  and  blue  if  green  blind.  An  explanation  of  this  behaviour  can  be  readily  obtained 
by  examining  the  forms  of  the  red  and  green  sensation  curves,  Fig.  299,  for  in  both  red 
and  green  blindness  a  yellow  light  is  that  which  stimulates  the  remaining  sensation  most 
strongly,  without  at  the  same  time  involving  the  blue.  In  both  types  of  case  therefore 
both  red  and  green  are  regarded  as  being  but  degraded  yellow.-.,  and  the  spectrum  is 
therefore  named  accordingly,  {b)  That  the  hypothesis  does  not  explain  why  these 
same  cases  call   white  white,  instead  of  bluish  green  or  purple. 

This  is  explained  by  the  fact  that  a  colour-blind  person  will  call  white  what  his 
fellows  who  have  normal  colour  vision  call  white,  because  he  has  learned  his  colour  names 
from  them.  In  the  same  way  a  green-blind  person  will  not,  call  the  leaves  of  a  tree  by 
a  wrong  colour,  although  he  will  readily  err  if  a  piece  of  paper  of  the  same  colour  as  a 
leaf  be  handed  to  him. 

The  various  types  of  colour  blind  which  have  normal  luminosity  curves  cannot 
be  explained  by  the  hypothesis  without  some  further  elaboration.  As  I  have  indicated 
however  they  fit  in  well  with  the  supposition  that  it  is  not  the  eye  but  the  higher  centres 
which  are  at  fault.  The  impulses  which  travel  up  the  optic  nerve  are  in  every  way 
normal;  the  error  occurs  in  their  interpretation.  This  would  appear  to  be  a  reasonable 
explanation  which  fits  in  with  the  other  postulates  of  the  hypothesis.  It  has  been 
advanced  by  Edridge  Green  as  part  of  another  hypothesis  of  colour  vision,  which  will 
be  given  later. 

3.  Contrast,  after  images,  and  allied  phenomena  have  not  been  adequately  dealt 
with.  Helmholtz  regarded  contrast  as  an  error  of  judgment,  but  Hering  showed  con- 
clusively that  such  could  not  be  the  case.  McDougall's hypothesis, which  is  to  a  large 
extent  founded  on  that  of  Young,  will  be  found  to  add  the  features  that  are  required 
for  the  explanation  of  after  images  and  contrast. 

HERING'S  HYPOTHESIS  states  that  there  are  in  the  retina  three  substances 
which  are  all  the  time  tending  to  dissociate  into  their  components.  They  are  however 
either  replaced  or  built  up  again  from  substances  in  the  blood,  as  quickly  as  they  are 
destroyed.  There  is  therefore  equilibrium  between  anabohsm  and  catabolism,  when 
the  eye  is  unstimulated,  and  while  this  is  the  case  no  nerve  impulses  travel  to  the  brain. 
Now  each  of  these  substances  is  dissociated  by  one  of  the  following  colours,  red,  yellow, 
white ;  and  is  built  up  when  green,  blue  or  black  fall  on  the  retina.  Thus  one  substance 
will  break  up  when  red  light  falls  on  it,  and  will  recombine  when  green  does.  There 
is  thus  a  red-green,  a  yellow-blue,  and  a  wliite-black  substance.  When  a  coloured 
light  falls  on  the  retina  these  three  substances  are  broken  down  or  are  built  up  in  varying 
amounts  and  corresponding  impressions  sent  to  the  brain.  Tested  by  experiment  this 
view  is  found  to  acquit  itself  as  follows  : — 

(1)  The  results  of  colour  mixture  are  readily  explained,  with  the  possible  exception 
of  the  formation  of  grey,  by  the  simultaneous  anabohsm  and  catabolism  of  one  and  the 
same  substance. 


586  PHYSIOLOGY 

(2)  Contrast,  alter  images  and  adaptation  arc  readily  explained  as  follows: — 
While  a  stimulus  Calls  on  the  retina,  the  three  visual  substances  which  were  previously 
in  equilibrium  with  their  breakdown  products,  are  caused  to  take  up  a  iww  position 
of  equilibrium.  On  cessation  of  the  stimulus  however  there  is  a  return  to  the  old 
position,  and  therefore  the  impulses  sent  to  the  brain  are  those  which  correspond  to  a 
sensation  of  an  opposite  character,  thus  causing  a  negative  after  image.  Contrast  is 
explained  by  supposing  that  anabolism  in  one  area  is  accompanied  by  a  stimulus 
to  catabolism  in  the  same  area,  but  the  effect  is  not  sharply  limited  but  tends  to  spread 

for  a  short  distal  in'  over  surrounding  areas,  and  thus  causes  a  change  in  their  equilibrium 
point  which  is  of  an  opposite  nature  to  that  of  the  stimulus  which  originates  them.  Thus 
blue  light  falling  on  a  part  of  the  retina  causes  anabolism  in  that  area,  which  is  followed 
by  an  increased  tendency  to  catabolism.  This  process  affects  the  surrounding  area,  pro- 
ducing the  same  change  and  therefore  the  same  sensation  as  would  a  yellow  image. 
Adaptation  is  explained  as  the  taking  up  of  a  new  equilibrium  point,  for  one  or  all 
of  the  three  substances. 

(3)  ( 'olour  blindness  is  explained  as  follows  :  Total  colour  blindness  by  the  presence 
of  the  black-white  substances  only.  Red-green  blindness  by  the  deficiency  of  this 
substance,  and  yellow-blue  blindness  in  a  similar  way.  Bui  we  find  by  experiment  that 
there  are  two  classes  of  red -green  blindness,  namely  those  which  are  red  deficient. 
and  those  which  are  green.  The  Hering  hypothesis  is  incapable  of  explaining  theii 
causation  in  its  present  form. 

EDRIDGE  GREEN'S  HYPOTHESIS  states  that  the  function  of  the  rods  is  to 
secrete  visual  purple.  This  pigment  under  the  action  of  light  stimulates  the  ends  of  the 
cones  and  causes  them  to  send  impulses  to  the  brain  which  vary  according  to  the 
wavelength  of  the  light  and  its  intensity.  The  rods  are  on  this  view  merely  secretory 
organs,  and  take  no  other  part  in  vision.  The  impulses  having  reached  the  brain  go 
first  to  a  light  perceiving  centre,  and  then  to  another  especially  developed  for  the 
appreciation  of  colour.  In  this  colour  centre  there  arc  three  separate  mechanisms,  which 
correspond  roughly  with  the  red,  green  and  blue  fundamental  colours,  but  which  may 
respond  to  other  frequencies  than  those  to  which  they  approximately  correspond. 
Suppose,  for  example,  that  a  monochromatic  yellow  light  is  falling  on  the  retina,  then 
it  is  absorbed  l>y  the  visual  purple,  and  thus  stimulates  the  ends  of  the  cones.  These 
then  send  up  the  optic  nerve  impulses  which  have  a  mean  frequency  corresponding 
to  yellow  light,  but  at  the  same  time  contains  impulses  of  other  frequencies  on  either 
side,  to  a  degree  which  depends  on  their  closeness  with  the  mean.  For  example  in 
the  above  case,  beside  impulses  of  frequency  of  yellow  light  there  are  also  some  which 
correspond  to  green  and  red.  These  impulses  having  reached  the  colour  centre  stiinii 
late  the  red  and  green  mechanisms  respectively,  while  those  corresponding  to  the  yellow 
also  stimulate  these  same  mechanisms,  but  in  proportion  to  the  energy  which  each 
receives.     This  view  may  now  be  examined  in  the  light  of  experiment. 

(1)  The  results  of  colour  mixture  would  appear  to  he  explained  by  it  with  the  excep- 
tion that  the  mechanisms  in  the  colour  centre  must  have  very  definite  mean  frequencies, 
for  otherwise  mixed  colours  will  not  be  able  to  match  the  whole  of  the  spectral  range. 

(2)  Simultaneous  contrast  and  after  images  are  explained  by  Edridge  Green  in  a 
way  which  1  find  difficult  to  understand  ;  it  would  therefore  be  best  not  to  attempt  to 
discuss  it. 

(3)  Colour  blindness  was  initially  explained  as  being  due  to  defective  appreciation 
in  the  colour  perceiving  centre.  The  shortening  of  the  red  end  of  the  spectrum  would 
be  due  not  to  the  inability  of  the  retina  to  react  to  the  stimulus,  but  to  fault  on  the  part 
of  the  colour  centre  when  receiving  the  nerve  impulses.  A  different  explanation  has 
been  offered  by  Houston,  who  has  recently  elaborated  the  hypothesis.  He  states 
that  colour  blindness  is  due  to  the  excessive  reaction  on  the  part  of  the  retinal 
apparatus,  which  causes  the  energy  of  the  stimulus  to  be  spread  over  too  wide  a  range 
of  frequencies.  If  such  were  the  case  one  would  expect  a  low  appreciation  of  colour, 
as  is  found  in  a  number  of  examples  of  colour  blindness,  hut  there  would  he  difficulty 


THEORIES  OF  COLOUR  VISION  587 

in  finding  an  explanation  of  these  cases  which  show  an  inability  to  respond  to  a  part 
of  the  spectrum.  Although  there  does  not  seem  to  be  any  special  difficulty  in  bo 
modifying  this  hypothesis  that  it  fits  in  with  all  the  varieties  of  colour  blindness,  yel 
it  would  seem  that  this  would  cause  it  only  to  be  more  and  more  like  the  theory  of  Young, 
with  tin's  important  difference,  that  according  to  Young's  theory  the  three  substances 
by  which  light  is  selectively  absorbed,  according  as  its  wavelength  corresponds  to  the 
icd, green  or  blue  part  of  the  spectrum,  is  in  the  retina,  whereas  the  three  mechanisms 
required  by  Edridge  (liven  are  in  the  brain.  Changing  their  situation  would  not  appear 
to  have  added  to  our  knowledge  of  them,  but  would  on  the  other  hand  appear  to  add 
greatly  to  our  difficulties,  for  it  is  impossible  to  understand  how  impulses  of  the  enor- 
mous frequency  of  light  could  be  transmitted  intact  up  the  optic  nerves,  as  Edridge 
Green  requires. 

McDOUGALL'S  HYPOTHESIS  is  not  antagonistic  to  Young's  theory,  as  the  two 
previous  views  have  been,  but  adds  valuable  suggestions  as  to  the  causation  of  contrast 
and  after  image  phenomena,  points  to  which  the  original  theory  gave  little  or  no  atten- 
tion. MoDougall  also  accepts  the  duplicity  theory.  He  commences  by  slating  that 
there  are  four  centres  for  the  two  eyes,  namely  red.  green,  blue  and  white  (the  mechanism 
of  which  is  the  rods),  and  that  these  centres  are  distinct  and  have  no  anatomical  iden- 
tity. Between  these  centres  there  is  antagonism,  the  red  centre  of  one  eye  against  the 
green  and  blue  centres  of  the  other  and  also  to  a  less  extent  against  those  of  itself. 
In  this  way  one  can  explain  not  only  binocular,  but  also  monocular  rivalry.  Contrast 
is  explained  in  a  somewhat  similar  manner  ;  thus  if  the  object  looked  at  consists  of  a 
red  area  on  a  grey  field,  the  red  stimulus  inhibits  the  appreciation  of  red  in  the  surround- 
ing field,  and  therefore  causes  it  to  have  a  blue-green  colour,  a  deduction  which  is 
confirmed  by  experiment.     After  images  are  dealt  with  in  a  somewhat  similar  manner. 

With  the  evidence  that  has  accumulated  up  to  the  present  before  us,  there  appears 
to  be  more  in  favour  of  Young's  hypothesis  than  is  to  be  found  for  its  rivals.  Further 
tli. in   that,   it    is  not  at  present  advisable  to  go. 


SECTION  XII 

BINOCULAR   VISION 

Binocular  vision  may  be  defined  as  the  co-ordinated  employment  of  two 
separate  visual  organs  in  order  to  produce  a  single  mental  inopression.  The 
advantages  of  binocular  as  opposed  to  monocular  vision  are  : — 

1.  Optical  defects  of  one  eye  are  less  important,  since  they  are  masked 
by  the  well-defined  images  of  the  other  eye. 

2.  Defective  vision  in  parts  of  the  visual  fields  of  both  eyes  is  hidden  so 
long  as  the  defects  do  not  affect  the  same  parts  of  both  fields.  Thus  the  blind 
spots  do  not  obtrude  themselves  under  ordinary  circumstances,  because  the 
corresponding  field  of  the  other  eye  contains  normal  retina. 

3.  The  combined  fields  of  the  two  eyes  are  larger  than  either  alone  because, 
while  the  features  restrict  the  nasal  halves  of  the  fields  of  both  eyes,  the 
combined  field  contains  the  unrestricted  temporal  areas  of  both  retinae. 

4.  Binocular  vision  under  certain  circumstances  provides  a  very  accurate 
perception  of  depth,  size  and  distance,  which  is  called  stereoscopic  vision. 

In  order  that  there  should  be  binocular  vision  the  following  conditions 
should  be  complied  with  : — 

1.  The  fields  of  the  two  eyes  must  overlap.  Animals  in  which  the  ej  e 
axes  are  parallel  have  the  greatest  overlap,  and  therefore  possess  the 
eompletest  binocular  vision. 

2.  Approximately  similar  images  must  be  formed  on  the  retina?,  because 
if  this  condition  is  not  satisfied,  antagonism  between  the  images  will  occur, 
as  described  above,  and  first  one  image  and  then  the  other  will  he  presented 
to  consciousness. 

3.  The  retinae  must  possess  physiologically  corresponding  points  in 
order  that  similar  images  formed  on  them  may  produce  one  conscious 
impression. 

4.  The  external  eye  muscles  must  so  adjust  the  visual  axes  that  the  centres 
of  the  fields  of  the  two  eyes  coincide  with  the  images  of  one  and  the  same 
object.  This  adjustment  is  called  fixation.  It  is  sometimes  described  as 
the  intersection  of  the  visual  axes  at  the  point  fixated. 

5.  The  oblique  muscles  must  rotate  the  eyes  about  their  axes  until 
corresponding  retinal  points  occupy  corresponding  meridians. 

The  rotation  adjustment  is  necessary  because  otherwise  identical  points 
of  the  retinae  might  not  correspond,  even  when  the  centres  did,  so  that  one 
image  would  appear  tilted  at  an  angle  with  the  other.  Fixation  is  partly 
a  voluntary  act  and  partly  a  reflex  process.  The  former  is  shown  by  the 
fact  that  the  eyes  may  be  directed  towards  an  imaginary  object  a  short 

588 


BINOCULAK  VISION  589 

distance  from  the  face,  so  that  the  eye  axes  are  strongly  converging  and  the 
accommodation  correctly  adjusted  to  the  same  plane.  The  presence  of  a 
reflex  phase  is  well  shown  by  the  fact  that  no  effort  of  the  will  is  required 
to  sustain  fixation  on  an  object  in  which  we  are  interested,  and  also  by  those 
cases  in  which  when  once  an  object  has  been  fixated,  there  is  found  to  be 
considerable  mental  difficulty  in  turning  the  gaze  elsewhere.  Rotation  fixa- 
tion on  the  other  hand  appears  to  be  entirely  reflex.  In  order  that  fixation 
should  be  obtained  when  the  gaze  is  directed  in  different  directions,  it  is 
necessary  that  there  should  be  close  association  between  the  corresponding 
muscles  of  the  two  eyes.  This  is  at  all  events  assisted  by  the  anatomical 
arrangement  of  the  3rd,  4th  and  6th  cranial  nerve  nuclei  which  has  been 
described  previously  (see  page  496). 

Not  only  are  the  corresponding  nuclei  on  the  two  sides  connected  by 
transverse  fibres  so  that  e.g.  either  the  superior  recti  or  the  inferior  recti 
move  together,  but  the  external  rectus  nucleus  of  one  side  is  joined  to  the 
internal  rectus  nucleus  of  the  other  by  the  dorsal  longitudinal  bundle,  so 
that  the  eyes  deviate  together  to  right  and  left.  Similar  connections  are 
to  be  found  between  the  nuclei  of  the  superior  and  inferior  obliques.  The 
relations  of  these  nuclei  to  the  cerebral  cortex  have  been  ascertained  by  elec- 
trical stimulation.  It  has  been  found  that  stimulation  of  the  median  third  of 
the  limb  of  the  angular  gyrus  on  either  side  causes  both  eyes  to  be  turned 
to  the  opposite  side.  The  right  gyrus  therefore  connects  with  the  nuclei 
of  the  right  internal  rectus  (3rd)  and  the  left  external  rectus  (6th). 
Since  both  these  nuclei  are  on  the  left,  the  fibres  from  the  gyri  must  cross 
in  order  to  reach  their  corresponding  nuclei :  this  they  do  at  the  level  of  the 
anterior  corpora  quadragemina.  The  angular  gyri  are  connected  to  both 
the  frontal  and  occipital  parts  of  the  cortex,  so  that  voluntary  movements 
of  the  eyes,  and  also  movements  under  the  action  of  light,  can  be  carried  out. 
Experimental  stimulation  of  the  semicircular  canals  is  found  to  cause 
conjugate  deviations  of  the  eyes.  But  stimulation  of  the  canals  is  effected 
naturally  by  a  rotation  of  the  head,  as  will  be  described  later.  The  conjugate 
deviation  of  the  eyes  would  appear  to  be  initiated  in  order  that  the  gaze 
might  remain  stationary  on  external  objects  in  spite  of  the  head  move 
incuts. 

The  way  in  which  involuntary  fixation  is  brought  about  may  be  described 
as  follows  : — when  an  image  falls  on  the  periphery  of  the  retina  an  impulse 
reaches  the  oculo-motor  nuclei  in  the  manner  described  above.  Thus, 
suppose  the  image  to  come  from  the  right,  it  will  fall  initially  on  the  left 
halves  of  both  retinae,  and  impulses  will  therefore  travel  to  the  left  occipital 
cortex.  From  here  they  will  pass  to  the  left  angular  gyrus,  causing  impulses 
to  travel  to  the  left  internal  and  the  right  external  recti.  Both  eyes  arc 
therefore  directed  to  the  right,  the  movement  being  such  as  to  bring  the 
image  on  the  fovea.  But  as  the  fovea  is  approached,  the  Lmpre  kn  sent  to 
consciousness  becomes  increasingly  distinct,  owing  to  the  higher  acuity  of 
the  fovea.  If  the  fovea  is  passed  the  image  begins  to  become  indistinct 
again,  and  therefore  the  movement  of  the  eyes  is  checked  as  soon  as  the  image 


590  PHYSIOLOGY 

has  reached  the  fovea.  In  this  way  fixation  is  effected.  If  the  acuity  of 
the  fovea  is  reduced  by  disease  or  by  working  in  a  bad  light,  the  definition 
of  the  image  does  not  sharply  improve  as  the  fovea  is  reached,  and  therefore 
the  movement  of  the  eyes  is  not  checked  until  the  image  has  reached  the. 
periphery  again.  But  here  the  degradation  of  the  image  calls  for  the  re- 
verse process,  which  again  causes  the  image  to  pass  over  the  fovea.  Repeated 
oscillations  of  the  eyes  therefore  occur,  which  are  called  nystagmus.  The 
condition  is  met  with  in  the  day  blind,  since  cone  vision  is  defective,  in 
persons  whose  visual  acuity  has  been  lowered  by  working  in  a  dull  light,  e.g. 
miners,  and  in  cases  of  poisoning  by  tobacco  and  alcohol. 

THE  HOROPTER.  Theory  shows  that,  even  when  fixation  is  properly 
effected  so  that  corresponding  retinal  points  occupy  the  same  meridians, 
images  formed  on  the  retinae  do  not  necessarily  fall  on  corresponding  points. 
For  this  to  be  the  case,  it  is  necessary  also  that  the  objects  from  which  those 
images  are  formed  should  occupy  certain  definite  positions  in  relationship 
with  one  another.  For  example,  if  an  object  10  feet  from  the  eye  is  fixated, 
the  images  of  other  objects  on  either  side  will  fall  only  on  corresponding 
points  if  these  lie  on  a  circle  of  5  feet  radius,  the  centre  of  which  lies  between 
the  observer  and  the  object  fixated.  For  calculation  shows  that  oidy  then  are 
the  images  formed  on  the  two  retime  the  same  distance  from  the  centre. 
The  form  of  the  curve  which  is  called  the  horopter  is  found  to  change  with 
the  different  directions  of  the  gaze.  When  the  gaze  is  directed  to  a  point 
on  the  floor  it  is  stated  that  the  horopter  almost  corresponds  with  the  plane 
of  the  floor. 

MONOCULAR  DEPTH  PERCEPTION.  The  perception  of  depth 
with  the  single  eye  is  found  to  depend  on  a  number  of  different  factors  which 
as  a  rule  operate  together  :-- 

1.  The  apparent  size  of  objects,  the  dimensions  of  which  are  known. 
Thus  the  size  of  a  man  being  approximately  known,  his  distance  away  is 
known  from  the  size  of  the  image  which  is  formed  on  the  retina.  The  further 
away  he  is  the  smaller  his  image  will  appear. 

2.  The.  colour  of  an  object  being  known,  the  effect  of  distance  in  modifying 
that  colour  is  used  in  depth  perception.  Thus  trees  which,  when  near,  look 
yellow-green,  when  seen  at  a  distance  through  an  intervening  layer  of  haze 
appear  blue-green  or  even  blue.  This  fact  is  made  use  of  by  artists  for 
expressing  distance. 

3.  The  partial  obstruction  of  a  distant  plane  by  objects  nearer  to  the 
observer. 

4.  The  shadows  which  one  plane,  casts  upon  another. 

5.  The  intensity  of  the  light  which  is  reflected  by  the  object  frequently 
varies  with  its  shape  and  position.  For  example,  the  shape  of  a  solid  sphere 
can  be  accurately  inferred  from  the  distribution  of  intensity  over  its  face. 

6.  By  perspective,  which  may  be  defined  as  the  geometrical  arrangement 
of  lines  in  the  image  formed  on  the  retina.  Thus  the  lines  of  a  tennis  ccurt 
seen  diagonally  from  one  side  are  all  found  to  converge  to  one  or  other  of 
two  points  on  the  horizon. 


BINOCULAR   VISION  591 

7.  By  the  intersection  of  objects  with  the  horizontal  plane.  Thus  the 
positions  of  trees  in  a  field  may  be  inferred  with  some  accuracy,  if  the  positions 
of  the  roots  of  the  trees  in  relationship  with  the  boundaries  of  the  field  be 
observed. 

8.  By  parallax,  that  is  the  rate  of  movement  of  objects  in  relationship 
with  one  another.  Thus  if  a  middle  plane  be  looked  at,  it  will  be  noticed 
that  objects  in  a  plane  behind  appear  to  move  in  the  same  direction  as  the 
observer,  while  those  in  a  plane  in  front  appear  to  move  the  opposite  way. 
Even  when  we  are  standing  still,  we  are  all  the  time  making  involuntary 
movements  which  cause  the  development  of  parallax.  This  process  is  prob- 
ably one  of  the  most  important  in  producing  the  monocular  effect  of 
depth. 

9.  By  the  effort  of  accommodation  required  to  sharply  focus  an  object, 
lu  man  the  accommodation  is  found  by  experiment  to  give  little  or  no  percep- 
tion of  depth,  possibly  because  the  function  is  involuntary.  It  is  thought 
that  in  birds,  in  which  the  ciliary  muscles  are  striated  and  are  under  voluntary 
control,  the  accommodation  may  give  valuable  information  of  distance. 

All  the  above  factors  operate  together  to  produce  an  appreciation  of 
distance  which  as  a  result  of  experience  reaches  a  very  high  order,  and  with 
the  exception  of  the  last  two,  are  used  by  the  artist  to  produce  the  effect  of 
solidity  and  realness.  Any  good  picture  shows  us  that  the  result  can  be  very 
convincing. 

STEREOSCOPIC  VISION  is  the  binocular  perception  of  depth.  It 
consists  of  all  the  factors  which  operate  in  the  case  of  each  eye  separately, 
and  in  addition  uses  : 

I.  The  convergence  ol  the  eye  axes  which  is  necessary  in  order  in  cause 
images  of  near  objects  to   form  on  the  fovea  simultaneously. 

"2.  The  dissimilarity  between  the  images  which  are  formed  on  the  two 
retina-. 

That  convergence  has  very  little  effect  on  the  perception  of  distance 
can  he  proved  by  placing  weak  prisms,  either  base  in  or  base  out,  in  front  of 
the  eyes  and  in  this  way  changing  the  convergence  of  the  eye  axes  without 
changing  any  other  condition.  It  is  found  that  the  apparent  positions  of 
objects  are  unaffected. 

That  there  is  dissimilarity  between  the  images  formed  on  the  retina  can 
be  easily  proved  by  experiment.  Thus  if  the  gaze  be  directed  towards  a 
distant  point,  and  the  finger  be  held  a  short  distance  from  the  nose,  the  finger 
appears  to  be  to  the  right  of  the  distant  point  with  the  right  eve  and  to  I  he 
left  with  the  left.  If  two  photographs  be  taken  of  the  same  scene,  but  with 
the  camera,  for  the  second  photograroh,  three  inches  to  one  side  of  its  posit  ion 
for  the  first,  it  is  found  that,  when  the  two  negatives  are  placed  so  that 
objects  on  the  horizon  correspond,  there  is  a  lateral  difference  of  position 
in  the  case  of  all  other  objects  situated  nearer  to  the  camera.  Measurement 
shows  that  the  nearer  the  object  the  greater  the  difference  in  position. 
this  is  the  case  it  is  clear  that  only  images  in  one  plane  can  be  formed  on 
corresponding  retinal  points  ;  images  in  all  other  planes  must  fall        points 


592 


PHYSIOLOGY 


Fig.  .'41  >< >.  The  eyes  are  directed  t"  the  point  6.  A  thread  hung  obliquely  at  a 
under  these  circumstances  gives  rise  to  the  images  shown  in  the  upper  figures 
— i.e.  two  images  which  do  not  lie  on  corresponding  points.  Nevertheless  the 
thread  is  seen  as  single. 


which  are  discrepant.  Two  questions  therefore 
arise:  (1)  do  we.  see  such  objects  doubled? 
(2)  if  we  see  a  single  image  only,  is  it  because 
one  of  the  images  is  displaced  from  conscious 
ness  by  the  antagonism  of  the  other  ?  An 
answer  is  given  by  the  following  experiment : — 
a  Brewster's  stereoscope  is  taken,  the  optical 
arrangement  for  which  is  shown  in  Fig.  302.     At 


Yy 


Fig.    30i.      To    show    the 

difference  in  the  images  of  m 
truncated  pyramid  as  given 
by  the  right  and  left  eyes. 

B  and  B  two  similar  lantern  slides  are  placed  which  show-  a  view  of  any 
distant  objects.  On  looking  through  the  instrument  at  the  point  S  the  direc- 
tions of  the  rays  are  changed  so  that  the  images  of 

the  slides  are  seen  to  overlap  one  another.     By  shift-  § 

ing  one  of  the  slides  the  images  may  be  made  to  fall 
on  corresponding  points  of  the  retinae,  and  they  then  /   \ 

form  a  single  combined  picture.  In  front  of  these 
slides  are  now  placed  another  pair  of  slides  which 
show  the  photograph  of  an  index  mark.  If  the 
indices  are  adjusted  so  that  they  occupy  correspond- 
ing positions  in  relationship  with  the  objects  on  the 
slides  below  them,  on  looking  into  the  instrument 
it  will  be  seen  that  these  marks  appear  to  lie  in  the 
same  plane  as  the  distant  objects  placed  on  the 
slides  below  them.  If  one  of  the  index  marks 
be  moved  towards  the  axis  of  the  instrument,  it 
will  be  seen  on  looking  into  the  eyepieces,  that  the 
indices  now  appear  to  lie  in  a. plane  considerably  in 


Fig.  302.     Brewster's 


BINOCULAB  VISION  593 

front  of  their  previous  position,  in  fact  that  the  closer  they  are  placed  to- 
gether, the  nearer  do  they  appear  to  the  observer.  But  the  indices  do  not 
show  double  images,  unless  they  are  moved  a  considerable  distance  to- 
gether, and  then  the  effect  of  distance  ceases.  If  one  of  the  index  slides 
be  removed  and  the  other  be  moved  towards  and  away  from  the  axis  of 
the  instrument,  the  index  is  not  found  to  shift  its  plane  towards  or 
away  from  the  instrument.  This  shows  that  for  position  to  be  appreciated 
both  images  must  be  presented  to  consciousness  simultaneously  without 
appearing  double. 

THE  ACUITY  OF  STEREOSCOPIC  VISION  has  been  investigated  in  such  a 
way  that  other  factors  which  normally  assist  distance  perception  were  excluded.  Two 
methods  have  been  used  :  (1)  to  adjust  the  position  of  a  thread  which  lies  between  and 
parallel  with  two  other  threads  until  they  all  appear  at  the  same  distance  from  .the 
observer ;  (2)  to  observe  the  fall  of  small  coloured  bodies  of  unknown  size,  and  then  to 
state  the  position  of  the  line  of  fall  in  relationship  with  a  fixation  mark.  The  former 
method  at  2  metres  distance  shows  an  average  error  of  1-5  mm.,  the  latter  method  at 
the  same  distance  an  error  of  40  mm.  The  difference  between  the  results  of  the  two 
methods  is  considerable  ;  but  it  should  be  noted  that  in  the  fall  method  the  object 
is  seen  only  for  -02  sec.  If  in  the  thread  method  the  threads  be  placed  horizontal  it 
is  found  that  the  appreciation  of  distance  is  greatly  impaired.  The  greatest  acuity 
is  found  when  the  threads  are  vertical.  If  however  the  head  is  turned  so  that  the  line 
joining  the  two  eyes  is  vertical,  the  greatest  acuity  is  found  when  the  threads  are 
horizontal.  This  would  be  expected  if  the  appreciation  of  distance  is  greatest  when  the 
parallax  of  the  objects  at  the  two  eyes  is  greatest.  Experiment  shows  that  the  recog- 
nition of  position  in  relationship  with  a  definite  fixation  mark  is  much  more  accurate 
than  recognition  of  absolute  distance  in  which  there  is  no  point  of  reference.  Thus  it 
is  well  known  how  inaccurate  the  estimation  of  the  distance  of  a  single  source  of  light 
at  night  may  be. 

HYPOTHESES  OF  DEPTH  PERCEPTION.  Javal's  view  was  that  the  move- 
ments of  the  eye  muscles,  which  are  necessary  in  order  to  direct  the  gaze  from  objects 
in  one  plane  to  those  in  the  next,  caused  impulses  to  travel  to  the  brain  which  are 
interpreted  in  terms  of  distance.  This  view  was  ruled  out  by  the  fact  that  images 
which  are  formed  on  the  retina  for  a  short  length  of  time  only  ('02  sec),  are  able  to 
be  perceived  in  relief. 

HERING'S  HYPOTHESIS  was  that  it  is  the  formation  of  similar  images  on  points 
of  the  retinae  that  do  not  correspond  which  causes  distance  perception.  If  the 
disparation  is  crossed  the  object  appears  nearer  than  the  fixation  mark  by  an  amount 
wlu'ch  depends  on  the  amount  of  the  disparation.  If  on  the  other  hand  the  disparation. 
is  uncrossed  the  object  is  recognised  as  being  further  away.  Hering  supposed  further 
that  crossed  disparation  acts  as  a  stimulus  to  convergence  and  accommodation,  while 
uncrossed  produces  the  reverse  effect.  We  may  now  inquire  how  this  hypothesis 
fits  in  with  the  facts.  To  commence  with,  if  depth  depends  on  disparatii  >n  it  is  clear  that, 
when  we  perceive  objects  lying  in  different  planes,  we  must  subconsciously  group  them 
according  as  they  fall  on  corresponding  retinal  points,  or  on  points  which  are  discrepant 
by  one,  two,  three  or  more  cone  widths,  and  whether  the  discrepancy  is  crossed  or 
uncrossed.  The  amount  of  the  discrepancy  must  be  some  whole  number  of  cone  widths, 
because  it  is  clearly  impossible  to  stimulate  half  a  cone  with  one  impression  and  tin- 
other  half  of  the  same  cone  with  a  different  one  and  obtain  two  distinct  sensations.  It 
is  clear  that  space  must  be  divided  so  far  as  stereoscopic  vision  is  concerned 
into  a  number  of  concentric  shells,  the  centres  of  which  correspond  with  the  position 
of  the  observer.  Now  the  thickness  of  these  shells  can  be  readily  calculated  :  at  1  i 
they  are  found  to  be  2  mm.  thick,  at  10  metres  200  mm.  thick,  and  at  100  metres  17 
metres   thick.     If    we    are   looking   at   a  fixation    mark   10   metres   away,    objects 

38 


594  PHYSIOLOGY 

100  mm.  nearer  to  and  100  mm.  further  from  the  observer  will  lie  in  the  thickness  of 
one  and  the  same  shell,  and  will  therefore  appear  the  same  distance  from  the  observer. 
Objects  between  100  and  300  mm.  nearer  to  the  observer  will  lie  in  the  shell  correspond- 
ing to  one  cone  discrepancy,  and  will  therefore  be  appreciated  as  being  at  a  different 
distance  from  the  observer,  appearing  nearer  if  crossed,  and  further  if  uncrossed.  The 
same  reasoning  applies  to  objects  at  other  distances.  If  this  calculation  is  correct 
it  should  be  necessary  to  place  objects  more  than  100  mm.  from  a  fixation  mark,  which 
is  itself  placed  at  10  metres,  in  order  that  a  difference  in  the  distance  from  the  observer 
should  be  appreciated.  Greet!  found  by  experiment  that  -,', , tli  the  distance  of  the 
fixation  mark  was  necessary  (i.e.  200  mm.),  the  observations  being  instantaneous  ones. 
If  time  be  allowed  for  prolonged  observation,  greater  accuracy  in  the  appreciation 
of  distance  is  obtainable,  because  different  points  of  fixation  can  be  used.  Suppose, 
for  example,  that  two  objects  20  mm.  apart  be  examined  at  a  distance  of  10  metres, 
under  instantaneous  observation  they  will  appear  identical  as  described  above ;  but  if 
the  examination  be  made  more  carefully,  it  will  be  found  that,  on  fixating  a  point  a  mean 
distance  of  100  mm.  away  from  the  objects,  the  distance  between  the  two  is  suddenly 
appreciated  because  the  demarcation  between  two  shells  now  falls  between  them.  It 
is  in  this  way  that  the  accuracy  of  extended  observation  becomes  greater  than  that 
obtainable  with  instantaneous.  The  limit  reached  by  experiment  is  stated  to  corre- 
spond to  a  displacement  at  the  retina  corresponding  to  the  ,V,th  diameter  of  a  cone. 
The  corresponding  values  for  the  acuity  of  stereoscopic  vision  would  be  iJiTth  those 
given  above,  namely  -2  mm.  at  1  metre,  -20  mm.  at  10  metres,  and  1  -7  mm.  at  100  metres. 
Hering's  view  would  therefore  appear  to  agree  well  with  the  results  of  experiment.  It 
remains  to  consider  the  type  of  cortical  mechanism  that  would  be  necessary 
for  the  estimation  of  the  discrepancy  between  the  images.  One  type  may  be  briefly 
described  as  follows  : — To  a  number  of  parallel  planes  in  the  left  side  of  the  cortex  are 
connected  the  terminal  ends  of  the  nerve  fibres  from  the  left  halves  of  the  two 
retinas.  At  the  middle  plane  fibres  from  exactly  corresponding  retinal  points  are 
connected  together.  At  planes  which  lie  superficially  to  the  middle  plane  are  connected 
other  terminations  from  the  same  fibres  but  with  a  crossed  lateral  discrepancy  of  one 
cone  in  the  1st  plane,  two  cones  in  the  2nd  plane,  three  cones  in  the  3rd  plane,  etc.  At 
planes  which  lie  deep  to  the  middle  one,  other  terminations  from  the  same  fibres  are 
connected  but  with  an  uncrossed  lateral  discrepancy  of  one,  two,  three,  etc.,  cones  as  the 
case  may  be.  On  looking  at  a  fixation  mark  on  a  uniform  background  therefore,  a 
series  of  impressions  of  the  mark  will  be  formed  on  all  these  planes,  but  in  the  central 
one  only  will  they  exactly  agree,  for  in  all  the  others  the  lateral  discrepancy  will  cause 
the  impressions  to  be  duplicated.  In  all  these  other  planes  there  will  thus  be  antago- 
nism, first  one  image  and  then  the  other  predominating.  When  these  images  are  com- 
bined in  consciousness,  the  stable  image  from  the  central  plane  will  suppress  the  unstable 
ones  from  all  the  other  planes,  the  result  being  a  single  picture  of  the  fixation  mark. 
If  there  are  in  front  of  the  fixation  mark  other  objects  lying  in  planes  at  different 
distances  from  the  observer,  the  impulses  sent  up  by  the  cones  to  the  cortical  plan 
will  not  correspond  at  the  central  plane,  because  their  images  no  longer  fall  on  corre- 
sponding points,  but  they  will  correspond  in  the  superficial  planes  where  the  discrepancy 
of  their  images  agrees  with  the  discrepancy  of  the  nerve  connections.  These  other 
planes  will  therefore  predominate  according  as  each  contains  the  identical  images, 
and  when  they  are  combined  in  consciousness  these  planes  will  suppress  all 
the  others.  Since  each  cortical  plane  represents  a  certain  lateral  discrepancy,  it 
must  also  represent  a  certain  distance  from  the  fixation  mark.  If  consciousness  recog- 
nises the  plane  in  which  stable  image  is  formed,  it  also  must  apjireciate  the  distance 
of  the  object  lying  in  that  plane  from  the  fixation  mark.  This  would  not  seem  any 
more  difficult  than  the  localisation  of  a  touch  on  the  skin.  So  far  as  we  are  able  to  judge 
there  is  nothing  inherently  impossible  in  the  arrangement  of  the  hypothetical  cortical 
mechanism  which  has  been  outlined  above,  and  therefore  Hering's  theory  would  appear 
to  be  very  plausible. 


PART  III 
HEARING 

PAGES 

Section  1. — Properties  of  sound    ..........     595 

,,        2. — Structure  of  Auditory  Apparatus  .......     600 

„        3. — Auditory  Sensations  .  ........     611 

SECTION  1 

PROPERTIES    OF    SOUND 

Sound  is  propagated  by  waves  consisting  of  alternate  compressions 
and  rarefactions  which  travel  through  the  medium.  Any  medium 
which  has  the  properties  of  elasticit}'  and  mass  can  conduct  sound ;  thus 
solids,  liquids  and  gases  are  all  efficient  conductors.  Since  sound  is  a  form 
of  wave  motion  it  exhibits  many  of  the  properties  which  are  found  in  the 
case  of  light,  namely  Reflection,  Refraction,  Diffraction,  etc.  But- 
owing  to  the  long  wavelengths  of  sound  waves  compared  with  those  of 
light,  the  effects  of  diffraction  are  relatively  of  greater  importance.  Therefore 
sound  does  not  form  sharp  shadows,  such  as  light  does,  and  is  found  to  bend 
round  obstacles  and  to  be  conducted  down  speaking  tubes,  etc.,  in  a  way  that 
would  be  impossible  if  sound  were  of  shorter  wavelength. 

SOURCES  OF  SOUND  are  so  well  known  to  us  that  the  fundamental 
property  of  a  source  of  sound  tends  to  be  forgotten,  namely  that,  to 
produce  sound,  motion  has  to  be  initiated  in  a  sound  conductor 
which  has  a  velocity  the  same  or  greater  than  that  of  the  trans- 
mission of  sound.  Thus  when  a  book  is  closed  with  a  snap,  the  book 
becomes  a  source  of  sound  when  the  velocity  at  which  the  air  is 
squeezed  from  between  its  pages  is  equal  to  the  velocity  of  sound  in  air.  A 
stick  stirred  in  water  becomes  a  source  when  the  ripples  (eddies)  it  produces 
have  the  necessary  velocity  to  cause  a  wave  motion.  Sounds  have  been 
divided  arbitrarily  into  two  classes,  namely  tones  and  noises ;  the  former 
produce  pleasant  and  the  latter  unpleasant  (harsh,  grating,  screeching,  etc.) 
sensations.  Between  the  two  extremes  fall  the  sounds  of  everyday  life. 
Thus  music  as  a  rule  consists  of  tones,  but  may  be  found  to  consist  of  chords 
which  examined  singly  could  be  grouped  as  noises.  And  so  at  the  other 
end  of  the  scale,  when  we  strike  a  single  stick  with  a  hammer  the  eft 
that  of  a  noise.  If  however  we  take  a  series  of  sticks  of  different  lengths 
and  strike  them  in  succession,  it  will  be  noticed  that  the  sound  produced  by 

595 


596  PHYSIOLOGY 

each  stick  corresponds  to  a  distinct  note,  and  tunes  may  be  played  on  such 
a   collection  of  sticks. 

SOUND  ANALYSIS  can  be  performed  in  a  number  of  ways ;  possibly  the 
simplest  method  is  to  record  the  excursions  of  a  flexible  diaphragm  on  a  rota- 
ting wax  cylinder,  as  in  the  phonograph.  When  thus  recorded,  sound  waves 
are  found  to  have  a  regular  sequence  when  they  consist  of  tones  and  an 
irregular  sequence  when  they  are  noises.  Sources  of  sound  which  produce 
the  former  therefore  vibrate  in  a  regular  manner  (for  example  the  limbs  of 
a  tuning-fork,  or  the  air  in  an  organ  pipe),  while  those  which  produce  the  latter 
vibrate  irregularly  (e.g.  a  cart  over  cobbles). 

INTENSITY  AND  PITCH.  In  a  similar  manner  loudness  or  intensity 
is  found  to  depend  on  amplitude  (as  in  the  case  of  light),  while  pitch  depends 
on  the  wavelength,  short  waves  having  a  high,  long  waves  a  low  pitch.  This 
can  be  proved  in  other  ways  :  thus,  if  a  violin  string  be  bowed  forcibly  the  ex- 
cursion of  its  string  at  each  vibration  is  greater  than  when  it  is  bowed  gently, 
and  the  amplitude  of  the  corresponding  alternating  waves  of  sound  varies 
in  proportion  to  that  of  the  vibrating  body  by  which  they  are  started.  By 
attaching  a  pointed  slip  of  paper  to  the  end  of  a  tuning-fork  and  so  record- 
ing its  vibrations  on  a  blackened  surface,  it  is  easy  to  see  the  connection 
which  exists  between  the  amplitude  of  vibrations  and  the  loudness  of  the 
sound  produced  by  the  vibrating  fork. 

That  the  pitch  of  a  tone  depends  on  tba  frequency  of  the  vibrations,  is 
shown  by  means  of  the  syren  and  the  klaxon.  As  the  speed  of  rotation 
increases,  and  therefore  also  the  number  of  impulses  imparted  to  the  air 
per  second,  so  the  note  appears  to  us  to  be  rising.  Since  sounds  of  high 
and  low  pitch  travel  with  the  same  speed,  the  distance  between  the 
waves  decrease  as  the  number  of  impulses  per  second  increases. 

LIMITS  OF  PITCH.  The  ear  is  unable  to  perceive  tones  the  pitch 
of  which  falls  above  or  below  certain  fairly  well-defined  limits.  If 
the  number  of  vibrations  is  less  than  about  thirty  per  second  no  musical 
tone  is  produced,  the  individual  vibrations  being  perceived  as  a  series  of 
pulses  in  the  surrounding  air,  and  it  is  only  when  we  increase  the  number 
to  about  forty  per  second  that  we  are  able  to  appreciate  the  pitch  of  the 
note  produced.  As  the  number  of  vibrations  per  second  is  increased  the 
note  rises  steadily  without  break  till  we  arrive  at  40,000  to  50,000  vibrations 
per  second.  Above  this  number  of  vibrations  the  human  ear  is  incapable 
of  perceiving  any  note  at  all,  though  it  is  probable  that  small  animals  can 
perceive  notes  still  higher  in  the  scale.  In  music  neither  the  lowest  nor 
the  highest  tones  are  used.  The  lowest  tone  of  large  organs,  that 
of  the  sixty-four  foot  pipe,  is  1 6  vibrations  per  second,  and  one  can  hardly 
speak  of  its  effect  as  that  of  a  musical  tone.  The  highest  notes  employed 
in  music  are  «4  and  c5  with  3520  and  4224  vibrations  per  second  on  the 
piano,  and  d5  with  4752  vibrations  on  the  piccolo  flute.  In  music  therefore 
we  only  employ  between  40  and  4700  vibrations  per  second,  i.e.  about 
seven  octaves. 

SOUND   AUGMENTORS.    Experiment  shows  that  the  intensity  of  the 


PROPERTIES   OF  SOUND  597 

tone  produced  by  a  sound  source  can  be  considerably  increased  by  the  use 
of  sound  augrnentors.  These  are  called  resonators,  sounding  boards  or 
trumpets  according  to  the  form  they  take  or  the  sound  source  (musical 
instrument)  to  which  they  are  applied.  If  from  any  string  instrument 
(e.g.  violin)  the  box  be  removed,  the  tones  generated  are  found  to  be 
greatly  reduced  in  intensity.  The  function  of  these  sound  amplifiers  appears 
to  be  to  transmit  the  vibrations  of  the  source  (e.g.  the  stretched  wire)  to  the 
greatest  possible  volume  of  air,  i.e.  to  turn  into  sound  as  much  of  the  kinetic 
energy  of  the  vibrating  wire  as  possible.  In  the  case  of  the  trumpet  or  horn, 
there  is  in  addition  the  effect  of  increasing  the  volume  of  sound  in  some  ch<  isen 
direction  at  the  expense  of  that  in  others.  This  effect  is  well  illustrated  in 
the  gramophone.  In  most  musical  instruments  the  amplifier  must  be 
capable  of  responding  to  a  large  range  of  tones  indifferently,  and  the  more 
perfectly  it  can  do  this  the  better  is  the  instrument.  Such  perfection  is  diffi- 
cult to  obtain,  and  more  usually  it  is  found  that  in  spite  of  all  care  one  note 
is  accentuated  more  than  others,  e.g.  '  the  wolf  note  '  of  the  violin.  Sound 
amplifiers  for  the  reed  stops  of  the  organ  are  on  the  contrary  made  as  sharply 
selective  as  possible,  in  order  that  of  the  many  tones  emitted  by  the  vibrating 
reed,  the  chosen  one  shall  alone  be  augmented.  This  form  of  amplifier  is 
called  a  resonator,  although  the  term  is  strictly  speaking  applicable  to  other 
classes  of  sound  amplifier,  e.g.  the  sounding  board.  This  power  of 
augmenting  one  chosen  tone  has  great  value,  because  in  a  musical  chord  it  is 
possible  at  once  to  detect  the  presence  of  any  particular  tone,  by  ascertaining 
whether  its  resonator  responds  when  the  chord  is  sounded.  For  such  analysis 
the  resonators  of  Helmholtz  are  generally  employed.  These  are  hollow 
vessels  open  at  one  end  and  haying  a  tube  at  the  other  to  which  the  ear  may 
be  applied.  A  series  of  graduated  sizes  are  used,  each  of  which  has  a  definite 
period  of  vibration  (pitch). 

TIMBRE  OR  QUALITY.  When  the  same  note  is  sounded  on  different 
instruments,  i.e.  tuning-fork,  violin,  piano,  trumpet,  human  voice,  every 
person,  whether  he  has  an  educated  musical  ear  or  not,  can  say  at  once  what 
kind  of  instrument  is  being  used.  This  fact  shows  that  the  sound  wave  pro- 
duced by  these  instruments  must  differ,  altogether  apart  from  any  differences 
in  amplitude  or  in  number  of  vibrations  per  second,  and  if  the  sound  waves 
produced  by  these  instruments  be  recorded  an  actual  difference  is  found  in 
the  shape  of  the  curve. 

If  a  stretched  wire  be  plucked  so  as  to  set  it  into  transverse  vibrations  it 
will  give  out  a  certain  note,  dependent  on  its  length,  its  thickness,  and  the 
tension  to  which  it  is  subjected.  If  its  length  be  halved  it  will  give  out  a 
note  which  is  of  double  the  number  of  vibrations  per  second.  If  only  one- 
third  of  the  wire  be  set  into  vibrations  the  sound  wave  produced  will  have 
three  times  the  number  of  vibrations  of  that  of  the  whole  string.  When  the 
string  is  free  to  vibrate  as  a  whole  the  segments  of  it  tend  to  vibrate  even 
while  the  whole  string  is  vibrating.  If  therefore  we  take  the  note  given  out 
by  the  whole  string,  the  '  fundamental  tone'  as  corresponding  to  132  vibra- 
tions per  second,  there  will  also  be  a  series  of  notes  superadded  to  the  fimda- 


598  PHYSIOLOGY 

mental  tone  with  vibrations  per  second  in  the  ratio  of] ,  2,  3,  4,  5,  and  6,  etc. 
Thus  if  the  fundamental  tone  be  c,  the  overtones,  or  harmonics,  will  be 
produced  as  is  shown  below  : 


-a 


12  3  4  5  6  7  8  9  10 

Vibrations  per  Second 

132    2x132        3x132  4x132      5x132        6x122      7x132        8x132         9x132  10x132 

Nearly  all  musical  instruments,  as  well  as  the  apparatus  for  producing 
the  human  voice,  resemble  a  stretched  wire  in  giving  out  overtones  in  addi- 
tion to  the  fundamental  tones,  and  the  difference  in  the  quality  of  various 
instruments  is  chiefly  determined  by  the  varying  predominance  of  the 
different  overtones.  In  some  the  higher  overtones  may  be  most  marked, 
in  others  only  the  lower  overtones.  The  tuning-fork  is  practically  the 
only  instrument  the  note  of  which  is  pure,  i.e.  free  from  harmonics  or  over- 
tones. It  must  be  remembered  that  these  different  tones  arrive  at  the 
external  ear  simultaneously.  We  do  not  have  some  particles  of  air  vibrating 
at  one  rate  and  other  particles  at  another  rate,  but  all  the  simple  vibrations 
of  which  each  component  tone  is  composed  are  combined  together  to  form  a 
compound  wave,  the  shape  of  which  differs  according  to  the  constituent 
vibrations  of  which  it  is  made  up,  and  to  the  time  relationship  (phase)  between 
them. 

Thus  in  the  diagram  (Fig.  303)  the  wave  shown  by  the.  continuous  line 


Fig.  303.     d,  a  compound  sound  wave,  which  may  be  analysed  into  a,  the 
fundamental  tone,  and  b  and  c,  the  first  and  second  overtones.     (Hensen.) 

is  compounded  of  the  series  of  simple  vibrations  represented  by  the  different 
dotted  lines.  The  component  fundamental  overtones  and  harmonics  can 
be  readily  identified  in  a  tone  experimentally  by  employing  the  series  of 
resonators  described  above.  By  practice  it  is  possible  to  train  the  ear  to 
recognise  strong  overtones  without  the  use  of  resonators. 


PROPERTIES   OF  SOUND  599 

THE   ORGAN   OF   HEARING 

From  a  knowledge  of  the  fundamental  properties  of  sound  it  is  possible 
to  infer  the  probable  features  of  the  organ  of  hearing.  In  its  simplest  variety 
the  organ  would  take  the  form  of  a  sounding  board  or  diajuhragm  which  would 
be  set  into  vibration  by  the  incident  sound  waves.  The  vibrations  of  this 
plate  would  be  identified  by  touch  cells  similar  to  those  found  in  he  skin. 
which  would  be  so  placed  that  the  diaphragm  during  its  motion  should  come 
into  contact  with  them.  Such  an  apparatus  would  respond  to  and  estimate 
the  total  intensity  of  sound.  To  identify  the  pitch  a  series  of  resonators 
woidd  be  required,  each  of  which  would  be  sharply  tuned  to  one  of  a  series 
of  tones.  Of  the  many  types  of  resonator  that  could  be  employed  a  series 
of  stretched  wires  would  appear  to  be  the  simplest  and  most  compact.  The 
receiving  apparatus  would  therefore  take  the  form  of  a  harp  with  a  touch 
cell  and  its  respective  nerve  attached  in  close  approximation  to  every 
chord. 

In  order  that  such  a  mechanism  may  be  formed  of  organic  material 
and  be  kept  nourished  during  life,  it  is  necessary  that  it  be  immersed  in  a 
liquid  similar  to  that  which  bathes  the  eye  media.  The  sound  waves  must 
therefore  be  transmitted  from  the  air  to  this  fluid.  In  order  that  this  may 
occur  it  is  necessary  that  the  sound  waves  reach  the  apparatus  either  (1) 
through  the  walls  of  the  chamber  containing  the  apparatus,  i.e.  bone  conduc- 
tion, or  (2)  through  a  membrane  separating  the  liquid  from  the  air,  or  (3)  • 
by  means  of  suitable  levers  which  would  impart  to  the  liquid  the  vibration 
of  an  external  diaphragm.  The  advantage  of  the  latter  method  would 
be  that  the  intensity  of  sound  reaching  the  apparatus  could  be  considerably 
increased.  This  desirable  result  could  be  still  further  achieved  by  concen- 
trating the  sound  waves  on  to  the  diaphragm  by  means  of  a  trumpet  and  by 
causing  the  trumpet  to  be  adjustable  in  different  directions.  The  position 
of  the  source  of  sound  could  then  be  ascertained. 

Such  an  organ  of  hearing  would  therefore  consist  of  three  different  parts  : 

(1)  the  horn  or  trumpet  with  its  adjusting  muscles,  called  the  external  ear ; 

(2)  the  diaphragm  and  levers  for  receiving  the  sound  vibrations  and  for 
transmitting  them  to  the  internal  mechanism,  called  the  middle  ear ;  and  (3) 
the  internal  mechanism  consisting  of  the  resonators  with  their  respective 
touch  cells  and  nerves  called  the  internal  ear. 


SECTION   II 
STRUCTURE    OF    AUDITORY    APPARATUS 

EXTERNAL    EAR 

• 

The  external  ear  consists  of  two  parts:  (1)  that  external  to  the  skull 
called  the  pinna  and  (2)  that  internal,  called  the  meatus.  The  pinna  in 
animals  is  a  horn-shaped  structure  which  is  provided  with  two  sets  of  muscles. 
The  immediate  response  to  a  slight  sound  is  a  pricking  of  the  ears  by  means 
of  the  intrinsic  muscles,  and  the  directing  of  the  orifices  towards  the  source  of 
sound,  through  the  action  of  the  extrinsic  muscles.  The  functions  of  the 
pinna  are  firstly  to  ascertain  approximately  the  direction  of  the  source  of 
sound,  and  secondly  to  concentrate  the  sound  waves  into  the  meatus.  It 
may  also  be  said  to  have  a  third  function,  namely  to  protect  the  internal  struc- 
tures; the  stiff  hairs  with  which  it  is  provided  must  prevent  to  a  considerable 
extent  the  entrance  of  foreign  bodies. 

In  man  the  pinna  is  undergoing  retrogression ;  not  only  has  it  lost  its 
trumpet  shape  but  also  it  has  become  almost  entirely  immobilised  from  disuse. 
It  is  improbable  therefore  in  man  that  pinna  has  any  power  of  accentu- 
ating sound  waves ;  this  is  borne  out  by  experiments  in  which  the  undulations 
are  filled  with  wax,  and  by  cases  in  which  the  pinna  has  been  cut  off. 

The  form  of  the  pinna  in  man  may  have  a  .slight  influence  in  the  judgment  of  the 
direction  from  which  sounds  proceed.  It  has  been  noticed  that  a  compound  tone 
changes  slightly  in  quality  as  its  position  in  relation  to  the  ear  is  altered.  This  is  partly 
due  to  the  fact  that  the  auricle  may  reflect  a  fundamental  tone  more  strongly  than 
the  partial  or  the  converse.  According  to  Rayleigh  this  difference  in  quality  is  deter- 
mined chiefly  by  the  fact  that  diffraction  of  the  sound  waves  occurs  as  they  pass  round 
the  head  to  the  ear  remote  from  the  source  of  the  sound,  so  that  the  partial  tones  reach 
the  two  ears  in  different  degrees  of  intensity  and  determine  a  difference  in  quality  of 
the  sound  as  heard  by  the  two  ears. 

THE  EXTERNAL  AUDITORY  MEATUS  in  man  is  about  one  inch  long  and 
directed  forwards,  inwards,  and  slightly  upwards.  Its  general  function,  other 
than  as  a  mere  conductor  of  the  sound  waves,  is  to  protect  the  delicate  vibrat- 
ing membrava  li/mpav  i  which  closes  its  inner  end.  This  it  does  partly  because 
of  its  narrow  tubular  shape  and  partly  owing  to  its  considerable  curvature. 
Opening  on  the  skin  of  the  meatus  are  special  sebaceous  glands  which  secrete 
a  yellow  wax  (cerumen)  with  bitter  taste  and  peculiar  odour.  The  wax  not 
only  protects  the  cuticle  of  the  ear  and  the  membrana  tympani  from  drying 
but,  together  with  the  hairs  at  the  orifice  of  the  meatus,  serves  to  repel 
insects  and  prevent  their  entering.  By  the  length  of  the  meatus  moreover 
the  drum  is  protected  from  draughts  and  its  temperature  is  maintained 
constant. 

600 


EXTERNAL  EAR 


601 


Fig.  3(14.     Diagrammatic  view  of  auditory  organ.     (After  Schapeb.) 
1,  auditory  nerve  ;  2,  internal  auditory  meatus  ;  3,  utricle  ;  5,  saccule  ;  fi,  canalis 
media  of  cochlea;    9,   vestibule  containing  perilymph:     12.   stapes;     13,   fenestra 
rotunda;    111.  incus;    18,  malleus;    17,  membrana  tympani;    Mi,  external  auditory 
meatus;  14,  pinna  of  external  ear  ;  23,  Eustachian  tube. 

In  animals  the  junction  between  the  pinna  and  meatus  is  so  fashioned  that 
1  he  orifice  can  be  restricted  by  means  of  a  constrictor  muscle.  This  permits 
the  intensity  of  sound  reaching  the  internal  mechanism  of  the  ear  to  be  con- 
trolled as  light  by  the  iris  in  the  case  of  the  eye. 

THE  MIDDLE   EAR 

This  consists  of  a  cavity  hollowed  out  of  the  temporal  bone,  which  com- 
municates externally  with  the  meatus,  internally  by  two  windows,  one  circu- 
lar and  the  other  oval,  with  the  series  of  chambers  forming  the  internal  car, 
below  by  means  of  a  long  duct  called  the  Eustachian  canal  with  the  throat. 
At  the  junction  with  the  meatus  is  a  special  bony  ring  to  which  is  attached  a 
thin  diaphragm,  the  membrana  tympani  (or  drum),  which  completely  closes 
the  orifice? 

THE  MEMBRANA  TYMPANI.     The    sound   waves    which    pass  down 
the  external  meatus  impinge  on  the  drum  of   the  oar  ami  set  this  into 
vibration.     The  vibrations  are  thence   transmitted   by   a   chain   of 
small  bones,  the  auditory  ossicles,  across  the  cavity  of  the  tympam 
the  fluid  which  bathes  the  terminations  of  the  auditory   nerve   in   the 
internal  ear.     Since  the  drum  of  the  ear  has  to  pick  up  and  trai 
vibrations  of  every  frequency,  and  to  reproduce  accurately  in  its  move- 
ment the  finest  variations  of  pressure  in  the  course  of  the  wave,  it  is 


602  PHYSIOLOGY 

essential  that  it  should  be  devoid  of  any  periodicity,  i.e.  a  tendency  to 
vibrate  at  a  certain  frequency.  If  such  periodicity  were  present  the  ear 
would  pick  out  and  magnify,  to  the  exclusion  of  the  other  overtones, 
some  particular  overtone  present  in  the  compound  tones  reaching  the  ear. 
The  perfect  aperiodicity  of  the  tympanic  membrane  is  secured  by  its 
structure  and  attachments.  The  membrane  is  composed  of  a  thin 
layer  of  fibrous  tissue  covered  externally  with  skin  and  internally  by  I  he 
mucous  membrane  of  the  tympanum.  To  its  inner  surface  along  its  whole 
length  is  attached  the  handle  of  the  malleus,  the  first  of  the  auditory  ossicles. 
This  attachment  of  an  elastic  membrane  to  a  mass  of  bone  would  itself  tend 
to  damp  any  vibrations  of  the  membrane.  By  the  attachment  of  the 
tendon  of  the  tensor  tympani  muscle  to  the  inner  surface  of  the  handle  of  the 
malleus,  the  middle  of  the  membrane  is  drawn  inwards,  so  that  it  forms  a  cone 
whose  walls  are  convex  outwardly.  The  membrane  is  built  up  of  circular 
and  radial  fibres,  the  circular  being  best  marked  towards  the  periphery. 
By  the  dragging  inwards  of  its  central  part  it  follows  that  the  tension  of  its 
constituent  fibres  varies  from  point  to  point  so  that  each  bit  of  the  membrane 
has  a  different  periodicity,  and  the  membrane  as  a  whole  be  aperiodic. 

By  exposing  the  tympanum  from  above  it  is  possible  with  a  micro- 
scope to  observe  the  actual  movements  of  the  handle  of  the  malleus  when 
sound  waves  fall  on  the  tympanic  membrane.  The  maximum  movements  at 
the  apex  of  the  cone  may  be  taken  as  about  '04  mm.,  but  sounds  are  easily 
audible  which  would  produce  movements  of  the  tympanic  membrane  quite 
imperceptible  under  this  method  of  examination. 

THE  OSSICLES.  Stretching  across  the  tympanum,  from  the  membrana 
tympani  to  the  outer  wall  of  the  internal  ear.  is  a  chain  of  ossicles,  which 
are  named  respectively  the  malleus,  the  incus,  and  the  stapes.  These  ossicles 
are  articulated  together,  so  that  a  movement  inwards  of  the  malleus  causes  a 
movement  inwards  of  the  base  of  the  stapes.  The  malleus,  or  hammer  bone, 
consists  of  a  thickened  head,  from  which  two  processes  run,  viz.  the  manu- 
brium, which  is  attached  to  the  tympanic  membrane,  and  the  processus 
gracilis,  by  which  it  is  anchored  to  the  walls  of  the  tympanic  cavity.  By 
means  of  three  ligaments  it  is  so  fixed  that  it  is  capable  of  rotating  only 
around  a  horizontal  axis,  which  passes  through  the  anterior  ligament,  the 
head  of  the  malleus,  the  body  of  the  incus,  and  the  short  process  of  the  incus. 
When  the  manubrium  is  pushed  inwards,  the  part  of  the  malleus  above  this 
axis  must  move  outwards.  The  incus,  sometimes  known  as  the  anvil  bone, 
is  articulated  with  both  the  stapes  and  the  malleus,  and  a  ligament  passes 
from  its  short  process  to  the  posterior  wall  of  the  tympanic  cavity.  The 
posterior  surface  of  the  rounded  head  of  the  malleus  fits  into  the  saddle- 
shaped  cavity  on  the  anterior  surface  of  the  incus,  while  the  tip  of  the  long 
process  of  the  incus  is  articulated  with  the  stapes.  Movement  inwards  or 
outwards  of  the  head  of  the  malleus  causes  rotation  of  the  incus  round  an 
axis  which  passes  from  the  tip  of  the  short  process  through  its  body.  Thus 
when  the  handle  of  the  malleus  moves  inwards  the  greater  part  of  the  body  of 
the  incus  and  of  the  head  of  the  malleus  moves  outwards  together,  while  the 


MIDDLE  EAE  603 

long  process  of  the  incus  moves  inwards.    The  stapes,  or  stirrup  bone,  is  fixed 
in  the  fenestra  ovalis  of  the  internal  ear.  in  the  inner  surface  of  the  tympanum. 


Fig.  305.  To  show  the  relations  of  the  malleus  and  incus  to  one  another.  The 
shaded  area  between  the  two  bones  shows  the  articular  surfaces  which  connect 
them.  The  overlapping  of  the  two  bones  at  the  lower  part  of  these  surfaces 
is  well  shown.  It  is  this  arrangement  which  causes  motion  to  be  conveyed 
from  one  to  the  other. 

by  the  annular  ligament.  It  is  placed  almost  at  right  angles  to  the  long 
process  of  the  incus,  and  therefore  is  pressed  into  the  foramen  ovale  when  this 
process  moves  inwards. 

THE  MUSCLES  found  in  the  tympanum  are  the  tensor  tympani,  which 
is  attached  to  the  handle  of  the  malleus,  and  the  stapedius  attached  to  the  base 
of  the  stapes.  The  tensor  is  innervated  by  a  motor  branch  of  the  5th  cranial 
nerve,  and  when  it  is  stimulated  it  draws  the  handle  of  the  malleus  inwards 
and  so  increases  the  tension  of  the  tympanic  membrane.  At  the  same  time 
the  plunger  of  the  stapes  is  displaced  into  the  oval  window,  thus  putting 
compression  on  the  contents  of  the  internal  ear.  The  contraction  of  the 
tensor  has  been  supposed  to  have  a  protective  function  and  has  been  com- 
pared to  the  sphincter  pupillae  (Helmholtz).  Others  hold  that  it  modifies 
the  response  to  low  and  medium  tones,  but  even  here  there  is  a  divergence  ol 
opinion,  because  while  some  hold  (I  think  correctly)  that  the  tensor  by  its 
contraction  decreases  the  natural  period  of  the  drum  and  thus  enables 
respond  to  rapid  changes  of  phase  and  high  tones,  others  have  held 
opposite  view.  Observation  shows  that  contraction  occurs  when  sounds 
(particularly  tones  of  high  pitch)  fall  on  the  drum,  and  that  the  contrai 
is  bilateral  even  if  the  stimulus  be  only  unilateral.  The  reflex  therefore 
travels  via  the  auditory  nerve  to  the  motor  centre  of  the  5th  nerve. 

Since  the  tensor  tympani  is  uncontracted  when  no  sounds  are  falling  on 


604  PHYSIOLOGY 

the  ear,  it  allows  the  drum  to  go  slack  and  therefore  tends  to  prevent  this 
membrane  from  becoming  stretched  through  being  continually  in  tension. 

The  stapedius  muscle  is  innervated  by  a  twig  from  the  facial.  Its  function 
is  problematical.  Some  say  it  antagonises  the  tensor  by  decreasing  the  ten- 
sion on  the  drum,  others  that  it  reduces  the  tension  on  the  contents  of  the 
internal  ear  by  reducing  the  pressure  of  the  stapes  on  the  oval  window. 
Hartridge's  view  is  that  the  function  of  this  muscle  is  to  cause  the  body  of 
the  incus  to  engage  with  the  spur  of  the  malleus  with  sufficient  force  to  pre- 
vent chattering  and  lost  motion  when  the  vibrations  are  being  transmitted 
from  one  bone  to  the  other. 

THE  EUSTACHIAN  CANAL  is  a  tube  about  35  mm.  in  length  which 
connects  the  middle  ear  with  the  pharynx.  Normally  it  is  kept  closed  in 
order  that  the  respiratory  rhythm  may  not  affect  the  pressure  in  the  tym- 
panum, and  that  the  noise  set  up  by  the  flow  of  air  and  the  voice  may  not 
be  heard.  When  the  canal  is  closed  the  middle  ear  becomes  a  closed  chamber 
which  appears  to  increase  the  response  to  low  tones.  Since  variations  in 
barometric  pressure  would  not  be  communicated  to  the  middle  ear  if  the 
canal  were  always  closed,  the  air  pressure  on  the  two  sides  of  the  drum  would 
be  found  to  vary.  This  is  avoided  by  a  periodic  opening  of  the  canal  which 
accompanies  the  act  of  swallowing.  When  the  throat  is  infected  the  inflam- 
mation often  spreads  to  this  canal  which  then  becomes  blocked  either  by 
mucus  or  the  swelling  of  its  mucous  lining.  The  air  in  the  middle  ear  is 
then  gradually  absorbed  and  the  difference  in  air  pressure  on  the  two  sides 
of  the  drum  decreases  its  response  to  sound,  and  the  affected  ear  thus  becomes 
partially  deaf. 

Temporary  deafness  also  occurs  if  the  barometric  pressure  is  suddenly 
altered  by  a  rapid  change  of  level  (as  in  an  aeroplane)  or  by  the  application 
of  external  pressure  (as  in  a  caisson  or  submarine).  The  deafness  is  however 
immediately  relieved  by  swallowing,  because  the  altered  pressure  is  communi- 
cated to  the  other  side  of  the  drum  through  the  opening  of  the  Eustachian 
canal. 

FUNCTIONS  OF  TYMPANUM.  The  function  of  the  tympanic 
apparatus  (consisting  of  drum,  bones  and  muscles)  is  to  transform 
the  energy  of  the  aerial  vibrations  incident  on  the  drum  into  a  series 
of  mechanical  movements  of  the  plunger  of  the  stapes,  by  which  the 
pressure  within  the  internal  ear  is  rapidly  varied.  The  evidence  may  be 
summarised  as  follows.  (1)  If  in  man  the  external  ear  be  made  to  form  a 
gas  chamber  which  is  connected  to  a  manometric  flame,  the  flame  shows 
vibration  when  sound  falls  on  the  drum,  which  could  only  be  caused  if  the 
drum  were  set  into  vibration.  (2)  If  the  drum  be  gilded  and  a  beam  of  light 
be  caused  to  fall  on  it,  the  extensions  of  the  beam  caused  by  vibrations 
of  the  drum  can  be  recorded  photographically,  and  are  found  to  accompany 
the  incidence  of  sound  waves.  (3)  If  to  the  chain  of  ossicles  a  light  writing 
lever  be  attached,  the  point  of  which  travels  over  a  rotating  smoked  drum, 
when  sounds  fall  on  the  drum  the  vibrations  are  recorded  showing  that 
the  ossicles  are  set  into  movement.     (4)  By  opening  the  middle  ear  from 


MIDDLE   EAR  605 

above  and  sprinkling  with  starch  grains  the  ossicles  as  they  lie  within  the 
movements  of  the  different  parts  can  be  readily  followed  under  a  low  power 
microscope.  When  the  drum  is  set  into  vibration  by  sound  waves  it  is  readily 
seen  that  the  whole  chain  of  ossicles  vibrates  so  as  to  convey  the  vibrations 
to  the  plunger  in  the  oval  window.  Many  experimenters  have  noted  the 
remarkable  way  in  which  the  apparatus  responds  to  vibrations  varying  very 
greatly  in  rate.  Tones  of  low  and  high  pitch  appear  to  be  recorded  with 
equal  impartiality  and  fidelity.  Experiment  therefore  confirms  our  sensa- 
tions which  show  that  the  ear  responds  to  vibrations  varying  from  40  to 
40,000  per  second.  It  is  stated  that  the  natural  period  of  the  ossicles  and 
drum,  owing  to  their  small  size,  is  very  much  more  rapid  even  than  4, ,,!,,,„ 
second,  and  it  is  because  of  this  that  the  system  is  able  to  respond  faithfully 
to  the  vibrations  of  longer  period  used  in  audition. 

Direct  observation  therefore  shows  that  the  ossicles  form  levers  which 
together  conduct  the  vibrations  from  the  drum  to  the  filunger  of  the  oval 
window.  It  is  necessary  to  consider  the  effect  of  this  lever  system 
on  the  amplitude  and  force  of  the  vibration.  Motion  is  applied  to  the  manu- 
brium of  the  malleus  and  is  communicated  to  the  long  process  of  the  incus. 
The  former  is  one  and  one-half  times  the  length  of  the  latter  and 
therefore  the  stapes  moves  with  two-thirds  the  amplitude  of  the  drum. 
If  the  levers  moved  without  friction  this  would  be  accompanied  by  an 
increase  in  the  force  of  the  vibrations  of  one  and  one-half  times.  But 
owing  to  the  air  which  surrounds  the  levers  and  thus  damps  their  vibration 
and  to  the  energy  required  to  set  them  in  vibration  on  account  of  their  mass, 
it  is  probable  that  the  force  of  the  vibrations  which  reaches  the  oval  window 
is  not  more  than  half  that  incident  on  the  manubrium.  The  drum  on  the 
other  hand  has  an  area  which  is  about  twenty  times  that  of  the  oval  window, 
and  the  energy  incident  on  the  drum  and  communicated  to  the 
manubrium  is  that  much  greater  than  if  the  sound  waves  were  incident  on 
the  oval  window  direct.  But  owing  to  the  energy  absorbed  by  the  levers  the 
magnification  is  probably  not  greater  than  ten  times,  that  is  one- third  of  the 
calculated  amount.  Two  other  features  of  the  chain  of  ossicles  should  be 
mentioned.  In  the  first  place  it  will  be  observed  that  the  axis,  about  which 
the  malleus  and  incus  rotate,  passes  through  the  bones,  so  that  the  big  mass 
formed  by  the  articular  surfaces  is  above  and  the  levers  below  the  axis  of 
rotation,  and  the  ossicles  are  approximately  balanced.  Secondly  the 
articulation  between  the  malleus  and  incus  is  saddle-shaped  and  there  is  a 
spur  on  the  malleus  which  engages  with  the  body  of  the  incus,  so  that, when  the 
tensor  tympani  muscle  relaxes  and  the  malleus  travels  outwards,  the  spur 
disengages  and  the  incus  is  therefore  not  forced  to.follow.  When  on  the  other 
hand  the  stapedius  muscle  is  in  tonic  contraction,  the  spur  is  in  engagement 
and  vibrations  are  therefore  communicated  from  one  bone  to  the  other.  J  i 
however  the  force  applied  is  excessive,  owing  for  example  to  a  box  on  the  ear, 
then  the  two  bones  separate  slightly  like  the  limbs  of  a  compass,  and  the  spur 
passes  the  body  of  the  incus  without  communicating  the  blow  to  it.  In 
this  way  rupture  of  the  annular  seal  between  the  plunger  of  the  stapes  and  the 
oval  window  is  prevented. 


606  PHYSIOLOGY 

INTERNAL    EAR 

Within  the  petrous  portion  of  the  temporal  bone  are  two  mechanisms 
anatomically  in  close  relationship  but  physiologically  entirely  separate. 
One  of  these  mechanisms,  which  is  called  the  cochlea,  belongs  to  the  auditory 
organ ;  the  other,  called  the  vestibule,  consists  of  a  series  of  organs  which  con- 
cern equilibration  and  have  no  connection  with  hearing. 

THE  LABYRINTHS  lie  one  within  the  other ;  the  outer  or  osseous 
labyrinth  is  hollowed  out  of  the  petrous  portion  of  the  temporal  bone,  and  it 
conforms  roughly  with  the  shape  of  the  membranous  labyrinth  within  it. 
Between  the  two  is  liquid  so  that,  as  in  the  case  of  the  brain,  no  constraint 
is  put  by  the  external  wall  on  the  soft  structures  which  it  contains.  This 
liquid  is  called  perilymph.  The  membranous  labyrinth  consists  of  a  series 
of  hollow  ducts  and  sacs  which  are  filled  with  liquid  called  the  endolymph. 
The  parts  of  the  membranous  labyrinth  and  the  relative  positions  which 
they  occupy  are  shown  in  Fig.  306.  From  before  backwards  they  will  be 
seen  to  consist  of  a  spiral  tube  called  the  cochlea,  the  saccule,  and  the  utricle 
to  which  are  connected  the  three  semicircular  canals. 

Of  these  structures  the  cochlea  alone  is  concerned  with  hearing,  as  the 
following  evidence  shows. 

(1)  Destruction  of  the  utricle  and  canals  causes  disturbed  equilibration, 
nystagmus  and  vomiting,  but  no  deafness. 

(2)  Destruction  of  the  cochlea  causes  deafness  but  no  disturbance  of 
equilibration. 

(3)  Fishes,  in  which  no  evidence  of  hearing  can  be  found,  possess 
utricle,  saccule  and  canals,  but  no  cochlea. 

THE  COCHLEA  is  a  tube  20  to  30  mm.  long  which  is  spirally  wound 
round  a  cone  of  bone  called  the  modiolus,  through  the  centre  of  which  enters 
the  auditory  nerve.  From  the  modiolus  a  spiral  lamina  of  bone  extends 
about  two-thirds  the  way  across  the  spiral  cochleal  canal  so  as  partially  to 
divide  it  into  two  equal  portions.  From  the  outer  edge  of  this  lamina  two 
membranes  extend  to  the  walls  of  the  canal,  so  that  the  latter  is  divided  through- 
out its  length  into  three  separate  ducts.  The  upper  duct  is  called  the  scala 
vestibuli,  the  middle  duct  between  the  two  membranes  the  scala  media, 
and  the  lower  the  scala  tympani.  The  two  membranes  dividing 
off  these  ducts  are  quite  different  in  structure  ;  whereas  the  upper,  called 
Reissner's  membrane,  is  a  thin  layer  of  cells  only,  the  lower  is  of  complicated 
arrangement  and  is  called  the  basilar  (base)  membrane.  To  the  latter  is 
attached  a  series  of  sensitive  hair  cells,  called  the  organs  of  Corti, 
connected  to  the  fibres  of  the  auditory  nerve,  which  run  through  the  osseous 
spiral  lamina  to  the  body  of  the  modiolus.  To  the  upper  edge  of  the  spiral 
lamina  is  attached  a  projecting  ledge  called  the  lamina  tectoria ;  this  is  so 
mounted  that  it  projects  over  but  probably  does  not  quite  touch  the  tips  of 
the  hair  cells.  If  however  the  basilar  membrane  is  displaced  upwards, 
the  hairs  touch  the  membrana  tectoria,  and  the  resulting  stimuli  are  com- 
municated to  the  auditory  nerve.  To  prevent  damage  to  the  hairs,  owing  to 
excessive  motion  of  the  basilar  membrane,  rods  of  Corti  are  placed  between 


INTERNAL  EAR 


607 


the  hair  cells  in  such  a  way  that,  when  they  come  in  contact  with  the  meni- 
brana  tectoria,  further  movement  of  the  basilar  membrane  is  prevt'iitccl. 


Fig.  306.    The  membranous  labyrinth. 

cm,    canalis     or   scala    media    of   the 

cochlea;  s,saeeule;  a, utricle;  sc.semi 

circular  canals. 


Fia.  307.     Vertical  section  through  the 
cochlea. 


The  way  in  which  motion  is  imparted  to  this  membrane  by  the  ossicles 
may  be  described  as  follows.  The  osseous  labyrinth  communicates  with  the. 
middle  ear  by  means  of  two  openings,  the  oval  window  and  the  circular  win- 
dow. The  oval  window  connects  with  the  upper  of  the  three  cochlear  canals. 
via  the  vestibular.  The  upper  canal  is  therefore  called  the  scala  vestibuli. 
The  lower  canal  connects  with  the  round  window  only,  and  since  the  round 
window  is  fitted  with  a  membrane,  the  canal  gets  the  name  scala  tympani 
(drum  or  membrane).  Fitting  into  the  oval  window  is  the  plunger  of  the 
stapes,  and  between  the  two  is  the  annular  seal  which  permits  motion  of  the 
plunger   without   allowing   escape   of   the   perilymph   from   the  labyrinth. 


Fig.  30S.     Vertical  section  of  the  first  turn  of  the  human  cochlea.     (G.   R) 
s.v.  scala  vestibuli :   .«.«,  scala  tympani  ;   </.<-,  scala  media  ;   sp. I,  spiral  lamin 
fibres;    l.gp,  spiral  ligament;    str.v,  stria  vascularis;    s.ap,   spiral   sulcus;    I' 
Reissner's  membrane;    /.  limbus  lamina-  spiralis;    m.t,    membrana  tectoria  ;    K '.  tunnel 
of  Corti ;    b,m.  basilar  membrane;    h.i,  h.e,  internal  and  external  hair-cells. 


608  PHYSIOLOGY 

The  circular  window  is  also  closed  by  its  membrane,  in  order  that  leakage  of 
perilymph  may  be  prevented.  When  the  plunger  of  the. incus  is  moved 
inwards  under  the  influence  of  sound  waves  on  the  drum,  the  perilymph 
being  incompressible  is  driven  inwards  into  the  vestibule.  From  the  vestibule 
a  corresponding  volume  of  liquid  is  displaced  into  the  scala  vestibuli  of  the 
cochlea.  This  drives  Reissner's  membrane  downwards,  and  thus  increases 
the  pressure  on  the  endolymph  in  the  scala  media.  The  basilar  membrane 
therefore  moves  downwards  and  the  hair-cells  are  drawn  further  away  from 
the  membrana  tectoria.  But  this  movement  of  the  basilar  membrane  presses 
on  the  fluid  contents  of  the  scala  tympani  which  communicates  with  the 
round  window,  and  therefore  causes  bulging  of  the  membrane  closing  that 
aperture.  Movement  inwards  of  the  plunger  is  therefore  accompanied  by 
movement  downwards  of  the  basilar  membrane  and  movement  outwards  of 
the  membrane  of  the  round  window  and  vice  versa.  Vibrations  of  the  ossicles 
are  in  this  way  communicated  to  the  basilar  membrane  and  to  the  hair- 
cells,  causing  stimulation  of  the  auditory  nerve.  The  basilar  membrane  is 
composed  principally  of  radial  fibres,  and  varies  in  width  from  end  to  end 
of  the  cochlea.  The  way  in  which  these  fibres  vibrate  under  the  influence  of 
sound  vibrations  will  be  considered  in  the  next  section,  but  one  further  point 
remains  for  consideration  here,  namely  the  compensation  of  the  cochlea 
against  the  effects  of  gravity  and  acceleration.  This  may  be  explained  by 
considering  a  cochlea  formed  of  a  straight  tube  having  the  fenestra  rotunda 
at  one  end  and  the  fenestra  ovale  at  the  other,  the  basilar  membrane  forming 
a  diaphragm  in  the  middle.  If  this  tubular  cochlea  were  so  placed  in  the 
skull  that  the  two  windows  were  at  the  same  level,  gravity  acting  on  the 
contained  liquid  would  not  cause  flow  to  occur  to  either  end.  But  if  the  head 
were  tilted  so  that  one  window  was  below  the  other,  the  fluid  would  tend 
to  run  towards  the  lower  window.  This  would  draw  the  basilar  mem- 
brane over  to  that  side,  causing  either  the  distance  between  the 
hair-cells  to  decrease  so  that  they  would  come  into  contact  with  the 
tectorial  membrane  and  thus  cause  stimulation  of  the  auditory  nerve  with 
a  sensation  of  sound,  or  such  an  increase  in  the  distance  that  response  to  feeble 
sounds  would  be  impaired.  It  will  be  seen  at  once  that  such  an  effect 
of  gravity  would  seriously  reduce  the  efficiency  of  the  organ  of  hearing. 
Compensation  could  be  to  a  considerable  extent  effected  by  bending  the  tube 
so  that  the  two  windows  were  as  close  together  as  possible.  The  hydrostatic 
pressure  would  thus  be  reduced  to  its  smallest  amount  in  the  event  of  the 
head  being  tilted  so  as  to  bring  one  window  vertically  over  the  other. 
Such  a  bent  tube  would  be  compensated  to  a  considerable  extent  against 
gravity  and  linear  accelerations  in  different  directions,  but  not  against  angu- 
lar acceleration,  for  on  turning  the  head  quickly  from  side  to  side  a  sound 
would  be  generated  in  the  ears.  In  order  to  compensate  for  this  effect  it  is 
necessary  to  bring  the  two  limits  of  the  tube  in  close  apposition  so  that  they 
form  a  U.  A  still  higher  degree  of  correction  would  be  obtained  if  the  U 
tube  were  now  wound  into  a  close  spiral.  But  if  the  two  limits  of  the  U 
tube  were  joined  with  the  basilar  membrane  forming  the  diaphragm  between 


INTERNAL    EAR 


609 


them,  a  very  close  mechanical  model  o£  the  cochlea  would  have  been 
obtained.  The  peculiar  shape  of  the  cochlea  would  therefore  appear  to  be 
explained  on  the  supposition  that,  it  is  compensated  against  accelerations 
and  gravity. 

THE  ORGAN  OF  CORTI.  The  end-organ  of  the  auditory  nerve 
is  represented  by  the  organ  of  Corti,  which  rests  on  the  basilar  membrane 
(Fig.  300).     It.  consists  of  a  double  row  of  stiff  cells,  the  inner  and  outer  roils 


Fig.  309.     Section  through  the  end-organ  of  the  auditory  nerve  in   the  cochlea 
(organ  of  Corti). 
BM,  basilar  membrane  ;   c,  canal  of  Corti ,   rc,  rods  of  Corti ;   ih  and  oh,  inner 
and  outer  hair-cells ;  sc,  sustentacular  cells  ;  An,  auditory  nerve  ;  mt.  membrana 
tectoria. 

of  Corti,  which  run  throughout  the  whole  length  of  the  scala  media  and  are 
surrounded  by  sense  epithelium,  the  hair-cells.  On  the  inner  side  of  the  rods 
of  Corti  there  is  a  single  row,  on  the  outer  side  three  rows  of  hair-cells.  Between 
the  hair-cells  are  the  sustentacular  cells,  or  cells  of  Deiters,  the  peripheral 
processes  from  which  join  together  so  as  to  form  a  reticulate  membrane 
over  the  hair-cells,  the  hairs  themselves  projecting  through  orifices  in  the 
membrane.  Resting  on  the  upper  surface  of  the  membrana  reticularis  is 
the  membrana  tectoria.  To  this  membrane  is  often  ascribed  a  damping 
effect  on  the  vibrations  of  the  structures  below.  Any  movement  of  the  basilar 
membrane  would  be  transmitted  to  the  rods  of  Corti,  and  by  these  to  the 
overlying  hair-cells.  With  every  vibration  these  would  move  in  the  line 
of  their  long  axis  so  that  their  hairs  would  move  up  and  down  and  possibly 
strike  against  the  under  surface  of  the  membrana  tectoria. 

Other  views  have  however  been  advanced  as  to  the  way  in  which  the  hair 
cells  become  stimulated.  Thus Wrightson  states  that  there  is  a  to  and  fro 
movement,  between  the  hair-cells  and  the  membrana  tectoria  so  that  the 
hairs  are  bent  first  to  one  side  and  then  to  the  other.  Keith  suggests  on  I  In- 
other  hand  that  the  hairs  are  embedded  in  the  membrana  tectoria  and  thai 
the  stimuli  are  set  up  by  the  pulling  and  bending  of  the  hairs  which  must 
occur  when  the  basilar  membrane  is  moved.  Further  research  is  required 
to  elucidate  this  point.  The  fibres  of  the  auditory  nerve  pass  up  through 
the  column  of  the  cochlea,  through  the  bipolar  ganglion  cells  which  form  the 
spiral  ganglion,  and  then  out  along  grooves  in  the  spiral  lamina  to  end  in 
arborisations,  partly  in  the  inner  hair-cells  and  purl  h  among  I  he  outer  hair- 
cells. 

NUTRITION    OF    COCHLEA.    The  organ  of  Corti  and  the  surrounding 
tu'ivs  appear  to  obtain  nutrition  from  three  different  sources.    (I)  Arterial  twig    pa 

39 


610  PHYSIOLOGY 

with  the  cochlear  branch  of  the  auditory  nerve  and  traverse  the  foramina  in  the  spiral 
lamina  alongside  the  outgoing  nerve  fibres,  to  join  with  several  arteries  which  run 
round  the  inside  of  the  cochlea.  The  largest  of  these  vessels  is  found  in  the  scala  media. 
Minute  branches  pass  from  these  to  the  hair-cells,  etc.  ;  the  venous  blood  being  collected 
in  corresponding  veins.  (2)  The  outer  wall  of  the  scala  media  is  highly  vascular,  a 
network  of  capillaries  lying  under  the  epithelium.  It  is  probable  that  oxygen  and 
food  pass  by  osmosis  into  the  endolymph  through  the  epithelium  and  that  waste  products 
.in-  removed  in  the  same  way.  (3)  Perilymph  excreted  in  the  utncle  and  saccule  pass 
up  the  scala  vestibuli  to  the  top  of  the  cochlea,  then  through  a  minute  pore  called 
the  helicotrema  into  the  scala  tympani  below  and  back  along  this  canal  to  escape 
from  the  internal  into  the  middle  ear  by  a  minute  opening  below  the  round  window. 
The  helicotrema  is  apparently  large  enough  to  insure  that  the  mean  pressure  in  the 
scala  vestibuli  shall  lie  equal  to  that  in  the  scala  tympani,  but  not  so  large  that  the 
momentary  differences  in  pressure,  caused  by  the  movements  of  the  stapes,  are  obli- 
terated. 


SECTION    [R 
AUDITORY  SENSATIONS 

HYPOTHESIS   OF    HEARING      ■ 

HELMHOLTZ'  HYPOTHESIS  was  th>1  the  organ  of  Corti  and  the 
basilar  membrane  form  together  a  series  of  automatically  recording  reso- 
nators. In  the  same  way  that  each  of  the  strings  of  a  piano  can  beset  into 
vibration  by  the  sounding  of  a  note  which  corresponds  with  it  in  pitch,  so 
also  can  the  different  fibres  of  the  basilar  membrane  vibrate  to  a  certain 
nole.  and  so  cause  stimulation  of  the  hair-cells  which  are  attached  to  it. 

Four  objections  have  been  made  to  this  hypothesis.  (I)  That  the  fibres 
of  the  basilar  membrane  are  so  short  that  they  could  not  respond  to  the  low 
notes  which  the  ear  is  able  to  hear.  The  answer  to  this  criticism  is  that  not 
only  the  length  but  also  the  tension  and  weight  of  a  cord  determine  its  vibra- 
tion rate.  In  the  case  of  the  basilar  membrane  the  tensions  in  the  fibres  are 
probably  minute,  while  the  weights  of  the  arches  of  Corti  and  the  hair  cells 
must  make  the  period  ol   vibration  so  much  the  Longer. 

(2)  That  the  separate  fibres  of  the  basilar  membrane  are  bound  together 
so  that  vibration  of  the  separate  fibres  would  be  impossible.  This  objection 
Helmholtz  met  by  calculating  that  a  uniform  membrane,  in  which  the  tension 
was  greater  from  side  to  sale  than  longitudinally,  would  be  able  to  respond  in 
the  manner  required. 

(3)  That  the  difference  in  length  of  the  fibres  is  not  sufficiently  greal 
for  the  short  ones  to  vibrate  to  note,  of  4000  vibrations  per  second,  while 
the  long  ones  vibrate  to  10  vibrations  per  second  only.  This  objection  also 
fails  when  we  reflect  that  not  only  length  but  also  tension  and  weight  di  fcer 
mine  the  period  of  vibration  of  a  stretched  cord.  However  accurately  we 
cm  determine  length  and  weight,  by  histological  examination  the  method 
tells  us  nothing  concerning  tension.     This  objection  therefore  must   fail. 

(-1)  That  if  the  cochlea  depends  for  its  action  on  the  resonance  of  the  basilar 
nitres,  we  should  expect  a  musical  note  to  seem  to  go  on  sounding  after  the 
note  has  actually  ceased.  Since  on  the  other  hand  we  know  from  our  own 
experience  that  words  such  as  '  utter.'  in  which  there  is  an  interval  of  silence 
between  the  two  "ts,"  arc  quite  different  from  '  udder, !  in  which  there  is  no 
interval  of  silence,  it  follows  that  the  fibres  of  the  basilar  membrane  have  not 
been  in  vibration  after  the  sound  ceased, and  therefore  probably  resonan 
the  basilar  membrane  is  imaginary.  If  on  the  other  hand  we  suppo 
fibres  to  be  highly  damped  so  that  they  come  to  resl  at  once  when  the  note 
ceases,  how  comes  it  that  they  can  so  readily  be  se1  in  motion  so  thai  in 
only  three  Or  four  vibrations  a  note   is  distinctly  heard.      The   answer   is,   I 

Gil 


612  .         PHYSIOLOGY 

think,  bo  be  obtained  from  the  fact  that  the  cochlea  is  filled  with  liquid. 
This  liquid  makes  the  basilar  membrane  '  dead  beat '  because  its  move- 
ments, when  the  liquid  is  still,  set  up  eddies  which  quickly  check  the  motion 
owing  to  the  viscosity  of  the  liquid.  On  the  other  hand  when  a  sound 
is  entering  the  ear  and  the  fluid  is  therefore  in  motion,  this  movement  is  the 
more  rapidly  imparted  to  the  basilar  membrane  because  of  its  continuity, 
but  even  if  it  consisted  of  separate  fibres  it  would  still  be  set  rapidly  into 
vibration  owing  to  the  viscosity  of  the  liquid.  In'this  way  one  can  explain 
both  the  rapid  response  and  the  rapid  damping  of  the  cochlea. 
In  favour  of  Helmholtz'  theory  we  have  the  following  evidence : 

(1)  In  boiler- makers'  disease  we  have  inability  to  hear  high  notes,  and 
we  find  that  it  is  the  short  fibres  of  the  basilar  membrane  which  are  degener- 
ated. 

(2)  In  experiments  in  which  the  ears  of  animals  have  been  stimulated  for 
long  periods  to  the  same  note,  subsequent  examination  has  shown  the  localisa- 
tion of  degeneration  to  one  part  of  the  organ  of  Corti.  With  a  high  note  the 
short  fibres  are  affected,  with  a  low  note  the  long. 

(3)  If  one  of  the  ears  be  fatigued  by  prolonged  stimulation  to  a  constant 
note,  its  response  to  the  same  note  is  found  to  be  inhibited,  but  notes  of  slightly 
longer  or  shorter  pitch  are  found  to  be  unaffected.  This  shows  clearly  that 
the  response  to  a  given  rate  of  vibration  must  affect  a  certain  limited  number 
of  hair  cells  and  nerve  fibres  only,  and  is  therefore  strongly  in  favour  of 
Helmholtz'  theory. 

(4)  Animals  whose  calls  have  a  small  range  of  pitch  (e.g.  birds)  have  short 
basilar  membranes  which  vary  but  little  in  length. 

(5)  Animals,  in  which  different  parts  of  the  cochlea  have  been  destroyed, 
appear  to  give  definite  evidence  for  deafness  to  high  notes  when  the  fine 
basilar  fibres  are  damaged,  and  deafness  to  low  notes  when  the  long  fibres 
have  been  removed. 

(6)  Patients  are  found  in  whom  there  are  islands  of  deafness,  that  is,  they 
are  deaf  to  a  limited  part  of  the  musical  scale.  The  Helmholtz  theory  readily 
explains  these  cases  as  being  due  to  local  disease  of  certain  basilar  fibres  or 
their  corresponding  hair-cells.  Further  there  are  cases  in  which  the  two  ears 
give  different  notes,  a  condition  called  double  disharmonic  hearing.  This  is 
easily  explained  by  a  change  in  the  natural  period  of  the  fibres  of  the  basilar 
membrane  in  the  diseased  ea~,  either  as  the  result  of  stretching  or  the  increased 
mass  due  to  inflammation. 

(7)  McKendrick  was  able  to  produce  a  model  of  the  cochlea  with  basilar 
membrane  and  organs  of  Corti.  He  found  that  parts  of  the  membrane  can 
be  made  to  vibrate  to  a  certain  pitch  and  not  to  others  as  the  Helmholtz 
hypothesis  requires. 

(8)  McKendrick  calculated  that  the  number  of  fibres  in  the  auditory  nerve, 
the  number  of  fibres  in  the.  basilar  membrane  and  the  number  of  hair-cells  and 
arches  of  Corti  were  sufficient  to  give  the  total  number  of  different  pitches 
(about  11,000)  in  the  auditory  scale. 

It  would  appear  therefore  that  the  evidence  in  favour  "I  Helmholtz'  hypothesis 


THEORIES  OF  HEARIXC  613 

is  very  convincing.     Other  theories  have  been  proposed  however  which  will  nov 
brief  consideration. 

RUTHERFORDS  HYPOTHESIS  compares  the  cochlea  to  a  telephone.  In 
the  same  way  as  the  diaphragm  of  the  receiver  is  set  into  vibration  by  the  sound  waves, 
and  starts  corresponding  variations  in  the  strength  of  the  current  conducted  to  the 
transmitter,  so  the  vibration  of  the  basilar  membrane  as  a  whole  causes  impulses  to 
be  sent  up  the  auditory  nerve  which  correspond  with  the  air  vibrations  received  by 
the  ear.  Analysis  does  not  take  place  in  the  cochlea  at  all  but  in  the  brain.  Wrightson, 
who  has  restated  this  theory  and  added  much  detail  to  it,  states  that  the  cerebral 
analysis  is  effected  by  differences  between  the  time  intervals  of  the  points  of  zero 
pressure  and  of  the  maximum  plus  and  minus  pressures. 

The  following  objections  may  be  stated  against  the  Rutherford-Wrightson  hypo- 
thesis. 

(1)  It  assumes  that  the  auditory  nerve  can  conduct  complicated  wave  forms,  intact 
as  to  pitch  and  amplitude,  at  rates  up  to  40,000  vibrations  per  second.  Rutherford 
in  this  connection  pointed  to  the  motor  nerves  of  the  bee's  wing  which  are  capable 
of  responding  to  transmitted  impulses  at  460  per  second.  Between  40,000  and  460 
is  however  a  big  gap  which  will  certainly  have  to  be  bridged  before  this  view  as  to  1  he 
transmission  of  the  vibrations  intact  to  the  brain  can  be  accepted. 

(2)  We  cannot  picture  a  cerebral  apparatus  which  can  analyse  these  complicated 
nerve  impulses  even  if  they  could  reach  it,  and  neither  Rutherford  nor  Wrightson  assist 
us  to  do  so.  The  relegation  of  the  powers  of  analysis  to  the  cerebral  cortex  is,  a1  i  In- 
present  at  any  rate,  equivalent  to  giving  up  any  attempt  to  explain  the  power  of  analysis 
possessed  by  the  organ  of  hearing. 

(3)  It  would  seem  that  a  very  much  simpler  organ  than  that  of  the  cochlea  would 
be  sufficient  to  convert  sound  waves  into  nerve  impulses  if  no  analysis  of  the  stimulus 
took  place  there. 

(4)  It  would  be  very  difficult  to  explain  on  this  hypothesis  the  localisation  of  degene- 
ration to  certain  notes,  or  the  deafness  to  certain  notes  which  accompanies  disease  of 
part  of  the  organ  of  Corti. 

(5)  This  hypothesis  does  not  explain  why  fatigue  to  one  note  leaves  the  response 
to  all  other  notes  apparently  unaffected  in  intensity. 

The  objections  to  this  hypothesis  are  therefore  of  a  formidable  character.  Much 
additional  evidence  in  its  favour  would  be  necessary  to  place  it  even  on  a  par  with 
the  theory  of  Helmholtz. 

WALLER'S  HYPOTHESIS  stated  that  the  basilar  membrane  vibrated  in  the  form 
of  pressure  patterns  which  are  similar  to  those  which  may  be  seen  on  a  vibrating  plate. 
Ewald  who  has  elaborated  this  view  found  by  experiment  that  the  patterns  take  tin- 
form  of  equidistant  stationary  nodes  or  ridges,  the  distance  between  which  varies  n  it  b 
the  pitch  of  the  note  entering  the  mechanism.  The  distance  between  the  nodes  is 
measured  by  the  hair-cells  and  corresponding  impulses  are  sent  to  the  auditory  centre. 
The  advantage  of  this  hypothesis  is  that  like  Helmholtz'  it  places  the  analysis  of 
the  sound  waves  in  the  cochlea  and  therefore  does  not,  like  Rutherford's  hypothesis, 
require  the  transmission  by  the  auditory  nerve  of  rapid  impulses  or  the  analysis  oi 
such  impulses  by  the  brain.  It  is  clear  however  that  so  far  as  our  present  know  ledge 
goes  the  evidence  is  all  in  favour  of  Helmholtz'  view. 

BEATS  AND  DISSONANCE.  The  overtones  of  any  sound,  at  any  rate 
the  lower  ones,  are  at  considerable  distance  from  one  another  on  the  musical 
scale,  and  therefore  differ  considerably  in  the  number  of  vibrations  of  which 
they  are  composed.  If  two  tuning-forks  be  sounded,  the  vibrations  of  which 
differ  only  by  one  or  two  per  second,  the  phenomenon  known  as  '  beats  is 
produced.  This  is  due  to  the  summation  or  interference  of  the  waves  from  the 
two  tuning-forks.     Let  us  suppose  we  have,  tuning-forks  vibrat  ing  one  at  100 


(il4  PHYSIOLOGY 

and  the  other  at  H>|  times  a  second,  and  I  bal  i  bey  begin  vibrating  together. 
At  first  the  waves  of  compression  started  by  each  fork  will  coincide,  so  that 
the  total  compression  of  the  air  a1  each  beal  will  be  the  compound  effect 
of  the  compression  produced  by  the  two  forks.  The  two  forks  will 
reinforce  one  another.  After  the  lapse  of  half  a  second  the  tuning-forks  will 
be  at  different  phases  of  their  excursion.  The  101  fork  will  be  moving  in  one 
direction  while  the  LOO  fork  is  moving  in  the  other,  so  that  the  compression 
produced  by  one  fork  coincides  with  the  expansion  of  the  air  produced  by 
the  moving  backwards  of  the  other  fork.  The  sound  produced  by  one  fork- 
is  therefore  diminished  by  the  sound  produced  by  the  other  fork,  and  the 
total  sound  is  less  than  either  of  the  two  forks.  At  the  end  of  one  second, 
the  phases  of  the  two  forks  once  more  corresponding,  we  shall  get  the  sound 
increased  in  loudness  ;  thus  there  is  an  alternate  waxing  and  waning  of  the 
sound  which  recurs  once  a  second  and  is  spoken  of  as  a  '  beat.' 

The  number  of  heats  per  second  may  be  used  to  determine  the  differences 
in  the  vibration  frequencies  of  two  forks.  Thus  two  forks  vibrating  one  at 
LOO  and  the  other  at  1 10  will  give  ten  beats  per  second.  As  the  number  of 
heats  increases  the  effect  produced  on  the  ear  becomes  more  and  more  dis- 
agreeable, just  as  the  rapid  alternation  of  illumination  produced  by  a  flicker- 
ing light  is  disagreeable  to  the  eye.  This  objectionable  character  of  the 
sound  is  most  marked  when  the  beats  recur  at  about  thirty-three  times  per 
second  ;  the  individual  beats  are  not  then  distinguished,  but  we  speak  of  the 
sound  as  discordant  or  dissonant. 

CONSONANCE.  The  opposite  condition  of  consonance  or  harmony  in- 
volves therefore,  in  the  first  place,  an  absence  of  beats,  i.e.  of  rhythmic 
oscillations  of  amplitude  of  sound  waves  which  reach  the  ear.  The  con- 
stituent tones  and  overtones  must  be  capable  of  being  combined  into  a 
compound  wave  of  regular  amplitude  and  rhythm.  In  the  most  complete 
consonance  the  component  notes  are  identical  as  concerns  at  any  rate  the 
greater  number  of  their  overtones.  The  most  complete  consonance  is 
attained  when  the  two  notes  which  are  sounded  together  are  identical. 
Almost  as  complete  is  the  consonance  obtained  when  a  note  is  sounded 
together  with  its  octave.  The  other  consonanl  intervals  which  are  employed 
in   music  are   as   follows  ; 

1  ;  2    .  .  .  .  .  .  .  <  Ictave 

2:3.  Fifth 

3:4 Fourth 

4:5 Major  third 

5 :  (I    .  .  .  .  .  Minor  third 

."■  :  s     .  .  .  .  .  .  .  .  Minor  sixth 

3:5.  .  .  .  .  .  .  .  Major  sixth 

It  will  be  noticed  that  in  all  these  consonant  combinations  the  vibration 
frequencies  of  the  notes  are  in  proportion  to  small  whole  numbers.  If  we 
put  down  not  only  the  fundamental  tones  of  these  notes  but  also  their  over- 
tones, we  shall  see  that  there  is  considerable  identity  as  regards  the  latter. 
In  the  case  of  the  octave  the  two  are  almost  identical,  the  only  difference 


CONSONANCE  AND    DISSONANCE  615 

being  the  ground  tone  of  the  lower  note,  and  the  identity  diminishes  as  we 
pass  from  the  cctave  through  the  thirds  to  the  sixths.  The  overtones  which 
are  identical  are  shown  by  black  type  : 


Fundamental  tone  Overtone 

(1.2. 3. 4.    5. 6. 7. 8. 9.  10 
I         ,  2  4  6  8  10 

f  2    .    4    .    6    •    8    .   10  .  12  .   14  .   16  .  18  .  20 
1        3  6  !•  12         IS  18 

I  •'!    •    <i    .    9    .  12  .    15  .    18  .  2]    .  24  .  27  .  30 
1        4        8  1?  16      20  24  28 

l  4    .     8    .    12   .    1(5   .  20   .   24   .   28   .   32   .   36   .    40 
1         5       10      15  20  25      30      35  40 

I  5     .    10    .    15    .    20    .   25    .   30    .    35    .    40    .    45    .   50 
\         6        12       is       24  30  36       42       48 

f  3    ,   6    .    9    .    12  .  15  .    18   .  21    .  24  .  27      30 
I         5  10  15  20  25  30 

I  8    .    10   .   24   .   32    .   40   .   48   .   56   .   64   .  72.     SO 
\  9         18       27       .'!(>       45       54        (>.">  72 

f  8    .    10   .   24   .   32   .   40   .   4S   .   56   .   (14   .   72    .    SO 
I         15  30  45  60  75        90 


Octave  1:2. 
Fit t  h  2  :  3      . 
Fourth  3:4. 
Major  t  liird  4  :  5 
Minor  third  5  :  6 
Major  sixth  3  :  5 
Second  8:9. 
Seventh  8 : 15 


In  the  second  and  seventh,  which  are  discordant,  it  is  only  the  eighth 
overtones  which  are  identical,  while  the  fundamental  tones  will,  as  a  rule,  be 
so  close  together  that  beats  will  be  produced  of  a  number  calculated  to  give 
dissonance.  Since  the  phenomenon  of  beats  depends  on  the  absolute  number 
of  vibrations  per  second,  they  are  more  easily  produced  by  two  notes  near 
together  at  the  lower  end  of  the  scale  than  at  the  upper  end.  Thus  the  dis- 
sonance is  quite  perceptible  in  a  major  third  at  the  lower  end  of  the  piano, 
but  disappears  at  the  upper  part,  since  here  the  beats  produced  are  so  rapid 
that  they  become  imperceptible. 

The  various  notes  used  in  music  are  obtained  by  employing  the  consonant 
intervals  which  we  have  given  above.  The  major  chord  is  composed  of  the 
fundamental  tone,  the  major  third  and  the  fifth.  If  we  take  '  c '  as  the 
fundamental  tone,  the  notes  of  the  chord  are  c,  e,  g,  with  vibration  fre- 
quencies corresponding  to  1,  -£,  :-i,  i.e..  4,  5,  6,  the  major  chord  from  g  is  g,  b, 
(I.  i.e.  three  notes  with  vibration  frequencies  corresponding  to  |,  ,s\  :('. 
i.e.  1 .  ">, '6.  The  major  chord  from  the  fourth,  /.  is  /.  a,  c.  with  the  vibration 
frequencies  *,  #-§■,  ',.-.  i.e.  4.  5,  (i.    The  C  major  scale  is  therefore  as  follows  : 


c 

D 

E 

F 

<; 

A 

B 

C 

1 

9 

5 

4 

3 

5 

15 

2 

Different  instruments  are  tuned  to  one  normal  note,  i.e.  to  A  with  4  to 
vibrations  per  second  (this  note  varies  somewhat  in  different  countries). 
Taking  this  as  the  normal,  the  vibration  frequencies  of  the  various  notes 
used  in  music  are  given  in  the  following  Table  : 


(116 


PHYSIOLOGY 


Note? 

Vibrations  per  second 

c . 

33 

66 

1 32 

264 

528 

1050 

2112 

I> . 

37-125 

74-25 

148-5 

297 

594 

1188 

2376 

E  . 

4 1  -25 

82-5 

165 

330 

660 

1320 

2640 

F  . 

44 

88 

176 

352 

704 

1408 

2816 

G  . 

49-5 

99 

198 

396 

792 

1584 

3168 

A  . 

55 

1  Hi 

220 

440 

880 

1760 

3520 

B  . 

61-875 

123-75 

247-5 

.  495 

990 

1980 

3960 

COMBINATION  TONES.  If  two  tuning-forks,  with  an  interval  of  one-fifth 
between  them,  are  sounded  together,  we  may  hear  a  weak  lower  tone,  the 
pitch  of  which  is  an  octave  below  that  of  the  lower  fork.  This  is  known  as 
a  '  combination  tone.'  The  combination  tones  are  divided  into  two  classes  : 
(1)  '  difference  tones,'  in  which  the  frequency  is  the  difference  of  the  frequen- 
cies of  the  generating  tones  ;  (2)  '  summation  tones,'  which  have  a  pitch 
corresponding  to  the  sum  of  the  vibrations  of  the  tone  of  which  they  are 
composed.  By  means  of  appropriate  resonators  these  tones  can  be  rein- 
forced, showing  that  they  have  an  objective  existence  and  are  not  produced 
in  the  ear  itself. 

Not  only  can  the  ear  appreciate  differences  between  different  musical 
instruments,  dependent  on  the  varying  overtones  present  in  the  sound  pro- 
duced by  each  instrument  but,  when  a  number  of  these  instruments  are 
sounded  simultaneously,  the  ear  can  pick  out  from  the  compound  sound  the 
notes  due  to  the  individual  instrument,  and  a  person  with  a  trained  ear  can 
with  ease  name  notes  composing  any  chord  struck  on  an  instrument  such  as 
the  piano. 

OHM'S  LAW.  This  power  of  analysis,  which  is  possessed  by  the  ear,  or 
at  any  rate  by  the  auditory  apparatus,  may  be  stated  in  the  form  of  the  law, 
known  as  Ohm's  law,  which  is  as  follows  : 

"  Every  motion  of  the  air  which  corresponds  to  a  composite  mass  of 
musical  tones  is  capable  of  being  analysed  into  a  sum  of  simple  pendular  vibra- 
tions, and  to  each  single  vibration  corresponds  a  simple  tone,  sensible  to  the 
ear  and  having  a  pitch  determined  by  the  periodic  time  of  the  corresponding 
motion  of  the  air." 

SOUND  LOCALIZATION.  Experiment  shows  that  man  and  animals 
can  appreciate  with  fair  accuracy  the  direction  from  which  a  sound 
is  coming.  There  has  been  considerable  speculation  as  to  how  this 
information  is  obtained,  and  although  the  subject  has  not  been  completely 
elucidated  it  appears  to  have  been  established  that  the  following  factors  are 
important. 

(1)  The  intensity  of  the  sounds  entering  the  two  ears.  When  a  sound  is 
coming  from  one  side  the  ear  on  that  side  receives  the  more  powerful  stimulus. 

(2)  The  relative  intensities  of  the  components  of  high  and  low  pitch  vary 
with  direction,  because  the  notes  of  long  wavelength  (low   pitch)  will  be 


SOUND  LOCALISATION  617 

diffracted  the  more  readily  round  the  head  to  the  ear  away  from  the  sound, 
than  will  those  of  short  wavelength  (high  pitch). 

(3)  The  sounds  reaching  the  nearer  ear  will  arrive  earlier  than  those 
stimulating  the  other,  because  of  the  time  taken  to  travel  round  the  head. 
The  nerve  impulses  from  the  two  ears  will  not  therefore  arrive  at  the  same 
instant,  and  by  an  appreciation  of  the  difference  in  time  the  approximate 
position  of  an  external  object  can  be  gauged. 

That  this  factor  is  of  great  importance  can  be  shown  by  experiment  in 
the  following  manner.  A  stethoscope  with  two  earpieces  is  fitted  in  position, 
and  to  its  mouthpiece  is  applied  a  loud  tuning-fork.  The  tube  connecting 
the  mouthpiece  to  one  of  the  earpieces  has  an  adjustable  U- piece  like  a 
trombone  so  that  the  distance  travelled  by  the  sound  in  reaching  that  ear 
can  be  varied.  The  other  tube  has  a  length  which  is  equal  to  that  of  the 
others,  with  the  U-piece  in  its  mid  position.  When  a  note  is  sounded  and  the 
U-piece  altered,  the  position  of  the  sound  appears  to  move  from  one  side  to 
the  other  according  to   which  ear  has  the  shorter  tube. 

(-t)  The  sounds  reaching  the  ears  travel  not  only  through  the  air  but  also 
through  the  bones  of  the  skull.  This  can  be  proved  by  placing  a  tuning-fork, 
which  has  been  sounded  and  allowed  to  fade  until  its  note  is  inaudible,  on 
one  of  the  teeth ;  the  sound  will  be  conveyed  by  the  root  of  the  tooth  to  bone, 
and  by  bone  conduction  to  the  ears.  Therefore  when  a  sound  enters  the 
right  ear,  it  will  travel  by  bone  conduction  to  the  left,  and  owing  to  its  rate 
of  travel  being  different  to  that  of  sound  in  air,  it  will  reach  the  left  ear  at 
a  different  instant  to  which  the  sound  travelling  round  the  head  will  reach  it. 
If  one  ear  is  facing  the  sound,  the  bone-conducted  sound  will  probably  reach 
the  other  ear  before  the  air-conducted  does.  On  the  other  hand  when 
both  ears  are  equidistant,  it  is  clear  that  the  air-borne  sound  will  arrive  first 
at  both  ears,  and  the  bone- conducted  sound  very  much  later.  By  an 
appreciation  of  the  difference  in  time  of  the  arrival  of  the  two  sounds  it  is 
probable  that  localisation  is  effected. 

(5)  In  animals,  the  ability  to  turn  the  ears  in  different  directions  and  so 
find  the  direction  of  maximum  intensity,  must  be  of  the  utmost  possible  value 
in  sound  localization. 


PART  IV 

VOICE    AND    SPEECH 

The  development  of  the  analytical  powers  of  the  auditory  apparatus 
is  so  closely  connected  with  that  of  the  faculty  of  speech  that  we  may 
conveniently  deal  with  the  latter  at  this  point  rather  than  relegate  it  to 
a  chapter  on  special  muscular  mechanisms.  We  may  first  consider  the 
mechanism  of  production  of  voice,  which  man  shares  with  many  other 
animals,  before  discussing  the  mechanism  of  the  wholly  human  faculty 
of  speech. 

Voice  is  produced  in  the  larynx,  a  modified  portion  of  the  wind-pipe. 
by  the  vibrations  of  two  elastic  bands,  the  vocal  cords,  which  are  set  into 
action  by  an  expiratory  current  of  air  from  the  lungs.  In  many  respects 
the  larynx  resembles  a  reed  instrument,  in  which  a  current  of  air  is  caused  to 
vibrate  by  the  vibrations  of  an  elastic  tongue.  Whereas  however  the  period 
of  the  vibrations  in  such  an  instrument,  and  therefore  the  note,  is  deter- 
mined by  the  length  of  the  tube  which  is  attached  to  the  reed  and  by  the 
lengths  of  the  reeds  themselves,  in  the  larynx  the  note  produced  by  the  blast 
of  air  is  modified  partly  by  alterations  in  the  tension  of  the  vocal  cord,  and 
partly  by  varying  the  strength  of  the  blast  of  air. 

ANATOMICAL  MECHANISM  OF  THE  LARYNX.  The  essential  framework 
of  the  larynx  is  formed  by  four  cartilages,  viz.  the  cricoid,  the  thyroid,  and  the  two 
arytenoid  cartilages.  The  cricoid  cartilage,  which  lies  immediately  over  the  upper- 
most ring  of  the  trachea,  is  shaped  like  a  signet  ring,  the  small  narrow  part  being 
directed  forwards  and  the  broad  plate  backwards.  The  thyroid  cartilage  consists  of 
two  parts  or  ate,  joined  together  in  front  and  forming  the  prominence  known  as  Adam's 
apple  ;  behind,  it  presents  four  processes  or  comua,  the  superior  of  which  are  attached 
by  ligaments  to  the  hyoid  bone,  while  the  inferior  comua  articulate  with  the  postero- 
lateral portion  of  the  cricoid  cartilage.  By  means  of  this  articulation  very  free  move- 
ment is  permitted  between  the  two  cartilages,  the  general  direction  of  movement  being 
one  of  rotation  of  the  cricoid  cartilage  on  the  thyroid,  round  a  horizontal  axis  directly 
through  the  two  articular  surfaces  between  the  two  cartilages,  while  movements  of  the 
thyroid  upon  the  cricoid  are  also  possible  in  the  upward,  downward,  forward,  and  back- 
ward directions.  The  two  arytenoid  cartilages  are  pyramidal  in  shape.  By  their  bases 
they  articulate  at  some  distance  from  the  middle  line  with  convex  articular  surfaces 
situated  in  the  upper  margin  of  the  plate  of  the  cricoid  cartilage.  The  anterior  angle 
of  the  base  is  the  vocal  process,  while  the  external  angle  is  the  muscular  process  of 
the  arytenoid.  The  crico-arytenoid  joints  permit  of  two  kinds  of  movements  of  the 
arytenoid  cartilages,  viz.  : 

(1)  Rotation  on  their  base  around  their  vertical  long  axis,  so  that  the  anterior 
vocal  process  is  rotated  outwards  and  the  muscular  process  backwards  and  inwards 
or  conversely. 

]  (2)  Sliding  movements  of  the  whole  arytenoid  cartilage  either  outwards  or  inwards, 
so  that  their  inner  margins  may  be  drawn  apart  or  approximated. 

618 


VOICE   AND  SPEECH 


619 


The  larynx  is  covered  internally  by  a  mucous  membrane  continuous  with  that  of 
the  trachea.  It  is  lined  with  ciliated  epithelium,  except  over  the  vocal  cords,  where 
the  epithelium  is  stratified.  The  two  vocal  cords,  or  thyro-arytenoid  ligaments,  con- 
sist of  elastic  fibres  which  run  from  the  middle  of  the  inner  angle  of  the  thyroid  cartilage 
to  be  inserted  into  the  anterior  angle  of  the  arytenoid  cartilages.  Their  length  in  man 
is  about  IE  mm.,  in  woman  about  II  mm.  The  cleft  between  them  is  known  as  the 
glottis,  or  rima  ghttidis. 

Two  ridges  of  mucous  membrane  above  and 
parallel  to  the  vocal  cords  are  the  false  vocal 
cords  (Fig.  310).  Between  the  true  ami  the  false 
vocal  cords  on  each  side  is  a  recess  known  as  the 
ventricle  of  Morgagni.  This  ventricle  permits 
the  free  vibration  of  the  vocal  cords.  The  false 
cords  take  no  part  in  phonation,  but  help  to  keep 
the  true  cords  moistened  by  the  secretion  of  the 
numerous  mucous  glands  with  which  they  are 
provided.  The  false  cords  are  also  used  in  hold- 
ing the  breath.  For  this  purpose  they  function 
in  a  similar  manner  to  the  mitral  valve  of  the 
heart.  It  is  found  that  animals  who  need  the 
thorax  to  be  fixed  in  order  that  they  may  climb 
or  strike  have  well  developed  false  cords.  The 
position  and  tension  of  the  vocal  cords  are 
determined  by  the  action  of  the  intrinsic 
muscles  of  the  larynx.  The  part  taken  by  the 
various  muscles  in  each  movement  cannot  be 
directly  ascertained.  We  can  in  most  cases  study 
only  the  direction  of  the  fibres,  and  judge, 
from  this  direction  and  consequent  isolated 
action  of  the  muscles,  the  part  taken  by  any 
given  muscle  in  the  production  of  voice.  The 
chief  muscles  (Fig.  311)  are  as  follows: 

(1)  The  crico-thyroid  muscle  is  a  short  trian- 
gular muscle  attached  below  to  the  cricoid 
cartilage  and  above  to  the  inferior  border  of  the 
thyroid  cartilage  ;  the  fibres  pass  from  below 
upwards  and  backwards.  When  this  muscle 
contracts,  the  cricoid  cartilage  is  drawn  up 
under  the  anterior  part  of  the  thyroid  cartilage, 
so  that  its  broad  expansion  behind,  with  the 
arytenoid   cartilages,   is  drawn   downwards  and 

backwards,  thus  putting  the  vocal  colds  on  the  stretch.       This  muscle  is  probably    the 
most  important  in  determining  the  tension  of  the  vocal  cord. 

(2)  The  posterior  crico-aryU  moid  muscle  arises  from  a  broad  depression  on  the  corre- 
sponding half  of  the  posterior  surface  of  the  cricoid  cartilage.  It  passes  upwards  and  out- 
wards, its  fibres  converging!  to  be  inserted  into  the  outer  angle  of  the  arytenoid  cartilage. 
These  muscles  rotate  the  outer  angle  of  the  arytenoid  cartilages  backwards  and  inwards. 
They  thus  cause  a  movement  outwards  of  the  anterior  angles,  so  that  the  glottis  is  widened. 
During  every  act  of  inspiration  there  is  a  widening  of  the  glottis,  which  is  probabhj 
effected  by  contraction  of  these  muscles.  If  they  are  paralysed  the  vocal  cord-  are 
approximated  and  tend  to  come  together  during  inspiration,  so  that  dyspnoea  m 
produced. 

(3)  The  lateral  crico-arytenoid  muscle  arises  from  the  upper  horde)  oi  the  cricoid 
cartilage  and  passes  backwards  to  be  inserted  into  the  muscular  process  ..t  tin  arytenoid 
cartilage.      These  muscles  when  they  contract  pull  the  muscular  process  of  the  arytenoid 


Fig.  310.  Anterior  half  of  the  larynx, 
seen  from  behind.  The  section  on 
the  right  side  is  somewhat  in  front 
of  the  left  side. 

e,  epiglottis  ;  e',  cushion  of  epi- 
glottis ;  I.  thyroid  cartilage;  8,  s', 
ventricle  of  larynx  ;  h.  great  cornu 
of  hyoid  bone  ;  t  n,  thyro-arytenoid 
muscle:  vl,  vocal  cords  Above  the 
ventricles  arc  the  false  vocal  cords, 
)■.  first  ring  of  trachea. 

A   Thomson.) 


620 


PHYSIOLOGY 


cartilage  forwards  and  downwards,  thus  approximating  the  vocal  cords  at  their  posterior 
ends  and  antagonising  the  action  of  the  posterior  crico-arytenoid  muscles. 

(4)  The  arytenoid  muscles  consist  of  transverse  fibres,  some  of  which  decussate, 
uniting  the  posterior  surface  of  the  two  arytenoid  cartilages.  When  they  contract 
they  draw  the  arytenoid  cartilages  together. 

(5)  The  thyro-arytenoid  muscles  consist  of  two  portions.  The  outer  fibres  rise  in 
front  from  the  thyroid  cartilage  and  pass  backwards  to  be  inserted  into  the  lateral 
border  and  the  muscular  process  of  the  arytenoid  cartilage.  Some  of  the  fibres  pass 
obliquely  upwards  towards  the  aryteno-epiglottidean  folds.  These  are  often  spoken 
uf  as  a  separate  muscle,  the  thyro-epiglottidean.     By  their  action  they  tend  to  draw 


Fig.  311.  Muscles  of  the  larynx.  (Sappey.) 
A,  as  shown  in  a  view  of  the  larynx  from  the  right  side. 
1,  hyoid  bone  ;  2,  3,  its  cornua ;  4,  right  ala  of  thyroid  cartilage  ;  5,  posterior  part  of 
the  same  separated  by  oblique  line  from  anterior  part;  6,  7,  superior  and  inferior  tubercles 
at  ends  of  oblique  line  ;  8,  upper  cornu  of  thyroid  ;  9,  thyro-hyoid  ligament ;  10,  cartilage 
triticea  ;  11,  lower  cornu  of  thyroid,  articulating  with  the  cricoid;  12,  anterior  part  of 
cricoid;  13,  crico-thyroid  membrane;  14,  crico-thyroid  muscle;  15,  posterior  crico- 
arytenoid muscle,  partly  hidden  by  thyroid  cartilage. 

B,  as  seen  in  a  view  of  the  larynx  from  behind. 
1,  posterior  crico-arytenoid  ;    2,  arytenoid  muscle  ;    3,  4,  oblique  fibres  passing  around 
the  edge  of  the  arytenoid  cartilage  to  join  the  thyro-arytenoid,  and  to  form  the  aryteno- 
epiglottie,  5. 

the  arytenoid  cartilages  forwards  and  to  relax  the  vocal  cords.  The  upper  fibres  may 
also  assist  in  depressing  the  epiglottis.  The  inner  fibres  are  called  the  mvxcuhis  vocalic. 
They  arise  from  the  lower  half  of  the  angle  of  the  thyroid  cartilage,  and  passing  back- 
wards in  the  vocal  cords  are  attached  to  the  vocal  processes  and  to  the  adjacent  parts 
of  the  outer  surfaces  of  the  arytenoid  cartilages.  Many  fibres  do  not  run  the  whole 
distance,  but  end  in  an  attachment  to  some  part  of  the  vocal  cord.  Although  their 
action  must  be  to  draw  the  arytenoid  cartilages  forwards,  yet,  since  they  are  contained 
in  the  vibrating  portion  of  the  vocal  cords,  they  cannot  by  their  contraction  relax 
these  cords.  It  is  probable  that  they  play  a  great  part  in  determining  the  tension  of 
the  vocal  cords  after  these  have  been  put  on  the  stretch  by  the  action  of  the  crico-thyroid 
muscles.  They  may  possibly  act  as  a  sort  of  fine  adjustment  of  the  tension,  the  coarse 
adjustment  being  represented  by  the  crico-thyroids. 


VOICE  AND  SPEECH  62] 


THE   PRODUCTION   OF  VOICE 


In  order  to  study  the  changes  in  the  Larynx  winch  are  associated  with 
voice  production  we  must  make  use  of  the  Laryngoscope.  The  principle 
of  this  instrument  is  very  simple.  A  large  concave  mirror  with  a  central 
aperture  is  fixed  before  one  eye  of  the  observer,  sitting  in  front  of  the  patienl 
or  person  to  be  observed.  The  latter  is  directed  to  throw  his  head  slightly 
backwards  and  to  open  his  mouth.  In  order  to  keep  the  tongue  out  of  the 
way  the  patient  is  made  to  hold  the  end  of  it  by  means  of  a  towel.  The 
mirror  is  then  so  arranged  as  to  reflect  light  from  a  lamp  into  the  cavity 
of  the  mouth.  A  small  mirror  fixed  in  a  handle  is  then  warmed,  so  as  to 
prevent  the  condensation  of  the  patient's  breath,  and  passed  to  the  back 
of  the  mouth  until  it  rests  upon  and  slightly  raises  the  base  of  the  uvula. 
By  this  mirror  the  light  reflected  into  the  mouth  from  the  large  mirror  is 
again  reflected  down  on  to  the  larynx,  and  a  reflection  of  the  larynx  and 
trachea  is  seen  in  the  mirror.  By  laryngoscopic  examination  we  can  see 
the  base  of  the  tongue,  behind  which  is  the  outline  of  the  epiglottis.  Behind 
this  again  in  the  middle  line  are  seen  the  two  vocal  cords,  white  and  shining 
(Fig.  312).  The  cords  appear  to  approximate  posteriorly;  between  them 
is  a  narrow  chink,  the  diameter  of  which  varies  with  each  respiration,  being 
wider  during  inspiration.  On  each  side  of  the  true  vocal  cords  are  seen 
the  pink  false  vocal  cords.  In  some  cases  the  rings  of  the  trachea,  and  even 
the  bifurcation  of  the  trachea  itself  (Fig.  312,  c),  may  be  seen  in  the  interval 
between  the  vocal  cords. 

In  order  that  the  vocal  cords  may  be  set  into  vibration,  they  must  be  put 
into  a  state  of  tension  and  the  aperture  of  the  glottis  narrowed,  so  as  to 
afford  resistance  to  the  current  of  air.  In  the  dead  larynx  it  is  possible 
to  produce  sounds  by  forcing  air  from  bellows  through  the  trachea,  after 
the  vocal  cords  have  been  put  on  the  stretch  by  pulling  the  arytenoid 
cartilages  backwards.  By  experimenting  on  patients  on  whom  tracheotomy 
has  been  performed,  it  has  been  found  that  the  pressure  of  air  in  the  trachea, 
necessary  to  cause  production  of  voice,  is,  for  a  tone  of  ordinary  loudness 
and  pitch,  between  140  and  240  mm.  of  water,  and  with  loud  shouting 
the  pressure  rises  to  as  much  as  945  mm.  of  water.  This  pressure  is  furnished 
by  the  contraction  of  the  expiratory  muscles,  i.e.  of  the  abdomen  and  of  the 
thorax.  Since  the  pitch  of  the  note  produced  rises  with  increasing  force 
of  the  blast,  while  the  tension  of  the  cords  remains  constant,  it  is  evidenl 
that,  in  the  act  of  '  swelling  '  on  a  note,  the  increased  pressure  necessary 
for  the  crescendo  must  be  associated  with  diminishing  tension  of  the  cords. 
It  is  the  failure  to  secure  this  muscular  relaxation  that  so  often  can 
singer  to  sing  sharp  when  swelling  on  any  given  note. 

The  voice,  like  the  sound  produced  on  any  musical  instrument,  may 
vary  either  in  pitch,  loudness,  or  in  quality  or  timbre.     The  range  ol 
individual  voice  is  generally  about  two  octaves.     The  pitch  oi  tic  voice 
usually  employed  is  determined  chiefly  by  the  length  of  the  vocal  cords. 
Thus  in  children  the  voice  is  high-pitched.     Before,  anil  at  puberty  there 


622 


PHYSIOLOGY 


is  a  considerable  development  in  the  size  of  the  larynx  in  both  sexes.  This 
is  especially  marked  in  the  male,  and  accounts  for  the  sudden  drop  in  pitch 
('  breaking  ')  of  the  voice.  In  the  female  the  increased  size  of  the  larynx 
is  chiefly  perceptible  in  the  increase  in  fulness  and  richness  of  the  voice 
which  occurs  at  this  age.     Even  when  we  take  all  the  voices  together, 


Fig.  312.  Three  laryngoscopy  views  of  the  superior  aperture  of  the  larynx  and 
MiiTuunding  parts  in  different  states  of  the  glottis  during  life.  (From  Czermak.) 
A.  the  glottis  during  the  emission  of  a  high  note  in  singing.  B,  in  easy  or 
quiet  inhalation  of  air.  C,  in  the  state  of  widest  possible  dilatation,  as  in  inhaling 
a  very  deep  breath.  The  diagrams  A'.  B',  C  have  been  added  to  C'zermak's 
figures  to  show  in  horizontal  sections  of  the  glottis  the  position  of  the  vocal  liga- 
ments and  arytenoid  cartilages  in  the  three  several  states  represented  in  the  other 
figures.  In  all  the  figures  so  far  as  marked,  the  letters  indicate  the  parts  as  follows, 
viz.  :  /.the  base  of  the  tongue;  e,  the  upper  free  part  of  the  epiglottis:  e',  the 
tubercle  or  cushion  of  the  epiglottis  ;  p  h,  part  of  the  anterior  wall  of  the  pharynx 
behind  the  larynx  ;  in  the  margin  of  the  aryteno-efpiglottidean  fold  »•,  the  swelling  of 
the  membrane  caused  by  the  cuneiform  cartilage;  s,  that  of  the  corniculum  ;  a, 
the  tip  of  the  arytenoid  cartilages  :  c  u,  the  true  vocal  chords  or  lips  of  the  rima 
glottidis  ;  c  v  s.  the  superior  or  false  vocal  cords  ;  between  them  the  ventricle  of 
the  larynx  ;  in  ('.  (  r  is  placed  on  the  anterior  wall  of  the  receding  trachea,  and  b 
indicates  the  commencement  of  the  two  bronchi  beyond  the  bifurcation,  which 
may  be  brought  into  view  in  this  state  of  extreme  dilatation. 

bass,  tenor,  alto,  and  soprano,  the  total  range  for  ordinary  individuals  does 
not  exceed  three  octaves.  In  singing  the  voice  may  be  produced  in  various 
ways,  i.e.  in  different  registers.  Thus  we  distinguish  the  chest  register,  the 
middle  register,  and  the  head  register.  The  deeper  notes  of  any  individual 
voice  are  always  produced  in  the  chest  register.  Observation  of  the  vocal 
cord  shows  that  when  producing  such  notes  the  glottis  forms  an  elongated 
slit,  all  the  muscles  which  close  the  glottis  and  increase  the  tension  of  the  cords 
being  in  action.     The  vocal  cords  are  relatively  thick  and  broad  and  can 


VOICE   AND  SPEECH  623 

be  seen  to  vibrate  over  their  whole  extent.  When  singing  with  the  head  voice, 
the  vibrations  of  the  cord  are  apparently  confined  to  their  inner  margins  ; 
the  aperture  of  the  glottis  is  wider  in  front  than  behind,  so  that  more  afr 
escapes  during  phonation  by  this  method  than  in  the  production  of  the 
chest  voice. 

In  order  to  change  the  pitch  of  the  note  the  following  means  are  probably 
employed  in  the  larynx  : 

(1)  Alteration  in  the  tension  of  the  vocal  cords. 

(2)  Alteration  in  the  length  of  the  part  of  the  vocal  cords  that  is 
free  to  vibrate,  which  can  be  accomplished  by  the  approximation  of  the 
arytenoid  cartilages  to  one  another,  or  by  their  approximation  to  the  thyroid 
cartilage. 

(3)  The  alteration  in  the  shape  of  the  vocal  cords,  which  is  determined  by 
the  activity  of  the  different  portions  of  the  internal  thyro-arytenoid  muscles. 

(4)  The  varying  pressure  of  the  blast  of  air  passing  through  the  glottis. 
The  loudness  of  the  tone  produced  is  practically  proportional  to  the 

force  of  the  blast  of  air  employed.  The  quality  or  timbre  of  the  voice 
depends  not  so  much  on  the  vocal  cords  as  on  the  accessory  resonating 
apparatus,  represented  by  the  trachea  and  chest  and  by  the  cavities  of  the 
mouth  and  nose.  The  greater  part  of  the  education  involved  in  voice  training 
is  directed  to  the  modification  of  the  shape  of  the  mouth  cavity,  so  as  to 
secure  the  greatest  possible  fulness,  i.e.  richness  in  overtones,  of  the  tone 
produced  in  the  larynx. 

THE   MECHANISM   OF   SPEECH 

The  sounds  employed  in  speech,  viz.  vowels  and  consonants,  are  produced 
by  modifying  the  laryngeal  tones  by  changes  in  the  shape  of  the  mouth  and 
nasal  cavities.  In  whispering  sjieech  there  is  no  phonation  at  all,  but  the 
sound  is  produced  by  the  issue  of  a  blast  of  air  through  a  narrow  opening 
between  the  lips,  between  the  tongue  and  soft  palate,  or  between  the  tongue 
and  the  teeth. 

VOWEL  SOUNDS  are  continuous,  whereas  the  consonants  are  pro- 
duced by  interruptions,  more  or  less  complete,  of  the  outflowing 
air  in  different  situations.  The  simple  vowel  sounds,  U,  0,  A. 
E  I,  (pronounced  as  in  Italian  oo,  oh,  ah.  eh.  ee).  are  tones, 
i.e.  are  produced  by  a  regular  series  of  vibrations.  These  tones 
take,  their  origin  in  the  mouth  cavity,  as  can  be  shown  easily  by  the  Eaci 
that  we  can  whisper  these  sounds  distinctly  without  any  phonation  what- 
ever. To  each  of  them  corresponds  one  or  two  distinct  notes,  the  pitch,  i.e. 
the  resonance,  of  which  is  regulated  by  the  shape  of  the  cavity  in  which 
they  are  produced.  There  has  been  much  controversy  as  to  whether  the 
pitch  of  these  notes  changes  at  all  with  the  pitch  of  the  voice,  or  varies 
in  different  individuals.  Some  said  that  they  did  not  change,  others  that 
their  pitch  kept  in  constant  ratio  with  the  pitch  of  the  note  sung  :  if  the  note 
doubled  in  pitch,  so  also  did  that  (ot  those  m  the  case  of  E  and  !)  ol  the  vowel, 
Several  methods  have  been  employed  for  investigating  this  point; 


624 


PHYSIOLOGY 


(1)  By  recording  the  vibrations  emitted  by  the  voice  by  means  <>f  the 
manometric  flame. 

(2)  By  recording  the  vibrations  by  means  of  a  gramophone. 

(3)  By  measuring  the  intensity  of  vibration  of  series  of  resonators.  All 
the  above  methods  show  that  there  must  be  some  change,  even  if  it  is  slight. 

(4)  By  running  a  gramophone  record  of  a  bass  voice  at  an  increased  speed 
so  that  the  notes  were  those  of  a  treble.  If  now  the  pitches  of  note  and 
vowels  were  in  constant  ratio  the  quality  of  the  vowels  should  not  change 
when  the  speed  is  thus  increased.  Experiment  shows  that  the  words  are 
greatly  altered,  losing  their  O's  and  A's  and  taking  E  and  I  instead. 
This  shows  clearly  that  change  in  pitch  of  the  vowels  is  not  nearly 
as  great  as  that  of  the  note  sung  with  them.  We  must  conclude  therefore 
that  neither  those  who  say  there  is  no  change,  nor  those  who  say  there  is  con- 
stant ratio,  are  right,  but  that  the  truth  lies  between  the  two  extremes.  The 
pronunciation  even  of  the  simplest  vowel  sound  differs  in  different  individuals. 
For  instance,  those  pronounced  by  a  Londoner  differ  from  those  pronounced 
by  a  man  from  Manchester  or  from  Yorkshire,  and  the  French  vowels  differ 
somewhat  in  pitch  from  those  employed  by  the  German,  and  these  again  from 
those  employed  by  the  average  Englishman. 

The  characteristic  notes  were  given  by  Helmholtz  as  follows : 

U  =  f 


0  =  V 
A  =  bu 

E  =  V,  V" 

1  =  £,  dlv 


TJ 


m 


m 


U  O  A  EI 

If  the  five  vowels  are  whispered  loudly,  the  gradual  rise  in  pitch  of  the 
tone  is  easily  perceptible.  We  do  not  in  this  way  however  note  the  lower 
component  of  the  sound  in  the  E  and  I  ;  this  can  be  brought  out  by  a 
single  device  (Fig.  313).  If  we  place  the  mouth  in  the  position  necessary 
to  produce  these  different  vowels,  and  then  percuss  over  the  cheek,  we 
obtain  the  typical  note  for  each  vowel,  the  air  in  the  mouth  cavity  being 
set  into  vibration  by  the  percussion.     Now  shift  the  linger,  which  is  to  be 


A  (or)  U  (oo) 

Fin.  313.     .Shape  of  the  oral  cavity  in  the  production  of  the  vowel  sounds,  .1,  U,  I. 
(Grutzner.) 


VOICE  AM)  SPEECH  625 

percussed,  so  that  it  lies  over  the  pharynx,  just  behind  the  angle  of  the  jaw, 
and  percuss  again.  The  note  will  be  observed  to  rise  with  U,  0,  A,  and 
then  fall  with  E,  I.  With  the  three  vowels  U,  0,  A,  we  have  a  single 
cavity  formed  by  the  lips,  the  palate,  and  the  tongue  ;  this  cavity  is  longest 
and  narrowest  with  U  and  shortest  and  most  open  with  A.  With  E  and  I 
the  dorsum  of  the  tongue  comes  up  against  the  front  part  of  the  soft  palate, 
so  that  the  mouth  cavity  is  divided  into  two,  the  anterior  short  narrow 
cavity,  and  the  posterior  broader  cavity  between  the  soft  palate  and  the 
base  of  the  tongue.  We  therefore  have  two  notes  produced,  one  in  each 
cavity.  The  change  in  shape  of  the  mouth  cavity  is  shown  in  the  figures. 
With  U  and  A  the  cavity  seems  to  be  single  ;  with  I  the  development  of 
a  pharyngeal  resonating  cavity  is  well  shown.  Diphthongs  are  produced 
by  changing  the  form  of  the  mouth  cavity  from  that  of  one  vowel  sound  to 
another,  thus  AI  (the  English  I)  =  ah-ee  run  together  and  abbreviated. 

CONSONANTS  are  sounds  produced  by  a  sudden  check  being  placed  in  the 
course  of  the  expiratory  blast  of  air  by  closure  of  some  part  of  the  pharynx 
or  mouth.  They  are  classified  into  labials,  dentals,  or  gutturals,  according 
as  the  check  takes  place  at  the  lips,  between  teeth  and  tongue,  or  between 
back  of  tongue  and  soft  palate.  Each  of  these  again  can  be  divided  into 
soft  and  hard  consonants  as  they  are  accompanied  or  not  with  phonation. 
Thus  when  we  pronounce  D  the  production  of  the  laryngeal  sounds  goes  on 
during  the  check  of  the  sound  produced  at  the  teeth,  whereas  with  T  there 
is  an  absolute  interruption  of  phonation  during  the  pronunciation  of  the 
consonant.  It  is  thus  practically  impossible  to  make  any  marked  difference 
between  hard  and  soft  consonants  when  whispering. 

In  the  production  of  nasal  sounds  such  as  NG  the  mechanism  is  the 
same  as  for  the  production  of  B,  D,  G,  except  that  the  posterior  opening 
of  the  nares  is  not  kept  shut  by  the  soft  palate,  so  that  part  of  the  sound 
comes  continually  through  the  nasal  passages,  when  it  acquires  a  peculiar 
resonance.  These  sounds  are  on  this  account  often  spoken  of  as  '  resonants.' 
The  aspirates  are  produced  by  the  passage  of  a  simple  blast  of  air  through 
a  narrow  opening  which  may  be  at  the  throat  as  in  H,  between  tongue  and 
teeth  as  in  TH,  or  between  lips  and  teeth  as  in  PH  or  F. 

The  vibratives,  such  as  R,  are  formed  by  placing  the  tip  of  the  tongue 
or  the  uvula,  or  the  lips,  in  the  path  of  the  blast  of  air  so  that  they  are  set 
into  vibration  by  the  blast.  In  English  the  vibrative  R  employed  is  entirely 
due  to  the  tongue. 

The  sibilants,  which  may  be  voiceless  as  in  '  S '  or  accompanied  with 
phonation  as  in  '  Z,'  consist  of  continuous  noises  produced  by  a  narrowing 
of  the  path  of  the  air  between  the  tongue  and  the  hard  palate.  They  are 
therefore  similar  in  production  to  the  aspirates.  In  the  production  of  the 
sound  '  L  '  the  tongue  is  applied  by  its  edge  to  the  alveolar  process  of  the 
upper  jaw,  so  that  the  air  or  voice  escapes  by  two  small  apertures  in  the 
region  of  the  first  molar  and  between  the  inner  side  of  the  cheek  and  the 
teeth.  The  acoustic  characters  of  these  various  consonants  are  still  but 
imperfectly  studied. 

40 


PART  V 

CUTANEOUS    SENSATIONS 

The  skin,  being  the  outermost  layer  of  the  body,  represents  the  tissue  or 
organ  by  which  the  organism  is  brought  into  relationship  with  its  environ- 
ment. In  the  widest  sense  of  the  term  the  skin  is  protective.  This  function 
it  discharges  by  virtue  not  only  of  its  physical  properties  but  also  of  its  rich 
endowment  with  sense  organs,  by  means  of  which  the  intracorporeal  events 
can  be  correlated  with  those  occurring  outside  and  immediately  affecting  the 
organism. 

We  are  accustomed  to  distinguish  several  qualities  of  sensation  among 
those  having  their  origin  in  the  skin,  the  chief  of  which  are  the  sense  of  touch, 
including  that  of  discrimination,  the  sense  of  pain  and  the  sense  of  tempera- 
ture. The  very  different  qualities  of  sensation  included  under  these  three 
classes  suggest  that  there  may  be  a  special  mechanism,  or  class  of  mechanism, 
for  each  sense,  and  a  careful  investigation  of  the  sensory  qualities  of  the 
skin  surface  bears  out  this  idea.  Isolated  stimulation  of  minute  areas  on  the 
skin  does  not  excite  all  the  sensations  together,  but  only  a  sense  of  touch  or 
of  pain,  or  a  sense  of  cold  or  warmth.  We  are  therefore  justified  in  dealing 
with  each  of  these  sensations  separately. 

THE  TEMPERATURE  SENSE 

By  means  of  the  skin  we  can  appreciate  that  a  body  coming 
in  contact  with  the  skin  is  either  cold  or  warm.  If  the  body  is  at 
the  same  temperature  as  the  skin,  as  a  rule  no  sensation  of  tempera- 
ture is  excited.  It  was  formerly  thought  that  the  sensations  both  of  heat 
and  cold  were  determined  by  the  excitation  of  one  and  the  same  end  organ. 
Warming  of  this  end, organ  would  produce  a  sensation  of  warmth,  while  a 
diminution  of  its  temperature  would  produce  the  sensation  of  cold.  Careful 
investigations  by  Blix  and  Donaldson  of  the  distribution  of  the  temperature 
sense  has  shown  that  this  opinion  cannot  be  maintained.  If  a  small  surface 
warmed  to  a  few  degrees  above  the  temperature  of  the  skin  be  moved  over 
any  part  of  the  surface  of  the  body,  e.g.  the  back  of  the  hand,  it  is  found  that 
the  warmth  of  the  instrument  is  not  appreciable  equally  at  all  parts  of  the 
surface  of  the  skin.  At  some  points  the  sensation  of  warmth  will  be  very 
pronounced,  but  between  these  points  the  sensation  of  warmth  may  be 
entirely  wanting  and  the  instrument  may  be  judged  to  be  of  the  same  tem- 
perature as  the  hand  itself.  In  this  way  a  series  of  '  warm  points  '  may  be 
mapped  out.     On  now  cooling  the  instrument  a  few  degrees  below  the 


CUTANEOUS  SENSATIONS 


627 


temperature  of  the  surface  of  the  body  and  then  moving  it  over  the  surface  in 
the  same  way,  it  will  be  found  again  that  the  coolness  of  the  instrument  is 
appreciated  only  at  certain  points  which  can  be  regarded  as  '  cold  points  '  and 
as  containing  the  nerve-endings  by  the  excitation  of  which  the  sensation  of 
cold  is  produced.  If  the  warm  points  be  pricked  out  in  red  ink  and  the 
cold  points  in  blue  ink, it  will  be  seen  that  they  do  not  in  any  way  correspond. 

A  convenient  instrument  for  this  purpose  is  the  one  invented  by  Miescher,  con- 
sisting of  two  tubes  cemented  together  and  communicating  at  a  small  flattened  extremity, 
which  is  applied  to  the  surface  of  the  skin  ;  through  the  tubes  water  can  be  led  at  any 
desired  temperature,  which  is  read  off  by  a  thermometer  placed  within  the  tube.  Having 
mapped  out  the  warm  spots  it  may  be  shown  that  they  are  excitable  by  means  of  mechani- 
cal or  electrical  stimuli  and  that  the  sensation  produced  is  the  same  as  if  they  had  been 
excited  by  their  adequate  stimulus,  viz.  a  rise  of  temperature. 


Cold  spots.  Heat  spots. 

Fig.  314.     Heat  and  cold  spots  on  part  of  palm  of  right  hand. 
The  sensitive  points  are  shaded,  the  black  being  more  sensitive  than  the  lined, 
and  these  than  the  dotted  parts.     The  unshaded  areas  correspond  to  those  parts 
where  no  special  sensation  was  evoked.     (Goldscheidek. ) 

EXACT  LOCATION  of  the  spots  is  rendered  difficult  by  the  irradiation 
of  the  sensation  produced,  so  that  it  is  difficult  to  refer  the  sensation  of 
warmth  or  cold  definitely  to  the  point  stimulated.  An  investigation  of  the 
topography  of  these  warm  and  cold  spots  shows  that  the  apparatus  for  the 
appreciation  of  cold  is  much  more  extensively  distributed  over  the  body  than 
that  for  the  appreciation  of  warmth,  as  is  evidenced  from  the  diagram 
(Fig.  314)  giving  the  topographic  distribution  of  the  cold  and  warm  sense- 
organs  on  the  palm  of  the  hand.  The  temperature  sense  is  best  marked  in 
the  following  regions  of  the  body  :  the  nipples,  chest,  nose,  the  anterior 
surface  of  the  upper  arm  and  the  anterior  surface  of  the  fore-arm,  and  the 
surface  of  the  abdomen.  It  is  much  less  marked  on  the  exposed  parts  of  the 
body,  such  as  the  face  and  hands,  and  is  but  slight  in  the  mucous  membranes. 
Thus  it  is  possible  to  drink  hot  fluid,  such  as  tea,  at  a  temperature  which 
would  be  painful  to  the  hand,  and  still  more  to  any  other  part  of  the  body. 
The  scalp  is  also  very  insensitive  to  changes  of  temperature.  The  acuteness 
of  the  temperature  sense  varies  considerably  with  the  condition  of  the  skin 
and  with  the  previous  stimulation  of  the  sense  organs.  Tin-  sense  i-^  most 
acute  at  about  ordinary  skin  temperature,  i.e.  between  27°  and  32  C.  At 
this  temperature  the  skin  can  appreciate  a  difference  of  !°  C.     When  the 


628  PHYSIOLOGY 

skin  is  very  cold  or  very  hot  the  temperature  sense  is  not  nearly  so  delicate. 
This  sense  presents  the  phenomenon  of  adaptation  in  a  marked  degree. 
It  is  a  familiar  experience  that,  on  coming  from  the  external  air  on  a  cold  day 
into  a  warm  room,  a  sensation  of  warmth  is  experienced  all  over  the  body. 
In  a  few  minutes  this  sensation  wears  off.  On  now  leaving  the  room  to  go 
outside  again,  the  sensation  of  cold  is  at  once  appreciated,  to  disappear  in  its 
turn  after  a  few  minutes.  The  effect  of  adaptation  is  still  better  shown  by 
the  experiment  of  taking  three  basins  of  water,  a,  b,  and  c  ;  a  contains  cold 
water,  b  tepid  water,  c  hot  water.  The  left  hand  is  immersed  in  the  cold 
water  and  the  right  hand  in  the  hot  water  for  a  few  minutes.  On  now  placing 
both  hands  into  the  basin  of  tepid  water  it  feels  hot  to  the  left  hand  and  cold 
to  the  right  hand.  Such  experiences  as  this  led  Weber  to  the  conclusion 
that  the  essential  stimulus  for  the  temperature  sense  was  not  the  actual 
temperature  to  which  the  sense  organs  were  subjected,  but  the  fact  of  a 
change  of  temperature.  He  imagined  that,  while  the  temperature  sense- 
organs  were  being  warmed,  a  sensation  of  warmth  was  produced,  and  when 
their  temperature  was  being  lowered,  a  sensation  of  cold.  Such  a  theory 
would  not  however  account  for  the  fact  that,  above  a  certain  tempera- 
ture, water  may  feel  warm  and  the  feeling  may  continue  so  long  as  the  skin 
continues  to  be  stimulated.  On  a  cold  day  the  air  may  feel  cold  to  the  face 
and  the  feeling  may  last  the  whole  time  that  the  face  is  exposed.  Moreover 
we  have  in  the  temperature  sense  conditions  which  remind  one  of  the  after 
images  which  occur  in  the  eye.  If  a  penny  be  pressed  on  the 
forehead  and  then  removed  the  sensation  of  cold  lasts  some  little 
time  after  the  penny  has  been  removed.  In  this  case  a  sensation 
of  cold  is  produced  although  the  end  organs  are  being  gradually 
warmed  up  after  the  removal  of  the  penny.  In  order  to  account 
for  these  facts  Hering,  at  a  time  when  the  differentiation  of  hot  and  cold 
spots  had  not  yet  been  effected,  suggested  that  the  temperature  sense  organs 
could  be  regarded  as  having  a  zero  point  at  which  no  sensation  was  produced. 
If  their  temperature  was  raised  above  this  point  a  sensation  of  warmth  was 
produced  and  vice  versa.  The  zero  point  however  was  not  a  fixed  one.  but 
could  move  upwards  to  a  certain  extent  on  prolonged  exposure  to  high 
temperature,  or  downwards  on  prolonged  exposure  to  a  low  temperature. 
In  the  light  of  the  researches  of  Blix  and  Goldscheider  we  should  have  to 
apply  Hering's  theory  of  a  zero  point  to  each  of  the  temperature  end  organs 
separately. 

A  cold  pencil  passed  over  a  warm  spot  evokes  no  sensation  whatsoever. 
If  however  a  pencil  considerably  warmer  than  the  skin  be  passed  over  a  cold 
spot,  this  may  be  excited  so  that  the  paradoxical  result  is  produced  of  a 
sensation  of  cold  as  the  result  of  stimulation  by  a  warm  body.  It  is  a 
familiar  fact  that  the  immediate  effect  of  entering  a  hot  bath  is  very  much 
the  same  as  that  of  entering  a  cold  bath,  viz.  a  rise  of  blood  pressure  and 
contraction  of  the  unstriated  muscles  of  the  skin  and  hair  follicles  with  the 
production  of  '  goose  skin.'  It  has  been  suggested  that  the  distinctive 
quality  of  a  sensation  of  hoi  as  compared  with  that  of  warm  is  due  to  the 


CUTANEOUS  SENSATIONS  629 

simultaneous  stimulation  of  warm  spots  and  cold  spots.  When  testing  the 
distribution  of  the  temperature  sense,  it  is  found  that  the  sense  of  cold  is 
evoked  more  promptly  than  that  of  warmth.  This  is  interpreted  as  showing 
that  the  end  organs  for  the  warm  sense  are  situated  more  deeply  than  those 
for  coli  1.     \\'e  have  no  evidence  as  to  the  histological  identity  of  these  organs. 

THE   SENSE   OF  TOUCH 

By  means  of  the  sense  of  touch  we  arrive  at  a  conclusion  as  to  the  qualities, 
such  as  shape,  texture,  hardness,  &c,  of  the  bodies  with  which  the  skin 
is  m  contact.  In  this  judgment  however,  very  many  other  sensations 
are  involved  besides  those  which  can  be  regarded  as  strictly  tactile.  Thus 
the  hardne:' .  of  an  object  signifies  its  resistance  to  deformation,  besides 
its  power  of  deforming  the  skin  surface  with  which  it  is  in  contact ;  the 
former  quality,  i.e.  of  resistance,  is  one  which  involves  the  muscular  sen.se. 
since  we  judge  of  it  by  the  extent  to  which  we  can  move  our  muscles  without 
causing  any  alteration  of  the  surface  of  the  object. 

The  tactile  sensibility  of  the  skin  as  a  whole,  like  its  temperature  sensi- 
bility, is  due  to  the  presence  in  it  of  a  number  of  touch  spots,  i.e.  small 
areas  which  are  extremely  sensitive,  separated  by  areas  almost  or  entirely 
insensitive  to  pressure.  The  tactile  sensibility  of  any  part  is  proportional 
to  the  number  of  such  toucli  spots  present.  If  the  calf  of  the  leg  be  shaved 
and  then  tested  by  pressing  on  it  with  a  fine  bristle  or  hair  it  will  be  found 
that  the  minimal  stimulation  used  evokes  sensation  only  at  certain  definite 
points,  the  '  touch  spots.'  In  a  square  centimetre  of  such  skin  there  may 
be  about  fifteen  touch  spots.  On  thrusting  a  fine  needle  into  one  of  these 
spots  a  sharply  localised  sensation  of  pressure  is  produced  unaccompanied 
by  any  painful  quality  and  often  described  as  having  a  '  shotty  '  character, 
as  of  a  little  hard  object  embedded  in  the  skin  and  there  pressed  upon. 
These  touch  spots  are  arranged  chiefly  around  the  hairs,  lying  usually 
on  the  side  from  which  the  hair  slopes.  They  vary  in  number  according 
to  the  part  of  the  body  which  is  the  subject  of  investigation.  Thus  the 
dorsal  surface  of  the  finger  contains  about  seven  times  as  many  touch  spots 
as  an  equal  area  between  the  shoulders.  In  some  regions,  such  as  the 
skin  over  subcutaneous  surfaces  of  bone,  as  much  as  one  centimetre  may 
intervene  between  two  neighbouring  touch  spots.  They  have  no  relation 
to  the  warm  and  cold  spots  ;  they  are  entirely  absent  from  the  cornea,  the 
glans  penis,  and  the  conjunctiva  of  the  upper  lid. 

RESPONSE  TO  DIFFERENT  STIMULI.  The  adequate  stimulus 
for  these  tactile  nerve  endings  is  not  so  much  pressure  as  deforma- 
tion of  surface.  It  appears  to  matter  little  whether  the  surface  be 
deformed  by  pulling  it  or  by  pushing  an  instrument  into  it.  The 
ineffectiveness  of  mere  pressure  is  shown  by  dipping  the  finger  into  a 
vessel  of  mercury.  The  sensation  of  pressure  is  noted  only  at  the  point 
where  the  finger  passes  through  the  surface  of  the  mercury,  and  this  is  fche 
only  part  where  there  is  an  actual  deformation  of  the  skin,  due  to  the  sudden 


630  PHYSIOLOGY 

passage  from  the  pressure  of  the  mercury  to  the  negligible  pressure  of  the 
outside  air.  The  tactile  apparatus  is  smarter  in  its  response  than  any  other 
of  the  sense  organs.  On  this  account  stimuli  are  still  perceived  as  discrete, 
when  they  are  repeated  at  a  rhythm  which  would  result  in  complete  fusion 
in  the  case  of  any  of  the  other  sense  organs.  Thus  if  a  bristle  be  attached 
to  a  tuning-fork  and  allowed  to  press  on  the  skin,  the  vibrations  of  the 
fork  are  perceived  by  the  ear  as  a  continuous  sound  and  by  the  skin  as 
a  series  of  discontinuous  taps.  Faradic  currents  when  applied  to  the 
skin  can  be  perceived  as  separate  when  repeated  at  the  rate  of  L30  per 
second.  The  sensations  evoked  by  placing  the  finger  against  the  edge  of  a 
cog-wheel  do  not  become  continuous  until  the  wheel  is  revolving  at  such  a 
rate  that  the  stimulation  on  the  skin  by  the  serrations  occurs  at  a  greater 
rate  than  500  or  600  per  second.  The  tactile  apparatus  resembles  all  the 
other  skin  sense  organs  in  showing  adaptation.  A  stimulus  after  continuing 
for  some  time  may  become  ineffective.  We  are  usually  entirely  unaware 
of  the  stimulation  of  our  skin  by  the  pressure  of  the  clothes,  and  even 
an  unwonted  stimulation,  such  as  that  of  the  mucous  membrane  of  the 
mouth  by  a  plate  carrying  artificial  teeth,  though  almost  unbearable  during 

==1 


I'm:.  315.     Hair  mounted  on  a  wooden  handle,  and  used 
by  von  Frey  for  testing  tactile  sensibility. 

the  first  day,  rapidly  becomes  less,  and  in  a  few  days  it  is  not  perceived 
at  all. 

In  order  to  test  the  sensitiveness  of  touch  we  may  use  the  method  in- 
troduced by  Hensen,  viz.  the  bending  of  a  glass-wool  fibre.  We  can 
determine  the  pressure  at  which  any  given  fibre  will  bend,  and  if  we  find 
by  trial  the  fibre  which  just  evokes  sensation  when  pressed  on  the  skin, 
we  know  exactly  the  force  which  we  are  applying  to  the  skin.  Von  Frey 
employed  hairs  of  different  thickness  for  the  same  purpose  (Fig.  315).  The 
following  represents  the  minimal  excitability  of  the  surface  of  different 
parts  of  the  body  when  tested  in  this  way. 


Tongue  and  nose  .... 

2 

Lips      ...... 

2-5 

Finger-tip  and  forehead 

3 

Back  of  finger        .... 

5 

Palm,  arm,  thigh  .... 

7 

Fore-arm        ..... 

8 

Back  of  hand         .... 

12 

( lalf,  shoulder           .... 

16 

Abdomen       ..... 

26 

Outside  of  thigh    .... 

26 

Shin  and  sole          .... 

28 

Back  of  lore  arm  .          .          ■  .       ■ 

33 

Loins    ...... 

48 

CUTANEOUS  SENSATIONS  63] 

The  sensitiveness  of  the  sense  organs  in  the  skin  is  probably  much 
greater  than  that  of  the  nerve  trunks  themselves.  Thus  Tigerstedt  found 
that  the  minimal  mechanical  stimulus  necessary  to  excite  the  exposed 
nerve  amounted  to  G"2  grm.  moving  at  140  mm.  per  second.  For  the  touch 
spots  von  Frey  found  that  0'2  grm.  moving  at  0"17  mm.  a  second  is  an 
adequate  stimulus. 

In  testing  the  sensibility  of  any  surface  it  is  important  to  remember 
that  the  hairs  themselves  form  very  effective  tactile  organs.  The  touch 
spots  are  distributed  in  greatest  profusion  around  hair  follicles,  and  there 
is  a  rich  plexus  of  nerve  fibres  round  the  root  of  each  hair.  A  slight  touch 
applied  to  the  hair  acts  on  these  as  on  the  long  end  of  a  lever,  the  hair  being 
pivoted  at  the  surface  of  the  skin,  so  that  pressure  on  the  hair  is  transmitted, 
increased  five  or  more  times  in  force,  to  the  hair  follicle  and  the  surrounding 
nerve  endings.  The  actual  sensibility  of  any  part  is  therefore  much  dimin- 
ished by  removal  of  the  hairs.  On  9  sq.  mm.  of  the  skin,  from  which  the 
hairs  had  been  shaved,  the  minimal  stimulus  necessary  to  evoke  a  tactile 
sensation  was  found  to  be  36  mg.,  whereas  on  the  same  surface  before  it  was 
shaved  2  mg.  was  effective. 

WEBER'S  LAW.  The  smallest  increment  or  decrement  of  stimulus 
which  determines  a  perceptible  difference  of  sensation  must,  according 
to  Weber's  law,  always  bear  the  same  ratio  to  the  whole  stimulus.  In 
measuring  such  differences  it  is  best  to  apply  the  stimulus  successively  to 
the  same  surface  of  the  skin  rather  than  simultaneously  to  adjoining  areas. 
The  time  interval  between  two  successive  stimuli  should  not  be  more  than 
five  seconds  and  the  duration  of  the  stimuli  should  be  equal.  Weber  found 
that  in  the  terminal  phalanx  of  the  finger  the  minimal  perceptible  difference 
was  about  one-thirtieth,  but  the  ratio  was  not  the  same  for  all  regions  of 
the  skin  nor  for  all  individuals.  The  following  represents  the  liminal 
difference  in  various  skin  regions  : 

Forehead,  lips,  and  cheeks   .         .         .         l/30th  to  l/40th 
Back  of  fore-arm,  of  leg,  and  of  thigh  ;  | 

back  of  hand,  and  first  and  second  ,-      1  /10th  to  1  /20th 

phalanx  of  finger,  &c.    .  .  .J 

All  parts  of  the  foot,  surface  of  leg,  and 

tliigh    ......         more  than  l/10th 

THE  SPATIAL  QUALITY  OF  TOUCH.  DISCRIMINATION.  If  any 
part  of  the  skin  be  stimulated  the  subject  of  the  experiment  can  tell  at  once 
the  exact  situation  of  the  excited  spot.  If  two  points  be  stimulated  simul- 
taneously excitation  is  perceived  as  double,  i.e.  as  proceeding  from  two 
points,  provided  the  distance  between  the  points  exceeds  a  certain  amount, 
varying  in  different  parts  of  the  body.  The  power  of  discrimination,  i.e. 
of  judging  whether  a  stimulus  is  single  or  double,  can  be  tested  by  arming 
the  points  of  a  pair  of  compasses  with  small  pieces  of  cork  and  then  seeing 
how  far  apart  the  points  must  be  when  pressed  on  the  skin  in  order  that  t  he 
stimulus  may  be  perceived  as  double.  The  following  Table  represents  this 
distance  for  various  regions  of  the  body : 


632  PHYSIOLOGY 

Distance  in  mm. 

Skin  region.  mm. 

Tip  of  tongue  ........  11 

2-3 
6-8 
11-3 
31-6 
540 
67-1 


Volar  surface  of  finger  tip 

Dorsum  of  third  phalanx 

Palm  of  hand  . 

Back  of  hand  . 

Back  of  neck   . 

Middle  of  back,  upper  arm,  and  thigl 


When  touch  spots  are  sought  out  for  stimulation  with  the  points  of  a 
compass,  the  distance  at  which  the  excitation  is  perceived  as  double  is 
much  diminished,  as  is  shown  by  the  following  Table  of  distances  for  the 
touch  spots  in  millimetres  : 

Skin  region.  Distance  of  touch  spota. 

Volar  side  of  finger  lips       .         .         .         .         .  til 

Palm  of  hand      .......  0-1 

Fore-arm  (flexor  .side)  ......  0-5 

Upper  arm  .......  0-6 

Back 0-4 

The  compass  points  are  perceived  to  lie  apart  with  a  special  distinctness 
when  they  are  applied  to  touch  spots  lying  on  different  lines  which  radiate 
from  the  hair  follicles.  The  figures  given  in  the  first  Table  have  no  relation 
to  touch  spots,  but  show  the  average  distance  over  which  an  excitation 
can  be  perceived  as  double. 

The  delicacy  of  discrimination  of  any  part  is  largely  associated  with 
its  mobility.  Thus  in  the  arm  the  delicacy  increases  continuously  from 
the  shoulder  to  the  finger-tip.  If  the.  localising  power  for  touch  on  the 
shoulder  be  taken  as  100,  that  of  the  finger  tips  will  be  represented  by  2582. 
In  the  same  way  there  is  a  continuous  decrease  of  the  distances  of  discrimina- 
tion as  we  pass  along  the  cheek  from  the  ear  to  the  lip,  i.e.  from  the  non- 
mobile  to  the  mobile  part.  The  power  of  discrimination  is  increased  to  a 
certain  extent  by  practice  and  largely  diminished  by  fatigue.  Any  factor 
which  diminishes  the  tactile  sensibility  of  the  part,  such  as  cold,  will  also 
diminish  the  power  of  discrimination. 

LOCALIZATION  OF  TOUCH.  The  fact  that  we  can  localise  the 
point  of  stimulation  shows  that  every  tactile  sensation  derived 
from  the  surface  of  the  body,  besides  the  qualities  of  intensity  and 
extensity,  has  also  associated  with  it  a  characteristic  quality  de- 
pendent on  its  position.  This  localised  quality  of  a  tactile  sensation  was 
called  by  Lotze  '  local  sign.'  Among  psychologists  there  has  been  much 
discussion  as  to  how  far  this  '  local  sign  '  is  an  inborn  attribute  of  the  sensa- 
tion of  every  point  on  the  body  surface,  or  how  far  it  is  acquired  by  ex- 
perience and  based  on  memory  of  movements  and  muscular  impressions. 
In  the  retina  we  have  a  sense  organ  which,  like  the  skin,  possesses  local 
sign,  but  in  far  higher  degree,  the  power  of  discrimination  of  the  retina 
being  three  thousand  times  as  great  as  that  of  the  most  sensitive  part  of 
the  skin.  Cases  of  congenital  cataract  occur  in  which  the  subjects  have 
been  blind  from  birth.     By  extraction  of  the  cataract  we  can  give  such 


CUTANEOUS  SENSATIONS  633 

persons  the  power  of  sight.  It  is  found  that  at  first  there  is  no  power  of 
localising  visual  impressions.  The  '  local  sign  '  is  developed  only  in  re- 
sponse to  experience,  by  comparing  simultaneous  visual,  tactile,  and  motor 
sensations.  By  analogy  we  might  ascribe  the  local  sign  of  cutaneous 
sensations  to  a  similar  causation.  Our  study  of  the  spinal  animal  has 
indeed  given  us  a  physical  or  histological  conception  of  local  sign.  We 
know  that  stimulation  of  any  part  of  the  body  evokes  an  appropriate  reaction, 
the  nature  of  which  is  determined  by  the  central  connections  of  the  entering 
nerve  fibres.  A  fibre  entering  at  one  segment  must  therefore  come  into 
relation  with  a  different  set  of  motor  cells  from  those  which  are  set  into 
action  by  a  fibre  entering  one  segment  lower  down.  Every  nerve  fibre 
from  the  skin  will  therefore  have  an  appropriate  complex  of  motor  paths 
in  functional  connection  with  its  central  endings,  and  when  the  activity  of 
these  reflex  paths  comes  to  be  represented  in  consciousness,  it.  is  evident 
that  the  sensation  derived  from  each  point  must  differ  from  that  derived 
in  >in  any  other  point  of  the  skin  by  virtue  of  the  differing  motor  events 
actually  or  potentially  excited  from  the  two  points.  In  ascribing  therefore 
'  local  sign  '  to  coincident  muscular  sensations,  and  to  the  memory  and 
experience  of  past  movements,  we  are  giving  but  an  imperfect  explanation  ; 
since  the  difference  between  the  sensations  from  different  parts,  which  are 
at  the  bottom  of  our  powers  of  localisation,  has  its  origin  in  the  structure 
of  the  central  nervous  system  itself  and  is  present  from  the  very  beginning 
of  the  evolution  of  a  reactive  nervous  system. 

PROJECTION  OF  TOUCH.  Since  the  alterations  in  the  surface  of  the  skin 
which  give  rise  to  tactile  sensations  are  habitually  caused  by  contact  with 
external  objects,  we  come  to  regard  the  sensations  themselves,  not  as 
changes  in  the  skin,  but  as  qualities  of  the  object  which  touch  the  skin,  i.e. 
we  project  the  sensation.  The  projection  is  however  not  so  great  as  in 
the  case  of  visual  sensations.  Cutaneous  sensations  we  always  consider 
as  qualities  of  an  object  immediately  affecting  and  altering  the  condition 
of  ourselves,  whereas  the  visual  sensations  are  referred  at  once  to  objects 
lying  right  away  from  ourselves,  so  that  we  are  not  aware  that  any  change 
has  taken  place  in  our  bodies  as  a  result  of  the  entering  of  rays  of  light  into 
the  eye. 

It  is  remarkable  to  what  extent  projection  of  touch  sensation  may 
occur.  Thus  a  surgeon  actually  lengthens  his  fingers  by  using  a  probe. 
When  he  is  probing  for  dead  bone  he  feels  the  grating  of  the  bone,  not  at 
his  finger-tips,  but  he  projects  the  sensation  to  the  end  of  the  probe.  In 
the  same  way  tactile  sensations  evoked  by  the  contact  of  bodies  with  the 
insentient  endings  of  hair  are  referred  to  the  ends  of  the  hairs  rather  than 
to  the  hair  follicles  where  the  nerve  impulses  actually  come  into  being. 

The  dependence  of  local  sign  on  habitual  experience  is  shown  by 
the  various  tactile  illusions,  such  as  the  well-known  experiment  of  Aris- 
totle. If  with  the  eyes  shut  we  cross  the  first  and  middle  fingers  and  bring 
them  in  this  position  in  contact  with  a  pea,  we  should  at  once  say  that  two 
peas  lay  under  the  fingers.     This  is  especially  marked  if  the  pea  be  rolled 


634  PHYSIOLOGY 

lid  wren  the  lingers.  The  two  sides  of  the  fingers  which  come  in  contact 
with  the  pea  usually  touch  two  different  objects,  and  these  parts  of  the 
skin  would  have  to  be  re-educated,  i.e.  their  local  sign  would  have  to  be 
changed  in  accordance  with  the  changed  conditions,  before  the  pea  would 
be  perceived  in  its  true  state  as  single. 

THE   PAIN   SENSE 

When  the  pressure  of  a  hard  object  on  the  skin  is  increased  beyond  that 
necessary  to  evoke  a  tactile  sensation,  at  a  certain  pressure  the  quality 
of  sensation  changes  and  it  becomes  painful.  For  the  evolution  of  the 
race  as  well  as  for  the  preservation  of  the  individual  this  pain  sense  is  all- 
important  ;  it  is  the  expression  in  consciousness  of  the  reflexes  of  self- 
preservation  which  can  be  evoked  in  the  spinal  animal  by  stimuli  which  are 
nocuous,  i.e.  calculated  to  do  actual  damage  to  the  tissues  of  the  body.  Thus 
when  a  sharp  point  is  pressed  on  the  skin  the  sensation  becomes  painful  just 
before  the  pressure  is  sufficient  to  cause  penetration.  The  so-called  trophic 
lesions  which  occur  in  parts  devoid  of  sensation  are  determined  for  the 
most  part  by  the  lack  of  the  pain  sense  and  the  consequent  failure  of  the 
preservative  reflexes  of  the  part.  It  is  remarkable  that  pain  may  result 
from  changes  in  organs  which  are  devoid  of  ordinary  sensibility.  Thus 
the  intestine  may  be  cut,  sewn,  or  handled  without  arousing  any  sensation 
whatsoever.  A  strong  contraction  of  the  muscular  wall  or  increased  dis- 
tension of  the  gut  will  however  evoke  a  griping  pain.  In  the  same  way 
the  ureters,  which  are  normally  devoid  of  sensation,  can  give  rise  to  ex- 
cruciating agony  when  they  are  contracted  firmly  on  a  retained  calculus. 

We  are  accustomed  to  distinguish  many  different  qualities  of  pain, 
but  on  analysis  it  will  be  found  that  these  qualities  depend  on  the  nature 
of  the  sense  organ  which  is  simultaneously  stimulated.  Thus  a  burning 
pain  denotes  simultaneous  stimulation  of  the  pain  sense  and  of  the  nerve 
endings  to  the  warm  spots.  A  throbbing  pain  results  when  the  vessels 
of  the  part  are  dilated  and  the  part  is  tense  with  effused  lymph,  so  that 
each  pulse  of  the  vessels  causes  an  exacerbation  of  the  painful  stimulation 
and  perhaps  also  stimulation  of  the  tactile  end  organs. 

The  sense  of  pain  has  often  been  ascribed  to  over-maximal  stimula- 
tion of  any  form  of  sensory  nerve.  Although  it  is  true  that  over-stimulation 
of  the  auditory  or  optic  nerve  by  a  loud  sound  or  a  bright  light  may  be 
extremely  unpleasant,  the  sensations  evoked  do  not  partake  of  the  characters 
of  painful  sensations  such  as  would  be  produced  by  pricking  or  burning  the 
skin.  Moreover  a  careful  investigation  of  the  sensory  points  on  the  skin 
brings  out  the  fact  that  there  are  besides  the  tactile  and  temperature  sj>ots, 
other  spots  from  which  only  painful  sensations  can  be  evoked.  We  have 
seen  already  that  over-stirnulation  of  a  touch  spot  does  not,  as  a  matter  of 
fact,  cause  pain.  The  pain  spots  which  are  distributed  among  the  touch  and 
temperature  spots  are  insensitive  to  a  low  grade  of  stimulus.  As  the 
strength  of  the  stimulus  is  increased  a  point  is  suddenly  reached  at  which 
the  sensation  evoked  is  painful.     Moreover  in  parts  of  the  body  tactile  and 


CUTANEOUS   SENSATIONS  635 

temperature  sense  are  entirely  wanting,  though  painful  impressions  can  be 

easily  evoked.  The  best  example  of  this  is  seen  in  the  cornea,  minimal 
stimulation  of  which  evokes  pain,  but  nothing  which  can  be  regarded  as 
a  tactile  sensation.  The  specific  quality  of  pain  sensation  is  shown  more- 
over by  the  fact  that  in  many  cases  of  disease  the  sense  of  pain  may  be 
abolished  without  the  sense  of  touch.  Such  a  patient  is  said  to  suffer 
from  analgesia,  but  not  anaesthesia.  When  pricked  on  an  analgesic  part 
the  patient  can  say  that  he  is  pricked,  but  has  no  objection  to  any  amount 
of  repetition  of  the  stimulus,  since  the  sensation  is  entirely  devoid  of  painful 
character.  In  the  case  of  the  skin  the  sense  organs  concerned  in  pain 
appear  to  be  the  free  intra-epithehal  nerve  endings.  Pain  is  found  to  differ 
somewhat  from  the  other  skin  sensations  in  being  much  more  uniformly 
distributed,  more  difficult  to  locate  accurately,  and  more  hardy.  Thus 
while  most  sense  organs  are  rendered  less  sensitive  by  cutting  off  blood 
supply,  pain  at  first  reacts  more  violently. 

THE   WORK   OF    HEAD    ON   CUTANEOUS   SENSIBILITY 

In  a  long  series  of  researches  on  man  Head  has  shown  that  three  different 
classes  of  sensations  may  be  evoked  by  stimuli  applied  to  the  surface  of 
the  body.  In  order  to  study  the  functions  of  the  afferent  nerves  Head 
has  investigated  not  only  the  condition  of  patients,  the  subjects  of  accidental 
division  of  cutaneous  or  other  nerves,  but  also  (in  conjunction  with  Rivers) 
the  effects  of  nerve  section  on  himself.  In  the  first  place,  it  is  necessary  to 
differentiate  deep  sensibility  from  cutaneous  sensibility  proper.  After 
desensitisation  of  any  given  area  of  the  skin  it  is  still  possible  in  this  area 
to  appreciate  deep  pressure  and  pain,  and  the.  localisation  of  the  situation 
of  the  pressure  is  fairly  accurately  carried  out.  On  the  other  hand,  the 
sensations  of  light  touch,  as  well  as  of  temperature  and  the  pain  evoked 
by  a  light  pin  prick,  are  absent.  The  sensations  of  pressure,  as  well  as  of 
deep  pain  or  pressure  pain,  are  therefore  carried  by  the  nerves  of  deep 
sensibility.  These  nerves  are  not  the  cutaneous  nerves,  but  are  derived 
from  the  sensory  elements  in  the  muscular  nerves.  To  the  fingers,  for 
instance,  they  run  in  the  tendons  of  the  muscles.  Simultaneous  division,  as 
by  a  circular-saw  cut,  of  the  cutaneous  nerves  and  tendons  to  the  fingers  will 
abolish  deep  as  well  as  superficial  sensibility.  Deep  sensibility  must  there- 
fore be  classified,  anatomically  at  any  rate,  with  the  '  organic  sensations  ' 
of  muscular  effort  and  of  position,  which  will  be  dealt  with  in  a  subsequent 
section. 

Cutaneous  sensibility  proper  Head  divides  into  two  categories,  namely, 
protopathic  and  epicritic  sensibility.  These  two  forms  of  sensibility  may 
be  studied  separately  on  an  area  of  skin,  which  has  been  desensitised  by 
section  of  its  cutaneous  nerves,  during  the  process  of  regeneration  of  these 
nerves. 

Prolopathic  sensibility  returns  to  the  skin  at  an  interval  of  seven 
to  twenty-six  weeks  after  the  nerve  section.  At  this  time  it  is  possible 
to  appreciate  in  the  area  under  investigation  the  sensation  of  pain,  and 


036  PHYSIOLOGY 

to  recognise  roughness  of  an  object  rubbed  on  the  skin.  Localisation 
is  still  somewhat  diffuse  and  inaccurate,  so  that  the  sensation  evoked  by 
stimulation  of  the  protopathic  area  may  be  referred  to  some  adjoining  normal 
part  of  the  skin.  The  temperature  sense  is  also  present,  but  of  a  low  grade. 
Thus  heat  over  38°  C.  and  cold  under  24°  C.  can  be  appreciated  as  such, 
but  the  intervening  temperatures  produce  no  sensation.  Sensations  evoked 
in  the  protopathic.  area  are  strongly  endowed  with  what  may  be  termed 
'  affective  '  character.  Thus  painful  stimulation  is  much  more  unpleasant 
when  applied  to  this  area  than  would  a  similar  stimulation  be  when  applied 
to  a  normal  area  of  skin. 

In  contradistinction  to  the  deep  sensibility  which  is  diffuse,  protopathic 
sensibilitv  is  distributed  in  spots,  so  that  heat  and  cold  spots  for  instance 
may  be  distinguished  as  on  the  normal  skin.  It  is  interesting  that  the 
glans  penis  is  normally  provided  only  with  protopathic  sensibilitv. 

E-picriticsensibilit.il  docs  not  return  to  the  desensitised  area  until 
one  to  two  years  have  elapsed  since  the  division  of  the  nerves.  With 
its  return  the  affective  character  of  the  protopathic  sensations  at  once 
disappears  and  is  replaced  by  an  accurate  discrimination  of  the  nature  and 
extent  of  the  stimulus"1;  the  tactile  sense  proper,  i.e.  the  appreciation  of  the 
lightest  touch  applied  to  the  skin  and  its  accurate  localisation,  belonging 
entirely  to  the  epicritic  sensations.  The  power  of  discriminating  the 
distance  between  two  points  applied  to  the  skin  simultaneously  is  also  a 
function  of  the  epicritic  sensibility. 

With  the  discriminating  tactile  sense  returns  also  the  power  of  appre- 
ciating fine  differences  of  temperature,  i.e.  differences  between  26°  and 
37°  C. 

This  classification  may  be  summed  as  follows  : 

Deep  sensibility     .  .  .   including    [Pressure  sense 

(.Pressure  pain 

[  Skin  pain 
Protopathic  sensibility     .  ,,         -:  Heat  over  38"  C. 

(characters:    high   threshold,  ^Cold  under  24°  C. 

painful  and  indefinite) 

/Tactile  sense  proper 
Pain  localisation 
Epicritic  sensibility  .  „        <  Discrimination 

(characters:  accurately  local-  Heat  and  cold  between 

ised,  low  threshold)  V     26°  and  37°  C. 

Head  and  Thompson  have  shown  that  on  entering  the  cord  these  various 
sensations  undergo  a  new  grouping.  Thus  the  pain  impulses,  which  arise 
in  and  are  carried  by  the  muscular  nerves,  the  nerves  of  deep  sensibility, 
unite  with  those  which  run  in  the  protopathic  system,  so  that  a  lesion  of  the 
cord  affecting  the  pain  tracts  will  abolish  all  forms  of  pain,  whether 
arising  from  the  skin  or  from  the  underlying  tissues.  In  the  same  way  all 
temperature  sensations,  whether  the  fine  ones  of  the  epicritic  system  or  the 
coarser  ones  of  the  protopathic  system,  run  together  in  the  cord.     If  the 


CUTANEOUS  SENSATIONS 


637 


heat  sense  is  affected  by  a  lesion  of  the  cord  all  forms  and  all  degrees  of  the 
sensation  are  affected  in  like  measure,  and  the  same  applies  to  the  sensations 
of  cold. 

The  conduction  paths  of  these  different  sensations  in  the  cord  are  shown 
in  Fig.  176  on  page  358. 

THE   HISTOLOGICAL  CHARACTER   OF  THE   ELEMENTS 
INVOLVED   IN  CUTANEOUS   SENSATIONS 

A  very  large  number  of  different  forms  of  sensory  nerve  endings  have 
been  described  in  relation  to  the  skin.  Their  exact  allocation  among  the 
different  cutaneous  senses  presents  considerable  difficulties. 


Fig.  316.     Skin  end  organs  and  the  sensations  which  they  arouse. 

As  regards  touch,  two  kinds  of  elements  are  probably  involved.  In 
the  first  place,  the  most  sensitive  tactile  apparatus  are  the  follicles  of  the 
short  hairs.  Around  these  follicles  we  find  a  sheaf  of  nerve  fibres,  some 
of  which  end  in  the  hair  papilla  and  others  form  a  ring  near  the  level  of  the 
openings  of  the  sebaceous  glands.  The  other  tactile  end  organ  is  Meissner's 
corpuscle.  The  distribution  of  these  in  the  skin  is  not  however  dissimilar 
to  that  of  the  power  of  discrimination,  with  which  they  may  be  specially 


638  PHYSIOLOGY 

connected.  Other  end-organs  which  are  supposed  to  be  stimulated  by 
changes  of  pressure  and  therefore  to  be  tactile,  are  the  organs  of  Ruffini 
which  occur  in  the  papillae  of  the  palm  and  fingers  and,  lying  more  deeply, 
the  elastic  tissue  spindles  as  well  as  the  Golgi  corpuscles  and  the  Pacinian 
corpuscles  in  the  subcutaneous  tissue. 

As  regards  pain,  we  know  that  in  the  cornea,  which  possesses  only 
the  pain  sense,  the  sensory  nerve-endings  are  in  the  form  of  branches  of 
axis  cylinders  among  the  epithelial  cells.  Similar  free  nerve  endings  occur 
in  the  epidermis  all  over  the  body,  and  it  is  therefore  imagined  that  these 
have  the  special  function  of  subserving  the  pain  sense.  We  have  at  present 
no  evidence  as  to  the  histological  character  of  the  organs  by  which  the 
sensations  of  heat  and  cold  are  aroused. 


PAET  VI 

SENSATIONS    OF    SMELL    AND    TASTE 

Every  living  organism  shows  a  susceptibility,  i.e.  a  power  of  reaction, 
to  cliemical  stimuli.  Thus  the  plasmodium  of  nryxomycetes,  placed  on  a 
strip  of  filter-paper  of  which  one  end  is  immersed  in  an  infusion  of  dead 
leaves  and  the  other  in  distilled  water,  will  crawl  along  the  paper  towards 
the  infusion  of  leaves.  If  the  infusion  of  dead  leaves  be  replaced  by  a 
weak  solution  of  quinine,  the  plasmodium  will  be  repelled  and  will  travel 
along  towards  the  vessel  of  water.  These  movements  of  attraction  and 
repulsion  are  spoken  of  as  positive  and  negative  chemiotaxis  respectively. 
A  similar  chemical  sensibility  accounts  for  the  clustering  of  aerobic  bacteria 
towards  the  surface  of  a  fluid,  i.e.  where  the  density  of  oxygen  is  greater,  or 
around  chlorophyll-containing  algae  which  are  giving  off  oxygen  in  the 
sunlight.  The  aggregation  of  leucocytes  round  microbes  or  other  foreign 
particles  in  the  tissues  is  also  determined  by  their  chemiotactic  sensibility. 
Chemiotaxis  then  represents  the  faculty  by  means  of  which  these  minute 
organisms  are  able  to  adapt  themselves  to  chemical  changes  in  their  environ- 
ment and  to  react  to  chemical  substances  at  a  considerable  distance  from 
themselves.  If  we  could  endow  these  elementary  organisms  with  con- 
sciousness and  with  a  sense  of  their  surroundings,  we  should  have  totsay 
that  they  became  aware  of  the  presence  of  some  harmful  or  attractive 
material  at  some  distance  from  themselves.  The  sensation  they  received 
from  these  distant  objects  would  be  therefore  a  projected  sensation. 

On  the  other  hand,  a  chemical  sensibility  of  the  body  surface  or  part 
of  it  furnishes  the  criterion  by  which  particles  are  accepted  and  ingested 
as  food  or  rejected  as  useless  or  harmful.  Consciousness  in  this  case  would 
be  of  something  affecting  and  in  contact  with  some  part  of  the  organism 
itself.  The  sensation  would  not  be  projected  further  than  the  periphery  of 
the  body. 

These  two  kinds  of  chemical  sense — the  projected  and  the  surface 
sense — are  found  throughout  almost  all  classes  of  the  animal  kingdom, 
and  in  the  higher  animals  at  least  are  known  as  the  senses  of  smell  and 
taste.  The  former  sense  in  many  animals  attains  a  high  degree  of  com- 
plexity and  is  prepotent  in  determining  the  behaviour  of  an  animal  in 
response  to  the  changes  in  its  surroundings.  In  the  elasmobranch  li  li- 
the olfactory  lobes  form  the  greater  part  of  the  higher  brain,  and  extirpation 
of  them  produces  a  loss  of  spontaneity  and  of  delayed  reactions  similar  to 
that  which  can  be  brought  about  in  higher  types  by  extirpation  of  the  whole 
of  the  cerebral  hemispheres. 


640 


PHYSIOLOGY 


The  sense  of  taste,  on  the  other  hand,  is  used  only  for  sampling  the  nature 
of  substances  taken  into  the  mouth  and  determining  their  ingestion  or 
rejection.  It  is  therefore  much  simpler  in  its  extent  and  more  susceptible 
of  analysis. 

THE  SENSE  OF  TASTE 
The  end  organs  which  subserve  the  function  of  taste  are  represented 
by  the  taste  buds.  These  are  oval  bodies  (Fig.  317)  embedded  in  the 
stratified  epithelium,  which  occur  scattered  over  the  tongue,  a  few  being 
also  found  on  the  hard  palate,  the  anterior  pillars  of  the  fauces,  the  tonsils, 
the  back  of  the  pharynx,  the  larynx,  and  the  inner  surface  of  the  cheek. 
On  the  tongue  they  are  found  chiefly  in  the  grooves  around  the  circumvallate 
papillae  of  man,  and  in  the  grooves  of  the  papillae  foliatse  of  rabbits.  A 
few  are  also  present  on  many  of  the  fungiform  papillae.  They  consist 
of  medullary  and  cortical  parts,  the  former  being  composed  of  columnar 
or  sustentacular  cells,  the  latter  of  thin  fusiform  cells,  the  taste  cells 
proper.  The  nerve  fibres  concerned  with  taste  end  in  arborisations  among 
these  taste  cells.  The  peripheral  end  of  the 
fusiform  cell  projects  as  a  delicate  process 
through  the,  orifice  of  the  taste  bud,  so 
that  it  can  come  in  contact  with  the  fluids 
contained  in  the  cavity  of  the  mouth.  A 
sapid  substance,  to  stimulate  these  organs, 
must  be  in  solution ;  hence  quinine  in 
powder  is  almost  tasteless,  owing  to  its 
slight  solubility  in  neutral  or  alkaline  fluids. 
DIFFERENTIATION  OF  TASTE.  The 
number  of  different  tastes  is  very  limited. 
We  distinguish  four  primitive  taste  sensa- 
tions, viz.  sweet,  sour,  bitter,  and  salt, 
some  authors  adding  to  this  an  alkaline 
taste  and  a  metallic  taste.  Many  sub- 
stances owe  their  distinctive  character  when 
taken  into  the  mouth  to  the  fact  that  they 
stimulate  not  only  the  taste' nerves  but 
also  the  nerve  endings  of  common  sensa- 
tion. Thus  acids,  when  in  weak  solution, 
have  an  astringent  character  besides  their 
sour  taste,  and  if  strong  produce  a  burning  sensation.  The  primitive 
taste  sensations  can  affect  one  another  if  excited  simultaneously. 
With  weak  stimulation  one  taste  may  practically  annul  another.  Thus 
a  dilute  solution  of  sugar  is  rendered  almost  tasteless  by  the  addition  to 
it  of  a  few  grains  of  common  salt.  If  the  primitive  taste  sensations  are 
more  strongly  excited  we  get  a  mixed  sensation,  in  which  the  components 
can  still  be  distinguished.  Thus,  adding  sugar  to  lemon  juice  not  only 
diminishes  its  acidity  but  produces  a  mixed  sensation,  the  quality  of  which 


Fig.  317.  Two  taste  buds 
from  the  tongue. 
e,  Stratified  epithelium  ; 
?V  opening  or  pore  of  taste 
bud  ;  s,  gustatory  cells  ; 
st,  sustentacular  cells. 

(KOIJUKEB.) 


SENSATIONS   OF  SMELL  AND   TASTE  641 

is  pleasant  and  in  which  the  components,  sour  and  sweet,  can  be  easily 
distinguished.  We  get  no  such  fusing  of  sensations  as  in  the  eye,  where 
a  sensation  of  white  light  may  result  from  stimulation  of  the  retina  by 
two  complementary  colours.  Stimulation  of  one  kind  of  taste  organ  heightens 
the  sensibility  of  the  other  taste  organs.  Thus  after  the  application  of  salt, 
distilled  water  may  taste  sweet. 

That  these  primitive  taste  sensations  are  served  by  different  nerve 
endings  is  shown  by  the  following  facts  : 

(a)  The  tongue  is  not  equally  sensitive  at  all  points  to  all  tour  tastes. 
Thus  the  back  of  the  tongue  is  more  sensitive  to  bitter,  while  the  tip  and 
sides  of  the  tongue  react  more  easily  to  sweet  and  sour  substances.  A  differ- 
ence may  be  detected  between  even  the  circuni vallate  papillae  themselves  ; 
a  mixture  of  quinine  and  sugar  applied  to  one  papilla  may  excite  chiefly 
a  bitter  taste,  while  with  an  adjacent  papilla  a  sweet  taste  may  predominate. 

(6)  By  certain  drugs  we  can  depress  the  sensibility  of  the  taste  organs, 
and  we  then  find  that  the  various  tastes  are  affected  to  different  degrees. 
Thus  on  painting  the  tongue  with  cocaine  the  first  effect  is  a  diminution 
of  tactile  and  pain  sensibility,  so  that  the  application  of  acid  evokes  a  very 
sour  taste  without  any  of  the  astringent  or  stinging  sensations  normally 
aroused  by  the  contact  with  the  acid.  After  this  point  the  taste  sensations 
are  also  abolished.  The  bitter  sensation  disappears  first,  then  the  sweet, 
and  then  the  sour,  while  the  taste  of  salt  appears  to  remain  unaffected.  On 
the  other  hand,  if  the  leaves  of  Gymnema  sylvestre  be  chewed,  the  sensations 
of  bitter  and  sweet  are  abolished,  leaving  intact  the  acid  and  salt  tastes, 
and  also  the  general  sensibility  of  the  mucous  membrane. 

TASTE  AND  CHEMICAL  CONSTITUTION.  There  is  no  doubt 
that  the  stimulating  effect  of  any  chemical  substance  on  the  taste 
nerves  has  relation  to  its  chemical  constitution.  Thus  a  sour  taste 
is  determined  by  the  presence  of  H  ions  ;  the  alkaline  taste  by  that 
of  OH  ions.  The  fact  that  certain  acids,  e.g.  acetic,  have  a  stronger  sour 
taste  than  would  correspond  to  their  dissociation,  i.e.  to  the  number  of  II 
ions  present,  is  due  to  the  fact  that  these  acids  penetrate  more  easily  into 
the  gustatory  cells  than  the  mineral  acids  with  a  larger  dissociation  co- 
efficient. All  the  «-amino-acids  have  a  sweet  taste.  On  the  other  hand, 
the  polypeptides  produced  by  the  combination  of  these  ammo-acids,  as 
well  as  the  peptones  derived  from  the  hydrolysis  of  proteins,  have  a  bitter 
taste.  Most  of  the  alcohols  and  sugars  have  a  sweet  taste,  while  the  metallic 
derivatives  of  these  substances  are  bitter.  We  do  not  yet  u u< lerstand  the 
law  which  determines  whether  any  given  substance  shall  have  a  taste  at 
all,  and  what  its  taste  should  be. 

The  nerves  of  taste  are  the  glossopharyngeal,  which  supplies  the  back 
part  of  the  tongue,  and  the  lingual  branch  of  the  fifth  nerve  and  the  chorda 
!  \  mpani,  which  supply  the  front  part.  All  these  fibres  are  probably  con- 
nected with  a  continuous  column  of  grey  matter  in  the  brain  stem,  which 
represents  the  splanchnic  afferent  nucleus  of  the  fifth  nerve,  the  nervus 
intermedins,    and    the   glossopharyngeal.     Some  authors  have  stated    that 

41 


642 


I'lfYSloLOKY 


all  the  taste  fibres  of  the  fifth  nerve  are  derived  from  the  glossopharyngeal 
by  the  communication  through  the  tympanic  plexus  and  the  chorda  tympani 
nerve,  while  Gowers  has  recorded  a  case  of  complete  unilateral  loss  of  taste 
in  which  there  was  a  lesion  destroying  the  fifth  nerve,  the  glossopharyngeal 
being  intact.  It  seems  possible  that  the  actual  region  of  the  taste  nerve- 
may  vary,  the  fibres  running  to  the  splanchnic  column  of  grey  matter  being 
contained  sometimes  in  the  fifth,  sometimes  in  the  glossopharyngeal,  and 
sometimes  in  both. 

Most  of  our  so-called  tastes  should  rather  be  designated  flavours,  and 
are  dependent,    not  on  the  gustatory  nerves,  but  on  the  sense  of  smell. 


Fig.  318.     Diagram  showing  origin  and  course  of  the  nerve  fibres  of  taste. 

When  the  olfactory  sense  is  destroyed  very  little  difference  is  to  be  perceived 
between  an  onion  and  an  apple.  The  epicure  with  a  fine  palate  has  really 
educated  his  sense  of  smell  and  would  be  but  little  satisfied  with  the  simple 
sensations  derived  from  his  four  sets  of  gustatory  end  organs. 


THE    SENSE    OF    SMELL 

The  psychical  analysis  of  olfactory  sensations  is  rendered  difficult 
by  the  fact  that  this  sense  in  man  plays  but  a  small  part  in  his  usual  adapta- 
tions. We  have  thus  to  deal  with  a  sense  which  is  in  many  respects  vestigial. 
We  see  traces  of  great  complexity  in  its  possibilities  of  performance,  but 
are  baffled  in  our  endeavours  to  reduce  the  whole  of  the  phenomena  to  the 
simpler  factors  of  which  they  are  composed.  Moreover,  like  all  vestigial  func- 
tions, the  extent  to  which  the  sense  is  developed  varies  from  one  individual  to 
another.  Many  for  instance  are  unable  to  appreciate  the  smell  of  vanilla, 
of  hydrocyanic  acid,  or  of  violets.  On  the  other  hand,  in  animals  such  as 
the  dog,  the  olfactory  sense  seems  to  play  a  great  part  in  determining 
behaviour,  and  the  nervous  associations,  which  are  the  physiological  basis 
of  ideas,  must  in  these  animals  be  largely  connected  with  olfactory  im- 


SENSATIONS  OF  SMELL  AND  TASTE 


643 


pressions.  Another  factor  which  diminishes  the  importance  of  olfactory 
sensations  in  man  is  the  ease  with  which  the  sense  organ  becomes  fatigued. 
It  often  happens  that  the  inmates  of  a  room  are  perfectly  comfortable 

and    may  perceive  no  fault  in  the  ventilation,  although  a  newcomer  fr 

the  outside  at  once  remarks  that  the  air  is  foul. 

THE  ORGAN  OF  SMELL  is  situated  at  the  upper  part  of  the  nasal  cavi- 
ties. Here  the  mucous  membrane  covering  the  superior  and  middle  turbinate 
bones  and  the  corresponding  part  of  the  septum  is  different  from  that 
covering  the  rest  of  the  nasal  passages.  Over  the  lower  parts  of  the  nasal 
cavities  the  mucous  membrane  is  of  the  ordinary  respiratory  type,  and 
is  composed  of  ciliated  columnar  epithelium  containing  a  number  of  goblet- 
cells.  In  the  olfactory  part  the  epithelium  is  much  thicker,  of  a  yellow 
colour,  and  apparently  composed  of  a  layer  of  columnar  cells  resting  on 
several  layers  of  nuclei.  These  nuclei  belong  to  the  olfactory  cells  proper. 
true  spindle-shaped  nerve  cells  with  one  process  extending  towards  the 
mucus  covering  the  free  surface,  while  the  other  is  continued  along  channels 
in  the  bone,  and  through  the  cribriform  plate  as  one  of  the  non-medullated 
olfactory  nerve  fibres.     These  nerve  fibres  dip  into   the  olfactory  lobes. 


Fig.  319.     Antero-posterior  section  through  the  nasal  fossal.     The  arrows  show 
the  direction  of  the  air  currents  during  inspiration. 

where  they  terminate  by  a  much-branched  arborisation  or  end  basket  in 
the  so-called  olfactory  glomeruli,  in  close  connection  with  a  similarly 
branched  dendrite  of  the  large  '  mitral '  cells  of  the  olfactory  lobe.  The 
axons  from  these  latter  carry  the  olfactory  impulse  towards  the  rest  of  the 
brain.  In  the  connective  tissue  basis  (dermis)  of  the  mucous  mem 
are  a  number  of  small  mucous  or  serous  glands  (Bowman's  glands)  whose 
office  it  is  to  keep  the  surface  of  the  membrane  constantly  moist. 


644  PHYSIOLOGY 

In  ordinary  respiration  the  stream  of  air  never  passes  higher  than  the 
anterior  inferior  border  of  the  superior  turbinate  bone,  so  that  it  does  not 
come  in  contact  with  the  olfactory  mucous  membrane.  The  sensations 
of  smell  which  are  aroused  during  ordinary  respiration  depend  on  diffusion 
from  the  respiratory  air  into  the  still  air  of  the  upper  olfactory  portion 
of  the  nasal  cavity.  The  direction  of  olfactory  attention  is  achieved  by 
sniffing  ;  in  this  act  the  nostrils  are  dilated  and  the  direction  of  the  anterior 
part  of  the  nasal  respiratory  chamber  altered,  so  that  the  stream  of  entering 
air  is  directed  towards  the  upper  olfactory  portion  of  the  cavity. 

The  fact  that  the  air.  which  enters  the  nasal  cavity  during  respiration, 
does  not  come  into  direct  relationship  with  the  olfactory  epithelium  has  the 
following  advantages  : 

(1)  The  cold  inspired  air  does  not  come  into  contact  with  and  cause 
damage  to  the  sensory  surface. 

(2)  Foreign  particles  carried  by  the  air  (including  bacteria)  do  not  get 
deposited  there.  The  position  of  the  epithelium  at  the  very  top  of  the 
nasal  cavity  is  an  additional  safeguard. 

(3)  The  olfactory  epithelium  is  not  dried  by  the  rush  of  dry  air 
across  it. 

(4)  Noxious  vapours  only  reach  it  indirectly  and  therefore  do  not  cause 
permanent  damage  as  they  otherwise  might. 

The  fact  that  we  are  able  to  perceive  smells  when  breathing  normally 
shows  that  the  odorous  substance  must  be  diffusible,  i.e.  gaseous  in  form. 
The  amount  of  substance  necessary  to  excite  sensation  is  extremely  minute. 
Thus  01  mg.  of  mercaptan  diffused  in  230  cubic  metres  of  air  is  still  distinctly 
perceptible.  In  this  case  a  litre  of  air  would  contain  only  "00000004  mg. 
of  the  substance,  and  the  amount  actually  in  contact  with  the  olfactory 
epithelium  would  be  still  smaller.  It  is  possible  however  to  show  the 
presence  of  these  odorous  substances  in  air  by  physical  means.  Tyndall 
pointed  out  that  air  containing  a  small  proportion  of  odorous  substances 
absorbed  radiant  heat  to  a  much  greater  degree  than  did  pure  air.  Thus 
in  one  experiment  air  containing  patchouli  absorbed  radiant  heat  thirty- 
two  times  as  strongly  as  the  pure  air.  Most  odorous  substances  possess 
large  molecules  and  have  therefore  high  vapour  densities.  On  this  account 
the  smell  tends  to  hang  about  objects,  the  rate  of  diffusion  of  the  vapour 
being  only  small. 

MODE  OF  ACTION  OF  SMELLS.  Since  the  endings  of  the  olfac- 
tory cells  are  bathed  in  fluid,  it  is  evident  that  the  odorous 
„  substances  must  be  dissolved  by  this  fluid  before  they  can  excite  the 
olfactory  nerve  fibres,  and  in  the  case  of  aquatic  animals  we  know 
that  the  projected  chemical  sense,  which  we  call  smell,  can  be  aroused  only 
by  substances  in  solution.  It  is  difficult  to  show  in  man  that  the  nerve 
endings  can  be  excited  by  solutions.  Most  of  the  experiments  have  been 
made  with  solutions  which  had  an  injurious  effect  upon  the  olfactory 
epithelium.  According  to  Aronsohn  it  is  possible  to  excite  sensations 
of  smell  if  the  nasal  cavity  be  filled  with  normal  saline  fluid,  containing 


SENSATIONS   OF  SMELL   AND   TASTE  645 

a  very  small  proportion  of  the  odorous  substance.  To  this  experiment 
ir  lias  been  objected  that  it  is  almost  impossible  to  till  the  nasal  cavities 
without  leaving  some  air  spaces,  so  that  the  olfactory  sensation  obtained 
might  have  been  due  to  stimulation  of  the  olfactory  cells  in  such  a  space 
There  is  however  no  a  priori  reason  to  deny  the  probability  of  Aronsohn's 
conclusions. 

Many  olfactory  stimuli  owe  their  peculiar  character  to  the  simultaneous 
stimulation  of  other  kinds  of  nerve  endings.  Thus  a  pungent  smell,  as  that 
of  ammonia,  chlorine.  &c,  in- 
volves stimulation  of  the  nerves 
of  common  sensibility,  i.e.  the 
fifth  nerve,  besides  stimulation 
of  the  olfactory  nerve. 

No  satisfactory  classification 
of  smells  has  yet  been  made. 
The  following  facts  tend  to  show 
that  there  are  a  number  of  primi- 

j.  .,  r        Fig.  320.     Zwaardemaker  8 

tive    sensations     ot    smell,    as  oi  olfactometer. 

other  sensations  : 

(a)  Certain  individuals,  whose 
olfactory    sense  is   in    other   re- 

spects  normal,  have  no  power  of  distinguishing  some  odours. 

(b)  The  olfactory  sense  is  easily  fatigued.  If  it  be  fatigued  so  as  to  be 
absolutely  insensitive  tor  one  kind  of  smell,  it  is  still  normally  excitable  for 
other  smells. 

(c)  It  is  possible  by  mixing  odoriferous  substances  in  certain  proportions 
to  annul  their  effect  on  the  olfactory  organ.  Thus  4  grm.  of  iodoform 
in  200  grm.  of  Peruvian  balsam  is  almost  odourless,  and  the  same  neutralisa- 
tion of  odour-  i-  obtained  if  the  odour  of  each  substance  lie  allowed  to  act 
separately  on  each   side  by  tubes  inserted  into  each  nostril. 

For  this  purpose  we  may  use  the  instrument  invented  by  Zwaardemaker    called 

the  olfad eter.    'Phis  consists  of  a   porous  cylinder  into  which  i-  inserted  a   tubi 

The  porou !  cj  Under  is  first  immersed  in  the  fluid  w  hose  porous  qualif  ii  -  are  to  be  tested, 
and  when  it  is  thoroughly  soaked  it  is  taken  out.  dried  outside  by  a  cloth,  and  inside 
hv  drawing  air  through  it  for  a  short  time.  One  end  ot  the  bent  tube  is  then  insert  d 
into  the  cylinder,  which  it  must  accurately  tit.  while  the  other  end  is  placed  in  one 
nostril.  The  small  wooden  screen  shown  in  Fig.  320  serves  to  shut  oil'  the  snail  of  the 
fluid  from  the  other  nostril.  When  the  observer  breathes  through  the  bent  tube,  the  amount 
of  vapour  taken  up  from  the  cylinder  will  depend  on  tin- amount  of  sum 
oil  therefore  can  hi-  diminished  or  increased  by  pushing  the  bent  tuhe  further  in.  or 
by  drawing  it  out.     If  tin-  tube  is  pushed  in  so  far  that  the  smell  is  only  just  perceptible, 

ength  of  the  tube  maybe  mea  ured      dt   ken  a    thi   in al  intensity  of  stimulus 

tor  the  given  substances,  in  it-  action  on  the  olfactoi  lings      This  unit  was 

called   by  the  inventor  ot   the  instrument  an  ■-    this  means  it   is   p 

to  make  quantitative  estimations  of  the  olfactory  sens i  one  individual  and  to  compare 

them  with  observations  made  on  other  individual  two  such  instruments 

it  is  |>  .ssihle  to  present  different  smells  to  the  two  nostrils.     0  sin  thi-  way 

combination   effects   which   can    l»-  compared   to  the  phenomenon   which   v 
studied  in  dealing  with  binocular  contrast. 


PART  VII 
SENSATIONS    OF    MOVEMENT    AND    POSITION 

In  studying  the  phenomena  of  reflex  movements,  as  presented  by  the  spinal 
animal,  our  attention  was  drawn  to  the  importance  of  the  afferent  impulses 
transmitted  to  the  central  organ  by  means  of  a  special  system  of  sense 
organs,  called  by  Sherrington  the  proprioceptive  system.  These  afferent 
impressions  intervene  at  a  later  period  in  every  reflex  action  than  do  the 
initiating  sensory  (exteroceptive)  impulses.  They  arise  as  a  result  of  the 
reflex  movement  itself,  and  serve  to  regulate  the  extent  of  this  movement 
as  well  as  the  co-ordinated  changes  in  the  other  muscles  of  the  body. 
Whether  they  be  synergic  or  antagonistic,  the  abolition  of  the  impulses 
arising  in  this  system  has  an  effect  similar  to  that  of  the  destruction  of  the 
governor  of  an  engine.  The  movements  excited  by  peripheral  stimulation 
become  excessive  and  conflicting  ;  there  is  no  longer  the  give-and-take  of 
the  antagonistic  muscles  surrounding  the  joint,  and  the  result  is  a  state  of 
disorder  and  inco-ordination,  termed  ataxy. 

Of  the  proprioceptive  impulses  a  certain  proportion  reach  the  cerebral 
cortex  and  arouse  states  of  consciousness  which  we  speak  of  as  sensations  of 
position,  movement,  or  resistance,  and  which  form  the  basis  of  judgments  as 
to  these  conditions.  In  consciousness  they  are  contrasted  with  the  sensa- 
tions arising  from  the  other  sense  organs  in  the  same  way  as  they  are  in  the 
subconscious  regulation  of  the  motor  adaptations  of  the  body.  'All  the 
senses  which  we  have  so  far  considered  give  us  information  of  things,  i.e.  of 
a  material  world  which  can  affect  ourselves,  but  which  we  conceive  of  as 
existing  altogether  apart  from  our  sensations  of  it.  Indeed  the  visual  and 
auditory  sensations  we  project  to  distances  remote  from  the  body.  The 
sensations  on  the  other  hand,  which  are  aroused  through  the  intermediation 
of  the  proprioceptive  system,  we  refer  entirely  to  ourselves.  By  them  we 
receive  information  of  the  condition  of  the  material  '  me,'  i.e.  of  ourselves 
as  things  apart  from  the  objects  which  surround  us  and  the  changes  in  which 
ordinarily  excite  our  activity. 

VOLITIONAL  MOVEMENTS.  Consciousness  we  have  seen  to  be 
developed  in  proportion  to  the  differentiation  of  the  educatable  associa- 
tion centres,  which  are  responsible  for  our  powers  of  ideation,  and 
by  means  of  which  the  different  reflex  movements  which  we  call 
volitional  are  carried  out.  guided,  augmented,  or  inhibited,  according 
to  the  past  experience  of  the  individual.  Volitional  movement  is  there- 
fore a  movement  determined  by  previous  neural  events,  of  which  a  part 

646 


SENSATIONS   OF  MOVEMENT  AND   POSITION  647 

at  any  rate  is  represented  in  consciousness  as  feeling,  emotion,  or  desire. 
Where  an  act  is  involuntary,  i.e.  does  not  need  the  guidance  of  experience, 
individual  or  racial,  for  its  performance,  the  afferent  impulses  which  arouse 
it  are  also,  as  a  rule,  devoid  of  representation  in  consciousness.  Thus  we 
have  no  sensation  of  the  passage  of  a  bolus  along  the  oesophagus.  The 
proprioceptive  impulses  also  only  affect  consciousness  where  they  are 
necessary  for  the  guidance  of  volitional  movement.  The  tactile  and  gusta- 
tory impressions  from  the  tongue  have  a  very  full  representation  in  conscious- 
ness. Volition  however  only  interferes  for  the  rejection  or  acceptance  of 
the  food  taken  into  the  mouth,  and  is  not  required  for  the  minute  direction  of 
the  movements  of  mastication  and  deglutition.  The  muscular  sensibility  of 
the  tongue,  and  therefore  our  voluntary  control  of  its  movement,  is  extremely 
slight,  although  there  must  lie  a  continual  flow  of  afferent  impressions  from 
the  tongue  to  the  lingual  motor  centres  to  guide  the  complex  movements  both 
ot  mastication  and  deglutition.  In  the  case  of  the  palate  muscles,  as  of  the 
oesophagus,  muscular  sensibility  is  not  highly  developed. 

It  has  been  suggested  that  afferent  impressions  from  the  muscles  can  play 
only  a  subordinate  part  in  our  sensations  of  movement,  since  we  are  not 
aware  of  the  part  taken  by  each  individual  muscle  in  any  given  move- 
ment. Such  a  statement  is  absurd.  We  have  no  objective  phenomenal 
experience  of  our  muscles.  All  that  we  are  aware  of  and  can  judge  of  by 
our  other  senses  is  the  movement  as  a  whole,  and  our  sensation  of  move- 
ment is  therefore  referred  to  the  whole  movement  and  not  to  the  individual 
muscles. 

The  sensations  arising  in  the  proprioceptive  system  can  be  divided 
into  two  main  classes  : 

(1)  The  sensation  of  the  relative  positions  of  parts  of  the  body. 

(2)  The  sensations  which  inform  us  of  the  position  of  the  head,  with 
regard  to  its  surroundings,  i.e.  with  regard  to  the  direction  of  the  pull  of 
gravity.  (It  must  be  remembered  that  '  downwards  '  always  means  towards 
the  centre  of  the  earth.  '  upwards  '  away  from  the  centre  of  the  earth,  i.e. 

osl  the  gravitational  forces.)  This  orientation  sense  depends  on  the  in- 
tegrity  of  a  special  sense  organ  contained  in  the  labyrinth  of  the  internal 
ear.     It  is  therefore  sometimes  spoken  of  as  the  labyrinthine  sense. 

THE   SENSE   OF   RELATIVE   POSITION,    INCLUDING   THE 
MUSCULAR   SENSE 

Without  using  our  eyes  we  are  able  at  any  moment  to  t  ill  the  position  of 
our  limbs.  If  one  arm  be  moved  passively  into  any  position  we  can  without 
difficulty  move  the  other  arm  into  an  exactly  similar  position.  We  thus 
know  the  extent  to  which  we  move  the  limb  and  the  static  position  attained 
as  the  result  of  the  movement.  If  the  movement  is  resisted,  we  are  able  to 
adjust  the  force  of  the  muscular  contrail  ion  to  the  resistance,  and  to  form 
therefore  a  fair  idea  as  to  the  strength  of  the  resistance. 

(«)  PASSIVE"  MOVEMENTS.  A  large  uumbei  of  differenl  sen-.-  organs 
contribute  to  the  formation  of  these  judgments.     In  the  appreciation  of 


648  PHYSIOLOGY 

passive  movement  t  be  chief  end  organs  involved  are  those  in  connection  with 
the  joints  and  their  ligaments,  though  it  is  probable  that  the  deeper  sense 
organs  in  the  soft  parts  around  the  joints  also  contribute  to  the  total  sensa- 
tions. Cutaneous  sensations  apparently  play  hut  little  part  in  the  judgments 
of  passive  movement.  It  is  true  that  the  alternating  movements  of  the  hind 
limbs,  which  occur  in  a  spinal  animal  when  it  is  held  up  by  the  hands  under 
the  fore  limbs,  are  started,  partly  at  any  rate,  by  the  stretching  of  the  skin 
of  t  he  thighs ;  but  t  his  effed  is  one  rather  of  initiation  of  movement,  and  can 
hardly  be  regarded  as  proprioceptive  in  character. 

The  strength  of  the  sensation  of  passive  movement  depends  on  the 
extent  of  the  movement  as  well  as  on  the  rate  with  which  it  is  carried  out. 
The  delicacy  of  perception  varies  in  different  joints.  Thus  in  some  joints 
a  movement  of  025°  per  second  is  appreciated  as  a  movement,  while  in  other 
joints  the  movement  must  be  as  extensive  as  T4°  per  second.  It  is  more 
easily  appreciated  when  the  joint  surfaces  are  pressed  together  than  when 
thev  are  pulled  apart,  showing  that  the  nerve-endings  in  the  joint  surfaces 
play  a  part  in  the  origination  of  the  sensations. 

(b)  THE  SENSE  OF  MOVEMENT  (MUSCULAR  SENSATION).  This  term 
is  applied  to  those  sensations  by  which  we  judge  of  the  extent  and  force  of 
any  active  movement  which  we  may  have  carried  out.  Many  authors  have 
ascribed  an  important  part  in  this  act  of  judgment  to  the  so-called  '  sense  of 
innervation,'  i.e.  a  sense  of  the  actual  energy  which  is  being  discharged 
from  the  motor  cells  of  the  central  nervous  system  to  the  muscles,  and  have 
thought  that  when  we  raise  a  weight  we  judge  of  its  amount,  not  by  the 
degree  of  stretching  of  the  muscle  or  pressure  on  sensory  nerves  in  the  muscle, 
but  by  the  amount  of  force  we  voluntarily  put  out  to  raise  the  weight.  The 
fact  however  that  we  can  judge  of  weights,  when  the  muscles  are  made  to 
contract  by  electrical  stimuli  and  not  by  voluntary  impulses,  shows  that  this 
sense  is  in  large  part,  if  net  entirely,  peripheral.  It  is  however  very  com- 
plex in  nature,  and  is  served  by  a  whole  array  of  different  end-organs  in 
the  skin,  joints,  tendons,  and  muscles.  The  muscles  themselves  are  known 
to  be  well  supplied  with  afferent  nerves.  Stimulation  of  the  central  end 
of  a  muscular  nerve  may  reflexly  excite  or  inhibit  movements  of  other 
muscles.  Sherrington  has  shown  that,  after  section  of  the  motor  roots, 
over  one-third  of  the  fibres  in  a  muscular  nerve  remain  undegenerated, 
provmg  their  connection  with  the  posterior  root  ganglia.  The  sensory  nerve- 
endings  in  the  muscle  are  represented  partly  by  the  tendon  nerve  endings 
and  partly  by  the  muscle  spindles.  The  former  are  richly  branched  end 
arborisations  of  nerve  fibres  on  the  surface  of  the  tendon  bundles.  The 
muscle  spindles  consist  of  one  or  more  muscle  fibres,  often  continuous  with 
normal  fibres,  enclosed  in  a  sheath  composed  of  several  layers  of  fibrous 
tissue  with  intervening  lymph  spaces.  One  or  more  nerve  fibres  pierce  this 
sheath  and,  after  making  many  spiral  turns  round  the  muscle  fibres,  branch 
freely  and  terminate  in  little  knobs  on  the  surface  of  the  fibres  (Figs.  321,  322). 
The  cross  striation  of  the  muscle  fibres  within  the  spindle  is  but  faintly 
marked.     It  is  evident  that  the  continuity  of  these  sense  organs  with  the 


SENSATIONS   OF  MOVEMENT   AND   POSITION  649 

contracting  muscle  ensures  in  the  best  possible  way  that  the  organs  should 
lie  affected  by   the  slightest  change  of  tension  of  the  muscle,  and  should 


Fig.  321.    A  neuromuscular  spindle  of  the  cat.     (Botfini.) 
c.  capsule:    pr.e,  primary  ending;    s.e.  secondary  ending;    pl.e,  plate  ending 
(all  these  are  probably  sensory  in  function). 


Fig.   322.     Part  of  a  muscle  spindle  more  highly  magnified. 
n,  nerve  fibres  passing  to  spindle  ;  a,  annular  endings  "I  axis  cylinders  ;  s.  spiral 
endings  ;   d.  dendritic  endings  ;  sh,  connective-tissue  sluyth  of  spindle.      (Kcffini.) 

transmit  information  of  the  state  of  tension  to  the  central  nervous  system. 

THE  PSYCHOLOGICAL  SIGNIFICANCE  OF  SENSATIONS  OF  MOVE- 
MENT. Not  only  are  these  organic  sensations  of  importance  as  affording 
us  information  of  the  condition  of  our  own  bodies  as  distinct  from  the  objects 
in  the  world  around,  but  they  enter  into  and  qualify  our  judgments  derived 
from  all  the  sensations  which  arise  in  the  special  sense  organs. 

When  we  regard  the  continuous  aimless  activity  of  a  healthy  baby,  we 
3ee  i  hat  all  ideas  of  space,  of  extension,  of  relative  position  arc  wanting,  or  at 
any  rate  are  not  present  to  guide  the  movements.  Hit  by  bit  muscular 
experience  is  acquired.  The  child  learn-  thai  a  given  movement  of  the  right 
arm  will  bring  the  hand  in  contact  with  something  which  is  exciting  the  left 
side  of  the  retina.  The  surface  of  the  thing,  if  of  sutlicient  extension,  can 
excite  tactile  sensations  in  all  the  fingers  of  the  right  hand.  By  inovin; 
finger  over  the  object  the  tactile  sensations  are  found  to  be  continuous:  by 
moving  the  whole  hand  forwards  the  thing  is  found  to  po extension  in 


650  PHYSIOLOGY 

a  direction  away  from  the  body,  and  therefore  in  the  third  plane  of  space. 
Thus  gradually  are  acquired  not  only  ideas  of  extension,  distance,  and  space, 
but  certain  movements  are  correlated  with  stimulation  of  definite  regions 
of  the  skin  or  of  the  retina.  Tactile  and  retinal  impressions  therefore  acquire 
local  sign,  and  power  is  acquired  of  moving  the  limbs  to  a  degree  and  in  a 
direction  adapted  to  stimuli  arising  from  any  part  of  the  tactile  or  retinal 
surfaces.  The  child  gradually  acquires  the  power  of  following  a  bright 
object  with  its  eyes,  i.e.  of  contracting  the  ocular  muscles  so  as  to  keep 
the  retinal  image  of  the  object  on  the  fovea  centralis,  and  up  to  adult  age 
we  are  still  engaged  in  this  balancing  of  muscular  movement  against  sense 
impressions — a  balancing  in  which  the  muscular  sensations  are  the  constant 
guide  and  criterion  of  success.  Only  by  the  muscular  sensations  are  we 
informed  whether  our  willed  movement  has  been  carried  out  or  not.  It 
is  in  virtue  of  the  muscular  and  allied  sensations  that  we  are  able  to  clothe 
our  visual  and  tactile  sensations  with  properties  of  extension,  solidity,  and 
resistance,  which  create  them  in  consciousness  as  parts  of  a  material  world. 


PART  VIII 

THE    LABYRINTHINE    SENSATIONS 

Throughout  almost  the  whole  of  the  animal  kingdom,  and  in  practically 
all  freely  moving  metazoa,  we  find  a  sense  organ  which  has  often  been 
designated  as  an  auditory  organ.  This  organ,  which  is  situated  in  the  integu- 
ment, is  in  the  form  of  a  small  sac  generally  open  to  the  exterior,  and  lined 
by  cells  provided  with  hairs  and  richly  supplied  with  nerves.  Resting  among 
the  hairs  is  a  small  concretion,  generally  of  carbonate  of  lime,  which  is  known 
as  an  otolith.  These  sacs  have  generally  been  regarded  as  auditory  in 
function,  hence  the  term  otolith  applied  to  the  concretion.  The  evidence 
for  audition,  i.e.  the  power  of  appreciating  vibrations  in  the  elastic  medium 
surrounding  them,  is  scanty.  Thus  in  fishes  this  power  has  been  stated  to  be 
absent  unless  the  vibrations  are  of  sufficient  amplitude  to  affect  the  sense- 
organs  of  the  skin*  On  the  other  hand,  there  is  evidence  that  these  otolith 
organs  are  connected  with  equilibration.  Section  of  the  nerves  going  to  them 
in  the  crayfish  causes  disturbance  of  locomotion.  Steinach  has  succeeded 
in  the  crayfish  in  replacing  the  concretion  by  a  small  particle  of  iron.  The 
animal's  behaviour  and  movements  were  perfectly  normal  until  it  was 
brought  within  a  powerful  magnetic  field.  Under  the  influence  of  this. 
field  the  effect  of  gravity  on  the  iron  particle  was  annulled  and  replaced  by  a 
force  of  attraction  in  another  direction,  and  the  effect  was  at  once  seen  as 
pronounced  disorders  of  locomotion,  the  animal  swimming  in  an  abnormal 
position. 

From  a  sac,  such  as  that  present  throughout  the  lower  animals, the  organ 
of  hearing  in  the  hi«her  vertebrata  is  developed.  Arising  as  a  pit  in  the 
epiblast  in  the  neighbourhood  of  the  hind-brain,  the  auditor}-  sac  becomes 
shut  off  from  the  exterior,  and  then,  by  an  outgrowth  in  various  directions, 
forms  the  complex  membranous  labyrinth  of  the  internal  ear.  This  mem- 
branous labyrinth,  as  we  have  seen,  can  be  divided  into  two  parts,  viz.  the 
canalis  media  of  the  cochlea  in  front,  and  the  saccule,  utricle,  and  semi- 
circular canals  behind.  The  canalis  media  of  the  cochlea  is  concerned  with 
the  reception  and  analysis  of  sound  waves.  In  the  lower  vertebrates  in 
which  auditory  sensations  are  wanting  the  cochlea  is  absent,  and  in  fishes 
is  represented  merely  by  a  small  diverticulum  known  as  the  lagena.  With 
the  development  of  air-breathing  vertebrates  we  see  the  first  signs  of  a  special 
organ  of  hearing.  Thus  a  primitive  cochlea  is  present  in  the  amphibia,  and 
especially  in  the  anura,  and  in  some  of  the  reptiles  as  well  as  in  birds  it, 
acquires  a  bend  and  shows  the  beginning  of  a  spiral  arrangement.  Only  in 
the  mammals  does  it  attain  a  degree  of  development  at  all  comparable  with 

*  Piper,  however,  has  detected   an   electrical    variation  in   the  eighth   nen 
fishes  in  response  to  a  sound  stimulus. 

651 


652 


PHYSIOLOGY 


that  found  in  man.  and  characterised  by  the  formation  of  one  and  a  half 
to  four  spiral  turns  in  the  cochlea  as  well  as  in  the  canalis  media. 

This  development  of  auditory  functions  cannot  involve  any  abrogation 
of  the  important  part  played  by  the  otolith  organ  throughout  all  the  lower 
classes  of  the  animal  kingdom.  In  man.  as  in  the  crayfish,  it  is  the  otolith 
organ  which  determines  his  behaviour  in  relation  to  the  force  of  gravity, 
and  is  therefore  responsible  not  only  for  the  maintenance  of  equilibrium 
but  also  for  the  sensations  which  enable  him  consciously  to  orientate  himself 
and  to  know  the  position  in  which  he  happens  to  be  at  any  given  moment. 

With  the  increasing  import- 
ance of  visual  sensations  in 
determining  the  behaviour 
of  the  animal,  (lose  connec- 
tions are  established  be- 
tween the  central  connec- 
tions of  the  nerves  running 
from  the  otolith  organ  and 
the  parts  of  the  brain  con- 
cerned with  the  innervation 
of  the  eye  muscles.  By 
this  means  the  position  of 
the  eyes  is  constantly  adap- 
ted to  the  position  of  the 
head. 

The  auditory  part  of  the 
internal  ear  has  already  been 
described.  That  part  of  the 
labyrinth  which  represents  the 
primitive  otolith  organ  consists 
of  a  bony  framework  containing 
perilymph,  in  which  is  contained 
the  membranous  labyrinth  with 
the  endings  of  the  vestibular 
division  of  the  eighth  nerve. 
The  osseous  labyrinth  consists 
of  a  cavity,  the  vestibule,  into 
which  open  behind  the  three  bony  semicircular  canals.  In  the  vestibule  are  con- 
tained two  little  membranous  sacs,  the  utricle  and  saccule,  the  cavities  of 
which  are  connected  by  means  of  the  saccus  enddymphaticus.  Into  the  utricle 
open  the  three  semicircular  canals,  the  three  canals  having  five  openings.  These  semi- 
circular  canals  are  arranged  in  three  planes.eaeh  of  which  is  at  right  angles  to  the  other 
two,  so  that  in  the  organ  are  represented  the  three  planes  of  space.  We  may  distinguish 
on  e  <ch  side  an  external  or  horizontal  canal,  an  anterior  or  superior  vertical  canal,  and 
a  posterior  vertical  canal.  The  two  outer  canals  lie  always  exactly  in  the  same  plane, 
which  is  practically  horizontal  in  the  normal  position  on  the  head.  Each  posterior 
vertical  canal  lies  in  a  plane  which  is  parallel  to  that  of  the  superior  vertical  canal  of 
the  opposite  side.  We  thus  sec  that  these  semicircular  canals  form  together  three  planes 
—one  horizontal  and  two  vertical,  the  two  latter  being  at  right  angles  to  one'another 
I  Fig,  323).  The  membranous  canal  lies  within  the  osseous  canal,  a  considerable  span 
intervening  between  the  two  canals.     At  one  end  the  osseous  canal  is  dilated  and  the 


Fig.  323.  Figure  from  Ewald  showing  the  situ- 
ation of  the  time  semicircular  canals  in  the 
skull  of  the  pigeon. 


THE  LABYRINTHINE   SENSATIONS 


653 


membranous  canal  undergoes  a  corresponding  dilatation  so  as  to  fill  up  the  whole  bony 
canal.  In  this  dilatation,  which  is  known  as  the  ampulla,  we  find  the  ending  of  a  branch 
of  the  vestibular  nerve  in  a  special  sense  epithelium  forming  the  crista  acustica  (Fig.  324). 
The  crista  is  composed  of  hair-cells  with  sustentacular  cells  between  them.  The  fibres 
of  the  vestibular  nerve  end  in  arborisations  among  the  hair  cells,  the  hairs  of  which 


Fio.  324.     End  organ  of  vestibular  nerve  in  ampulla  of  semicircular  canal  ('crista 
acustica '). 

project  into  the  endolympb  filling  the  ampulla.  In  the  utricle  and  saccule  we  also  find 
special  sense-organs,  known  as  the  macula  acustica.  the  structure  of  which  is  very  similar 
to  that  of  the  crista  in  the  ampullae.  Among  the  hairs,  however,  of  the  macula  is  found 
a  small  concretion  of  carbonate  of  lime,  the  otolith. 

The  first  accurate  experimental  investigation  of  the  functions  of  these 
different  parts  we  owe  to  Flourens.  This  observer  showed  that,  whereas 
extirpation  of  the  cochlea  caused  deafness,  extirpation  of  the  vestibule  and 
semicircular  canals  left  the  auditory  sense  intact,  but  caused  marked  dis- 
orders of  equilibration.  That  the  peculiar  arrangement  of  the  semicircular 
canals  in  the  three  planes  of  space  was  connected  in  some  way  with  the 
functions  of  these  structures  was  also  indicated  by  Flourens'  observation  that 
destruction  of  the  horizontal  canals  on  each  side  gave  rise  to  continual 
movements  of  the  head  from  side  to  side  in  the  plane  of  the  injured  canals. 
By  many  physiologists  the  results  obtained  by  Flourens  were  ascribed  to 
continued  irritation  of  the  peripheral  sense  organs  or  of  the  central  parts  of 
the  brain  in  consequence  of  the  lesion.  The  accurate  experiments  of  (Joltz, 
and  especially  those  of  his  pupil  Ewald,  showed  that  these  effects  might  last 
twelve  to  eighteen  months,  or  be  permanent .  and  must  therefore  be  regarded 


654 


PHYSIOLOGY 


as  an  AusfaUserscheinung,  i.e.  as  due  to  abolition  of  a  function  and  not  to  tin- 
arousing  of  a  function  by  abnormal  stimulation. 

Most  of  the  experiments  on  this  subject  have  been  carried  out  on  pigeons 
on  account  of  the  easy  accessibility  of  their  semicircular  canals.  Confirma- 
tory observations  have,  however,  been  made  on  mammals.  After  destruc- 
tion of  all  the  canals  or  of  the  whole  membranous  labyrinth  on  both  sides, 
disturbances  of  equilibrium  are  aroused  which  may  last  for  a  considerable 
time.  The  animal  can  neither  stand,  nor  fly,  nor  maintain  any  fixed  attitude, 
but  is  constantly  moving  about  incoherently  and  often  so  violently  that 
it  is  necessary  to  pad  its  cage  in  order  to  prevent  it  from  injuring  itself. 
Although  the  movements  are  so  violent,  very  little  guidance  suffices  to  stop 
them  altogether.     Any  support  given  by  the  hand  enables  the  animal  to  rest 

quietly.  After  some  months  these 
disorders  gradually  disappear,  and 
the  animal  learns  to  guide  its  move- 
ments by  sensations  of  touch  and 
sight  alone  ;  but  they  are  instantly 
brought  back  in  all  their  severity  if 
the  eyes  be  bandaged,  so  as  to  de- 
prive the  co-ordinating  centres  of 
the  guiding  visual  sensations. 

The  same  effect  is  produced  if 
that  part  of  the  brain  which  alone  is 
educatable,  viz.  the  cerebral  cortex, 
be  excised.  Extirpation  of  the  cere- 
bral hemispheres  in  pigeons  causes 
no  disorders  of  equilibrium,  but  ex- 
tirpation, after  destruction  of  the 
labyrinth,  brings  back  the  dis- 
orders which  were  noted  during 
the  first  days  after  the  operation,  and  these  disorders  are  now  per- 
manent. Recovery  even  in  the  presence  of  the  cerebral  hemispheres 
is,  however,  never  really  complete.  Although  the  animal  may  be  able  to 
walk  and  fly  very  fairly,  it  suffers  from  a  loss  of  power  and  loss  of  tone 
which  affect  all  its  muscles,  but  especially  those  moving  the  trunk  and  neck. 
If  the  labyrinth  has  been  extirpated  only  on  one  side,  then  this  loss  of  tone 
is  noticed  chiefly  on  the  opposite  or  contralateral  side  of  the  body  (Fig.  325). 
Loss  of  tone  after  complete  destruction  is  well  shown  in  the  following  experi- 
ment devised  by  Ewald  : 

A  small  lead  bullet  is  hung  by  a  thread  to  the  beak  of  the  pigeon.  As 
the  bird  moves  about  the  bullet  swings,  the  head  following  its  movements  ; 
finally  the  bullet  happens  to  fall  over  the  beak  of  the  animal — the  head  is  now 
found  to  be  fixed  in  the  position  shown  in  the  figure  (Fig.  32C).  The  anterior 
muscles  of  the  neck  are  too  weak  and  toneless  to  restore  the  head  to  its 
normal  position  against  the  weight  of  the  bullet.  No  such  phenomena  are 
presented  by  a  normal  bird. 


Fig.  325.  Abnormal  posture  of  pigeon, 
in  which  the  labyrinth  had  been  ex- 
tirpated on  one  side  five  days  pre- 
viously.    (Ewald.) 


THE  LABYRINTHINE   SENSATIONS 


655 


Fig.  326.  After  complete  destruction  of 
the  two  labyrinths  the  neck  muscles  become 
so  weak  that  they  are  unable  to  overcome  the 
weight  of  a  bullet  attached  to  the  beak. 


The  same  absence  of  tone  is  seen  in  mammals.  A  dog  with  both 
labyrinths  destroyed  may  jump  down  from  a  table  once,  but  will  not 
repeat  the  experiment,  since  the  muscles  of  the  fore  limbs  are  too 
toneless  to  support  the  head  against  the  shock  of  the  jump,  an. I  he 
knocks  his  head  against  the 
ground  as  his  legs  collapse  under 
him.  If  only  one  canal  be  put  out 
of  action,  as,  for  instance,  by 
.stopping  it  with  dentist's  amal- 
gam,  the  head  is  thrown  into  oscil- 
lations in  a  corresponding  plane, 
or  perhaps  rather  we  should  say 
that  when  the  head  oscillates  in 
this  plane  there  are  no  correspond- 
ing sensations  set  up  which  tend 
to  inhibit  the  movements.  The 
same  effect  may  be  produced 
temporarily  by  painting  any  one 
of  the  canals  with  cocaine  so  as 
to  paralyse  its  nerve  endings. 
The  converse  experiment  of 
isolated      stimulation      of      one 

canal  has  also  been  effected  by  Ewald.  For  this  purpose  Ewald,  by 
means  of  a  dentist's  burr,  opened  one  bony  canal  at  two  spots.  By  the 
hole  furthest  away  from  the  ampulla  he  introduced  an  amalgam  stopping, 
so  as  to  prevent  any  current  of  fluid  backwards  through  the  canal.  Over 
the  second  hole  he  fixed,  by  means  of  plaster  of  Paris,  a  tube  which  was 
connected  by  a  flexible  rubber  tube  with  a  rubber  ball.  By  this  means, 
while  the  bird  was  sitting  quietly  on  its  perch,  he  could  suddenly  blow  upon 
the  exposed  membranous  canal  without  disturbing  the  bird  in  any  way. 
By  the  air  pressure  thus  produced  on  the  canal  a  stream  of  endolymph  was 
caused  in  the  direction  of  the  ampulla.  Every  time  this  was  done  he  found 
that  the  animal  moved  its  head  and  eves  in  the  direction  of  the  current  and 
always  exactly  in  the  plane  of  the  canal  which  was  being  stimulated.  By 
this  means  proof  was  brought  of  the  correctness  of  the  theory  put  forward 
bv  Breuer  and  Mach,  viz.  that  the  specific  stimulus  of  the  nerve  endings  in 
the  ampulla  is  afforded  by  the  current  of  the  endolymph  in  the  semicircular 
canals. 

Since  the  endolymph  is  a  fluid  with  inertia  it  will  not  immediately  follow 
a  rotational  movement  of  the  bony  walls  of  the  semicircular  canals.  Thus  a 
sudden  turning  of  the  head  from  left  to  right  will  cause  movement  of  endo- 
lymph towards,  and  therefore  increased  pressure  on.  the  ampullary  nerve 
endings  of  the  right  horizontal  canal,  and  movement  of  endolymph  away 
from,  and  therefore  diminished  pressure  on.  the  corresponding  ampulla  ol 
the  left  side.  In  this  way.  for  movement  in  any  given  plane,  the  two 
corresponding  semicircular  canals  of  the  two  sides  are  synergic  and  unite  in 
sending  impulses  which  guide  the  equilibrating  centres,  and  inform  us  of 


656  PHYSIOLOGY 

the  position  of  our  head  in  apace.  "  <  >ne  canal  can  be  affected  by  and  trans- 
mit the  sensation  of  rotation  about  one  axis  in  one  direction  only  :  and  for 
complete  perception  of  rotation  in  any  direction  about  any  axis  six  semi- 
circular canals  are  required  in  three  pairs,  each  pair  having  its  two  canals 
parallel  (in  the  same  plane),  and  with  their  ampullae  turned  opposite  ways. 
Each  pair  would  thus  be  sensitive  to  any  rotation  about  a  line  at  right  angles 
to  its  plane  or  planes,  the  one  canal  being  influenced  by  rotation  in  the  one 
direction,  the  other  by  rotation  in  the  opposite  direction  "  (Crum  Brown). 
These  reflex  movements  of  head  and  eyes  are  the  invariable  result  of  move- 
ments set  up  in  the  endolymph,  and  occur  equally  well  in  the  absence  of 
the  cerebral  hemispheres.  If  an  animal  or  man  be  placed  on  a  turntable 
and  rotated,  his  first  tendency  will  be  to  turn  his  head  and  eyes  in  the  opposite 
direction  to  that  of  rotation  in  order  to  preserve  fixation.  If  the  rotation 
be  continued,  the  endolymph  gradually  takes  up  the  movement  of  the  sur- 
rounding parts  of  the  head,  and  if  the  eyes  be  closed,  no  movement  of  head 
or  eyes  is  observed.  If  now  the  rotation  is  stopped,  the  endolymph  will  tend 
to  go  on  moving,  and  the  effect  will  be  the  same  as  if  a  movement  of  rotation 
were  suddenly  begun  in  the  opposite  direction.  Head  and  eyes  will  now  be 
turned,  without  any  voluntary  impulse,  in  the  direction  of  the  previous 
rotation,  and  in  consciousness  there  will  be  an  actual  sensation  of  rotation 
in  the  opposite  direction.  This  sensation  is  in  opposition  to  the  sensations 
derived  from  other  parts,  and  hence  the  feeling  of  giddiness  and  the  actual 
disorders  of  equilibrium  which  are  its  concomitants. 

That  this  feeling  of  giddiness  on  rotation  is  due  to  impulses  started  in  the 
semicircular  canals  is  shown  by  the  fact  that,  in  a  large  number  of  deaf-mutes 
where  these  organs  are  imperfectly  developed,  it  is  impossible  to  produce 
giddiness  and  the  associated  eye  movements  by  passive  rotation. 

THE   FUNCTION    OF   THE   OTOLITHS 

The  semicircular  canals  are,  as  we  have  seen,  a  higher  development  of 
the  otolith  organ.  The  primitive  part  of  this  organ  is  represented  by  the 
maculae  in  the  utricle  and  saccule.  It  is  to  these  organs  that  we  must 
ascribe  our  powers  of  appreciating  the  static  position  of  the  head,  as  well 
as,  to  a  slight  degree,  movements,  not  of  rotation,  but  in  one  plane  forwards 
or  1  uick  wards. 

A  consideration  of  the  structure  of  the  otolith  organ  shows  at  once  that 
the  incidence  of  the  weight  of  the  otoliths  on  the  hairs  of  the  macula  will  vary 
according  to  the  position  of  the  head.  Thus  in  the  diagram  (Fig.  2C0,  p.  397) 
in  a  (normal  jwsition)  the  chief  weight  of  the  otolith  falls  on  the  hairs  from 
b  in  c  whereas,  when  the  head  has  been  rotated  round  a  right  angle  so  that 
the  man,  for  instance,  is  lying  on  his  right  side,  the  chief  weight  of  the  otoliths 
will  tall  on  the  hairs  at  c.  The  nerve-endings  stimulated  by  the  weight  of  the 
otoliths  will  therefore  vary  according  to  the  position  of  the  head.  The  cere- 
bellum and  its  associated  structures  represent  a  mechanism  for  the  regulation 
of  the  movements  of  the  trunk  as  a  whole  and  the  position  of  its  centre  of 
gravity  in  relation  to  the  position  of  the  head. 


BOOK  III 
THE    MECHANISMS   OF   NUTRITION 


12 


CHAPTER   IX 

THE    EXCHANGES    OF   MATTER   AND    ENERGY 
IN    THE    BODY 

GENERAL  METABOLISM 

All  the  energy  which  leaves  the  body  as  heat  01  work  is  derived  from 
processes  of  oxidation,  the  carbon,  hydrogen,  nitrogen,  and  sulphur  of  the 
art's  uniting  with  oxygen  in  the  body  and  being  eliminated  iu  the  form 
of  carbon  dioxide,  water,  urea  and  allied  substances,  and  stdphates.  Iu  a 
starving  animal  this  discharge  of  energy  must  be  associated  with  a  loss  of 
body  substance.  The  necessity  for  taking  food  is  determined  by  the  need  of 
replacing  this  loss.  The  foodstuffs  cannot,  like  the  coal  or  fuel  of  a  steam- 
engine,  be  utilised  directly  as  a  source  of  energy,  but  must  be  built  up  to  a 
_iee  into  the  structure  of  the  living  protoplasm.  The  total 
amount  of  living  material  in  the  body,  though  maintained  fairly  constant 
in  the  adult  animal,  may  yet  undergo  alterations  under  varying  conditions. 
and  these  alterations  are  naturally  more  marked  in  the  growing  animal.  We 
have  in  this  chapter  to  inquire  into  : 

(1)  The  nature  and  amount  of  the  sul  ch  may  serve  as  food- 

si  art's  and  are  necessary  for  maintaining  the  weight  of  the  body  constant  or 
providing  for  its  growth; 

The  relation  between  the  total  amount  of  material  taken  up  by  the 
body  and  the  total  amount  given  out ; 

(3)  The  variations  iu  the  total  chemical  exchanges  determined  by 
variations  in  the  output  of  energy  by  the  body;    and 

(4)  The  significance   of  the  vat  iss  -   of  foodstuffs  as  sour. 
energy  and  in  the  replacing  of  tissue  was 

We  have  therefore  to  make  balance-sheets  of  two  kinds,  namely  :  (1)  an 
accurate  comparison  of  the  ingests  (food  and  oxygen)  aud  the  egesta  (carbon 
dioxide,  water,  urea,  el  -  showing  the  amouut  of  potential 

energy  introduced  into  the  body  compared  with  the  amount  of  energ 
free  iu  the  body. 


SECTION  I 

METHODS    EMPLOYED    IN    DETERMINING   THE 
TOTAL    EXCHANGES    OF   THE    BODY 

The  determination  of  the  material  exchanges  of  the  body  involves  an 
accurate  comparison  of  its  income  and  output.  The  income  consists  of  the 
foodstuffs  and  oxygen.  The  foodstuffs  may  be  divided  into  two  classes, 
namely,  (1)  the  organic  foodstuffs,  which  on  oxidation  may  serve  as  sources 
of  energy,  and  (2)  the  inorganic  foodstuffs,  such  as  salts  and  water. 

The  latter  class  neither  add  to  nor  subtract  from  the  total  energy  of  the 
organism,  but  their  presence  is  a  necessary  condition  of  all  vital  processes, 
and  as  they  are  contained  in  the  various  excreta  a  corresponding  amount 
must  be  present  in  the  food  hi  order  to  make  good  this  loss. 

In  spite  of  the  bewildering  complexity  of  the  nature  of  the  foods  taken 
by  man,  their  essential  constituents  can  always  be  assigned  to  the  three 
classes,  proteins,  fats,  and  carbohydrates,  and  any  analysis  of  the  food  must 
give  the  relative  amounts  present  of  these  three  classes  of  substances.  The 
approximate  analysis  of  the  foodstuffs  presents  little  difficulty.  The ' 
nitrogen  is  determined  by  Kjeldahl's  method.  The  figure  thus  obtained 
is  multiplied  by  the  factor  6-25,  and  the  resulting  figure  is  taken  to  represent 
the  total  protein  in  the  food.  Of  course  such  a  valuation  may  give  too  high 
a  value  when  the  foodstuff  is  one  that  is  rich  in  nitrogenous  extractives. 
The  total  fat  is  determined  by  extracting  the  food  in  a  Soxhlet  apparatus 
with  ether.  It  is  advisable  to  precede  this  extraction  by  an  extraction  with 
boiling  alcohol.  The  total  ethereal  and  alcoholic  extract  obtained  is  reckoned 
as  fat.  The  amount  of  water  is  determined  by  drying  the  foodstuffs  at 
110°  C,  and  the  amount  of  inorganic  constituents  by  ashing  the  dried 
remainder.  Carbohydrates  may  be  determined  directly  by  boiling  the  food 
with  dilute  acids  in  order  to  convert  all  its  disaccharides  and  polysaccharides 
into  hexoses,  which  are  then  reckoned  as  glucose,  and  estimated  by  their 
copper-reducing  power.  In  most  cases  however,  the  total  protein,  fat,  and 
ash  are  subtracted  from  the  dried  weight  of  the  food  and  the  remainder  is 
taken  as  carbohydrate. 

Although  the  methods  for  the  analysis  of  foodstuffs  are  by  no  means  difficult, 
the  total  analysis  of  the  food  during  a  metabolism  experiment  may  become  extremely 
tedious  on  account  of  the  very  large  number  of  analyses  which  have  to  be  performed. 
The  labour  is  lightened  by  the  fact  that  nearly  all  the  ordinary  foodstuffs  have  been 
subjected  to  analysis  and  their  average  composition  published  by  the  Agricultural 
Board  of  the  United  States.  Since  however  the  foods  vary  in  composition,  especially 
in  water  content,  from  time  to  time,  a  calculation  of  the  total  income  of  proteins, 

660 


THE  TOTAL  EXCHANGES  OF  THE  BODY  661 

fats,  and  carbohydrates  from  data  given  by  workers  in  other  lands  must  present  a 
considerable  margin  of  error.  In  order  to  attain  greater  accuracy,  some  observers 
have  made  in  the  form  of  biscuits  or  of  preserve  a  complete  food  which  is  prepared 
in  large  quantities  at  the  beginning  of  the  experiment  and  used  as  the  sole  diet  through- 
out the  experiment.  Pfliiger,  for  instance,  converted  the  horse-flesh,  witli  which  he 
desired  to  feed  his  dogs  in  a  metabolism  experiment,  into  sausage  meat  which  was 
sealed  up  in  cases  and  sterilised.  The  sausage  meat  having  been  analysed  at  the 
beginning  of  the  experiment,  it  was  only  necessary  thereafter  to  weigh  the  amount 
eaten  by  the  dog  in  order  to  know  accurately  the  total  amount  of  protein,  fat,  and 
carbohydrate  ingested  by  the  animal.  In  experiments  on  man  it  has  been  endeavoured 
to  obtain  the  same  result  by  limiting  the  food  to  a  few  articles  of  diet  which  could 
be  accurately  analysed  in  each  case.  The  monotony  of  such  a  diet  tends  to  interfere 
with  the  success  of  the  experiment,  since  the  subject  of  the  experiment  loses  his  appetite 
and  his  processes  of  nutrition  are  not  normally  carried  out.  It  is  usually  possible  to 
steer  a  middle  course  between  the  two  extremes  of  too  much  and  too  little  variation 
of  diet,  and  so  to  obtain  values  for  the  composition  of  the  ingesta  wliich  cannot  differ 
very  largely  from  their  true  composition. 

The  material  output  of  the  body  consists  of  the  products  of  combustion 
of  the  foodstuffs,  which  are  turned  out  by  the  various  channels  of  excretion, 
namely,  the  kidneys,  the  alimentary  canal,  the  lungs,  and  the  skin.  These 
excreta  must  therefore  be  collected  and  analysed.  In  addition  to  the  main 
sources  of  excretion,  small  quantities  of  material  are  lost  by  the  shedding 
of  the  cuticle,  by  the  growth  and  cutting  of  the  hair  and  nails,  and  so  on.  In 
most  cases  the  losses  in  this  way  are  so  small  that  they  may  be  disregarded. 
The  nitrogen  of  the  foodstuffs  and  that  derived  from  the  disintegration  of 
the  tissues  of  the  body  is  excreted  almost  exclusively  in  the  urine,  a  small 
amount  being  thrown  out  by  the  alimentary  canal.  The  total  nitrogen  must 
be  therefore  determined  both  in  the  faeces  and  in  the  urine.  The  nitrogen  in 
the  faeces  is  derived  from  two  sources.  Part  represents  those  nitrogenous 
constituents  of  the  tissues  which  have  resisted  the  digestive  processes  of  the 
alimentary  canal.  There  is  in  addition  a  certain  amount  derived  from  the 
intestine  itself.  During  complete  starvation  faecal  masses  are  formed  in  the 
intestine,  and  it  has  been  calculated  that  in  a  normal  individual  about  one 
gramme  of  nitrogen  a  day  is  excreted  by  the  mucous  membrane  of  the  gut  and 
contributes  to  the  formation  of  the  faeces.  It  is  usual  therefore  to  regard 
one  gramme  of  the  nitrogen  of  the  faeces  as  belonging  to  the  output  of  the 
body  and  representing  the  result  of  nitrogenous  metabolism,  while  the 
balance  is  taken  as  belonging  to  undigested  foodstuffs,  and  is  subtracted 
from  the  total  nitrogen  of  the  latter  in  reckoning  the  real  income  of  the  body. 
A  small  amount  of  nitrogen  is  also  lost  by  sweat,  but  this  can  be  disregarded 
unless  the  sweating  is  profuse,  when  the  loss  of  nitrogen  by  this  channel  may 
rise  to  as  much  as  4  per  cent,  of  the  total  nitrogenous  output  of  the  body. 
Although  a  trace  of  ammonia  has  been  described  as  occurring  in  the  expired 
air,  the  amount  is  so  minute  that  any  loss  of  nitrogen  by  the  lungs  can  be 
neglected.  That  the  loss  both  by  lungs  and  skin  under  ordinary  circum- 
stances can  be  disregarded  is  shown  by  the  fact  that  it  is  possible  to  account 
directly  for  the  whole  nitrogen  of  the  body  by  a  comparison  of  the  compo- 
sition of  the  food  with  that  of  the  urine  and  faeces.  If.  lor  instance,  an  animal 
is  kept  on  a  sufficient  diet  wliich  contains  a,  perfectly  regular  amount  of 


662 


PHYSIOLOGY 


nitrogen,  after  a  few  days  a  condition  known  as  nitrogenous  equilibriumia  set 
up,  i.e.  the  total  nitrogen  of  fares  and  urine  is  exactly  equal  to  the  total 
nitrogen  of  the  food.  The  same  thing  applies  to  the  alphur,  as  is  shown 
in  the  following  Table  (quoted  by  Tigerstedt)  : 


Days  of                Nitrogen 
experiment               oi  food 

Nitrogen              Percent, 
excrel  ed              differ  mce 

Sulphur 
3ted 

Sulphur 
excreted 

1-7     .      .      j        154-81 
8-17  .      .            213-72 

153-02             -  0-51 
213-2G              -  0-21 

12-77 

12-79 

In  order  to  express  the  nitrogenous  metabolism  in  terms  of  protein, 
we  use  the  factor  employed  in  estimating  the  amount  of  protein  in  the 
food,  i.  e.  we  multiply  the  total  nitrogen  of  the  excreta  by  6-25.  This  will 
give  the  total  protein  which  has  been  broken  down  during  the  period  of  the 
experiment.  Much  more  important  from  the  energy  standpoint  is  the  deter- 
mination of  the  total  processes  of  oxidation  of  the  body,  information  on 
which  is  given  by  a  comparison  of  the  oxygen  intake  with  the  output  of 


Fig.  327.     HaklanePembrey  respiration  apparatus, 
c,  chamber  for  animal;   M,  gas  meter. 

carbon  dioxide  and  water.  The  estimation  of  these  substances  presents 
much  greater  difficulties  than  the  investigation  of  the  nitrogenous  exchange 
and  involves  the  use  of  some  form  of  respiration  apparatus. 

The  following  are  the  chief  methods  which  have  been  employed  for  this  purpose  : 
I.  THE  METHOD  OF  HALDANE.  This  method  is  extremely  convenient  when 
dealing  with  the  gaseous  exchanges  of  small  animals,  such  as  mice,  rats,  guinea-pigs 
or  rabbits.  The  animal  is  placed  in  the  chamber  c,  which  may  be  simply  a  wide- 
mouthed  bottle  (Fig.  327).  This  chamber  is  supplied  with  a  thermometer,  and  can 
be  kept  at  any  desired  temperature  by  immersion  either  in  warm  or  cold  water.  On 
the  inlet  side  of  the  bottle  is  a  series  of  tubes  or  bottles,  some  of  which  contain 
sulphuric  acid  and  pumice-stone,  while  the  others  contain  soda  lime.  On  the  outlet 
side  of  the  vessel  is  a  corresponding  series  of  vessels  for  the  absorption  of  water  and  of 
carbon  dioxide.  On  the  further  side  of  these  vessels  is  a  gas  meter.  During  an  ex- 
periment air  is  sucked  through  the  whole  apparatus  by  means  of  an  aspirator  or  a  water 
pump,  the  amount  of  air  passing  through  the  apparatus  being  measured  by  the  meter. 
The  animal  is  thus  supplied  with  pure  air  freed  from  water  vapour  and  from  carbon 
dioxide.  Any  water  or  carbon  dioxide  produced  by  the -animal  is  absorbed  by  the 
vessels  interposed  in  the  course  of  the  outgoing  air.  These  vessels  are  weighed  at  the 
beginning  of  the  experiment  and  at  the  end,  and  the  difference  in  weights  will  there- 
fore give  the  amounts  of  carbon  dioxide  and  water  which  have  been  discharged  by 
the  animal. 

The  intake  of  oxygen  by  the  animal  is  determined  indirectly.      Since  it  gives  off 


THE  TOTAL  EXCHANGES  OF  THE  BODY  663 

only  carbon  dioxide  and  water,  and  absorbs  only  oxygen  during  its  stay  in  the  chamber, 
the  loss  of  weight  of  the  animal  during  its  stay  in  the  chamber,  subtracted  from  the 
total  amount  of  carbon  dioxide  plus  water  it  gives  off,  will  represent  the  amount  of 
oxygen  absorbed. 

The  advantage  of  this  apparatus  is  that  it  can  be  fitted  up  in  any  laboratory,  and 
is  accurate  for  the  purposes  to  which  it  is  applied.  It  is  not  however  appropriate 
for  long-continued  experiments  or  for  experiments  on  larger  animals  or  on  man 
himself.  Most  of  the  data  with  regard  to  the  respiratory  exchange  under  various 
circumstances  have  therefore  been  obtained  by  one  of  the  following  methods. 

II.  THE  METHOD  OF  REGNAULT  AND  REISE-T.  The  principle  of  this  method 
consists  in  placing  the  animal  th.at  is  to  be  the  subject  of  investigation  in  a  closed 
chamber  containing  a  given  volume  of  air.  The  carbon  dioxide  produced  by  the  animal 
is  absorbed  by  means  of  caustic  alkali,  and  the  oxygen  consumed  by  the  animal  is  made 
good  by  allowing  oxygen  to  flow  into  the  chamber  from  a  gasometer.  The  inflow  of 
oxygen  is  regulated  so  as  to  keep  the  pressure  of  air  in  the  chamber  constant.  At 
the  end  of  the  experiment  the  alkali  is  titrated  and  the  amount  of  carbon  dioxide 
absorbed  thus  determined.  The  air  in  the  chamber  is  also  analysed  so  as  to  be  certain 
that  it  contains  an  excess  neither  of  carbon  dioxide  nor  of  oxygen.  The  amount  of 
oxygen  absorbed  by  the  animal  is  known  already,  the  oxygen  which  has  been  allowed 
to  flow  in  having  been  measured. 

A  modification  of  this  method  has 
been  devised  by  Benedict  and  is  espe- 
cially applicable  to  clinical  purposes. 
In  this  method  the  individual  who  is 
the  subject  of  the  experiment  breathes 
through  a  nose-piece  into  a  wide  metal 
tube,  the  mouth  being  kept  closed. 
The  metal  tube  forms  part  of  a  closed 
system  through  which  a  current  of  air 
is  maintained  by  means  of  a  pump.  In 
the  course  of  the  current  of  air  are.  inter- 
posed vessels  for  the  absorption  of 
carbon  dioxide  and  of  water,  and  the 
volume  of  gas  in  the  system  is  main-  Fig.  32S.  Air  circuit  in  Benedict's  respiration 
tained  constant   by  admitting    oxygen  apparatus. 

to  it  in  proportion   as    the   oxygen  of 

the  system  is  used  up  in  respiration.  In  Fig.  32S  is  given  a  diagrammatic 
scheme  of  the  air  circuit,  and  in  Fig.  329  a  diagram  of  the  arrangement  of  the  whole 
respiration  apparatus,  showing  the  nose-piece  for  breathing,  the  tension  equaliser, 
the  air-purifying  apparatus,  and  the  oxygen  cylinder.  The  tension  equaliser,  a,  is 
attached  to  the  ventilating  pipe  near  the  point  of  entrance  of  the  air  into  the  lungs. 
It  consists  of  a  pan  with  a  rubber  diaphragm  (which  may  be  conveniently  made  from 
a  lady's  bathing-cap).  As  the  air  is  drawn  into  the  lungs  the  rubber  diaphragm  sinks. 
to  rise  again  with  expiration.  The  respiratory  movements  can  thus  proceed  without 
altering  appreciably  the  pressure  within  the  closed  system  of  tubes.  By  the  admission 
of  oxygen  the  supply  of  oxygen  is  adjusted  so  as  to  keep  t he  bag  from  becoming  either 
too  much  distended  or  too  much  flattened.  As  the  air  leaves  the  lungs  and  passes 
into  the  constantly  moving  current  of  air,  it  is  carried  along  by  the  pump  and  flows 
through  two  Wolff's  bottles  containing  strong  sulphuric  acid  and  pumice  for  the  remova  1 
of  water  vapour.  It  then  passes  through  a  brass  cylinder,  c,  filled  with  soda  lime 
for  the  absorption  of  carbon  dioxide.  From  here  it  passes  again  through  sulphuric 
acid  in  a  Kipp  generator  for  the  absorption  of  water  given  off  by  the  soda  lime.  Since 
the  air  so  deprived  of  moisture  would  be  uncomfortable  to  breathe,  it  is  then  carried 
through  another  Kipp  generator  containing  water  with  a  trace  of  sodium  carbonate 
for  the  neutralisation  of  any  acid  fumes  which  may  be  given  off  by  t  bi  sulphuric  acid. 
It  then  passes  back  to  the  tube  from  which  the  subject  is  breathing.  In  this  way  it  is 
possible  to  determine  very  accurately  the  amount  of  oxygen  used  up  and  the  amount 


664 


PHYSIOLOGY 


of  carbon  dioxide  given  off  in  the  course  of  an  experiment  lasting  one  to  I  luce  hours 
or  longer.  The  oxygen  consumption  is  measured  by  weighing  the  cylinder  of  this 
gas,  chosen  small  for  this  purpose,  before  and  after  the  experiment. 

III.  PETTENKOFER'S  METHOD.  In  the  apparatus  designed  by  Pettenkofer 
the  animal  or  man  was  placed  in  a  chamber  through  which  a  constant  current  of  fresh 
air  was  passed.  The  amount  of  air  passing  through  the  chamber  was  measured  by 
means  of  a  meter.  Throughout  the  experiment  continuous  samples  both  of  the  air 
entering  the  chamber  and  of  the  air  leaving  the  chamber  were  taken.  The  analyses 
of  these  samples  served  to  show  the  composition  of  the  whole  air  entering  and  leaving 
the  chamber,  and  therefore  the  changes  in  the  air  caused  by  the  presence  of  the  animal. 
The  advantage  of  this  apparatus  is  that  an  adequate  ventilation  can  be  kept  up,  and 
the  apparatus  can  be  built  of  any  size.  In  the  apjiaratus  of  Tigerstedt  built  on  this 
plan  the'eharnber  had  a  capacity  of  100-6  cubic  metres,  and  was,  in  fact,  a  small  room. 
A  small  respiratory  apparatus  has  been  built  by  Atwater. 

IV.    ZUNTZ     AND     GEPPERT'S 
l\lj?|      (~~~~\  METHODS.     For  many  purposes  the 

*g*      '  methods'devised  by  Zuntz  and  Geppert 

present  many  advantages,  especially 
when  it  is  desired  to'take  the  respiratory 
exchanges  in  man  or  any  animal  during 
a  limited  period  of  time.  The  subject  of 
the  experiment  has  his  nostrils  clamped 
and  breathes  into  and  out  of  a  face- 
piece.  This  face-piece  is  provided  with 
valves  either  of  aluminium  or  of  animal 
membrane,  which  serve  to  separate  the 
in-going  from  the  out-going  current 
of  air.  In  the  course  of  the  out-going 
current  is  placed  a  very  delicate  gas 
meter  which  presents  practically  no 
resistance  to  the  air  current.  A  branch 
from  the  efflux  tube  passes  to  a  gas 
analysis  apparatus.  By  an  ingenious 
method  it  is  arranged  that  an  abquot 
part  of  the  whole  of  the  out-going  air  is 
drawn  off  into  this  apparatus,  so  that 
the  experiment  can  be  interrupted  at 
any  time,  and  the  analysis  of  this  sample 
will  give  the  average  composition  of  the 
expired  air,  and  therefore,  on  multipli- 
cation by  the  total  gas  passing  through 
the  gas  meter,  the  total  output  of 
carbon  dioxide  during  the  course  of  the 
observation.  One  advantage  of  this  method  is  that  the  apparatus  is  portable,  and  can 
be  applied  to  the  investigation  of  the  respiratory  exchanges  of  patients  in  hospitals 
or  of  man  or  animals  while  they  are  walking  about.  It  has  been  used,  for  instance, 
by  Zuntz  and  his  pupils  in  an  interesting  series  of  researches  on  the  gaseous  metabolism 
of  men  at  high  altitudes. 

V.  THE  DOUGLAS  BAG.  By  far  the  most  convenient  method  for  estimating 
the  respiratory  exchanges  of  man  under  varying  conditions  is  the  use  of  the  Douglas 
Bag.  Li  this  method  the  subject  for  experiment  breathes  through  a  mouthpiece 
provided  with  valves  into  a  bag  of  about  100  litre  capacity.  The  valves  are  so  arranged 
that  he  inspires  from  the  external  air  and  expires  into  the  bag.  After  from  two  to 
ten  minutes  the  bag  is  removed,  the  time  being  accurately  noted.  The  amount  of 
air  expired  during  this  time  is  measured  by  emptying  the  bag  through  a  gas  meter. 
A  sample  of  its  contents  is  analysed  and  the  oxygen  and  f  :02  in  it  determined.  Since 
the  composition  of  the  external  air  is  known,  the  analysis  and  measurement  of  the 


Fig.  329.     Arrangement   of    apparatus   in 
Benedict's  method  for  determination  of 
respiratory  exchange. 
N,  tubes  inserted  into  nostrils  of  patient ; 
A,  tension  equaliser;    c,  cylinder  contain- 
ing soda  lime  for  adsorbing  C02. 


THE  TOTAL  EXCHANGES  OF  THE  BODY 


605 


expired  air  gives  the  respiratory  metabolism  during  (lie  time  of  the  observation. 
The  bag  is  carried  on  the  back  of  the  individual,  so  that  it  does  not  interfere  with  his 
movements.  This  method  has  been  used  for  determining  the  metabolism  of  soldiers 
in  training,  of  munition  workers,  etc. 

By  means  of  one  or  more  of  these  methods  we  may  arrive  at  a  correct 
idea  of  the  total  income  and  output  of  an  individual  for  periods  of  many 
days.  The  following  details  by  Tigerstedt  may  serve  as  an  example  of  the 
results  obtained  in  such  an  experiment.  The  experiment  lasted  two  days. 
The  subject  was  a  man  of  twenty-six  years  of  age,  weighing  about  65  kilos, 
who  had  previously  taken  no  food  for  five  days.  The  following  Tables 
represent  his  material  income  and  output. 


Corrugated 


Side  tube  for 
sampling  (with  dtp) 


Fig.  330.  Douglas'  Big  for  determining  respiratory  exchange  in  man. 
Total  Income 


Total 
amount 

N. 

•      Water 

i 

£ 

Fat 

Of 

Ash 

< 

Bread  . 

373 

7-3 

36 

337 

46 

4 

278 

9 



Butter 

388 

0-4 

37 

.■;;,  i 

3 

337 

4 

7 

— 

Cheese 

110 

4-3 

56 

60 

27 

35 

— 

5 

— 

Salt  meat 

26 

1-1 

16 

10 

9 

— 

2 

— 

Milk     . 

2313 

11-3 

2047 

266 

71 

85 

95 

16 

— 

Broth  . 

658 

11-8 

580 

78 

74 

— 

— 

9 

Beer 

1413 

1-2 

1273 

77 

8 

— 

67 

3 

."id 

Beef  steal; 

7(10 

20-6 

533 

167 

129 

33 

7 

Potatoes 

152 

Oil 

359 

93 

0 

1 

82 

5 

Water  . 

2:!.'!r> 

59-3 

2335 

371 

I!I7 

525 

61 

59 

Totals       . 

8773 

831-6 

72::. 

1439 

066 


PHYSIOLOGY 

Total  Output 


Total 

a: i 

N. 

c. 

Water    Solids 

Protein     Fat 

Carbo- 
hydrate 

Asli 

21 
15 

Respiration   . 
Urine    . 
Fteces  . 

2701 

2564 

455 

41-5 

4-8 

453-0 
32-5 
43-8 

2248      — 

2490      — 

363     91-6 

30        20 

27 

Totals      .          .        5720 

46-3 

529-3 

510]     91-6 

30        20 

27 

36 

As  we  should  expect  in  a  man  who  had  previously  fasted  five  days,  this 
balance-sheet  shows  a  marked  retention  of  the  food  taken  in,  i.  e.  a  marked 
excess  of  income  over  output.  Thus  of  the  nitrogen  ingested,  13  grrn.,  which 
is  equivalent  to  81-3  grm.  of  protein,  was  retained;  of  the  carbon,  302  grm. 
was  retained.  Of  this  302  grm.,  42-7  grm.  would  be  contained  in  the  81-3 
grm.  of  protein,  so  that  the  rest  of  the  carbon,  namely,  259-6  grm.,  was 
probably  laid  down  in  the  form  of  fat.  This  would  correspond  to  339  grm. 
of  fat.  Of  the  salts  contained  in  the  ash  of  the  food,  25  grm.  were  retained 
in  the  body.  The  carbon  and  nitrogen  reappearing  in  the  excreta  serve  as 
an  index  of  the  amount  of  metabolism  of  the  foodstuffs  which  had  occurred 
during  the  two  days.  In  order  to  supply  the  energy  requirements  of  the 
body  during  the  time  of  the  experiment,  498  grm.  of  carbohydrate,  59  grm. 
of  alcohol,  and  138  grm.  of  fat  had  been  completely  oxidised.  The  amount 
of  protein  used  up  during  this  time  can  be  obtained  by  multiplying  the 
nitrogen  of  the  urine  plus  1  grm.  of  nitrogen  of  the  faeces  by  the  factor  6-25, 
and  is  found  to  amount  to  271-9  grm. 

THE  ENERGY  BALANCE-SHEET  OF  THE  BODY 
The  energy  income  of  the  body  is  measured  by  the  potential  energy  of  the 
foodstuffs,  i.  e.  the  amount  of  energy  which  can  be  evolved,  either  as  heat, 
work,  or  in  any  other  form,  by  the  oxidation  of  the  foodstuffs  to  the  end- 
products  which  occur  in  the  body.  Since  it  is  convenient  to  have  a  uniform 
method  of  expressing  the  total  potential  energy  of  a  foodstuff,  we  generally 
express  it  in  calories,  and  speak  of  the  heat-value  of  a  foodstuff.  The 
heat  value  of  any  given  food  is  the  amount  of  large  Calories1  which  it 
evolves  on  complete  combustion  with  oxygen,  and  is  determined  by  burning 
a  weighed  quantity  of  the  dried  foodstuff  in  oxygen  in  the  bomb  calorimeter. 
The  following  heat  values  have  been  obtained  for  different  foodstuffs  : 


Substance 
Lean  meat 
Lard 
Butter    . 
Grape  sugar 
Cane  sugar 
Starch    . 


Heat  value 
5-656  (or  5-345  Rubner) 
!)-423 
9-231 
3-692 
4-116 
4191 


1  A  calorie  is  the  amount  of  heat  necessary  to  raise  a  gramme  of  water  from  15°  C. 
to  16°  C.  A  large  Caloric  (printed  with  a  capital  C)  is  the  heat  required  to  raise  a  kilo- 
gramme of  water  from   15°  C.  to  16°  C,  and  is  therefore  equal  to  1000  small  calories 


THE  TOTAL  EXCHANGES  OF  THE  BODY  667 

In  the  case  of  some  foodstuffs  it  is  necessary  to  draw  a  distinction 
between  the  absolute  heat  value  and  the  physiological  heat  value.  Since 
carbohydrates  and  fats  undergo  complete  oxidation  in  the  body  to  carbonic 
acid  and  water,  their  physiological  heat  values,  i.  e.  the  values  of  these  food- 
stuffs to  the  organism,  are  identical  with  their  absolute  heat  values.  Pro- 
teins however  do  not  undergo  complete  oxidation.  When  they  are  oxidised 
in  the  bomb  calorimeter  the  nitrogen  is  set  free  in  a  gaseous  form.  In  the 
animal  body  no  nitrogen  is  eliminated  in  the  gaseous  form,  the  whole  of  it 
being  excreted  as  nrea  and  allied  substances  still  endowed*with  a  considerable 
store  of  potential  energy,  which  can  be  set  free  when  their  oxidation  is  com- 
pleted in  a  calorimeter.  In  order  to  determine  the  physiological  heat  value 
(if  protein,  we  must  subtract  from  its  absolute  heat  value  the  heat  value  of 
the  excretory  products  in  the  form  of  which  it  leaves  the  body.  The 
physiological  heat  value  of  proteins  has  been  determined  by  Eubner  in  the 
following  way  :  A  dog  was  fed  with  the  same  protein  which  had  served  for 
the  determination  of  the  absolute  heat  value.  AYhile  the  dog  was  receiving 
this  food  its  urine  was  collected,  dried,  and  its  heat  value  determined  by 
combustion  in  the  calorimeter.  It  was  found  that  for  each  gramme  of 
protein  which  had  undergone  disintegration  in  the  body  an  amount  of  urine 
was  passed  corresponding  to  a  heat  value  of  1-0945  Calories.  The  heat  value 
of  the  faeces  formed  under  the  same  diet  was  0-1854  Calorie  for  each  gramme 
of  protein.  Eubner  further  reckoned  that  a  certain  amount  of  heat  would 
be  required  for  the  solution  of  the  proteins  and  of  the  urea,  and  reckoned 
this  at  0-05  Calorie.  The  reduced  or  physiological  heat  value  of  protein  is 
therefore  equal  to  5-345  -  (1-0945  +  0-1854  +  0-05)  =  4-015  Calories. 

A  determination  of  the  heat  values  of  the  various  foodstuffs  shows 
minute  differences  between  individual  members  of  the  same  class.  Since  it 
is  impossible  to  reckon  out  accurately  the  relative  amounts  of  the  different 
kinds  of  protein,  carbohydrate,  etc.,  contained  in  each  diet,  Eubner  has 
calculated  the  average  physiological  heat  values  of  the  three  classes  of  food- 
stuffs.    These  figures  have  been  universally  adopted,  and  are  as  follows  : 

1  grin,  protein  =  4-1  Calories 

1  grm.  fat  =  9-3       „ 

]  grin,  carbohydrate  =  4-1       ,, 

These  figures  are  accurate  only  for  a  diet  containing  the  normal  pro- 
portion of  vegetable  to  animal  foods — 60  to  40.  The  heat  value  of  vegetable 
protein  is.  as  a  rule,  less  than  that  of  animal  protein.  It  has  been  pointed 
out  that  these  figures  are  rather  too  low  for  the  food  as  ingested  and  too 
high  if  taken  to  represent  food  as  digested.  Taking  the  normal  mixture 
of  foods  used  in  civilised  countries,  the  following  figures  give  more  accurately 
(he  energy  available  from  any  given  diet  (allowing  for  the  loss  in  digestion)  : 

Carbohydrates  Proteins  Fats 

4  Calories  per  gramme         4  Calories  per  gramme         8-9  Calories  per  gramme 

Careful  experiments  have  shown  that  just  as  there  is  no  loss  of  matter 
in  the  body,  so  also  the  sum  of  the  energies  put  out  by  the  body  is  equal  to 
the  sum  of  the  energy  obtained  by  the  oxidation  of  the  tissues  and  of  the 


068 


PTTYSIOLOCiY 


foodstuffs  in  the  body  during  the  same  time.  In  an  earlier  chapter  I  have 
quoted  the  results  of  an  experiment  by  Rubner  on  a  dog,  which  demonstrated 
this  equivalence,  as  proving  the  important  fact  that  the  fundamental 
doctrine  of  the  Conservation  of  Energy  applies  to  the  organised  as  to  the 
inanimate  world.  Similar  results  have  been  arrived  at  by  Atwater  in  a 
series  of  experiments  with  a  special  calorimeter  on  man.  It  may  be  sufficient 
heTe  to  give  the  figures  from  one  such  experiment : 


a 

b 

c 

d 

c 

f 

g 

h 

' 

Date 

Culs. 

(  als. 

(ills. 

Cals. 

Cals. 

Cals. 

Cals. 

Cals, 

, 

Dec.  9-10 

2519 

IK) 

142 

-85 

+  3 

2349 

2414 

+  65 

+2-8 

10-11 

2519 

110 

133 

-25 

-44 

2345 

2386 

+41 

+  1-7 

11-12 

2519 

110 

132 

-21 

-93 

2391 

2413 

+  22 

+0-9 

12-13 

2519 

110 

133 

-14 

-55 

2345 

2375 

+  30 

+  13 

Total  4  days 

10,076 

440 

540 

-145 

-189 

9430 

9588 

+  158 

Average  one  day 

2519 

110 

135 

-36 

-47 

2357 

2397 

+40 

+  1-7 

a 

a 

•s 

S  + 

3  ° 
•a  — 
6  + 

If- 

+| 

SS 

+| 

3 
-a 
& 

3 

S 

3 
.3 
| 

l~+ 

•3 

c 

It 

•3  S 

It 

- 

5  ■ 

Sfe 

lS 

h'5- 

§■§- 

■3 

■3  £** 
iS  °  M 

If  we  take  into  account  the  great  difficulties  of  such  an  experiment,  we 
cannot  but  be  impressed  with  the  closeness  of  agreement  between  the  total 
output  of  energy  reckoned  as  heat  and  measured  by  the  warming  of  a  given 
volume  of  water  and  the  total  income  of  energy  as  estimated  from  the 
chemical  reactions  involved  in  the  metabolic  changes  which  had  taken 
place  during  four  days  of  the  experiment.  The  important  result  which 
comes  out  in  such  experiments  is  that  the  foodstuffs  produce  the  same 
amount  of  energy  when  oxidised  in  the  body  as  when  burnt  to  the  same 
end  products  outside  the  body,  so  that  it  becomes  easy  in  any  given  research 
to  sum  accurately  the  energy  income  of  the  body. 

The  Atwater  calorimeter  has  been  improved  to  such  an  extent  by  Bene- 
dict and  his  fellow-workers  that  it  has  practically  replaced  all  other  forms 
for  physiological  purposes.  It  consists  of  a  room  or  chamber  with  double 
non-conducting  walls.  All  round  the  inner  wall  of  the  room  are  fitted  coils 
of  pipes  through  which  a  stream  of  water  flows.  The  pipes  are  fitted  with 
discs  so  as  to  take  up  rapidly  heat  produced  in  the  room.  The  current  of 
water  is  accurately  adjusted  so  as  to  maintain  the  temperature  of  the  inner 
wall  constant.  As  the  inner  wall  and  outer  wall  are  kept  at  the  same  tem- 
perature, no  heat  is  lost  to  the  exterior,  the  whole  of  the  heat  produced  by 


THE  TOTAL  EXCHANGES  Of  THE   BODY 


669 


the  animal  or  individual  in  the  chamber  being  communicated  to  the  water 
passing  through  the  chamber.  The  temperatures  of  the  entering  and  leav- 
ing water  are  taken  by  accurate  thermometers  reading  to  a  hundredth  or  a 
thousandth  of  a  degree  Centigrade.  Knowing  the  amount  of  water  that  has 
passed  through  in  a  given  time  and  the  difference  in  temperature  during  the 
same  time,  it  is  easy  to  calculate  the  amount  of  heat  given  off  by  the  animal 
under  investigation.  It  is  generally  convenient  to  maintain  a  constant 
difference  of  temperature  between  the  entering  and  leaving  water  by  appro- 
priate adjustment  of  the  amount  of  water  passing  through  the  apparatus. 
The  equality  of  temperature  between  the  inner  and  outer  casing  is  recorded 


Oxygen  enters .' 

Flu.  331.     Diagram  to  show  the  principle  of  the  Atwater-Benedict  calorimeter. 
(After  Halliburton.) 

by  electric  themio  couples,  any  difference  of  temperature  being  at  once 
compensated  by  electrically  warming  the  cooler  part.  The  chamber  con- 
tains a  bicycle  or  other  arrangement  for  the  performance  of  mechanical 
work.  It  is  adequately  ventilated  by  a  current  of  air  passing  through  an 
apparatus  similar  to  that  of  Benedict,  described  on  p.  663.  It  is  thus 
possible  to  estimate  simultaneously  the  total  heat  production  of  an  individual 
as  well  as  the  respiratory  changes,  including  both  carbon  dioxide  output 
and  oxygen  intake.  The  general  principle  of  the  calorimeter  is  shown  in 
the  diagram  (Fig.  331).  The  calorimeter  is  also  supplied  with  bed,  table, 
chair,  etc.,  and  food  can  be  introduced  through  a  double  window  so  that 
an  experiment  may  be  continued  over  two  or  three  days  on  one  and  the 
same  individual. 


SECTION  II 

METABOLISM    DURING   STARVATION 

It  will  tend  to  simplify  our  task  if  we  deal  first  with  the  results  of  the 
experiments  which  have  been  made  on  the  metabolic  exchanges  of  animals 
during  starvation,  i.  e.  during  a  period  when  the  whole  energy  involved  in 
the  maintenance  of  the  movements  of  respiration  and  circulation,  and  in 
the  maintenance  of  the  body  temperature,  etc.,  is  derived  from  the  animal's 
own  tissues.  It  must  be  remembered  that  the  tissues  of  an  animal  comprise 
two  distinct  classes.  In  the  first  class  must  be  placed  the  living  machinery 
of  the  body,  generally  composed  of  proteins  or  their  near  allies.  In  the 
second  class  are  the  fatty  tissues  of  the  body,  which  form  no  part  of  the 
ordinary  machinery,  but  function  simply  as  a  storehouse  of  material  which 
can  be  utilised  for  the  production  of  energy.  In  addition  to  the  store  of  fat 
there  is,  in  a  well-fed  animal,  a  certain  reserve  of  carbohydrate  in  the  form 
of  glycogen,  deposited  in  the  liver  and  the  muscles.  This  store  of  glycogen 
is  drawn  upon  to  a  large  extent  at  the  beginning  of  a  period  of  starvation. 
The  total  amount  of  glycogen  present  at  any  time  is  generally  so  small  in 
comparison  with  the  fat  of  the  body  that  it  cannot  provide  the  energy 
necessary  for  the  maintenance  of  life  during  prolonged  inanition,  although 
it  plays  an  important  part  during  the  first  one  or  two  days  of  a  period  of 
starvation. 

Contrary  to  general  belief,  the  condition  of  an  animal  which  is  completely 
deprived  of  food  is  not  a  painful  one.  For  this  statement  we  have  not  only 
such  evidence  as  can  be  derived  from  inspection  of  animals  placed  in  this 
condition,  but  also  evidence  derived  from  men  who  have  voluntarily  or 
involuntarily  been  deprived  of  food  for  considerable  periods.  Especially 
instructive  in  this  connection  are  the  cases  of  the  so-called  professional 
'  fasting  men,'  two  of  whom,  Succi  and  Cetti,  have  been  subjected  to  com- 
plete metabolic  investigation  during  the  period  of  their  starvation.  During 
the  first  day  or  two  there  is  a  craving  for  food  at  meal-times.  This  how- 
ever passes  off,  and  during  the  later  portions  of  the  experiment  even  the 
desire  for  food  may  be  entirely  absent.  As  might  be  expected,  the  restric- 
tion of  food  is  followed  by  a  diminution  in  the  amount  of  water  required 
by  the  animal.  The  essential  characteristic  of  the  state  of  inanition  is  an 
ever-increasing  weakness,  accompanied  by  a  strong  disinclination  to  under- 
take any  mental  or  physical  exertion  whatsoever.  The  animal  passes  its  time 
in  a  state  of  sleep  or  semi-stupor.  In  the  case  of  Succi,  who  fasted  for  thirty 
days,  considerable  muscular  exertion  was  undertaken  on  the  twelfth  and 
on  the  twenty-third  day  of  starvation  without  any  appreciable  ill-effects. 
A  strong  effort  of  the  will  must  have  been  necessary  in  his  case  to  overcome 
the  automatic  instinct  to  preservation  of  life  by  the  utmost  economy  in  the 
expenditure  of  energy.    The  pulse  rate  and  the  body  temperature  remain 

670 


METABOLISM  DURING  STARVATION 


671 


nearly  normal  until  a  few  days  before  death,  which  is  ushered  hi  by  an 
increase  in  the  somnolent  condition  of  the  animal  and  by  a  gradual  slowing 
of  respiration  and  fall  of  temperature.  The  urine  is  naturally  diminished 
with  diminution  in  the  output  of  urea  and  in  the  amoiuit  of  water  consumed. 
Some  faeces  are  formed,  and  may  be  voided  during  or  at  the  close  of  the 
starvation  period.  In  Succi  their  amoimt  varied  from  9-5  to  22  grm.  a  day 
and  contained  from  0-3  to  1-0  grm.  nitrogen.  On  microscopic  examination 
they  consisted  of  an  amorphous  material  enclosing  a  number  of  crystals  of 
fatty  acids. 

During  the  whole  of  the  starvation  period,  energy  is  being  used  up  in  the 
body  for  the  maintenance  of  its  temperature  and  the  vital  movements  of 
respiration  and  circulation.  Since  this  energy  is  derived  from  the  destruc- 
tion and  oxidation  of  the  tissues  of  the  body,  there  must  be  a  steady  loss 
of  body  weight.  In  experiments  on  man  the  daily  loss  of  weight  during  the 
first  ten  days  amounts  to  between  1  and  1-5  per  cent,  of  the  original  total 
weight.  This  loss  of  weight  does  not  affect  all  parts  of  the  body  alike.  It 
might  be  imagined  that,  since  the  loss  of  weight  is  determined  by  the  using 
up  of  the  tissues  of  the  body  for  the  production  of  energy,  those  organs 
which  are  most  active  should  show  also  the  greatest  loss  of  weight.  The 
very  reverse  of  this  is  the  case,  as  will  be  seen  from  the  following  Table  : 


Percentage  Loss  of 

Weight  of  Different  .Organs  and  Tissues  during 

Starvation.     (Voit.  ) 

o^si»&  •s-sgxsr 

Fat 

07                          — 

Spleen 

67                          63 

Liver 

5 1                         57 

Testes     . 

Hi 

Muscles 

31                         30 

Blood     . 

27                         18 

Kidneys 

20                          21 

Skin  and  hairs 

21 

— 

Intestine 

18 

— 

Lungs     . 

18 

19 

Pancre.i 

17 

— 

Heart     . 

3 

— . 

Brain  and  spil 

;.l  cord 

3 

0 

Those  organs  of  the  body  which  are  most  necessary  for  the  maintenance 
of  life,  the  brain,  the  heart,  the  respiratory  muscles,  such  as  the  diaphragm, 
undergo  very  little  loss  of  weight.  Of  the  other  tissues  the  fat,  which  is  a 
mere  reserve  to  prov  de  for  such  contingencies,  is  drawn  upon  first,  and 
during  starvation  97  per  cent,  of  the  total  fat  of  the  body  may  be  consumed. 
The  nitrogen  needs  of  the  body  during  starvation  seem  to  be  supplied  chiefly 
at  the  expense  of  the  muscles  and  glands,  which  waste  to  a  very  marked 
de<ree.  The  muscles  being  used  simply  as  reserve  material,  it  is  easy  to 
understand  the  condition  of  lethargy  and  muscular  inactivity  which  charac- 


672 


PHYSIOLOGY 


terises  the  state  of  inanition.  During  the  starvation  all  tissues  of  the  body 
undergo  a  process  of  slow  autolysis  or  disintegration,  giving  up  the  products 
of  this  process  to  the  common  circulating  fluid.  The  nutritional  demands 
of  a  tissue  are  determined  by  its  activity.  Hence  the  active  tissues  of  the 
body  take  up  the  material  set  free  from  all  the  other  cells  of  the  body  and 
so  maintain  their  weight  at  the  expense  of  all  other  parts.  A  similar  pre- 
dominance of  the  nutrition  of  active  over  inactive  tissues  is  to  be  observed 
in  cases  of  partial  starvation,  i.  e.  where  the  deprivation  of  food  applies  only 
to  a  single  food  constituent.  Thus  Voit,  in  a  series  of  experiments,  fed 
pigeons  on  a  food  which,  while  normal  in  all  other  respects,  contained  a 
deficiency  of  calcium  salts.  On  killing  the  birds  after  a  certain  length  of 
time,  it  was  found  that  while  the  bones  used  in  the  necessary  movements 
of  the  animals  presented  a  normal  appearance,  the  others,  such  as  the 
sternum  and  skull,  showed  a  marked  deficiency  of  linie  salts  and  had  under- 
gone a  process  of  rarefaction  giving  rise  to  the  condition  known  by  patho- 
logists as  osteoporosis.  Many  other  instances  of  the  sacrifice  of  a  temporarily 
useless  tissue  on  behalf  of  tissue  of  high  physiological  value  are  known. 
Thus  the  salmon  and  its  congeners,  which  hve  part  of  the  year  in  the  sea, 
lay  their  eggs  and  undergo  their  early  development  in  the  fresh  water  of  the 
upper  reaches  of  rapid  streams.  An  adult  salmon  leaves  the  sea  in  the  early 
summer  months  in  a  magnificent  state  of  muscular  development,  fit  to 
perform  the  prodigious  feats  'of  swimming  which  are  required  in  order  to 
get  it  over  the  rapids  of  the  river  which  it  has  to  ascend.  It  takes  no  food. 
In  the  upper  reaches  of  the  stream  or  river  there  is  a  growth  of  the  genital 
glands,  ovaries,  or  testes.  The  whole  material  for  the  growth  of  these  large 
organs  is  derived  from  the  atrophy  of  the  skeletal  muscles.  In  this  case 
we  have  the  growth  of  an  active  tissue  at  the  cost  of  an  inactive  one,  the 
activity  however  being  determined,  not  by  the  direct  call  upon  it  from 
the  environment,  but  by  what  we  may  speak  of  as  the  '  physiological 
habit '  of  the  animal. 

The  animal  organism,  in  the  complete  absence  of  food,  deals  with  the 
resources  of  its  bodily  tissues  with  the  utmost  possible  economy.  The  total 
metabolism  therefore  sinks  rapidly  during  the  first  two  days  of  starvation, 
and  then  remains  practically  constant.  There  is  indeed  a  slight  continuous 
diminution  with  the  fall  in  body  weight,  but  the  total  metabolism  per  kilo 
body  weight  till  within  a  day  or  two  before  death  is  a  constant  quantity. 
This  is  shown  in  the  following  Table  of  the  output  of  energy  in  man  during 
a  five  days'  period  of  starvation  (Tigerstedt) : 

Metabolism  during  Starvation  (Man) 


Day  of  experiment 

Nitrogen  output 

Fat  oxydised 

Total  Calories 

Calories  per  kilo, 
body  weight 

1 

1216 

204-8 

2231 

33-3 

2       .          .          . 

12-85 

190-3 

2112 

32-1 

3       .          .          . 

13-62 

179-9 

2032 

31-3 

4       .          . 

13-67 

176-4 

2003 

31-3 

5       . 

11-44 

180-0 

1979 

31-4 

METABOLISM  DURING  STARVATION 


673 


THE    METABOLISM    OF    CARBOHYDRATE,    FAT,    AND 
PROTEIN    DURING    STARVATION 

Since  during  starvation  no  energy  is  supplied  to  the  body  from  without 
in  the  shape  of  foodstuffs,  we  can  regard  the  whole  expenditure  of  the 
animal  during  its  period  of  starvation  as  occurring  at  the  expense  of  its 
capital.  The  amount  of  carbohydrate  which  can  be  stored  up  as  glycogen 
or  other  forms  is  strictly  limited.  In  many  experiments  the  glycogen  meta- 
bolism has  therefore  been  entirely  disregarded,  and  it  has  been  estimated 
that  the  chemical  capital  of  the  body  consisted  entirely  of  proteins  and  fats. 
The  glycogen  metabolism  however,  during  the  first  day  of  a  period  of  starva- 
tion, may  form  a  considerable  fraction  of  the  total  metabolism  of  the  body, 
and  can  hardly  be  excluded  without  introducing  serious  errors. 

The  relative  parts  played  by  protein,  carbohydrate,  and  fat  respectively  in  the 
chemical  exchanges  of  a  starving  animal  may  be  determined  in  the  following  way  : 
The  amount  of  protein  consumed  is  given  by  estimating  the  total  nitrogen  of  the 
excreta  by  Kjeldahl's  method  and  multiplying  the  result  by  the  factor  6-25.  The 
loss  of  weight  of  the  body  minus  the  protein  consumed  may  be  roughly  taken  as  equiva- 
lent to  the  fat  plus  carbohydrate  consumption.  But  this  is  only  a  rough  method, 
since  the  quantity  of  water  in  the  tissues  may  undergo  considerable  variations,  and 
so  affect  the  total  weight  of  the  body.  For  any  accurate  results  the  respiratory  ex- 
changes must  be  measured,  including  both  oxygen  intake  and  carbon  dioxide  output. 
After  deducting  the  carbon  dioxide,  due  to  the  combustion  of  the  carbon  of  the  proteins, 
which  does  not  appear  in  the  urine  in  combination  with  nitrogen,  the  remainder  of 
the  carbon  dioxide  is  derived  entirely  from  carbohydrate  and  fat  metabolism.  Know- 
ing the  respiratory  quotient  and  the  total  amount  of  carbohydrate  and  fat  metabolism, 
it  is  possible  to  come  to  a  conclusion  as  to  how  much  of  the  carbon  dioxide  is  derived 
from  oxidation  of  glycogen  and  how  much  from  the  oxidation  of  fat.  A  very  efficient 
check  on  this  calculation  is  furnished  if  the  individual  or  animal  can  be  placed  at  the 
same  time  in  an  accurate  calorimeter,  as  in  Benedict's  experiments,  owing  to  the  fact 
that  a  gramme  of  fat,  when  converted  into  carbon  dioxide  and  water,  produces  more 
than  double  the  amount  of  heat  which  would  be  evolved  by  the  complete  oxidation 
of  glycogen.  In  Benedict's  experiments  the  heat  value  of  the  metabohsm  calculated 
by  the  above  method  agreed  with  the  heat  as  actually  measured  by  the  calorimeter 
within  0-5  per  cent.,  whereas  if  the  total  carbon  of  the  first  day  had  been  reckoned 
as  fat,  the  discrepancy  would  have  been  as  high  as  5  per  cent,  in  many  cases.  The 
influence  of  glycogen  metabolism  on  that  of  protein  during  the  first  and  second  days 
of  fasting  is  shown  in  the  following  experiments  (Benedict) : 


Glycogen  r 

First  day 

Second  day 

tetabolised 

N. 
eliminated 

Glycogen  metabolised 

X. 
eliminated 

Total 

Per  kilo. 

Total 

Per  kilo. 

S.A.B.        .           181-6             3-15 
S.A.B.        .           135-3             2-31 
S.A.B.        .             64-9             109 
H.C.K.       .           165-6             2-33 
H.R.D.      .             32-8             0-59 

5-84 
10-29 

12-24 
9-39 
13-25 

29-7 
18-1 
231 
44-7 

41-0 

0-52 
0-31 
0-39 

0-64 
0-76 

11-04 
11-97 
12-45 
14-36 
13-53 

The  total  metabolism  per  kilo  body  weight  very  soon  attains  a  constant 
level.     The  relative  part  taken  in  the  production  of  the  total  energy  by  fats 
43 


674 


PHYSIOLOGY 


and  proteins  respectively  may  vary  from  animal  to  animal  according  to 
the  amount  of  fat  available  in  the  body.  If  the  animal  has  been  receiving 
previoiis  to  the  experimenl  a  diet  rich  in  protein,  the  excretion  of  nitrogen 
and  urea  in  the  urine  diminishes  rapidly  during  the  first  days  of  starvation. 
During  the  first  two  days  therefore  a  considerable  proportion  of  the  neces- 
sary energy  is  obtained  at  the  expense  of  protein.  Between  the  third  and 
fifth  day  however,  the  nitrogenous  excretion  reaches  a  minimum,  at  which 
point  it  remains  approximately  constant  to  within  a  day  or  two  before  death. 
If  the  animal  has  been  receiving  a  diet  very  poor  in  protein,  the  excretion 
of  nitrogen  may  be  low  throughout  the  whole  course  of  the  experiment. 
These  facts  are  illustrated  by  the  curves  in  Fig.  332,  which  show  the  output 


Fio.  332.    Three  experiments  on  the  output  of  urea  during  starvation  (dog). 
(Tigerstedt,  after  Voit.) 
In  (1)  (thin  line),  the  dog   received  2500  grm.   meat   per   day   before   the  ex- 
periment; in  (2)   (thick  line),  the  diet  was  1500  grm.  meat;  and  in  the  third 
experiment  the  meat  was  reduced  to  a  minimum. 


of  urea  in  three  experiments  on  a  dog  under  different  conditions  of  nutrition. 
In  the  first  experiment  the  dog,  before  the  experimental  period,  had  been 
receiving  2500  grm.  of  meat  daily;  in  the  second  it  had  been  receiving 
1500  grm.  of  meat,  and  in  the  third  only  a  small  quantity,  which  was  not 
accurately  measured.  Although  there  is  a  great  difference  between  the 
urea  output  during  the  first  day  of  the  experiments,  the  urea  output  during 
the  sixth  to  eighth  days  is  identical.  In  many  cases  for  a  few  days  before 
death  there  is  a  rise  of  protein  metabolism.  This  rise  is  synchronous  with  a 
practically  complete  disappearance  of  fat  from  the  body.  The  animal  now 
has  to  supply  all  its  requirements  at  the  expense  of  the  protein  tissues,  which 
therefore  waste  rapidly  and  account  for  the  increased  excretion  of  nitrogen. 
This  is  shown  in  the  following  experiment  of  Rubner  on  a  rabbit : 


METABOLISM  DURING  STARVATION 


675 


Days 
1-3   . 
4-5   . 

Average  daily  out- 
put of  nitrogen 
.     1-67  grin.  . 
.      1-46     „       . 

Average  amount  of 

fat  oxidised  daily 

10-3  grm. 

10-3    „ 

6-8  . 

.     3-21     „ 

2-4    „ 

We  see  therefore  that  during  starvation,  apart  from  the  first  day  or  two, 
the  animal  derives  the  main  portion  of  its  necessary  energy  from  the  com- 
bustion of  fats,  provided  that  there  is  a  sufficient  store  of  these  substances  in 
the  body.  A  certain  consumption  of  protein  is  unavoidable.  Since  protein 
comes  from  the  working  tissues  of  the  body  they  are  spared  so  far  as  possible, 
and  it  is  only  when  the  stored  fat  is  used  up  that  any  large  call  is  made  on 
the  tissue  protein. 


BASAL   METABOLISM 

During  starvation  the  energy  output  of  the  body  furnished  by  the  con- 
sumption of  its  own  tissues  is  determined  (a)  by  the  amount  necessary  to 
keep  the  body  alive — i.  e.  to  maintain  its  warmth  and  to  furnish  the  energy 
for  respiratory  movements,  contractions  of  the  heart,  etc. ;  (b)  the  energy 
necessary  to  carry  out  any  work  that  is  performed. 

The  energy  requirements  under  (a)  represent  the  '  Basal  Metabolism  ' 
of  the  body.  We  have  already  seen  that  this  varies  with  the  weight  of  the 
individual ;  but  if  a  number  of  different  animals  are  compared,  their  meta- 
bolism per  kilo  is  found  to  be  greater  the  smaller  the  animal,  as  is  shown 
in  the  following  table  : 


Body  weight, 
kilos. 

Calbi  lea  per  kilo, 
body  weight 

-Man 

706 

32-9 

Dog  1       .          .          . 

.30-4 

35-3 

Dog  2       . 

17-7 

45-0 

Dog  3       .          .          . 

3-1 

85-3 

Rabbit  1 

2-9 

50-2 

Rabbit  2 

2-05 

58-5 

Guinea  pig 

0-672 

223-1 

This  is  due  to  the  fact  that  the  chief  expenditure  of  energy  is  devoted  to 
maintaining  the  temperature  of  the  body,  and  the  smaller  the  animal  the 
larger  is  its  surface  and  therewith  its  heat  loss  relatively  to  its  weight.  The 
basal  metabolism  therefore  is  a  function  of  the  surface  of  the  body, 
and  in  the  above  table  a  comparison  of  metabolism  per  square  metre  body 
surface  shows  that  it  is  practically  the  same  in  all  cases.  As  shown  in  the 
following  Table,  we  may  say  that  a  warm-blooded  animal  requires  a  daily 
expenditure  of  about  1000  Calories  per  square  metre  body  surface  in  order 
to  maintain  its  temperature  and  carry  out  filch  motor  processes  as  are 
essential  to  life. 


676 


jmiysioi,o<;y 


Body  weight 

Calories  per  square 
metre  body  surface 

Animal  1      . 

30-40 

977 

2 

23-70 

1069 

3 

19-20 

1135 

4 

17-70 

1040 

»        5 

10-90 

1 109 

6 

ti-45 

1054 

7 

3-10 

1091 

The  same  thing  applies  to  man.  If  we  desire  to  determine  the  basal 
metabolism  of  any  given  individual  we  must  find  out  his  surface.  If  we 
know  the  height  and  weight,  the  surface  can  be  calculated  by  the  following 
formula  (Du  Bois)  : 

S  =  -007184  x  W0425  X  H0-725 

where  S  is  the  surface  in  square  metres, 
W  the  weight  in  kilograms, 
H  the  height  in  centimetres. 

In  adult  man  the  basal  metabolism  according  to  Du  Bois  is  about  40 
Calories  per  square  metre  per  hour.  The  basal  metabolism  however  is 
not  the  same  in  the  same  individual  under  all  kinds  of  conditions,  but 
depends  on  the  state  of  nutrition  of  the  animal.  Thus  in  fattening  an  animal 
the  basal  metabolism  increases  steadily  as  the  animal  gets  fatter.  It 
requires  much  more  food  to  keep  a  fat  animal  fat  than  to  maintain  it  before 
fattening  in  its  original  condition.  The  figure  40  Calories  per  square  metre 
per  body  surface  applies  to  a  well-nourished  individual.  If  the  food  normally 
supplied  to  the  individual  be  diminished,  he  can  go  on  working  as  before, 
obtaining  his  energy  at  the  expense  of  the  fat  and  muscular  tissues  of  his 
own  body.  But  when  under  this  regime  the  weight  has  fallen  about  12  per 
cent,  it  is  found  that  the  basal  metabolism — i.  e.  the  requirements  of  the 
individual  merely  to  keep  himself  alive — is  also  largely  reduced.  Thus 
in  a  squad  of  men  investigated  by  Benedict,  the  food  normally  taken  ranged 
from  3200  to  3600  Calories  per  day.  After  these  men  had  by  restriction  of 
diet  suffered  a  loss  of  12  per  cent,  in  their  body  weight,  they  were  able  to 
maintain  themselves  at  this  reduced  weight  and  to  carry  out  the  same 
work  as  before  on  a  diet  of  2300  Calories.  In  one  case  where  a  man  5  ft. 
2  in.  had  on  a  restricted  diet  been  reduced  in  weight  from  115  lb.  to  84  lb., 
his  basal  metabolism  was  found  to  be  diminished  from  40-5  to  33 'Calories 
per  square  metre  of  body  surface  per  hour. 


SECTION  III 

THE    EFFECT    OF    FOOD    ON    METABOLISM 

During  the  starvation  the  energy  requirements  of  the  animal  are  supplied 
by  the  actual  consumption  of  the  tissues  of  the  body.  When  food  is  taken 
it  has  to  supply  the  losses  effected  in  this  way.  It  is  convenient  however, 
to  consider  food  as  having  a  twofold  destiny,  viz.  (1)  to  supply  the  energy 
necessary  to  maintain  the  body  alive  and  for  the  performance,  of  work; 
(2)  to  replace  the  wear  and  tear  of  the  body.  So  far  as  the  latter  function 
is  concerned  the  proteins  of  the  food  take  a  position  apart  from  the  other 
two  classes — fats  and  carbohydrates.  Every  working  cell  of  the  body 
and  every  muscle  fibre  consist  for  the  most  part  of  proteins  with  only  small 
amounts  of  fats  and  carbohydrates.  To  repair  the  wear  and  tear  of  the 
machine  of  the  body  therefore  proteins  are  absolutely  necessary.  To 
supply  the  energy  requirements  of  the  body  any  or  all  of  the  three  classes 
of  foodstuffs  can  be  utilised. 

A  starving  man  is  diminishing  in  weight  and  is  putting  out  energy  as  a 
result.  In  the  example  cited  on  p.  072  the  man  was  losing  about  13  grm. 
nitrogen  a  day  and  was  putting  out  about  2000  Calories.  These  Calorics 
came  partly  from  the  combustion  of  protein  and  partly  from  the  oxidation 
of  the  fat.  It  would  manifestly  be  useless  to  try  to  stay  the  loss  from  the 
body  by  giving  the  man  13  grm.  of  nitrogen  in  the  food  in  the  form  of 
protein,  since  this  would  give  him  only  320  Calories  towards  his  basal 
requirements  of  2000.  We  should  find,  in  fact,  that  the  effect  of  such  an 
administration  would  be  practically  to  double  the  output  of  nitrogen  from 
the  body  and  to  increase  slightly  the  total  output  of  energy.  In  the  dog  it 
would  be  possible  to  stop  the  diminution  of  the  body  weight  and  the  waste 
of  tissues  by  giving  an  amount  of  protein  equal  to  five  times  the  loss  during 
starvation.  In  man  such  an  amount  would  be  too  great  for  his  assimilating 
powers,  and  it  would  be  necessary  to  give  in  addition  to  the  protein  fats 
and  carbohydrates.  Since  the  body  reacts  somewhat  differently  to  these 
three  different  classes  of  foodstuffs,  it  will  be  convenient  to  deal  with  them 
separately. 

THE    INFLUENCE    OF   PROTEINS 

The  protein  taken  in  with  the  food  on  a  pure  protein  diet  lias  a  twofold 
function  to  perform.  In  the  first  place,  every  functional  activity  of  the 
living  tissues  is  probably  associated  with  a  certain  amount  of  wear  and  tear. 
and  results  in  the  production  of  disintegration  products  which  are  not  in  a, 
condition  to   be  resynthetised  into  living  working  protoplasm.     We  know 

077 


678 


PHYSIOLOGY 


for  instance  that,  from  every  mucous  surface,  dead  cells  are  being  continually 
cast  off  and  that  a  constant  disintegration  of  red  blood  corpuscles  goes  on, 
resulting  in  the  production  of  the  bile  pigments;  and  we  are  warranted  in 
extending  the  operation  of  these  changes  of  which  we  have  ocular  evidence 
to  the  case  of  other  cells,  such  as  those  of  the  liver  and  of  the  muscles,  where 
direct  proof  of  destruction  of  tissue  during  normal  metabolism  is  more 
difficult  to  obtain.  It  is  certain  that  some  portion  of  the  nitrogen  excreted 
during  complete  starvation  must  come  from  this  source,  and  that  one  of 
the  functions  of  protein  food  is  the  replacement  of  tissue  which  has  been 
lost  in  this  way.  When  however  we  are  feeding  an  animal  on  a  pure 
protein  diet,  by  far  the  larger  portion  of  the  food  is  utilised  for  meeting 
the  energy  requirements  of  the  body.  In  this  function  protein  food,  apart 
from  accidents  of  digestibility  and  structural  adaptation  of  the  animal's 
digestive  arrangements  to  its  habits  of  life,  presents  no  apparent  advantages 
over  the  other  two  classes  of  foodstuffs.  Its  value  to  the  animal  is  repre- 
sented by  its  physiological  heat  value.  It  may  be  represented  therefore 
numerically  as  4-1,  and  is  equivalent  to  the  value  of  carbohydrate1  and  is 
far  inferior  to  the  value  of  fats  with  a  heat  equivalent  of  9-3.  If,  instead  of 
giving  to  the  starving  animal  a  pure  protein  diet,  we  administer  a  mixed  diet 
containing  a  sufficient  quantity  of  fat  or  carbohydrate,  or  of  both  substances, 
to  meet  the  normal  energy  requirements  of  the  body,  we  can  restrict  the 
utilisation  of  protein  more  nearly  to  the  replacement  of  tissue  waste  in  the 
body,  and  are  therefore  able  to  attain  nitrogenous  equilibrium  with  a  much 
smaller  proportion  of  protein  than  is  possible  when  this  substance  furnishes 
the  whole  diet.  In  omnivora,  such  as  man,  it  is  easy  to  attain  nitrogenous 
equilibrium  on  a  mixed  diet  with  a  smaller  nitrogen  turnover  than  is  found 
during  starvation.  In  the  experiment  given  on  p.  672  the  average  nitrogen 
output  during  starvation  was  about  12  grm.  of  nitrogen.  In  Succi,  the 
fasting  man,  the  nitrogen  output  varied  from  11-19  grm.  on  the  fifth  day 
to  2-82  grm.  on  the  twenty-first  day. 

Daily  Nitrogen  Excretion  of  Succi  in  Starvation 


Day 

N. 

Day 

N. 

Day 

N. 

1   . 

.   170 

8  .    .    .    9-74 

15  •.    .    .   5-05 

2  . 

.   11-2 

9 

10-05 

16 

4-32 

3  . 

.   10-55 

10 

7-12 

17 

5-4 

4   . 

.   10-8 

11 

6-23 

18 

3-6 

5  . 

.   11-19 

12 

6-84 

19 

5-7 

6  . 

.   11-01 

13 

5-14 

20 

3-3 

7  . 

8-79 

14 

4-66 

21 

2-82 

Chittenden  has  shown  that  in  man  a  perfectly  normal  nutrition  may 
be  maintained  on  a  mixed  diet  containing  about  7  grm.  of  nitrogen  daily. 
In  the  cases  investigated  by  Chittenden  the  energy  output  of  the  men  could 
be  regarded  as  normal,  corresponding  to  32-35  Calories  per  kilo  body  weight. 
If  the  amount  of  fat  and  carbohydrate  be  very  largely  increased  it  is  possible 
to  maintain  nitrogenous  equilibrium  on  even  smaller  quantities  of  protein. 

1  This  may  be  expressed  by  saying  that  protein  is  isodjmamic  with  an  equal  weight 
of  carbohydrate. 


THE  EFFECT  OF  FOOD  ON  METABOLISM 


679 


Thus  nitrogenous  equilibrium  was  attained  by  Siven  on  a  diet  containing 
33  grm.  of  protein  daily  (=  5  grm.  of  nitrogen),  but  in  this  case  the  carbo- 
hydrates and  fats  were  increased  to  such  an  extent  that  the  man  was  taking 
in  78-5  Calories  per  kilo  per  day.  These  results  suggest  that  the  qualitative 
metabolism  of  the  body  is  determined  by  the  relative  amount  of  foodstuff 
supplied  to  the  body  and  circulating  in  its  juices  at  any  given  time,  and  that 
preponderance  of  one  foodstuff  will  tend  to  excite  the  cells  of  the  body  to 
the  utilisation  of  this  foodstuff  at  the  expense  of  the  other  two.  That  such 
is  the  case  is  shown  by  a  study  of  the  effect  of  increasing  each  class  of  food 
on  the  metabolism  of  the  body  as  a  whole. 

Most  of  the  experiments  on  the  influence  of  variations  in  the  quantity 
of  protein  food  have  been  made  on  camivora,  such  as  the  dog  and  cat. 
Within  very  wide  limits  the  output  of  nitrogen  is  proportional  to  the  intake. 
This  is  shown  in  the  Tables  by  Voit  given  below,  representing  two  experi- 
ments on  dogs. 

In  Experiment  I  the  animal  had  been  fed  for  some  days  with  500  grm.  of 
meat  per  diem.  The  fact  that  he  was  excreting  nitrogen  corresponding  to 
547  grm.  shows  that  this  amount  was  insufficient  and  that  he  was  not  yet  in 
a  condition  of  nitrogenous  equilibrium.  Each  day  he  was  using  up  47  grm. 
of  the  protein  tissues  of  his  body  in  addition  to  the  500  grm.  supplied  in 
the  food.  On  increasing  his  food  threefold  to  1500  grm.  the  nitrogenous 
output  was  also  increased,  but  a  state  of  nitrogenous  equilibrium  was  not 
reached  until  the  eighth  day  of  the  experiment.  During  the  six  days  inter- 
vening 778  grm.  of  meat  had  been  retained  in  the  bod}',  i.  e.  there  had  been 
a  retention  of  protein,  probably  in  the  form  of  increased  muscular  substance. 
The  amount  is  too  great  to  be  accoimted  for  by  retention  of  the  disintegration 
products  of  the  protein  in  the  body.  It  must  have  been  stored  up  in  the 
form  of  protein  and  probably,  to  a  large  extent  at  any  rate,  as  actual  living 
tissue. 


Experiment  I 

Experiment  II 

Day 

Daily  meat 
ratton 

Flesh  loss 
per  day 

Day 
1      . 

Daily  meat 
ration 

1500 

Flesh  loss 
per  day 

1500 

1       . 

500 

547 

2 

1500 

1222 

2     . 

1000 

1153 

3 

1500 

1310 

3     . 

1000 

1086 

4 

1500 

1390 

4      . 

1000 

1088 

5 

1500 

1410 

5     . 

1000 

1080 

6 

1500 

1440 

6     . 

1000 

1027 

7 

1500 

1450 

8 

1500 

1500 

■ 

In  the  second  experiment  the  diminution  of  the  protein  of  the  food  was 
followed  by  a  loss  of  protein  from  the  body,  the  output  being  greater  t  ban 
the  income.  The  excess  however  was  rapidly  diminishing  and  equilibrium 
had  been  practically  attained  on  the  last  day  of  the  experiment.  During 
this  time  the  animal  had  excreted  14-8  grm.  of  nitrogen  more  than  it  had 


C80 


PHYSIOLOGY 


received  in  its  food,  which  would  correspond  to  a  diminution  of  the  protein 
store  of  its  body,  reckoned  as  muscular  substance,  by  434  grin.  Many  such 
experiments  have  been  performed,  and  they  all  agree  in  showing  that  in 
carnivora  a  very  appreciable  storage  of  nitrogen  can  take  place  in  the  body. 
In  cats  it  is  sometimes  possible  to  double  the  body  weight  by  administration 
of  a  large  protein  diet.  Since  no  fat  is  laid  on  at  the  same  time  and  the 
animals  are  in  a  fine  healthy  condition,  one  must  conclude  that  the  greater 
portion  of  the  storage  takes  place  by  a  growth  of  muscle  substance.  The 
degree  to  which  the  storage  can  take  place,  is  however  variable  and  is 
generally  smaller  in  dogs  than  in  cats.  However  much  protein  is  given,  the 
limit  is  finally  arrived  at  where  no  further  laying  on  of  protein  tissues  of  the 
body  is  possible,  and  the  animal  then  enters  into  a  state  of  nitrogenous 
equilibrium,  when  he  excretes  a  quantity  of  nitrogen  exactly  equal  to  that 
taken  in.  This  equivalence  of  income  and  output  signifies  that  the  extent 
of  the  total  metabolism  of  the  body  is  affected  by  the  amount  of  protein 
supplied  in  the  food,  and,  as  a  matter  of  fact,  the  total  energy  output  of  the 
body  rises  and  falls  with  the  quantity  of  protein  in  the  food.  This  is  shown 
in  the  following  Table  by  Pettenkofer  and  Voit,  in  which  the  figures  have 
been  recalculated  bv  PfluKer. 


^Nitrogen  in  food! 

Nitrogen  output 

Fat  gain  or  loss 

Total  Calories 

1    . 

0 

5-61 

-98 

1067 

2 

17 

20-37 

-61 

1106 

3     . 

34 

36-69 

-43 

1360 

4     . 

51 

51-00 

-24 

1552 

5     . 

61 

59-74 

-36 

1893 

C     . 

68 

69-50 

+  8 

1741 

7 

85 

85-41 

+   4 

2181 

We  see  therefore  that  carnivorous  animals  can  satisfy  their  total  energy 
.requirements  at  the  expense  of  protein.  When  the  protein  income  is  in 
excess  of  their  requirements  a  small  amount  is  laid  on,  probably  as  increased 
muscular  tissue.  The  most  marked  effect  is  however  an  increased  meta- 
bolism, which  rises  in  proportion  to  the  nitrogenous  income.  The  limit  to 
this  increase  is  set  by  the  powers  of  the  alimentary  canal  to  digest  the 
protein.  The  rise  in  metabolism  consequent  on  protein  food  is  very  rapid 
and  affects  the  gaseous  exchanges  as  well  as  the  output  of  nitrogen.  Magnus 
Levy  and  Falk  found  that  a  large  protein  meal  might  increase  the  respiratory 
exchanges  40  per  cent.,  an  increase  which  lasted  seven  hours.  The  nitro- 
genous output  also  rises  immediately  after  a  protein  meal,  so  that  50  per 
cent,  of  the  nitrogen  of  the  ingesta  may  appear  in  the  urine  within  seven 
hours  after  the  meal. 

The  whole  of  these  results  cannot  be  strictly  applied  to  omnivorous 
animals,  such  as  man.  In  these  it  is  impossible  to  supply  all  the  energy 
requirements  of  the  body  on  a  pure  protein  diet.  Even  if  a  man  eats  as  much 
meat  as  he  can.  he  will  be  unable  to  obtain  sufficient  energy  for  his  daily 


THE  EFFECT  OF  FOOD   ON  METABOLISM  681 

requirements.  Whereas  the  average  daily  requirements  of  a  man  amount  to 
about  3000  Calories,  1  lb.  of  lean  meat  (i.e.  entirely  devoid  of  fat)  would  yield 
only  about  400  Calories,  and  even  if  he  took  4  lb.  of  meat  daily,  an  amount 
which  is  impossible  for  most  individuals,  he  would  only  be  obtaining  about 
1600  Calories.  The  cures  for  obesity,  in  which  a  large  protein  diet  plays  an 
important  part,  owe  their  efficiency  to  this  fact.  They  are  in  all  cases  practi- 
cally equivalent  to  a  state  of  semi-starvation.  Many  experiments  have  been 
made  on  the  influence  of  variations  in  the  quantity  of  protein  in  a  mixed  diet. 
Within  wide  limits  the  output  of  nitrogen  is  strictly  proportional  to  the  intake. 
A  normal  adult  man  seems  to  be  unable  to  store  up  protein  in  any  form,  and 
differs  in  this  respect  from  carnivora,  such  as  the  dog  or  cat.  The  only  way 
in  which  protein  can  be  laid  on  in  the  body  is  by  furnishing  a  physiological 
si  imulus  to  the  growth  of  muscle,  i.  e.  by  constant  exercise.  Without  this  it 
is  not  possible  to  produce  growth  of  the  muscles  of  the  body,  however  much 
protein  we  may  gave  in  the  diet.  The  conditions  are  however  different 
when  dealing  with  an  individual  in  whom  from  some  cause  or  other  the 
muscular  tissues  have  not  attained  their  full  development.  Thus  in  growing 
individuals  a  certain  amount  of  the  protein  of  the  food  is  always  retained  in 
the  body  and  laid  on  as  tissue  protein.  In  convalescence  after  severe  fever, 
during  which  a  great  wasting  of  the  muscles  has  taken  place,  forced  feeding 
with  large  amounts  of  protein  has  been  found  to  give  rise  to  a  considerable 
retention  of  protein  in  the  body.  This  process  goes  on  only  until  the  muscles 
have  attained  their  normal  condition  of  development.  When  the  tissues 
have,  so  to  speak,  reached  '  par,'  the  possibility  of  laying  on  protein  tissues 
ceases.  On  the  other  hand,  protein  food  has  in  man,  as  in  animals,  a  specific 
stimulating  effect  on  metabolism,  so  that  the  respiratory  exchanges  are 
largely  increased  as  a  result  of  a  heavy  protein  meal.  This  effect  has  been 
named  by  Buhner  the  '  specific  dynamic  effect  '  of  protein.  We  shall  have 
occasion  later  to  discuss  its  significance. 

THE   INFLUENCE   OF   FATS   AND   CARBOHYDRATES 

If  either  fats  or  carbohydrates  be  given  to  a  starving  animal  a  certain 
sparing  of  the  fat  of  the  body  takes  place,  but  this  effect,  according  to  some 
observers,  is  accompanied  by  a  distinct  increase  in  the  metabolic  exchanges 
of  the  body.  As  regards  the  protein  metabolism,  Cathcart  finds  that 
while  administration  of  fat  increases  the  nitrogen  output  during  starvation, 
carbohydrate  food  causes  a  diminution  in  the  nitrogen  output,  and  thus 
exercises  a  marked  sparing  effect  on  the  proteins  of  the  body.  Voit  found 
that  during  starvation  or  with  an  insufficient  protein  diet  addition  of  fat 
to  the  food  increased  the  total  metabolism.  When  sufficient  protein  was 
being  supplied,  the  addition  of  fat  caused  no  increase  in  the  total  metabolism, 
the  whole  of  the  fat  in  the  food  being  laid  on  as  fat  in  the  body.  The  stimu- 
lating effect  of  fat  on  metaoolism  is  but  slight.  Magnus  Levy  found  that 
the  increase  in  the  metabolism  on  the  administration  of  I'm  to  a  starving 
animal  was  minimal  and  never  exceeded  10  per  cent. 

Carbohydrates  have  a  somewhat  greater  influence  on  metabolism.     This 


682  PHYSIOLOGY 

stimulating  influence  on  metabolism  is  however  much  less  than  that  observed 
on  the  administration  of  large  doses  of  protein,  and  is  hardly  noticeable 
after  a  moderate  carbohydrate  meal  in  a  normally  nourished  individual. 
If  carbohydrate  be  given  in  excess  of  the  daily  energy  requirements,  the 
greater  proportion  of  it  remains  in  the  body,  being  stored  up  to  a  small 
extent  as  glycogen  but  mainly  in  the  form  of  fat. 


SECTION  IV 


THE  EFFECT  OF  MUSCULAR  WORK  ON  METABOLISM 

When  an  animal  performs  muscular  work  the  energy  for  the  work  is  derived, 
as  we  have  already  seen,  from  the  oxidation  directly  of  the  tissues  of  the 
body  but  ultimately  of  the  foodstuffs.  This  increased  oxidation  must 
result  in  increased  respiratory  exchanges;  both  the  intake  of  oxygen  and 
the  output  of  C02  must  be  raised.  It  is  a  matter  of  common  experience 
that  any  muscular  exertion  is  attended  with  deeper  and  more  rapid  breath- 
ing which,  if  the  exertion  is  severe,  may  attain  to  a  condition  of  dyspnoea. 
In  order  to  determine  the  quantitative  relationship  between  the  increased 
oxidative  processes  of  the  body  and  the  actual  work  accomplished,  we  must 
investigate  the  respiratory  exchanges  of  an  individual  by  one  of  the  methods 
described  on  p.  662,  in  the  first  place  during  complete  rest,  in  the  second 
place  while  he  is  doing  a  measured  piece  of  work.  The  following  Table 
represents  the  respiratory  exchanges  in  a  trained  muscular  subject  during 
complete  rest  and  while  doing  moderate  or  severe  work,  viz.  riding  a  bicycle 
with  a  brake.     Each  observation  lasted  from  ten  to  fifteen  minutes. 


Condition                C°2  eliminated 
|     per  minute 

Oxygen  absorbed 

per  minute 

Respiratory 
quotient 

Pulse  rate 

K^ite 

Lying       .          ._               200 
Moderate  work.              1720 
Severe  work      .              2227 

243 
1834 
3265 

•83 
•94 
•98 

56 
150 
166 

20 
32 
38 

The  '  severe  work '  in  this  table  was  carried  to  exhaustion,  so  that 
the  respiratory  exchanges  represent  the  maximal  augmentation  of  which 
the  individual  was  capable.  This  augmentation  may  amount  to  between 
ten  and  fourteen  times  the  normal  resting  exchanges.  Similar  results  are 
obtained  in  observations  extending  over  longer  periods  of  time.  Thus  in 
one  experiment  the  average  output  of  C02  during  a  six  hours'  period  of  rest 
and  starvation  was  189-6  grm.  During  a  rest  experiment  with  food  the 
average  output  for  the  same  period  was  230-4  grm.  During  work  the 
average  output  in  the  same  individual  during  six  hours  rose  to  705  grm. 
of  carbon  dioxide  on  a  carbohydrate  diet,  and  to  634-8  grm.  on  a  diet  con- 
taining a  large  amount  of  fat.  The  oxidation  of  carbon  was  therefore 
increased  more  than  threefold  as  a  result  of  muscular  work. 

We  can  find  out  the  relation  between  the  actual  work  done  and  the 
energy  expended  on  doing  the  work,  either  directly  by  allowing  the  work  to 

683 


684 


PHYSIOLOGY 


be  done  in  a  calorimeter  and  measuring  the  total  output  of  heat  by  the 
individual  at  rest  and  during  work,  or  by  calculating  from  the  respiratory 
exchanges  the  amount  of  heat  which  must  be  se1  free  by  the  oxidation  of 
the  constituents  of  the  body  consumed  in  the  performance  of  muscular 
work.  In  the  following  Table  are  given  the  results  of  an  experiment  by 
Atwater  in  which  the  total  energy  output  of  a  man  was  reckoned  in  the 
form  of  heat  by  means  of  the  calorimeter.  The  work  done  by  the  man 
on  a  stationary  bicycle  with  a  brake  was  also  accurately  determined,  and 
is  given  in  the  Table  in  terms  of  its  heat  equivalent,  viz.  as  Calories. 

Energy  per  Day 


Meal  eliminated 

External 
wori;  in 
Calories 

Total 
in 

Calories 

Nature  of  experiment 

I  :\  radial  ion 

and 
conduction 

In  nrinp          In   watel 

°j            vaporised 
■    '. '            from  lungs 
'"'^            and  skin 

Rest  with    food    (average   of 
four  days) 

Rest    fasting     (four     experi- 
ments)    (average     of     live 
days)         .... 

Work  (fourteen  experiments) 
(average  of  forty -six  days)  . 

J  850 

1605 
3802 

26 

21 

29 

521 

561 
743 

546 

2397 

2187 
5120 

In  the  above  experiments,  the  mean  expenditure  of  energy  on  the  work 
days  was  5120,  and  on  the  rest  days  (with  food)  2397  Calories,  a  difference 
of  2723  Calories.  This  represents  the  excess  metabolism  over  resting  require- 
ments, which  must  take  place  in  order  that  the  body  may  perform  work  equal 

to  516  Calories.     The  fraction 


total  energy  evolved  minus  resting  metabolism 
is  spoken  of  as  the  '  mechanical  efficiency  '  of  the  body.  In  the  above 
case  it  equals  one-fifth,  and  the  body  is  said  to  have  a  20  per  cent, 
efficiency.  Of  course  a  certain  proportion  of  this  excess  of  energy  over 
work  done  is  accounted  for  by  the  increase  in  the  work  which  must  be 
performed  by  the  respiratory  muscles  and  heart  in  the  state  of  greater 
activity  which  is  imposed  upon  them  by  the  external  work,  and  is  necessary 
for  the  proper  provision  of  the  active  muscles  with  increased  food-supply 
and  oxygen.  Even  if  we  neglect  these  factors  altogether,  the  efficiency 
of  the  body  as  a  machine  corresponds  to  between  16  and  25  per  cent.,  an 
efficiency  which  exceeds  that  of  the  best  of  our  steam-engines  and  is  only 
equalled  by  certain  internal-combustion  engines. 

In  some  cases  the  mechanical  efficiency  may  attain  even  a  higher  figure, 
so  that  as  much  as  30  per  cent,  of  the  increased  metabolism  accompanying 
muscular  work  may  be  transformed  into  mechanical  energy.  Can  we 
employ  these  results  to  throw  light  on  the  nature  of  the  constituents  of 
the  body  which  undergo  oxidation  to  furnish  the  energy  of  muscular  work  ? 


THE  EFFECT  OF  MUSCULAR  WORK  ON  METABOLISM    685 

In  the  experiment  already  quoted  the  oxidation  of  carbon  was  increased 
more  than  threefold  during  a  six-hour  period  of  work.  This  carbon  might 
form  part  of  the  molecule  of  protein,  fat  or  carbohydrate;  but  if  we  com- 
pare the  protein  metabohsm  of  the  same  individual  during  these  experiments 
no  corresponding  alteration  is  observed.  During  rest  and  starvation  the 
average  output  of  nitrogen  per  day  corresponded  to  the  destruction  of 
82  grrn.  of  protein.  During  rest  and  with  an  approximately  sufficient  amount 
of  food  the  average  daily  consumption  of  protein  was  98-8  grm.  During  a 
work  day,  in  which  the  individual  received  the  same  amount  of  protein  in 
the  food  and  a  somewhat  insufficient  quantity  of  carbohydrates  and  fats, 
the  consumption  of  protein  was  109-4  grm.  Thus  there  was  a  three-  to 
fourfold  increase  of  the  carbon  metabolism  of  the  body,  but  only  a  10  per 
cent,  increase  in  the  protein  metabohsm. 

There  is  another  method  by  which  we  can  arrive  at  some  idea  of  the 
nature  of  the  material  which  is  furnishing  by  its  oxidation  the  necessary 
energy  for  the  performance  of  muscular  work.  It  is  evident,  if  we  compare 
the  formula}  of  a  carbohydrate  and  a  fat  respectively,  that  it  will  require  a 
relatively  larger  amount  of  oxygen  to  oxidise  the  fat  than  is  necessary  in  the 
case  of  the  carbohydrate.  In  the  latter  there  is  sufficient  oxygen  to  combine 
with  all  the  hydrogen  present  and  form  water.  The  whole  of  the  oxygen 
therefore  which  is  taken  in  is  employed  in  the  oxidation  of  the  carbon, 
and  one  volume  of  oxygen  will  produce  one  volume  of  carbon  dioxide.  Thus  : 
C6H1206  +  602  =  6H20  +  6C02.  If  the  whole  of  the  animal's  energy 
requirements  were  furnished  by  the  oxidation  of  carboydrates,  the  output 
of  carbon  dioxide  expired  would  be  exactly  equal  in  volume  to  the  oxygen 

■     ,         ,     ,  .  ,    ,  •      ,  ,      CO,  expired 

inspired,  and  the  respiratory  quotient  of  the  animal,  namely,     -—       . 

would  be  equal  to  unity.  In  fats  the  amount  of  oxygen  is  only  sufficient  to 
combine  with  four  atoms  of  the  hydrogen  of  the  molecule.  When  fats 
undergo  oxidation,  of  the  oxygen  used  only  a  portion  is  devoted  to  the 
formation  of  carbon  dioxide,  the  rest  being  employed  in  the  oxidation  of 
hydrogen  to  water.  In  an  animal  using  only  fats  the  carbon  dioxide  output 
of  the  body  would  be  considerably  less  than  the  oxygen  intake  and  its 
respiratory  quotient  would  be  less  than  unity.  The  respiratory  quotients 
for  protein,  fats,  and  carbohydrates  are  given  in  the  following  Table. 

Material  Respiratory  auotient  -^ 

Carbohydrates  .......      1*0 

Animal  fat 0-707 

Protein    ........      0-81 

The  respiratory  quotient  in  an  animal' at  any  given  time  is  therefore 
determined  by  the  nature  of  the  substances  which  are  undergoing  oxidation 
in  its  body.  If  the  performance  of  muscular  work  involved  special  chemical 
processes,  a  metabolism  of  one  of  the  main  constituents  of  the  body  in 
preference  to  either  of  the  others,  this  sudden  change  in  the  quality  of  the 
metabolism  should  show  itself  in  the  respiratory  quotient. 


686  PHYSIOLOGY 

According  to  Speck  and  Low}-,  moderate  muscular  work  which  is  not 
associated  with  dyspnoea,  although  attended  by  a  large  increase  in  the 
carbon  dioxide  output  and  the  oxygen  intake  of  the  body,  does  not  alter  the 
respiratory  quotient.  This  is  probably  correct  if  the  respiratory  changes 
are  taken  over  a  sufficient  length  of  time,  when  the  respiratory  quotient 
must  depend  on  the  food  which  is  furnished  to  the  body  however  the  energy 
of  this  body  is  expended.  When,  however,  as  in  Benedict's  and  Cathcart's 
experiments,  quoted  in  the  Table  on  p.  683,  the  observations  are  of  short 
duration,  muscular  exercise  is  almost  always  found  to  be  associated  with  a 
rise  in  the  respiratory  quotient,  which  lasts  too  long  to  be  accounted  for  by 
a  mere  washing  out  of  the  carbon  dioxide  from  the  blood  and  the  body 
tissues.  After  the  cessation  of  the  exercise  the  respiratory  quotient  sinks 
below  normal.  The  respiratory  quotient  however  rarely  rises  even  during 
exercise  to  1,  as  it  would  if  the  muscular  work  were  performed  solely  at  the 
expense  of  carbohydrates. 

These  results  suggest  that,  while  muscular  work  can  be  performed  at  the 
expense  of  any  of  the  foodstuffs  or  of  the  three  classes  of  constituents  of 
the  body,  carbohydrate  is  the  immediate  or  the  most  readily  available  source 
of  muscular  energy.  When  the  body  passes  suddenly  from  a  resting  to  an 
active  condition,  the  first  call  is  therefore  on  the  carbohydrates  of  the  blood 
and  those  stored  up  in  the  muscles  and  liver,  whereas  after  exercise  these 
carbohydrate  stores  are  slowly  replenished  probably  at  the  expense  of  the 
proteins.  The  fact  that  the  body  can  draw  on  its  fat  stores  for  the  perform- 
ance of  muscular  work  suggests  that  this  substance  may  also  serve  as  a 
source  of  muscular  energy,  and  in  default  of  evidence  that  the  body  is  able 
to  convert  fats  into  carbohydrates,  we  must  assume  that  under  certain 
conditions  the  fats  or  their  decomposition  products  may  be  directly  utilised 
by  the  muscles. 

The  lowering  of  the  respiratory  quotient  which  follows  severe  exercise 
suggests  either  that  the  metabolic  processes  of  the  body  are  being  performed 
at  the  expense  of  proteins  and  fats  while  the  body  is  replenishing  its  limited 
stores  of  carbohydrates,  or  else  that  carbohydrates — e.  g.  sugar  or  glycogen — 
are  being  manufactured  out  of  proteins  and  possibly  fats  in  order  to  make 
good  the  exhaustion  of  carbohydrate  resulting  from  the  exercise. 

Since  the  carbonic  acid  secreted  during  exercise  may  result  from  the 
oxidation  of  protein,  fat,  or  carbohydrate,  we  cannot  deduce  directly  the 
total  energy  set  free  in  the  body  by  an  estimation  of  the  C02  output  alone. 
The  respiratory  quotient  must  also  be  determined  in  order  to  throw  light 
on  the  real  amounts  of  fat  and  carbohydrate  consumed,  and  in  accurate 
experiments  the  output  of  nitrogen  in  the  urine  must  be  also  measured. 
Ever}T  gramme  of  nitrogen  in  the  urine,  if  resulting  from  the  oxidation  of 
protein,  corresponds  to  the  intake  of  84  grin,  oxygen  and  to  the  output 
of  9-35  grm.  carbon  dioxide.  If  the  amounts  of  C02  and  oxygen  corre- 
sponding to  the  protein  metabolism  be  deducted  from  the  total  respiratory 
exchanges,  the  remainder  must  be  due  to  the  metabolism  of  fat  and  carbo- 
hydrate, and  the  respiratory  quotient  obtained  after  deducting  the  gaseous 


THE  EFFECT  OF  MUSCULAR  WORK  ON  METABOLISM    687 


exchanges  due  to  protein  metabolism  will  give  the  proportions  of  fat  and 
carbohydrate  oxidised.  The  following  Table  gives  the  relative  combustion 
of  carbohydrate  and  fat  for  a  given  respiratory  quotient : 


K.C). 

101 1  . 

0-95  . 

0-90  . 

0-85  . 

0-80  . 

0-75  . 

0-707  . 


Carbohydrate 

Fat 

100  per  cent. 

0  per  cent. 

83 

17 

66 

34 

49 

51 

32 

OS 

15 

8.5 

rnnm 

0 

too 

crnrpn  n-ff  mi  mrirlnti 

Calories  for  one  litre 
oxygen 

5-047 

4-985 

4-924 

4-863 

4-801 

4-739 

4-686 


of  carbohydrate  or  fat  metabolised  in  the  body,  we  can  now  measure 
accurately  the  total  energy  available  from  the  chemical  changes  thus  deter- 
mined. The  number  of  Calories  set  free  in  the  body  for  every  litre  of  oxygen 
taken  in  are  also  given  in  the  above  table. 

It  will  be  noticed  that  in  contradiction  to  popular  opinion  the  proteins  do  not  play 
any  special  part  in  relation  to  muscular  exercise.  The  special  value  of  protein  is  for 
building  up  the  body  and  for  repairing  directly  wear  and  tear.  As  a  source  of  energy 
it  presents  no  advantages  over  carbohydrate  and  fat;  in  fact,  it  may  be  in  some 
respects  inferior  to  this  latter  substance  or,  at  any  rate,  less  economical,  owing  to  the 
fact  that  ingestion  of  protein  causes  an  increased  metabolism,  the  whole  of  which 
appears  in  the  form  of  heat.  If  an  animal  after  a  protein  meal  be  made  to  work,  the 
increased  metabolism  due  to  the  specific  dynamic  action  of  the  protein  is  still  observed 
over  and  above  that  due  to  the  performance  of  work.  The  output  of  energy  of  a  man 
on  a  large  meat  diet  doing  a  certain  amount  of  work  will  therefore  be  greater  than 
if  the  same  amount  of  work  were  performed  on  a  diet  consisting  largely  of  carbo- 
hydrates and  fats.  On  the  other  hand,  in  training  we  have  to  consider  not  only  the 
performance  of  work  done  during  the  training,  but  also  the  necessity  of  building  up 
the  muscular  tissues  of  the  body.  Under  these  conditions  therefore,  there  is  some 
reason  for  a  plentiful  supply  of  protein  in  the  diet.  When  however  a  man  has  to 
undertake  a  certain  amount  of  muscular  exercise  every  day  and  has  arrived  at  the 
full  development  of  his  muscular  system,  there  is  no  need  to  attempt  to  supply  the 
energy  for  his  movements  at  the  expense  of  foods  rich  in  protein,  such  as  meat.  In 
many  cases  the  beneficial  effects  of  so-called  meat  are  due  to  its  content  in  fat — this 
foodstuff  presenting  advantages  over  carbohydrates  when  large  quantities  have  to 
be  ingested  to  supply  the  daily  energy  requirements  of  the  body. 


SECTION  V 

THE    SIGNIFICANCE    OF   THE    FOODSTUFFS 

In  order  to  keep  an  animal  alive  a  certain  amount  of  food  must  be  supplied 
to  replace  the  loss  to  the  body  of  its  tissues  and  of  its  reserves  of  carbo- 
hydrates and  fat,  which  are  being  continually  consumed  for  the  provision  of 
the  energy  necessary  to  keep  the  animal  warm  and  for  the  performance  of 
the  internal  and  external  movements  of  the  body.  The  actual  amount 
of  food  required  will  depend  on  the  size  of  the  animal,  on  the  temperature 
of  the  surrounding  medium  and  on  the  muscular  work  performed.  For 
supplying  this  energy  any  of  the  three  classes  of  foodstuffs  may  be  utilised, 
the  value  of  each  being  given  by  the  Calories  which  are  evolved  when  the 
foodstuff  is  oxidised  to  the  end  stages  which  it  attains  in  the  body.  Thus 
carbohydrates  and  proteins  are  isodynamic — i.  e.  give  rise  to  the  same  amount 
of  energy  in  the  body  for  a  unit  weight — one  gramme  of  each  giving  out 
4-1  Calories.  Weight  for  weight  fat  has  double  the  value  of  either  of  these 
two  classes,  its  Calorie  value  being  9-3.  This  isodynamic  equivalence  of  the 
foodstuffs  is  however  interfered  with  to  a  certain  extent  by  the  specific 
dynamic  action  already  spoken  of,  in  virtue  of  which  protein  has  an  excitant 
action  on  the  processes  of  oxidation  occurring  in  the  body,  so  that  an  animal 
fed  on  a  largely  protein  diet  will  give  out  more  heat  and  consume  more  food 
than  if  it  were  fed  on  a  diet  of  the  same  Calorie  value  but  in  which  carbo- 
hydrates preponderate.  This  specific  dynamic  action  is  not  altogether 
lacking  to  carbohydrates  and  fats.  Thus,  according  to  Rubner's  experi- 
ments, for  every  100  Calories  of  protein  ingested  there  is  an  increased 
heat  production  over  the  fasting  level  of  30  to  35  Calories,  while  fat 
gives  an  increased  heat  production  of  about  12  per  cent.,  and  sugar 
of  about  5  per  cent.  On  account  of  this  specific  dynamic  action  an 
average  mixed  diet,  in  order  to  maintain  the  body  in  a  state  of 
equilibrium,  must  have  a  Calorie  value  of  13  to  14  per  cent,  higher  than 
the  sum  total  of  the  Calories  given  off  during  fasting.  Thus,  supposing 
a  man  while  fasting  and  in  bed  gives  off  1800  Calories  a  day,  which  would 
be  derived  from  using  up  the  tissues  of  his  body,  he  would  under  the  same 
circumstances  give  off  about  2000  Calories  if  he  received  a  minimum  mixed 
diet  just  sufficient  to  maintain  his  body  weight  constant.  This  specific 
dynamic  action  of  protein  might  be  regarded  as  mere  waste  or  '  luxus 
consumption'  since  it  results  only  in  the  production  of  heat  and  cannot 
be  utilised  for  the  performance  of  muscular  work.  It  must  be  remembered 
however  that  a  certain  amount  of  heat  production  is  necessary  in  order 


THE'  SIGNIFICANCE   OF   THE  FOODSTUFFS  689 

to  maintain  the  temperature  of  the  body,  and  this  must  be  greater  the  lower 
the  temperature  of  the  surrounding  medium.  In  cold  surroundings  a  large 
amount  of  the  food  must  always  be  applied  to  maintain  the  body  tem- 
perature, and  for  this  purpose  the  excess  heat  involved  in  the  ingestion  of 
protein,  and  to  a  less  extent  of  other  foods,  can  be,  and  is,  utilised.  Hence 
it  comes  about  that  in  order  to  exhibit  this  specific  dynamic  action,  the 
animal  must  be  kept  at  a  temperature  of  about  33°  Centigrade.  Below  this 
temperature  the  specific  dynamic  action  of  the  foodstuffs  becomes  less 
and  less  apparent,  and  is  finally  merged  in  the  heat  production  necessary, 
whether  food  is  taken  or  not,  to  keep  up  the  temperature  of  the  body. 

Even  regarded  simply  as  a  source  of  energy,  proteins  are  distinguished 
from  carbohydrates  and  fats  by  the  fact  that  no  means  are  provided  for  the 
storage  of  proteins  in  the  body  other  than  by  the  growth  of  muscular  and 
other  tissues.  This  growth  is  normal  in  the  young  animal,  and  in  the  adult 
in  convalescence  from  wasting  diseases  and  during  recovery-  from  a  period 
of  starvation  or  of  insufficient  feeding.  There  is  a  certain  maximum  of 
growth  beyond  which  the  living  tissues  of  the  body  caimot  attain.  Arrived 
at  this  stage  the  body  cannot  add  to  its  protein  store,  and  all  the  protein 
therefore  that  is  ingested  and  absorbed  from  the  alimentary  canal  is  at 
ouce  broken  down  and  burnt  up  in  the  body.  If  we  examine  the  curve 
of  nitrogenous  excretion  in  the  urine  we  find  that  practically  all  the  nitrogen 
taken  in  as  protein  in  the  food  is  turned  out  within  twelve  to  sixteen  hours. 
Thus,  if  a  man  is  on  a  mixed  diet  sufficient  for  his  daily  needs,  a  doubling 
of  the  protein  in  the  diet,  leaving  the  other  constituents  unchanged,  will 
result  in  a  doubling  of  the  nitrogenous  excretion  and  a  storing  of  the  fats 
and  carbohydrates  that  would  otherwise  have  been  consumed,  so  that  these 
will  be  laid  on  as  fat  in  the  body.  On  the  other  hand,  an  increase  of  the  fats 
or  carbohydrates  will  not  increase  the  carbon  metabolism  of  the  body, 
but  any  excess  above  the  daily  needs,  if  absorbed,  is  stored  up  in  the  body 
in  the  form  of  fat.  To  increase  the  protein  metabolism  therefore,  all  that 
is  necessary  is  to  increase  the  protein  in  the  body ;  to  increase  the  carbo- 
hydrate and  fat  metabolism  it  is  necessary  to  increase  the  metabolism  as  a 
whole  either  by  increased  muscular  exercise  or  by  exposure  to  cold. 

Protein  is  also  distinct  from  fats  and  carbohydrates  in  that  it  is  essential 
for  the  repair  of  the  wear  and  tear  of  the  tissues.  We  may  thus  speak  of 
the  protein  of  the  food  as  having  a  twofold  destiny.  A  certain  proportion 
is  used  to  repair  tissue  waste ;  the  ammo-acids  into  which  it  is  resolved 
in  the  intestines  circulate  in  the  blood,  and  each  living  cell  picks  out  those 
amino-acids  which  are  essential  to  building  up  the  protoplasm  of  the  cell. 
Protein  with  this  destiny  exerts  no  specific  dynamic  action,  and  this  action 
is  therefore  lacking  in  the  infant,  which  is  storing  up  in  the  form  of  new  tissue 
the  greater  proportion  of  the  protein  which  it  takes  up  in  its  food.  The 
rest  of  the  protein,  after  resolution  to  amino-acids,  loses  its  nitrogen,  which 
appears  in  the  urine  chiefly  in  the  form  of  urea,  and  the  remaining  part 
of  the  protein  molecule  then  undergoes  rapid  oxidation.  The  oifero  a  "t 
the  urine  is  therefore  derived  partly  direct  from  the  nitrogen  rapidly  split 


690  PHYSIOLOGY 

ofi  from  the  protein  of  the  food,  partly  from  the  disintegrated  proteins, 
which  have  formed  part  of  the  living  fabric  of  the  cells. 

Folin  has  brought  forward  a  number  of  facts  which  point  not  only  to  a 
twofold  origin  of  the  nitrogen  of  the  urine  but  also  to  a  qualitative  difference 
in  the  two  orders  of  protein  metabolism.  Whereas  in  the  urine  of  man  on 
a  normal  diet  the  urea  nitrogen  forms  85  per  cent,  or  more  of  the  total 
nitrogen,  a  reduction  of  the  protein  ration  to  the  minimum  necessary  to 
meet  the  nutritional  requirements  of  the  body  causes  not  only  an  absolute 
diminution  of  the  urea  but  a  large  relative  diminution  when  compared  with 
the  other  constituents  of  the  urine,  such  as  creatinin.  He  concludes  there- 
fore that  the  nitrogenous  end-products  of  nutritional  metabolism  are  different 
from  those  of  the  energy  metabolism.  There  is  also  a  difference  in  the 
time-relations  of  the  two  orders  of  inetabolisrn.  Whereas  the  nitrogen, 
which  furnishes  no  energy  to  the  body,  is  rapidly  eliminated  when  protein 
is  being  utilised  for  the  supply  of  energy  to  the  body,  the  occurrence  of 
increased  tissue  waste  causes  a  rise  of  nitrogenous  excretion,  which  comes 
on  slowly,  often  after  the  lapse  of  a  day,  and  may  last  two  or  three  days. 
The  process  of  protoplasmic  disintegration  appears  therefore  to  occur  in  a 
series  of  stages,  which  occupy  a  considerable  time  and  end  in  the  production 
of  substances  qualitatively  distinct  from  that  substance,  urea,  which  is  the 
almost  exclusive  nitrogenous  end-product  of  the  energy  metabolism  of 
protein. 

ACTION   OF   THE   PRODUCTS   OF   PROTEIN   DIGESTION 

Proteoses,  Peptones  and  Amino-acids.  In  the  digestion  of  the 
naturally  occurring  proteins,  the  first  products  of  hydration  consist  of  a 
mixture  of  substances  known  as  proteoses  and  peptones.  In  the  further 
processes  of  digestion,  under  the  influence  of  the  ferments  of  the  pancreas 
and  small  intestine,  these  substances  are  converted  into  the  amino-acids 
which  we  have  learnt  to  regard  as  the  proximate  constituents  of  the  protein 
molecule.  Many  experiments  have  been  performed  in  order  to  determine 
the  nutritive  value  of  these  digestive  products.  In  nearly  all  cases  it  has 
been  found  that  the  meat  in  the  diet  of  an  animal  can  be  replaced  by  a 
corresponding  quantity  of  the  products  of  digestion  of  the  same  meat 
without  interfering  with  the  nitrogenous  equilibrium  of  the  animal,  and 
Loewi  and  others  have  shown  that  the  same  result  may  be  attained  by 
feeding  an  animal  on  the  products  of  pancreatic  digestion  of  protein,  i.  e.  a 
mixture  consisting  almost  entirely  of  amino-acids.  Since  the  proteins  of 
the  body  differ  in  their  composition  from  the  majority  of  the  proteins  of 
the  food,  it  is  evident  that  each  food-protein  molecule  has  to  be  entirely 
disintegrated  and  reconstructed  before  it  can  take  its  place  in  the  body  fabric ; 
and  it  is  therefore  only  natural  that,  so  far  as  metabolism  is  concerned,  the 
results  should  be  identical  whether  we  feed  the  animal  with  the  ordinary 
food-protein  or  with  the  products  of  its  metabolism.  This  latter  mode  of 
feeding  cannot  however  be  regarded  as  presenting  any  advantages.  Under 
normal  circumstances  the  food  molecules  are  broken  down  by  degrees.     Their 


THE  SIGNIFICANCE   OF   THE  FOODSTUFFS  691 

products  of  hydrolysis  are  set  free  hi  small  quantities  at  a  time  and  can 
be  therefore  absorbed  and  disposed  of  in  proportion  as  they  are  set  free. 
On  the  other  hand,  a  sudden  flooding  of  the  alimentary  canal  with  a  large 
quantity  of  the  products  of  digestion  introduces  an  abnormal  factor  wlrich 
must  tend  to  produce  wastage  of  nitrogen  in  the  body  and  to  disturb  the 
normal  chain  of  processes  involved  in  the  regular  course  of  digestion. 

THE  BIOLOGICAL  VALUE  OF  DIFFERENT  FORMS  OF  PROTEIN 
In  consequence  of  the  wide  variation  in  the  composition  of  the  proteins 
contained  in  the  different  tissues  of  the  body,  it  is  necessary  that  the  food 
shall  include  all  the  amino-acids  in  proper  quantities  and  proportions. 
Hence  it  follows  that  all  proteins  are  not  equivalent  as  regards  their  capacity 
for  replacing  tissue  waste  or  serving  for  the  growth  of  the  animal  body. 
Those,  in  which  nearly  all  the  amino-acids  are  represented  and  which  contain 
these  in  proportions  approximating  the  average  of  those  found  in  the  chief 
animal  proteins,  will  be  more  valuable  than  those  in  which  one  or  more  of 
the  chief  amino-acids  are  absent,  or  in  which  there  is  a  large  preponderance 
of  one  or  more  of  the  amino-acids  which  are  required  only  in  small  pro- 
portions for  building  up  the  tissues  of  the  animal  body.  As  an  example 
of  the  first  type  we  may  instance  collagen  and  gelatin,  and  zein  the  chief 
protein  of  maize.  Collagen  and  gelatin  on  digestion  yield  the  ordinary 
amino-acids  of  the  fatty  series  and  also  a  certain  amount  of  phenyl  alanine 
and  proline.  The  oxyphenyl  group  which  occurs  in  other  food  proteins 
in  the  form  of  tyrosine,  as  well  as  the  indol-containing  group  tryptophane, 
are  absent,  so  that  gelatin  if  pure  gives  neither  Millon's  test  nor  the  Hopkins- 
Adamkiewicz'  test.  Hence  gelatin  cannot  entirely  replace  the  proteins  of 
the  food.  As  its  capacity  for  yielding  energy  to  the  body  equals  that  of 
any  other  protein,  and  since  it  supplies  also  a  number  of  the  amino-acids, 
it  can  replace  to  a  large  extent,  but  not  entirely,  other  forms  of  protein 
which  are  not  deficient  in  the  above-mentioned  amino-acids.  Physiologists 
have  indeed  succeeded  in  maintaining  animals  for  a  short  time  in  a  state 
of  nitrogenous  equilibrium  on  a  diet  containing  as  its  sole  nitrogenous  con- 
stituent a  mixture  of  gelatin  with  tyrosine  and  tryptophane.  In  the 
same  way  zein  yielding  no  tryptophane  nor  tyrosine  is  incapable  by  itself 
of  supporting  life,  though  this  can  be  accomplished  if  lysine,  tyrosine  and 
tnptophane  are  administered  at  the  same  time. 

As  an  example  of  the  second  type  we  may  instance  the  protein  of  wheat 
flour.  A  reference  to  the  Table  on  p.  89  shows  that,  whereas  caseinogen, 
the  protein  of  milk,  contains  only  15  per  cent,  of  glutamic  acid  and  serum 
albumin  only  7  per  cent.,  gliadin,  the  chief  protein  of  flour,  contains  as  much 
as  36  per  cent.  If  wheat  flour  is  the  main  or  sole  source  of  protein  to  the 
body  it  is  evident  that  a  large  amount  of  glutamic  acid  will  be  hi  excess 
of  the  amount  required  to  replace  tissue  waste.  These  differences  in  chemical 
composition  between  the  proteins  are  of  significance  when  the  protein  of 
the  food  is  reduced  to  the  minimal  amount  required  to  replace  tissue  waste, 
and  under  such  circumstances  marked  differences  are  observed  between  the 


692 


PHYSIOLOGY 


biological  value  of  proteins.  These  differences  in  nitrogen  value  were 
determined  by  Thomas  in  the  following  way.  On  a  diet  containing  large 
quantities  of  .starch  and  sugar  and  only  a  trace  of  protein  he  found  the 
minimal  loss  of  body  protein.  Ho  then  investigated  how  much  of  each 
of  the  various  proteins  must  be  added  to  the  diet  in  order  to  prevent  any 
loss  of  tissue  protein.  He  arrived  at  the  following  biological  values  for 
the  proteins  investigated  : 


Ox  meat 

.     104 

( Iherry  juice 

.     79 

Cows'  milk 

.      100 

Yeast  . 

.     71 

Fish    .... 

95 

Casein 

.      70 

88 

Nutrose 

.      09 

Cauliflower 

84 

Spinach 

.     64 

Crab  meat  . 

79 

Peas     . 

.     56 

Potatoes 

.       79 

Wheat  flour 
Cornmeal 

.     40 
.     30 

The  practical  outcome  of  this  experiment  is  that  when  there  is  scarcity 
of  protein,  animal  protein  is  more  economical  than  vegetable  protein,  and 
that  if  it  is  necessary  to  live  on  a  purely  vegetable  diet  this  should  be  mixed, 
so  that  all  the  amino-acids  required  in  the  body  may  be  represented  in  the 
diet. 

THE  INORGANIC  FOODSTUFFS 
If  an  animal  be  fed  with  the  proper  quantities  of  fats,  proteins,  and 
carbohydrates,  from  which  all  the  salts  have  been  removed  as  completely 
as  possible,  it  rapidly  shows  a  distaste  for  the  food,  becomes  ill,  and  dies  in 
a  shorter  time  than  if  it  were  receiving  no  food  at  all.  Part  of  the  symptoms 
which  occur  in  these  cases  are  due  to  the  production  of  acid  substances,  e.  g. 
sulphuric  acid,  in  the  course  of  metabolism  of  the  proteins.  It  is  possible 
to  obviate  this  acid  intoxication  by  administering  sodium  carbonate  with 
the  food.  This  admixture  however  suffices  to  prolong  the  life  of  the  animal 
only  for  a  short  time.  It  is  evident  therefore  that  the  inorganic  constitu- 
ents of  the  food,  although  yielding  no  energy  to  the  body,  are  as  essential  for 
the  maintenance  of  life  as  the  energy-yielding  foodstuffs,  namely,  proteins, 
carbohydrates,  and  fats.  In  the  course  of  this  work  we  shall  have  occasion 
to  study  the  intimate  dependence  of  the  functions  of  various  tissues,  such  as 
skeletal  and  heart  muscle,  on  the  presence  of  salts  in  normal  proportions  in 
the  fluids  with  which  they  are  bathed.  Animals  in  a  state  of  salt  hunger  show 
by  the  disorders  of  digestion  which  occur  that  the  presence  of  salts  is  equally 
requisite  for  the  due  performance  of  the  processes  of  secretion  and  absorption. 
Towards  the  end  of  the  experiment  the  animal  vomits  its  food,  which  shows 
no  signs  of  digestion  even  .when  it  has  lain  some  hours  in  the  stomach. 
Forster  has  shown  that  in  salt-hunger  the  body  is  continually  giving  off 
inorganic  constituents  in  the  urine.  The  amount  of  these  is  smallest  when 
it  is  supplied  richly  with  organic  foodstuffs.  It  seems  that  the  salts  of  the 
body  exist  in  a  state  of  unstable  combination  with  the  tissue  constituents, 
especially  the  proteins.  If  the  amount  of  food  supplied  is  insufficient,  the 
animal  lives  on  its  own  tissues,  thus  setting  free  salts  which  appear  in  the 


THE  SIGNIFICANCE  OF  THE   FOODSTUFFS  693 

urine.    The  loss  of  salts  to  the  body  will  therefore  be  in  direct  proportion  to 
the  degree  in  which  the  animal  is  living  at  the  expense  of  its  own  tissues. 

ACCESSORY   FOOD   SUBSTANCES   OR   FOOD    HORMONES 

If  we  feed  an  animal  on  a  mixed  diet  containing  proteins,  fats,  carbohy- 
drates and  salts  in  the  proper  proportions  but  in  a  state  of  purity,-  e.  g.  a 
mixture  of  caseinogen,  starch,  sugar,  salts  and  lard,  we  find  that  the  animal 
becomes  ill,  ceases  to  grow  if  a  young  animal,  and  finally  dies.  This  is  due 
to  the  fact  that  practically  all  fresh  foods  contain  small  traces  of  substances 
whose  chemical  nature  lias  not  been  determined,  but  which  are  essential 
for  the  utilisation  of  the  food,  for  the  maintenance  of  health,  and  for 
the  production  of  growth.  These  substances  are  destroyed  by  prolonged 
heating  or  exposure  to  an  alkaline  medium,  or  often  by  simple  drying  of  the 
tissue  in  which  they  exist.  Different  accessory  substances  are  contained 
in  different  foods  or  in  different  parts  of  the  same  food.  Thus,  for  instance, 
in  races  whose  staple  diet  consists  of  rice,  prolonged  feeding  with  polished 
rice — i.  e.  rice  in  which  the  husks  have  been  removed — leads  to  the  production 
of  the  disease  known  as  beri-beri.  This  is  distinguished  by  the  occurrence 
of  pains,  weakness  in  the  limbs,  loss  of  sensibility  in  the  skin,  oedema, 
and  heart  weakness.  A  similar  disease  in  which  the  affection  of  the  nerves 
(polyneuritis)  is  the  main  disorder  may  be  produced  by  the  same  means 
in  fowls  or  pigeons.  If  whole  rice  be  eaten  this  disease  does  not  occur  and 
the  disease  may  be  cured  by  adding  the  polishings — i.  e.  the  part  of  the 
rice  -rain  which  has  been  removed — to  the  polished  rice  before  eating.  It  is 
evident  that 'some  substance  is  present  in  the  outer  layer  of  the  rice  grain 
which  is  essential  to  the  normal  nutrition  of  the  body.  The  same  substance 
occurs  in  the  husks  and  germ  of  wheat,  in  yeast,  and  in  smaller  quantities 
in  various  vegetables  and  milk. 

Another  'deficiency  disorder' — viz.  scurvy — has  been  long  known  and 
described.  It  occurs  usually  when  bodies  of  men  are  cut  off  for  a  long 
time  from  fresh  food,  especially  vegetables.  Its  main  symptoms  are  weak- 
ness, skin  disorders,  small  haemorrhages  under  the  skin,  haemorrhage  from 
the  gums  and  other  mucous  membranes.  Scurvy  is  prevented  or  cured  by 
the  administration  of  fresh  food,  especially  that  belonging  to  the  crucifer 
order,  and  of  fruit  juices,  the  best  being  juices  of  oranges  and  lemons. 

It  seems  that  the  normal  process  of  growth  in  a  young  animal  is 
dependent  on  the  existence  of  another  accessory  substance  which  is  soluble 
in  fat  and  exists  in  considerable  quantities  in  milk  and  milk  fat  (butter). 
It  is  also  present  in  other  animal  fats,  but  not  in  lard.  It  is  probable  that 
this  substance  is  present  also  in  fresh  green  vegetables,  and  is  taken  by  the 
animal  with  it  s  food  and  deposited  in  the  fat  of  its  tissues  or  excreted  with 
the  fat  of  the  milk.  The  absence  of  the  substance  in  lard  may  be  d\ie  to  the 
fact  that  pigs  are  fattened  not  as  a  rule,  on  green  vegetables,  but  on  grain, 
especially  maize;  further  investigations  are  necessary  on  this  point.  In 
the  absence  of  this  substance  growth  may  cease.  Its  deficiency  may  lead 
to  the  production  of  rickets,  a  disease  of  young  children  characterised  by 


694  PHYSIOLOGY 

swelling  of  the  ends  of  the  long  bones  at  the  junction  of  the  epiphysis  with 
the  shaft  and  by  softening  of  the  bones  as  a  whole,  so  that  these  bend  under 
the  weight  of  the  body,  giving  rise  to  bow  legs,  deformities  of  the  pelvis,  etc.1 
At  the  present  we  are  justified  in  defining  three  kinds  of  food  hormones, 
viz. : 

(1)  Fat-soluble  substance  A,  which  is  contained  in  butter  and  is 
essential  to  growth.  This  substance  is  also  present  in  many  green 
vegetables. 

(2)  Water-soluble  substance  B,  present  in  the  outer  parts  of  most 
grain,  in  eggs,  yeast,  etc.  The  absence  of  this  substance  leads  to  the  pro- 
duction of  beri-beri.     It  is  sometimes  known  as  the  anti-neuritic  substance. 

(3)  A  substance  present  in  fresh  vegetables,  destroyed  by  boiling  or 
even  by  drying  of  the  vegetables,  and  to  a  smaller  extent  in  meat  and  fresh 
milk.  The  absence  of  this  substance  gives  rise  to  scurvy,  so  it  can  be  spoken 
of  as  an  anti-scorbutic  substance. 

1  Funk  has  suggested  the  name  of  Vitamine  for  these  substances,  but  although  this 
term  is  often  used  it  is  misleading,  since  there  is  no  evidence  that  this  substance  as  a 
class  is  either  basic  in  nature  or  has  any  relation  to  amines. 


SECTION   VI 

THE    NORMAL    DIET    OF    MAN 

Having  learnt  the  significance  of  food  in  general  and  of  the  different  food- 
stuffs in  the  animal  economy,  we  are  in  a  position  to  examine  the  actual 
requirements  of  the  normal  human  individual.  This  involves  a  considera- 
tion not  only  of  the  total  energy  requirements  of  man  according  to  age, 
size,  sex  and  occupation,  but  also  of  the  proper  distribution  of  the  foodstuffs 
in  the  diet. 

We  have  seen  that  the  energy  requirements  of  a  warm-blooded  animal 
are  a  function  of  its  surface.  Knowing  the  weight  and  height  of  a  man 
we  can  determine  his  surface  by  Du  Bois'  formula  (p.  676).  The  average 
height  and  weight  of  English  adults  is  171  cm.  and  70-3  kilos,  corresponding 
to  a  surface  of  1-772  square  metres.  The  basal  metabolism  of  a  man  is 
equal  to  40  Calories  per  square  metre  per  hour,  so  that  the  average  man  will 
have  an  hourly  basal  metabolism  of  71  Calories.  This  is  the  energy  output 
in  bed  and  during  sleep.  When  he  is  taking  food  this  amount  must  be 
increased  by  about  10  per  cent.,  and  if  he  is  up  and  about  a  further  increase 
in  metabolism  will  be  evoked  by  the  muscular  movements,  exposure  to 
cold,  etc.  If  we  divide  the  twenty-four  hours  into  three  portions — eight 
hours'  sleep,  eight  hours  awake  and  eight  hours'  work — we  must  allow  the 
basal  metabolism  for  the  eight  hours'  sleep,  basal  metabolism  increased  by 
about  30  per  cent,  for  the  eight  hours  during  which  the  man  is  up  and  about 
and  taking  meals,  and  the  basal  metabolism  plus  an  additional  amount 
for  work  during  the  eight  working  hours.  It  is  by  no  means  easy  to  decide 
what  figure  should  be  accepted  as  representing  the  average  work  of  an 
adult  man.  It  is  usual  to  take  this  as  involving  an  energy  output  of  1000 
Calories.  Of  these  Calories  20  per  cent.,  or  even  more,  may  under  favourable 
conditions  be  transmuted  into  mechanical  work,  so  that  1000  Calories  would 
be  sufficient  to  provide  for  the  performance  of  about  100,000  kilogrammetres 
of  external  work.  With  these  assumptions  we  arrive  at  the  following  energy 
requirements  for  an  adult  working  man  : 

8  hours'  sleep  at  71  (Basal  Metabolism)  .  .  .       568  Calories. 

8  hours  awake  at  92  (Basal  Metabolism  plus  30  per  cent.)       736         „ 
8  hours' work  (Basal  Metabolism  plus  1000  Calories)        .     1568        „ 

Total 2872 

Some  additional  expenditure  of  energy  will  be  involved  in  travelling, 
so  that  we  are  justified  in  accepting  the  figure  usually  given  for  the  energy 

695 


696  PHYSIOLOGY 

output  of  an  average  working  man  as  3000  Calories.  It  must  be  remem- 
bered that  this  figure  is  only  an  average — that  is  to  say,  it  applies  to  a  man 
of  average  size  and  weight  and  doing  a  certain  amount  of  work.  A  small 
man  will  require  less  and  a  tall  man  more.  A  man  in  sedentary  employ- 
ment— e.  g.  typewriting,  clerking,  etc. — may  not  expend  more  than  200  to 
400  Calories  in  the  performance  of  external  work;  mental  exertion  causes 
no  appreciable  rise  in  the  metabolic  exchanges.  Such  a  man  would  there- 
fore have  a  total  energy  output  of  not  more  than  2400  Calories  a  day.  On 
the  other  hand,  a  heavy  worker,  such  as  a  navvy,  may  easily  expend  2000 
or  more  Calories  a  day  in  the  performance  of  external  work.  It  is  not 
surprising  therefore  that  investigation  of  the  diets  actually  in  use  among 
different  classes  of  men  shows  very  wide  divergencies.  An  examination  of 
the  actual  energy  output  as  measured  by  the  C02  excretion  during  work 
gave  the  following  approximate  energy  requirements  for  men  in  different 
occupations  : 


Occupation 

Energy  Requirements 

Tailor 2500 

Bookbinder  . 

2800 

Shoemaker    . 

2850 

Metal  worker 

3200 

Painter 

3250 

Carpenter 

3200 

'Stone  mason 

4400 

Woodcutter  . 

5000 

The  energy  requirements  of  women  will  show  corresponding  variation 
according  to  occupation,  but  will  be  in  general  less  in  consequence  of  their 
smaller  size  and  surface.  Du  Bois  has  shown  that,  in  addition  to  the  influence 
of  size,  women  have  a  lower  basal  metabolism  per  square  metre  of  surface, 
viz.  37  Calories  per  hour  as  against  40  in  the  case  of  men.  The  average 
height  and  weight  of  Englishwomen  are  159-3  cm.  and  55-7  kilos,  corre- 
sponding to  a  surface  of  1-511  square  metres  and  to  an  hourly  output  of 
56  Calories.  In  estimating  the  total  energy  requirements  of  an  average 
woman  we  may  reckon  her  work  as  two-thirds  that  of  a  man,  and  as  involv- 
ing an  expenditure  of  660  Calories  per  day.  We  then  arrive  at  the  following 
table  for  the  energy  requirements  of  the  average  woman  : 

8  hours'  sleep  at  56         .  .  .  .  .  .  .       448  Calorics. 

8  hours  awake  at  73  (Basal  Metabolism  plus  30  pjer  cent.)         584  „ 

8  hours'  work  (Basal  Metabolism  plus  600  Cats.)         .  .      1108  ,, 

Total 2140 

It  must  be  remembered  that  woman's  work  is  rarely  finished  when  she 
goes  home  from  her  occupation,  so  that  a  certain  amount  ought  to  be 
reckoned  for  housework.  We  shall  not  be  far  wrong  then  in  accepting 
the  usual  estimate  of  a  woman's  requirements  as  four-fifths  of  those  of  a 
man,  viz.  2400  Calories.  Here  again  it  must  be  remembered  that  this  is 
merely  an  average  figure,  and  that  the  requirements  of  different  women 
correspond  to  their  occupation  and  environment,  and  may  vary  from  1800 
Calories  up  to  3000  Calories,  or  even  more. 


THE  NOEMAL  DIET  OF  MAN 


697 


In  children  a  computation  of  the  energy  requirements  is  rendered  more 
difficult  by  two  factors.  In  the  first  place  the  processes  of  growth  are 
attended  with  an  active  metabolism,  so  that  the  metabolism  is  more  energetic 
in  the  young  animal  than  in  the  adult,  even  if  we  take  into  account  the 
relative  surfaces  in  the  two  cases.  Thus  the  basal  metabolism  per  square 
metre  in  boys  of  varying  ages  was  found  by  Du  Bois  to  be  as  follows  : 


ean  Age 

6-5    . 

Ras.il  Metabol 
square  metre  per  hour 
.     57-5 

12-6    . 

50-4 

1.3-7    . 

19-25  . 

40-7 

In  addition  to  this  increased  basal  metabolism,  if  the  processes  of  growth 
are  to  occur  normally,  there  must  be  an  excess  of  matter  taken  with  the 
food  over  that  excreted,  since  the  growing  animal  is  always  putting  on 
weight.  Between  the  ages  of  eleven  and  sixteen  both  sexes  put  on  weight 
at  about  4  kilos  a  year,  which  is  equivalent  to  adding  to  the  body  a  store 
of  about  800  Calories  per  month.  The  second  difficulty  is  due  to  the  fact 
that,  while  children  do  not  perform  any  measurable  work,  they  are  in  a 
constant  state  of  muscular  activity,  and  this  aimless  activity  of  a  child  is  of 
great  value  in  determining  its  healthy  nervous  and  muscular  development. 
The  amount  of  this  activity  seems  related  to  the  amount  of  food  taken — 
the  increased  energy  of  a  child  directly  after  a  meal  is  a  familiar  pheno- 
menon. If  food  is  withheld  or  diminished  this  activity  declines,  but  in  this 
way  energy  is  saved  and  the  whole  of  the  lessened  food  may  go  to  maintain 
the  temperature  of  the  body  and  the  normal  processes  of  growth. 

We  may  thus  obtain  a  development  of  the  child  not  differing  appre- 
ciably from  the  normal  on  widely  varying  amounts  of  food,  and  it  becomes 
difficult  to  say  what  is  the  average  or  the  optimum  amount  that  a  child 
should  have.  Judging  from  the  analysis  of  the  food  actually  taken  in  the 
families  of  working  men  and  others  in  receipt  of  sufficient  incomes,  it  would 
appear  that  the  amounts  laid  down  by  Lusk  do  not  err  on  the  insufficient 
side,  although  they  are  far  less  than  are  actually  given  in  many  well-to-do 
families  and  in  high  class  schools,  where  great  importance  is  attached  to 
games  and  other  forms  of  exercise.  Lusk  expresses  the  requirements  of  the 
different  classes  and  ages  in  terms  of  the  '  average  man  '  taken  as  1. 


Class 
Average  man 
Average  woman 
Children    0-6    (both  sexes) 
6-10 
10-14 
Girls   II  upwards 
Boys  14  upwards 


efficient 

Energy  Requirements 

1 

3000 

0-83 

2500 

0-5 

1500 

0-7 

2100 

0-83 

2500 

0-83 

2500 

1 

3000 

These  figures  represent  the  actual  energy  output  of  the  average  individual, 
and  are  therefore  equivalent  to  the  food  which  must  be  digested  and  absorbed 


698  PHYSIOLOGY 

from  the  alimentary  canal  in  order  to  make  good  the  loss.  No  food  under- 
goes complete  digestion,  the  average  loss  being  about  10  per  cent,  with  an 
ordinary  mixed  diet,  as  is  shown  in  the  following  Table  : 


Percentage  of  Foodstuffs.  Absorbed 

Protein              Fat          Carbohydrate 

Asli 

.  Total  Energy 

Average  of  5  experiments         92-6               94               97-7 

77-4 

90-5 

Three  thousand  net  Calories  (i.  e.  energy  requirements)  require  therefore 
an  intake  of  food  with  a  Calorie  value  of  3300.  If  the  food  consists  mainly 
of  vegetable  products  it  may  be  necessary  to  increase  still  further  the  allow- 
ance for  loss  in  digestion,  since  on  a  diet  such  as  rye  bread  as  much  as  33 
per  cent,  of  the  total  energy  of  the  food  may  be  lost  in  the  fseces.  The 
Table  of  food  requirements  for  various  ages  and  sexes  will  be  as  follows  : 


Children     0-6 

.      1650  Calories. 

6-10 

.     2300 

10-14 

.     2750 

Females  14  and  upwards    . 

.     2750 

Males  14  and  upwards 

.     3300 

These  values  are  for  average  well-nourished  individuals.  It  has  already  been 
pointed  out  that  in  a  state  of  semi-starvation,  accompanied  by  loss  of  weight,  the  basal 
requirements  may  be  reduced  considerably.  As  a  result  of  a  number  of  experiments 
Chittenden  came  to  the  conclusion  that  there  was  a  definite  advantage  to  be  gained 
by  reducing  not  only  the  protein  intake  of  the  body  but  also  the  total  food.  For  a 
prolonged  period  Chittenden  himself  lived  on  a  diet  containing  about  6  grm.  of  nitrogen 
daily  with  a  heat  value  of  about  1600  Calories,  and  in  another  individual  the  intake 
of  nitrogen  was  9-9  grrn.  and  the  heat  value  of  the  food  2500  Calories.  Although 
such  a  limitation  of  the  diet  may  be  advantageous  in  a  certain  number  of  cases,  there 
is  no  evidence  which  would  warrant  its  general  application ;  and  the  experience  of 
Germany  during  the  last  three  years  of  W2r  has  shown  that  a  forced  limitation  of  food 
to  about  two-thirds  of  what  we  have  put  down  as  normal  has  resulted  finally  in  a 
decrease  of  efficiency  of  mind  and  body  and  in  a  marked  diminution  in  the  resistance 
to  infection,  especially  tuberculosis. 

DISTRIBUTION    OF    FOODSTUFFS    IN    A    NORMAL    DIET 

A  Committe  of  the  Royal  Society  has  laid  down  the  following  as  a  proper 
diet  for  the  '  average  man  '  : 

Protein  Fat  Carbohydrate  Total  energy  value 

100  grammes  100  grammes  500  grammes  3400  Calories. 

Since  the  energy  for  muscular  work  and  that  necessary  to  maintain  the 
body  temperature  may  be  furnished  by  any  of  the  three  classes  of  food- 
stuffs, wide  variations  are  possible  in  the  relative  proportions  of  the  food- 
stuffs without  injury  to  health.  It  is  important  however  to  consider  the 
limits  within  which  these  variations  are  permissible. 

Proteins. — As  a  rule  an  average  mixed  diet  with  a  Calorie  value  of  3300 
will  contain  about  100  grm.  of  protein.  .  If  the  diet  is  mainly  vegetable  the 
proportion  of  protein  will  tend  to  fall.  We  have  already  seen  that  a  certain 
amount  of  protein  is  essential  to  replace  tissue  waste.     This  amount  may  be 


THE  NORMAL  DIET  OF  MAN  699 

determined  by  finding  the  minimum  quantity  on  which  nitrogenous  equi- 
librium can  be  maintained,  while  the  Calorie  needs  of  the  body  are  sufficiently 
satisfied  at.  the  expense  of  carbohydrate  and  fat.  Under  these  conditions  it 
has  been  found  that  35  to  40  grm.  of  protein  may  suffice.  Iu  these  experi- 
ments the  protein  was  largely  milk  protein.  Where  animal  protein  is  entirely 
absent  from  the  food  a  larger  amount  of  vegetable  proteins  will  be  necessary, 
since  they  are  of  lower  '  biological  value,'  and  it  is  safe  to  lay  down  as  a 
rule  that  for  an  average  man  the  protein  ration  should  not  be  diminished 
below  70  grm.  per  day.  This  should  include  different  kinds  of  protein 
and  if  possible  a  certain  proportion  of  animal  protein,  so  as  to  ensure  that 
all  the  essential  ammo-acids  are  supplied  in  the  food. 

Some  authorities  have  recommended  the  diminution  of  protein  to  the  minimum 
amount  on  the  idea  that  the  kidneys  and  other  organs  may  suffer  from  the  strain  of 
eliminating  excess  of  nitrogenous  waste  products.  But  the  energy  metabolism  of 
protein  results  almost  entirely  in  the  formation  of  urea,  an  innocuous  substance,  which 
can  have  little  harmful  effect  on  the  kidneys,  even  if  we  make  the  unjustifiable 
assumption  that  these  organs,  unlike  other  organs  of  the  body,  suffer  as  a  result  of  their 
normal  functional  activity.  There  is  no  doubt  that  many  of  the  disorders  of  middle 
life  may  be  put  down  to  over-feeding  and  lack  of  muscular  exercise,  but  there  is  just 
as  much  reason  to  ascribe  these  evils  to  the  carbohydrates  as  to  the  proteins  of  the  . 
diet.  Indeed,  it  has  been  found  that  for  men  leading  a  sedentary  life  a  moderate 
protein  and  fat  diet  is  more  suitable  than  one  consisting  chiefly  of  carbohydrates.  In 
this  case  the  normal  stimulation  to  oxidation  of  the  foodstuffs — viz.  muscular  exercise — is 
absent,  and  the  stimulating  effect  of  proteins  on  metabolism,  their  specific  dynamic 
action,  useless  when  muscular  work  has  to  be  performed,  is  under  these  conditions 
of  real  value  to  the  organism.  • 

Carbohydrates  are,  as  a  rule,  the  most  abundant  and  cheapest  con- 
stituents of  any  diet,  and  form  the  greater  part  of  cereals  and  tubers  and  of 
the  pulses.  Only  in  the  arctic  regions  may  there  be  a  lack  of  this  con- 
stituent of  the  diet.  A  certain  amount  of  carbohydrate  is  essential  for  man. 
We  shall  see  later  that  sugar  is  always  present  in  the  circulating  blood  and 
is  necessary  for  the  normal  functioning  of  the  tissues,  especially  of  the 
muscles.  In  the  absence  of  carbohydrate  in  the  food  this  sugar  is  manu- 
factured by  the  body  out  of  protein.  Moreover  under  the  same  circum- 
stances there  is  a  deficient  oxidation  of  the  fats,  so  that  the  half-oxidised 
products  of  fat  metabolism  accumulate  in  the  body,  giving  rise  to  acid 
intoxication.  However  in  temperate  climates  a  shortage  of  carbohydrates 
can  arise  only  under  artificial  conditions,  and  no  need  exists  for  laying  down 
a  minimum  below  which  this  constituent  of  the  diet  should  not  be  reduced. 

Fats  can  be  produced  by  the  animal  body  from  carbohydrate.  It  would 
thus  seem  that,  given  sufficient  carbohydrates  in  the  food,  there  should  be 
no  absolute  need  for  fats  in  the  diet.  It  is  stated  by  Hindhede  that  a  man 
can  be  kept  alive  and  can  work  normally  on  a  diet  in  which  fat  is  practically 
absent.  In  such  cases  it  is  essential  that  plenty  of  green  food  be  provided 
in  order  to  supply  the  fat-soluble  accessory  substance  normally  contained 
in  the  fats  of  milk  and  of  meat.  This  statement  may  be  true,  but  it  is 
certain  that  it  cannot  be  applied  to  all  human  beings.  In  practice  we  have 
In  provide  £oi  each  race  a  minimum  desirable   quantity  of  fat,  which  will 


700  PHYSIOLOGY 

differ  in  different  races  and  be  larger  in  northern  than  in  southern  races. 
Thus  the  Japanese  soldier  is  content  with  20  grm.  of  fat  daily,  while  in  our 
country  the  average  man  would  not  be  content  with  less  than  75  grm.  of 
fat  per  day.  Seventy-five  grammes  of  fat  has  a  Calorie  value  of  about  680 — ■ 
i.  e.  nearly  25  per  cent,  of  the  daily  requirements,  and  we  may  conclude 
as  a,  general  rule  that  one-fourth  of  the  total  energy  of  the  diet  should  be 
supplied  in  the  form  of  fat. 

There  are  proba  bly  three  reasons  for  this  craving  for  fat.  In  the  first 
place,  fat  is  easily  assimilated  and  is  almost  entirely  absorbed  in  the 
alimentary  canal;  but  whereas  the  greater  part  of  the  carbohydrate  food 
is  absorbed  three  hours  after  food  has  been  eaten,  the  chief  absorption 
of  fat  occurs  between  five  and  six  hours  after  a  meal.  On  this  account 
a  meal  lacking  in  fat  is  deficient  in  staying  power,  and  individuals 
deprived  of  fat  get  hungry  sometimes  before  the  next  meal  and  their  work 
and  efficiency  diminishes.  The  lumbermen  of  Canada  satisfy  their  huge 
needs  in  Calories — 6000  to  8000  a  day^by  a  diet  in  which  there  is  a  large 
proportion  of  fat  pork  and  in  which  the  fat  represents  35  to  40  per  cent, 
of  the  Calories. 

In  the  second  place,  the  bulk  of  food  must  be  of  considerable  importance, 
especially  when  the  total  food  required  by  the  energy  needs  of  the  body  is 
very  large.  Weight  for  weight  fat  has  more  than  double  the  Calorie  value 
of  si  arch  and  sugar.  But  the  difference  in  bulk  is  still  greater,  since  fat  is 
taken  without  admixture  in  a  pure  form,  whereas  the  other  foods  are  all 
mixed  with  a  considerable  proportion  of  water.  The  proteins  in  meat 
form  only  15  to  20  per  cent,  of  the  total  bulk.  Starch  cannot  be  taken  except 
mixed  with  large  quantities  of  saliva.  When  ordinarily  cooked  it  is  swollen 
lip  with  probably  five  to  ten  times  its  amoimt  of  water.  Even  after  absorp- 
tion the  same  necessity  for  increasing  the  bulk  of  carbohydrates  with  water 
persists.  Even  glycogen  does  not  occur  to  a  larger  amount  in  the  liver 
than  12  per  cent.,  a  figure  which  may  be  largely  surpassed  by  fat,  and  in 
adipose  tissue  there  may  be  as  much  as  80  per  cent,  of  fat.  When  carbo- 
hydrate goes  into  the  circulation  it  is  changed  into  sugar,  and  as  sugar  it 
needs  twenty  times  its  weight  of  water  to  carry  it.  "It  acts  therefore  to 
some  extent  in  the  same  way  as  common  salt.  Just  as  an  extensive  diet 
of  salt  may  produce  dropsy',  so  a  diet  of  carbohydrate  increases  in  the  first 
place  the  water  content  of  the  body,  and  this  factor,  when  associated  with 
inanition  and  fat  shortage,  may  itself  produce  actual  dropsy.  The  question 
of  bulk  is  probably  one  of  the  most  important  factors  in  determining  the 
need  for  fat.  The  human  alimentary  canal,  at  any  rate  in  the  races 
of  Western  Europe,  has  been  developed  so  as  to  cope  with  a  diet  in  which 
20  to  25  per  cent,  of  the  energy  is  presented  in  the  form  of  fat.  In  order  to 
get  the  same  energy  from  carbohydrates  the  alimentary  canal  would  have  to 
be  much  larger.  Theoretically  then  the  absence  of  fat  can  be  made  up  by 
an  increased  supply  of  carbohydrates.  But  this  can  be  carried  out  only 
in  a  certain  number  of  individuals  and  under  certain  conditions.  The 
ordinary  individual  deprived  of  fat  diminishes  his  total  intake  of  food  and 


THE  NORMAL  DIET  OF  MAN  701 

exists  on  a  lower  metabolic  level.  It  is  a  notable  fact  that  during  the 
shortage  of  fat  in  this  country  in  1918  there  was  no  appreciable  increase. 
in  the  consumption  of  cereals.  It  was  easier  to  live  on  the  stored-up  fat  of 
the  body  than  to  adopt  a  stuffing  process  with  carbohydrates. 

In  the  third  place,  it  seems  that  carbohydrates  are  more  subject  to 
fermentative  changes  in  the  intestines  than  fats.  Overloading  the  intestines 
with  carbohydrates  in  many  individuals  leads  to  abnormal  fermentation, 
the  production  of  gases,  and  general  discomfort.  We  may  conclude  then 
that,  although  man  can  dispense  with  fat  provided  he  receives  a  full  diet 
of  protehis  and  carbohydrates  with  the  proper  accessory  substances,  yet 
to  develop  his  full  efficiency  as  a  working  machine,  fat  is  an  essential 
ingredient  of  his  diet  and  should  furnish  not  less  than  20  to  25  per  cent,  of 
the  total  energy  of  his  food. 

The  significance  of  Mi  at. — Butcher's  meat,  according  to  the  cut,  contains  from  15  to 
20  per  cent,  protein,  and  from  15  to  30  per  cent.  fat.  Its  importance  in  the  dietary  is 
greater  in  northern  latitudes,  depending  in  part  on  questions  of  supply  and  of  racial 
habit.  A  diet  rich  in  meat  is  a  diet  rich  in  .animal  protein  and  fat,  and  the  protein 
of  such  a  diet  will  be  considerably  more  than  is  required  for  the  mere  repair  of 
tissue  waste.  Under  these  conditions  the  fate  of  proteins  in  the  body  is  somewhat 
different  to  that  of  the  other  foods,  viz.  fats  and  carbohydrates.  These  other  foods 
are  either  stored  up  in  the  body  in  the  form  of  fat,  if  in  excess,  or  they  are  burnt  up 
in  proportion  to  the  needs  of  the  working  tissues.  Proteins  however,  unless  there  is 
actual  need  of  repair  of  wasted  muscles  in  consequence  of  antecedent  disease  or  starva- 
tion, are  not  stored  up  in  the  body  of  the  adult,  but  are  burnt  up  in  proportion  as 
fchey  arc  supplied  in  the  food.  Every  protein  meal  therefore  raises  the  production 
of  heat  in  the  body,  and  this  production  of  heat  is  in  addition  to  the  heat  which  is 
produced  by  any  muscular  work  undertaken  at  the  same  time.  A  large  meat  diet, 
apart  from  its  content  in  fat,  is  of  no  special  advantage  for  the  performance  of  muscular 
Work,  and  is  a  distinct  disadvantage  when  this  work  has  to  be  accomplished  at  a  high 
external  temperature.  On  the  other  hand,  a  diet  in  which  there  is  a  large  proportion 
of  meat  is  of  value. to  men  in  sedentary  occupations  in  a  cold  or  temperate  climate, 
since  it  enables  them  to  maintain  their  body  temperature  without  the  necessity  of 
bodily  exercise.  The  idea  that  the  heavy  worker  requires  a  large  supply  of  butcher's 
meat  is  of  doubtful  foundation,  though  there  is  no  doubt  that,  in  occupations  involving 
exposure  to  cold  and  wet,  a  large  supply  of  meat  will  add  to  the  comfort  of  the  individual 
by  keeping  him  warm. 

One  other  fact  is  .of  importance  in  this  connection.  Meat  is  not  only  easily  cooked 
and  presented  in  a  palatable  form,  but  its  flavour  renders  other  kinds  of  foods  accept- 
able, at  any  rate  to  most  inhabitants  of  the  temperate  and  northern  parts  of  Europe. 
It  is  thus  habit  rather  than  strict  physiological  principles  which  will  probably  govern 
the  quantity  of  meat  regarded  as  desirable  in  the  normal  diets  of  such  people. 

The  significance  of  Sugar. — Sugar  is  the  only  food  which  is  chemically  purified  before 
forming  part  of  the  diet.  As  a  source  of  energy  to  the  body  it  is  nearly  equivalent  to 
an  equal  weight  of  starch.  Its  taste  however  renders  it  of  value  by  increasing  the 
I  i.i  lit  ability  of  other  foods,  and  on  this  account  a  sufficient  supply  of  sugar  should  be 
available  for  those  classes  whose  facilities  for  cooking  are  defective.  Sugar  is  readily 
absorbed  from  the  alimentary  canal  and  is  the  most  useful  food  for  sustaining 
muscular'  effort. 

We  thus  see  that  a  dietary  to  maintain  a  man  in  health  and  efficiency 
must  fulfil  the  following  requirements  : 

(1)  It  must  have  a  sufficient  Calorie  value  (3300  for  the  average  man). 

(2)  It  must  contain  protein,  fats  and  carbohydrates.    The  quantity  of 


702  •    PHYSIOLOGY 

each  of  the  first  two  should  be  not  less  than  70  grm.  a  day.  The  protein 
should  have  a  mixed  origin  and  should  include  a  certain  amount  of  animal 
protein. 

(3)  It  should  include  a  certain  proportion  of  fresh  foods,  such  as  green 
vegetables,  meat  and  eggs,  and  in  the  case  of  children,  milk,  in  order  to 
supply  the  necessary  accessory  food  substances. 

(4)  It  must  contain  a  proper  proportion  of  the  salts,  especially  sodium, 
calcium,  potassium,  chlorides  and  phosphates. 

(5)  It  must  be  palatable.  Appetite  is  an  essential  factor  for  the  secre- 
tion of  the  digestive  juices  and  therefore  for  the  digestion  and  assimilation 
of  the  food,  so  that  good  cooking  becomes  an  important  condition  for  the 
maintenance  of  health.  The  use  of  various  flavouring  agents  and  condime?its, 
which  is  general  throughout  all  races,  is  therefore  physiologically  justified. 

ALCOHOL.  When  alcohol  is  taken  by  man  in  moderate  quantities,  the  - 
greater  part  of  it  undergoes  oxidation  and  leaves  the  body  as  carbon  dioxide 
and  water.  About  10  per  cent,  which  escapes  oxidation  is  excreted  unaltered 
by  the  lungs  and  urine.  This  oxidation  of  alcohol  is  a  result  of  true  utilisa- 
tion, since  the  addition  of  a  certain  amount  of  alcohol  to  the  food  does  not 
result  in  an  increase  of  the  output  of  carbon  dioxide.  In  small  quantities 
therefore  alcohol  can  act  as  a  food.  This  f miction  however  is  quite  un- 
important, and  is  overshadowed  by  the  poisonous  action  of  this  substance. 
A  man  unaccustomed  to  its  action  cannot  take  more  than  16  to  25  grm. 
without  experiencing  its  poisonous  effects.  This  amount  of  alcohol  represents 
a  total  heat  value  only  of  112  to  175  Calories,  i.  e.  only  about  5  per  cent, 
of  the  total  energy  requirements  of  the  body.  Very  rarely  therefore 
can  we  be  justified  in  administering  alcohol  as  a  food.  Its  value  in  a  diet 
is  entirely  that  of  an.  accessory  or  adjuvant  in  exciting  appetite  by  its 
taste  and  smell,  an  advantage  largely  counterbalanced  by  the  danger 
of  introducing  a  poison  into  the  body  which  on  long  continuance  tends  to 
set  up  various  degenerative  changes  in  the  tissues;  and  if  taken  in  any 
quantity  at  one  time,  it  causes  a  temporary  abolition  of  those  processes  of 
inhibition  and  control  which  have  been  the  determining  factors  in  the 
survival  of  the  race  throughout  the  struggle  for  existence. 


/ 


CHAPTER   X 
THE    PHYSIOLOGY    OF    DIGESTION 

CHANGES    UNDERGONE    BY    THE   FOODSTUFFS    IN    THE 
ALIMENTARY   CANAL 

The  use  of  the  process  of  digestion  is  to  alter  the  foodstuffs  so  as  to  fit 
them  for  absorption  into  the  blood,  by  means  of  which  they  may  be  carried 
to  all  parts  of  the  body.  In  most  cases  the  foodstuffs  cannot  be  utilised 
in  their  original  form  by  the  living  cells.  When  we  nourish  ourselves  at 
the  expense  of  an  animal  or  plant,  we  are  taking  in  not  only  the  current 
coin  of  the  organism  which  is  being  used  for  the  supply  of  energy  to  its  vital 
processes,  but  also,  and  to  a  much  larger  extent,  the  framework  forming 
the  machinery  of  the  organism  as  well  as  its  stores  of  carbohydrate  or  fat. 
The  foodstuffs  as  we  ingest  them  are  in  the  most  inactive  form  possible. 
Practically  all  are  colloidal,  neutral,  and  tasteless,  and  present  no  tendency 
to  unite  with  oxygen  or  indeed  to  undergo  any  change  whatsoever,  apart 
from  the  interference  of  liviug  organisms  such  as  bacteria.  In  a  starving 
animal  the  stores  of  carbohydrate  and  fat  aud  the  protein  structure  of  the 
inactive  living  cells  have  to  be  converted  into  a  soluble  form — transformed, 
so  to  speak,  into  currency — before  they  can  be  utilised  by  other  living  cells, 
such  as  those  of  the  heart,  for  the  discharge  of  their  normal  functions  and 
the  maintenance  of  the  life  of  the  animal.  In  the  same  way,  when  we  take 
these  colloidal  or  insoluble  substances  into  our  alimentary  canal,  they  have 
to  be  rendered  soluble  or  diffusible,  in  order  to  allow  of  their  easy  trans- 
ference across  the  wall  of  the  gut  into  the  blood  and  their  transport  to  the 
tissue  cells.  The  cells  of  the  body  cannot  deal  with  all  kinds  of  carbohydrate. 
Most  animal  cells  will  starve  when  presented  with  starch,  dextrin,  or  any 
of  the  disaccharides,  such  as  maltose,  lactose,  or  cane  sugar.  It  is  necessary 
therefore  that  all  the  carbohydrates  shall  be  reduced  in  the  alimentary  canal 
or  in  its  walls  to  the  form  of  monosaccharides.  As  regards  proteins,  the 
processes  of  digestion  have  a  different  significance  according  as  we  are  dealing 
with  their  value  as  givers  of  energy  or  their  value  as  builders  up  of  the  living 
protoplasm.  If  the  proteins  of  the  food  are  to  be  oxidised  and  utilised  as  a 
source  of  energy,  they  must  be  rendered  soluble  so  as  to  enable  them  to  be 
absorbed  and  carried  to  those  parts  of  the  body  where  they  may  undergo 
deamination  and  complete  oxidation.  If  they  are  to  be  built  up  as  integral 
parts  of  living  cells,  to  take  the  place  of  molecules  which  have  been  destroyed 

703   » 


704  PHYSIOLOGY 

in  the  wear  and  tear  of  functional  activity,  the  change  must  be  almost  equally 
profound.  The  proteins  of  the  cells  from  different  parts  of  the  body  have 
different  molecular  constitutions.  Not  only  do  they  differ  among  them- 
selves, but  they  differ  very  largely  from  many  of  the  proteins  which  may 
be  taken  in  with  the  food.  A  child  is  able  to  obtain  material  for  the  growth 
of  his  brain  cells,  his  muscle  cells,  or  his  liver  cells,  from  a  diet  containing 
protein  in  the  form  of  caseinogen,  or  of  vegetable  gluten,  or  of  meat  fibrin. 
A  reference  to  the  Table  on  p.  89  will  show  the  striking  difference  in  com- 
position between  the  various  proteins  of  the  food  and  the  proteins  which 
have  to  be  formed  from  them  in  the  living  tissues.  It  is  evident  that  to  form 
serum  albumin,  for  instance,  out  of  wheat  gliadin,  an  entire  reconstruction 
is  necessary.  This  can  only  be  accomplished  by  taking  the  protein  mole- 
cule to  bits,  and  by  selecting  certain  of  its  constituent  parts  and  building  these 
up  in  the  proper  proportions  to  make  a  new  protein  molecule.  For  the 
purposes  of  nutrition  therefore,  the  changes  in  the  protein  molecule  must 
be  greater  the  more  variation  there  is  in  the  composition  of  the  protein  of 
the  food  from  the  composition  of  the  proteins  of  the  tissues. 

In  primitive  alimentary  canals  every  cell  fining  the  canal  may  be  en- 
dowed with  amoeboid  properties  and  capable  of  devouring  the  food  particles, 
the  subsequent  changes  in  the  latter  to  fit  them  for  their  journey  through 
the  rest  of  the  body  being  performed  in  the  body  of  the  cell  itself.  In  all  the 
higher  animals  however  including  ourselves,  the  greater  part  of  the  prepara- 
tion of  the  food  is  accomplished  extracellularly  in  the  lumen  of  the  alimentary 
canal,  and  the  changes  are  effected  by  means  of  special  digestive  juices, 
which  are  formed  by  the  activity  of  masses  of  cells  produced  as  outgrowths 
from  the  wall  of  the  canal.  The  digestive  juices  attack  the  foodstuffs  by 
means  of  ferments,  and  in  every  case  the  action  of  these  ferments  is  hydro- 
lytic,  the  foodstuffs  taking  up  one  or  more  molecules  of  water  and  under- 
going dissociation  into  simpler  molecules.  Since  each  class  of  foodstuff 
requires  a  different  ferment,  a  great  variety  of  ferments  is  concerned  in  the 
processes  of  digestion. 

As  the  end-result  of  digestion  the  many  kinds  of  food  taken  by  man 
are  reduced  to  a  fairly  small  number  of  simpler  bodies.  These  end-products 
aie : 

(1)  Carbohydrates.  The  monosaccharides  :  glucose,  fructose  or  Isevulose, 
and  galactose. 

(2)  Fats.    Fatty  acids,  or  (in  alkaline  medium)  soaps,  and  glycerin. 

(3)  Proteins.  Here  we  have  a  great  variety  of  mono-  and  diamino-acids, 
which  may  be  enumerated  as  follows  : 

Mono- amino- acids 


Glycine  (atoinoacetio  acid) 

Alanine  (aminopropionic  acid)  . 

Serine  or  oxyalanine  (oxyaminopropionic  acid) 

Amino  valerianic  acid 

Leucine  (aminoisobutylacetic  acid)     . 

Isoleucine  (aminocaproic  acid)  . 


Monobasic   acids    of    fatty 
series 


THE   PHYSIOLOGY  OF  DIGESTION"  705 

Aspartic  acid  .......     It..,      .        ., 

„,    ,       .        .,  Dibasic  acids 

Glutamic  acid  .......      j 

Phenylalanine  .......      "|  Benzene  (aromatic)   deriva- 

Tyrosine  (oxy phenylalanine)      .  .  .  .  ■      I      tives 

Proline  (pyrrolidine  carboxylic  acid)  .  .  ■      \ 

Oxy  proline  (oxypyrrolidine  carboxylic  acid)         .  .        Heterocyclic  compounds 

Tryptophane  (indolaniinopropio'nic  acid)     .  .  .J 

DlAMINO-ACIDS   AND    THEIR   COMPOUNDS 

Lysine  (diaminocaproic  acid)     .  .  .  .  .     ^ 

Argiivine  (guanidinaminovalerianic  acid)     .  .  .       ,-The  '  liexone  bases  ' 

Histidine  (iminazolalanine)        .....      J 

,  -r..       ...         ,    ,       .        .  ,  ,  I  Derived  from  a   12-carbon 

Dianunotrioxvdodecoic  acid  .  .  .  <  .  , 

J  (_     acid 

Cystine  (derived  from  aminothjopropionic  acid)  .  .       Sulphur-containing  body 

Those  constituents  of  the  food  which  undergo  no  oxidation  in  the  body, 
such  as  the  water  and  salts,  are  practically  unchanged  in  the  alimentary 
canal,  and  are  absorbed  in  their  original  form  into  the  blood. 


t.j 


SECTION    I 
DIGESTION    IN    THE    MOUTH 


It  is  a  common  experience  that,  when  food  is  taken  into  the  mouth,  there  is 

a  flow  of  a  liquid, '  saliva,'  into  this  cavity.     Saliva  is  the  product  of  secretion 

of  three  pairs  of  large  salivary  glands  situated  in  the  neighbourhood  of  the 

mouth  and  pouring  their  secretions  into  this  cavity  ,by  means  of  ducts. 

It    is    possible  to   collect  the   fluid    secreted 

by  each  of  these  glands  separately;  and  it 

is  found  that  the  saliva  varies  in  properties 

according    to    the    gland    from    which    it    is 

derived.      In    addition  to  these    large    glands 

the  whole  mucous  membrane  of  the  mouth  is 

beset  with  small  glands. 

The  saliva  is  in  most  cases  a  mixture  of 
the  secretions  of  all  three  pairs  of  salivary 
glands  as  well  as  of  the  small  glands  of  the 
mucous  membrane.  When  collected  it  forms 
a  colourless  cloudy  liquid,  slimy  in  character. 
The  cloudiness  is  due  to  the  presence  of  a 
number  of  former!  elements  consisting  of 
desquamated  epithelial  cells,  disintegrating 
leucocytes,  and  gland  cells,  as  well  as  coagu- 
lated clumps  of  mucin.  Its  reaction  "is  in 
healthy  individuals  slightly  alkaline.  Its 
specific  gravity  varies  between  1002  to  1008. 
coagulable  proteins,  mucin,  and  in  some  cases  a  diastatic  ferment,  ptyalin, 
and  traces  of  potassium  sulphocyanate.  Its  average  composition  is  as 
follows  : 


Fig.  333.    Dissection   to  dis 
play  the  salivary  glands. 

a,  sublingual  gland;  b,  sub 
maxillary  gland;  c,  pajotid 
gland ;  d,  common  opening 
ducts  of  submaxillary  and  sub 
lingual  glands;  i,  opening  ol 
duct  ol'  parotid  gland. 

Its  chief  constituents  are 


0-5 

to  1-0 

0-4 

„  0-6 

0-1 

„  04 

0-00 

„  0-016 

100  parts  mixed  saliva  contain  : 

Total  solids   .  .  .  .  .        "  . 

Inorganic  solids      ....... 

Organic  solids  (mucin,  serum  albumin,  serum  globulin) 
Potassium  sulphocyanate         ..... 

Freezing-point  (A)  =  —  0-07  to  —  0-34 

Potassium  sulphocyanate  is  an  almost  constant  constituent  of  human  saliva,  though 
it  is  often  absent  in  that  of  other  animals,  such  as  the  dog.  It  is  generally  present' 
to  the  extent  of  "01  per  cent.,  so  that  on  the  addition  of  a  drop  of  ferric  chloride  to 

706 


DIGESTION   IN  THE  MOUTH  707 

saliva  a  definite  red  colour  is  obtained.  So  far  as  we  know  it  is  formed  in  the  body 
whenever  cyanides  or  organic  nitriles  in  small  quantities  make  their  appearance  in  the 
circulating  fluid,  either  as  the  result  of  administration  or  perhaps  as  by-products  in 
the  normal  processes  of  metabolism.  The  conversion  of  the  poisonous  cyanides  into 
the  almost  innocuous  sulphocyanates  seems  to  be  a  means  by  which  the  organism 
protects  itself  against  the  poisonous  effects  of  the  former.  The  channels  of  excretion 
of  the  sulphocyanate  are  by  the  salivary  glands,  the  kidneys,  and  possibly  by  the 
gastric  juice. 

THE   USES   OF   SALIVA 

The  main  function  of  saliva  is  to  moisten  the  food  and  so  facilitate  its 
mastication  and  deglutition.  The  presence  of  the  mucin  is  of  special  value 
for  the  latter  process  since  it  renders  the  mass  of  food  slippery.  In  animals 
such  as  dogs,  where  the  saliva  is  devoid  of  any  digestive  ferment,  this  must 
represent  its  sole  function.  In  man  and  some  of  the  herbivora  the  saliva 
exerts  a  well-marked  digestive  effect  on  one  of  the  foodstuffs,  namely,  starch. 
If  a  warm  solution  of  starch  be  taken  into  the  mouth,  kept  there  for  one 
minute,  and  then  expelled  into  a  test-tube,  the  starch  will  be  found  to  have 
entirely  disappeared,  its  place  being  taken  by  a  reducing  sugar.  The  stages 
of  the  action  of  saliva  on  boiled  starch  can  be  followed  more  easily  if  its  action 
is  retarded  by  keeping  the  mixture  cool,  or  at  a  temperature  not  above 
25°  C.  The  first  change  is  a  conversion  of  the  opalescent  gelatinising  starch 
solution  into  a  clear  solution  which  no  longer  sets  on  cooling,  but  still  gives 
a  blue  colour  with  iodine.  The  fluid  contains  what  is  known  as  soluble  starch. 
The  soluble  starch  then  undergoes  hydrolytic  dissociation  into  a  dextrin, 
which  gives  a  red  colour  with  the  iodine  and  is  therefore  known  as  erythro- 
dextrin,  together  with  maltose.  The  erythrodextrin  is  then  hydrolysed  into 
an  achroodextrin  (giving  no  colour  with  iodine)  and  maltose,  and  the  achroo- 
dextrin  is  still  further  broken  up  into  dextrin  and  maltose.  The  conversion 
of  starch  into  maltose  is  never  complete,  though  if  the  maltose  be  removed 
by  dialysis  as  it  is  formed,  it  was  found  by  Lee  to  be  possible  to  convert  as 
much  as  95  per  cent,  of  the  starch  into  reducing  sugar.  The  stages  in  the 
conversion  are  represented  in  the  following  Table  : 

Starch 
soluble  starch 


(cry thro-)  dextrins  maltose 


(achroo-)  dextrins  maltose 

The  process  by  which  the  huge  starch  molecule  is  converted  into  dextrins 
and  maltose  is  a  very  complicated  one,  and  a  number  of  intermediate  com- 
pounds of  dextrins  and  maltose  can  exist  between  those  whose  presence  is 
revealed  by  their  varying  reaction  to  iodine. 

Ptyalin  is  most  active  in  a  neutral  medium,  so  that  the  addition  of 
minute  traces  of  acid  to  the  saliva  increases  its  diastatic  power.  In  the 
presence  of  "••*-  mineral  acid  ptyalin  is  rapidly  destroyed,  "003  per  cent. 


708  PHYSIOLOGY 

hydrochloric  being  sufficient  for  this  purpose.  It  acts  most  rapidly  at  the 
body  temperature.  At  0°  C.  its  action  is  still  just  perceptible.  If  heated  to 
60°  C.  it  is  destroyed. 

We  have  seen  that  boiled  starch  solution  is  changed  by  saliva  when  kept 
only  a  few  seconds  in  the  cavity  of  the  mouth.  When  the  starch  is  in  the 
solid  condition,  as  in  biscuits  and  most  farinaceous  Eoods,  its  stay  in  the 
mouth  during  the  normal  process  of  mastication  is  qoI  lung  enough  to  allow 
of  any  considerable  hydrolysis  occurring.  When  a  meal  is  taken,  the  food 
which  is  swallowed  forms  a  mass  lying  in  the  fundus  of  the  stomach.  This 
mass  is  penetrated  only  with  difficulty  by  the  acid  gastric 'juice  secreted 
by  the  mucous  membrane  of  the  stomach  within  five  minutes  of  the  taking 
of  food.  Even  half  an  hour  after  a  meal  the  interior  of  the  mass  of  food  in  the 
stomach  may  be  still  found  to  be  neutral  or  slightly  alkaline.  The  food 
therefore,  thoroughly  moistened  by  and  mixed  with  saliva,  remains  in  the 
stomach  for  thirty  to  forty  minutes  before  the  salivary  ferment  is  destroyed 
by  the  penetration  of  the  acid  gastric  juice.  During  this  time  the  ptyalin 
continues  to  exert  its  effect,  so  that  we  may  say  that  the  chief  part  of  the 
salivary  digestion  occurs  actually  in  the  stomach,  and  results  in  an  almost 
complete  alteration  of  the  starch  into  dextrins  and  maltose.  Unboiled 
starch  is  attacked  with  extreme  slowness  by  the  diastatic  ferments  either  of 
the  saliva  or  the  pancreatic  juice,  so  that,  if  taken  by  man,  large  quantities 
are  unutilised  and  reappear  in  the  fasces.  Thirty  to  forty  minutes  after  a  meal 
the  food  becomes  thoroughly  soaked  with  the  acid  gastric  juice,  and  salivary 
digestion  gives  place  to  gastric  digestion. 

THE   SECRETION   OF   SALIVA 

The  mucous  membrane  of  the  mouth,  especially  on  the  under  surface  of 
the  tongue,  presents  a  number  of  small  glands  which  contribute  by  their 
secretions  to  the  moistening  of  the  mouth.  The  greater  part  of  the  saliva 
is  formed  in  man  by  three  pairs  of  glands,  viz.  the  sublingual  and  the 
submaxillary  glands,  situated  in  the  floor  of  the  mouth  below  the  jaw,  and 
the  parotid  gland,  lying  in  the  cheek  over  the  ramus  of  the  inferior  maxilla. 

The  arrangement  of  these  glands,  esjiecially  of  those  in  the  floor  of  the  mouth, 
varies  somewhat  in  different  animals.  In  the  dog  and  cat  the  sublingual  gland  is 
wanting,  its  place  being  taken  by  a  gland  situated  somewhat  further  back  and  known  as 
the  retrolingual  gland.  In  the  pig  both  retrolingual  and  sublingual  glands  are  present 
in  addition  to  the  submaxillary,  and  one  may  sometimes  find  traces  of  the  retro- 
lingual gland  in  man.  Many  animals,  e.  g.  the  dog,  also  possess  a  gland  situated  in  the 
orbit,  which  pours  its  secretion  into  the  mouth — the  orbital  gland.  These  glands  can 
be  divided,  according  to  their  structure  and  the  nature  of  the  secretion  which  they  form, 
into  several  classes.  Among  the  salivary  glands  of  the  mucous  membrane  we  may 
distinguish  two  types,  the  mucous  gland  and  the  serous  gland.  In  specimens  hardened 
and  stained  by  the  ordinary  methods,  the  mucous  gland  is  distinguished  by  the  fact 
that  its  short  duct  opens  into  wide  alveoli,  the  lining  cells  of  which  are  distended 
with  mucin  and  therefore  present  a  clear  unstained  space  in  the  section.  In  the 
other  type,  the  serous  gland,  the  duct  lined  with  columnar  cells  branches  into  a 
series  of  acini  which  present  a  well-marked  lumen  and  are  lined  with  small  granular 
cells  with  a  very  distinct  and  well-staining  nucleus.  The  same  general  distinction 
can  be  made  out  in  the  large  salivary  glands.      The  parotid  gland.-.=ki  man  and  in 


DIGESTION  IN  THE  MOUTH 


709 


all  the  higher  mammalia  is  a  typical  serous  gland,  though  here  and  there  a 
mucous  cell  may  be  occasionally  seen.  The  orbital  gland  of  the  dog  represents 
practically  one  of  the  mucous  glands  of  the  general  mouth  cavity  on  a  large  scale. 
The  sublingual  and  submaxillary  glands  in  man  represent  a  third  type.  Most  of  the 
alveoli  are  mucous  in  character.  At  the  ends  of  the  alveoli  are  seen  crescent-shaped 
cells  between  the  mucin-distended  cells  and  the  basement  membrane.  These  are 
known  as  the  demilune  cells,  or  the  Crescent  cells  of  Gianuzzi.  In  some  cases  these 
mucous  alveoli  with  demilunes  may  be  found  alongside  of  typical  serous  alveoli. 


Fig.  334.     a,  serous  gland;  B,  pure  mucous  gland  from  mouth.     (K6ixiker.) 
a,  ducts;  /,  fat-cells. 

Thus  in  man  the  submaxillary  gland  is  usually  a  mixed  gland,  the  serous  alveoli 
predominating.  The  sublingual  gland  is  also  mixed,  but  with  a  predominance  of  the 
mucous  alveoli.  In  the  monkey  the  submaxillary  gland  is  almost  entirely  serous. 
In  the  dog  the  submaxillary  gland  is  a  pure  mucous  gland  with  demilunes,  while  the 
retrolingual  and  sublingual  gland  when  present  are  of  the  mixed  type.  In  the  rabbit 
the  submaxillary  gland  is  serous,  while  the  sublingual  gland  is  mucous.  In  ths  cat 
the  submaxillary  is  mucous,  the  retrolingual  is  mixed,  and  the  sublingual,  when 
present,  is  mixed,  with  predominance  of  the  mucous  type. 

The  normal  behaviour  of  the  salivary  glands  during  digestion  is  best 
studied  by  aid  of  a  method  used  long  ago  by  de  Graaf  and  ^introduced  with 
considerable  elaboration  of  late  years  by  Pawlow.  It  is  possible  without  any 
disturbance  of  the  animars  nutrition  to  transplant  the  papilla,  on  which  the 
duct  opens,  to  the  outside,  so  that  the  saliva  from  any  particular  gland  shall 
flow  externally  instead  of  into  the  cavity  of  the  mouth.  By  attaching  a  small 
funnel  to  the  fistulous  opening,  it  is  easy  to  collect  the  pure  saliva 
unmixed  with  the  secretion  of  any  other  of  the  glands. 

By  this  method  it  has  been  found  that  as  soon  as  food  is  introduced  into 
the  mouth  there  is  a  secretion  of  saliva,  the  relative  extent  to  which  different 
glands  are  involved  varying  according  to  the  nature  of  the  stimulation. 
Thus  with  meat  there  is  only  a  small  amount  of  secretion,  which  is  derived 
chiefly  from  the  submaxillary  and  sublingual  glands,  and  is  rich  in  organic 
constituents.  When  dry  material,  such  as  dry  powdered  meat,  is  introduced 
the  flow  of  juice  is  more  copious  and  more  watery.  The  same  effect  may 
be  produced  in  the  dog  by  psychic  excitation.  Thus  salivation  may  be 
induced  by  showing  food  to  the  dog,  or  even  by  the  suggestion  that  dry 
powder  is  to  be  introduced  into  the  mouth.  A  comparison  of  the  juices 
obtained  from  different  glands  shows  that  the  serous  and  mucous  glands 
differ,  as  might  be  expected,  in  thenature  of  their  secretion.  A  serous  gland, 
such  as  the  parotid,  gives  a  thin  watery  secretion  almost  free  fiom  mucin,  but 
containing  small  traces  of  coagulable  protein.    The  mucous  gland  delivers 


710 


PHYSIOLOGY 


a  secretion  which  is  viscid  from  the  presence  of  mucin,  and  contains  also  a 
small  trace  of  coagulable  protein.  Both  in  parotid  and  mucous  saliva  the 
percentage  of  salts  is  very  low,  so  that  the  freezing-point  of  these  fluids 
is  considerably  higher  than  that  of  the  blood  plasma.  In  the  dog  the  saliva 
is  free  from  any  ferments.  In  man  ptyalin — the  starch-splitting  ferment — 
is  found  in  the  saliva  from  both  kinds  of  gland,  though  it  predominates  in  that 
obtained  from  the  parotid  gland.  The  total  amount  "of  saliva  which  may  be 
obtained  varies,  of  course,  in  different  animals.  Each  gland  may  however 
in  the  course  of  the  day  give  an  amount  of  juice  far  exceeding,  e.  g.  ten  or 
twelve  times,  its  own  weight.  In  man  it  is  reckoned  that  over  one  litre  of 
saliva  may  be  formed  every  twenty-four  hours,  and  in  the  herbivora,  such  as 
the  horse,  the  total  diurnal  production  must  amount  to  many  litres;  500 
grm.  of  hay  alone  may  evoke  the  secretion  of  a  litre  of  saliva. 


Fig.  335.     Diagram  of  nerve  supply  to  submaxillary  gland. 
Sm.G,   submaxillary   gland;   N.L,   lingual  nerve;     Ch.T,   chorda   tympani; 
Sm.Gl,  submaxillary  ganglion;   Sm.I),   Wharton's  duct;     V..T,   jugular  vein; 
C.A,  carotid  artery ;  G.C.S,  superior  cervical  ganglion  ;  N.S,  sympathetic  fibres 
ramifying  on  facial  artery.     (After  Foster.) 


The  intimate  dependence  of  the  secretion  of  saliva  on  the  events  occurring 
in  the  mouth  shows  that  the  activity  of  the  salivary  glands  must  be  excited 
by  reflex  means.  The  afferent  nerves  in  this  reflex  are  those  that  supply  the 
mucous  membrane  of  the  mouth,  i,  e.  the  fifth  nerve  and  the  glossopharyngeal. 
The  efferent  channels  of  the  reflex  were  discovered  by  Ludwig.  Each  one  of 
the  large  salivary  glands  receives  nerve  fibres  from  two  sources,  viz.  from  the 
cerebrospinal  and  from  the  sympathetic  system.  It  is  probable  that 
the  cerebro-spinal  supply  is  derived  always  from  one  part  of  the  cerebral 
axis,  namely,  from  the  filaments  which  make  up  the  nervus  intermedius. 
From  this  point  they  diverge  in  their  course  to  the  glands.  The  fibres  to  the 
submaxillary,  the  sublingual,  and  the  retrolingual  glands  pass  into  the 
facial  nerve,  and  then  from  this  nerve  along  the  chorda  tympani  to  the  lingual 
division  of  the  fifth  nerve.  The  lingual  nerve  passes  below  the  duct,  and 
just  before  it  crosses  the  two  ducts  of  the  submaxillary  and  retro-  or  sub- 
lingual glands,  it  gives  off  a  small  branch  backwards,  namely,  the  chorda 
tympani,  which  runs  along  the  submaxillary  duct  to  be  distributed  to  the 
glands,  and  in  its  course  gives  off  fibres  also  to  the  retrolingual  (Fig.  335). 


DIGESTION   IN  THE  MOUTH  711 

The  fibres  are  apparently  finally  distributed  to  the  secreting  alveoli, 
.where  they  end  freely  on  the  secreting  cells  just  below  the  basement  mem- 
brane. They  do  not  however  take  an  uninterrupted  course.  By  means 
of  the  nicotine  method  Langley  has  shown  that  all  the  fibres  to  the  sublingual 
and  the  submaxillary  glands  end  somewhere  near  the  glands  in  connection 
with  ganglion  cells.  From  the  ganglion  cells  fresh  relays  of  fibres  are  given 
off  which  pass  to  the  gland  cells  themselves.  The  fibres  going  to  the 
submaxillary  gland  are  connected  with  scattered  cells  lying  in  the  substance 
(if  the  gland  itself;  in  the  cat  those  passing  to  the  retrolingual  gland  are 
connected  for  the  most  part  with  the  ganglion  cells  which  make  up  the 
so-called  'submaxillary  ganglion.'  The  fibres  to  the  sublingual  gland  in 
man  probably  take  a  similar  course. 


Fig.  336.     Diagram  of  the  arrangement  of  the  nerve  supply  to  the  submaxillary 

gland,  as  exposed  in  an  actual  experiment. 

Duct,  Wh,  Wharton's  duct  (of  submaxillary);  Duct.R.L,  retrolingual 

duct;  i  li.'l'y.  chorda  tympani  nerves.     (Alcock  and  Ellison.) 

The  fibres  to  the  parotid  gland  pass  along  the  glossopharyngeal  nerve 
and  its  tympanic  branch  (nerve  of  Jacobson)  to  the  tympanic  plexus.  Hence 
the  fibres  are  carried  by  the  small  superficial  petrosal  nerve  to  the  otic 
ganglion,  and  thence  by  the  auriculo-temporal,  which  is  a  branch  of  the 
third  division  of  the  fifth  nerve. 

The  sympathetic  supply  to  all  these  glands  is  contained  in  fine  filaments 
on  the  walls  of  the  arteries  with  which  they  are  supplied.  The  fibres  are 
derived  ultimately  from  the  spinal  cord,  whence  they  issue  by  the  upper  three 
anterior  dorsal  nerve  roots.  They  pass  into  the  stellate  ganglion,  round  the 
ansa  Vieussenii  to  the  inferior,  and  so  to  the  superior  cervical  ganglion 
of  the  sympathetic.  Here  the  fibres  end  around  the  cells  of  the  ganglion, 
and  a  fresh  relay  of  fibres,  chiefly  non-medullated,  arise  from  the  cells  and 
travel  on  the  walls  of  the  branches  of  the  external  carotid  artery  to  their 
destination. 

The  effect  of  stimulating  the  peripheral  ends  of  the  cere bro -spinal  nerves 
going  to  the  glands  presents  a  general  resemblance,  whichever  be  the  gland 
involved.  Within  a  period  of  half  to  two  seconds  after  the  stimulation  has 
been  applied,  a  secretion  of  saliva  is  produced,  presenting  similar  characters 


712 


PHYSIOLOGY 


to  that  which  would  be  obtained  from  the  gland  under  normal  conditions  if 
it  were  provided  with  a  permanent  fistula.  The  concent  ration  of  the  saliva 
as  well  as  its  rate  of  secretion  depends  on  the  strength  of  the  stimulus.  The 
following  Table  (Heidenhain)  shows  the  effect  on  the  amount  and  composition 
of  submaxillary  saliva  obtained  by  weak  and  strong  stimulation  of  the 
chorda  tympani  nerve : 


Strength  of  stimulus 

Quantity  in  one               Per  cent,  of 
minute                    organic  solids 

Per  cent,  of  salts 

Weak       . 

Strong 

Weak 

0-17                          0-84 
0-72                         2-06 
017                          1-67 

0-20 
0-46 
0-26 

With  the  strong  stimulus  the  amount  of  saliva  was  increased  over  four- 
fold, while  the  percentage  of  organic  substances  in  the  saliva  was  raised  from 
084  to  2-06  per  cent.  There  was  at  the  same  time  an  increase  in  the  per- 
centage of  salts.  If  the  excitation  be  continued  for  a  considerable  time, 
there  is  a  gradual  rise  in  the  percentage  of  inorganic  salts  and  a  fall  in  the 
percentage  of  organic  matter. 

The  cranial  nerves  going  to  these  glands  have  another  important  effect, 
namely,  vaso-dilatation.  It  was  shown  by  Claude  Bernard  that  on  exciting 
the  chorda  tympani  the  flow  from  the  vein  of  the  submaxillary  gland  might 
increase  four  to  eight  times,  and  indeed  to  such  an  extent  that  the  blood 
passing  through  the  gland  did  not  stay  there  long  enough  to  lose  its  oxygen. 
Moreover,  the  dilatation  of  the  arterioles  removes  the  normal  resistance  which 
serves  to  damp  and  obliterate  the  pulse  between  the  arteries  and  the  veins. 
As  the  result  of  exciting  the  chorda  therefore,  the  blood  coming  from  the 
vein  may  show  distinct  pulsation,  and  may  have  a  brilliant  scarlet  hue  just 
as  if  it  were  derived  from  an  artery.  The  same  dilatation  has  been  observed 
to  attend  excitation  of  the  cranial  supply  to  the  parotid  gland. 

The  effects  of  exciting  the  sympathetic  nerve  supply  differ  according  to 
the  gland  and  the  animal  which  is  the  subject  of  experiment.  In  the  dog 
excitation  of  the  cervical  sympathetic  causes  the  secretion  of  a  few  drops 
of  thick  viscid  saliva  from  the  submaxillary  gland.  In  this  animal  no 
secretion  is  obtained  at  all  from  the  parotid  gland  on  exciting  the  sympathetic, 
but  the  influence  of  the  excitation  is  shown  by  the  occurrence  of  histological 
changes  in  the  gland  cells.  In  the  cat  the  submaxillary  saliva  obtained  on 
sympathetic  excitation  may  be  as  copious  as  and  even  more  watery  than 
the  saliva  obtained  from  the  submaxillary  on  stimulation  of  the  chorda 
tympani.  We  shall  have  later  on  to  discuss  how  far  these  results  are  to  be 
ascribed  to  a  fundamental  difference  in  the  point  of  attack  of  impulses 
carried  to  the  secreting  cells  by  the  two  sets  of  nerve  fibres,  and  how  far  to 
the  varying  effects  of  the  cranial  and  sympathetic  nerves  respectively  on 
the  blood  vessels.  It  must  be  remembered  that  the  sympathetic  nerve 
carries  the  vaso-constrictor  fibres  to  most  or  all  of  the  vessels  of  the  head  and 


DIGESTION  IN  THE  MOUTH 


713 


neck  and  therefore  in  most  cases  we  should  expect,  and  we  find,  that  stimu- 
lation of  this  nerve  causes  vascular  constriction  in  the  gland  affected.  Before 
attempting  to  decide  this  point  we  must  study  in  somewhat  greater  detail  the 
changes  which  occur  in  the  gland  concomitantly  with  the  secretion. 


.(Lymph  spaces 


,  -Secreting 
cells. 

-  Blood 
capillary 


Duct. 


Basement 
membrane 

Fio.  337.  Diagram  to  show  relation  of 
thejsecreting  cells  of  a  gland  to  the 
bloocl  and  lymph  supply. 


CHANGES   IN   THE   GLAND   ACCOMPANYING   SECRETION 
The  fact  that  a  sub-maxillary  gland  of  the  dog  under  favourable  condi- 
tions will  secrete  its  own  weight  of  saliva  in  five  minutes,  and  will  continue 
to  secrete  for  many  hours  afterwards,  shows  that  there  must  be  a  continual 

renewal  of  the  fluid  which  is  turned  out 
in  the  secretion.  The  source  of  this 
fluid  must  be  the  blood  which  is  circu- 
lating through  the  gland.  If  we  refer  to 
the  diagrammatic  representation  of  the 
elements  which  make  up  a  secreting  lobule 
and  which  may  be  involved  in  the  act  of 
secretion  (Fig.  337),  we  see  that  between 
the  lumen  of  the  duct  and  the  blood, 
which  must  be  regarded  as  the  source  of 
the  fluid,  the  following  layers  of  cells 
intervene  :  (1)  the  endothelium  of  the 
blood  capillaries  ;  (2)  the  basement  mem- 
brane ;  (3)  the  epithelial  cells  of  the  gland 
proper.  We  have,  in  the  first  place,  to  decide  to  which  of  these  elements 
can  be  ascribed  the  chief  part  in  the  act  of  secretion. 

The  secretory  activity  of  the  submaxillary  gland,  whether  evoked 
reflexly  by  the  introduction  of  acids  into  the  mouth  or  directly  by  the 
injection  of  pilocarpine  or  by  stimulation  of  the  peripheral  end  of  the  chorda 
tympani  nerve,  is  always  associated  with  a  considerable  dilatation  of  the 
vessels  of  the  gland,  and  a  consequent  large  increase  in  the  blood-flow  through 
the  gland,  which  may  amount  to  between  three  and  eight  times  the  quantity 
passing  during  rest.  Such  an  increase  hi  the  supply  of  blood  is  necessary 
in  order  to  afford  a  source  for  the  large  quantity  of  fluid  which  is  turned  out 
in  the  saliva.  Another  effect  of  the  dilatation  will  be  to  raise  the  pressure 
in  the  capillaries  of  the  gland.  We  cannot  however  regard  this  rise  of 
pressure  in  the  capillaries  as  an  essential  factor  in  the  act  of  secretion.  If 
atropine  be  adrmnistered,  excitation  of  the  chorda  causes  the  same  vaso- 
dilatation as  before,  though  no  secretion  is  produced.  Moreover  Ludwig 
showed  that  the  force  with  which  the  secretion  is  turned  out  into  the  ducts 
of  the  gland  is  greater  than  that  represented  by  the  blood  pressure.  The 
blood  pressure  in  the  capillaries  must  be  considerably  lower  even  with  full 
vascular  dilatation  than  the  pressure  in  the  carotid  artery.  If  two  mano- 
meters be  connected,  one  with  the  carotid  artery  and  the  other  with  the 
duct,  it  will  be  found  that  on  stimulating  the  chorda  tympani  nerve  the 
secretion  will  be  excited,  and  the  mercury  will  be  driven  up  by  the  pressure 


714 


PHYSIOLOGY 


(X^a^'o^***'. 


000M 


Fig.  338.  Tracing  of  volume  of  submaxillary 
gland,  showing  effect  of  stimulation  of  the 
chorda  after  administration  of  10  mg.  atro- 
pine. The  blood  pressure  (lowest  line)  was 
unaltered  by  the  stimulation.     (Bunch.)  ,    j 


of  the  secretion  in  the  corresponding  manometer  until  it  attains  a  height 
which  may  be  double  that  of  the  mercury  in  the  manometer  connected  with 
*  the  carotid  artery,  and  therefore  must  be  still  greater  than  the  pressure  in  the 
capillaries  of  the  gland.  This  ex- 
periment, which  is  easy  to  repeat, 
showed  the  impossibility  of  the 
act  of  secretion  being  in  any  way 
determined  by  a  process  of  filtra- 
tion. We  have  now  further  evi- 
dence that  work  is  done  in  the 
production  of  the  salivary  secre- 
tion, evidence  which  was  not 
available  when  Ludwig  first  car- 
ried out  the  experiment  just  de- 
scribed. When  a  fluid  containing 
salts  in  solution  is  filtered  through 
a  porous  membrane,  the  filtrate  has 
the  same  content  in  salts  as  the 
original  fluid.  We  can  effect  a 
separation  of  dissolved  salts  from 
a  fluid  by  filtration  under  pressure 
through  some  membrane  which  is 
impermeable  to  the  salts,  e.g.  a 
membrane  of  copper  ferrocyanide 
— a  so-called  semipermeable  mem- 
brane. Under  these  circumstances 
a  very  large  pressure  is  necessary 
in  order  to  cause  the  filtration  of 
any  fluid  at  all,  a  pressure  which 
is  equal  to  the  osmotic  pressure 
exerted  by  the  substances  in  solu- 
tion. Thus  if  we  were  filtering 
a  1  per  cent,  solution  of  NaCl 
through  a  semipermeable  mem- 
brane, we  should  have  to  exert  a 
pressure  of  about  seven  atmo- 
spheres in  order  to  obtain  a  filtrate 
free    from    sodium    chloride.     To 

obtain  a  filtrate  containing  half  the.  amount  of  sodium  chloride,  if  such 
were  possible,  would  therefore  need  a  pressure  of  about  three  and  a  half 
atmospheres.  On  comparing  the  osmotic  pressures  of  saliva  and  blood 
respectively — and  for  this  purpose  we  can  employ  the  depression  of  freez- 
ing-point as  our  index — we  find  that  the  molecular  concentration  of  saliva, 
and  therefore  its  osmotic  pressure,  is  always  very  much  less  than  that  of 
the  blood  plasma,  and  may  vary  between  half  and  three-quarters  of  the 
latter.     Supposing  the  membrane  separating  the  lumen  of  the  duct  from  the 


Fig.  339.  Tracing  of  volume  of  submaxillary 
gland,  showing  decrease  on  excitation  of 
chorda.     (Bunch.) 


DIGESTION  IN  THE  MOUTH  715 

blood  vessels  could  be.  regarded  as  endowed  with  the  properties  of  a  semi- 
permeable membrane,  we  should  need,  in  order  to  effect  the  separation,  a 
pressure  ten  to  twenty  times  as  large  as  the  arterial  blood  pressure.  We 
must  conclude  then  that  work,  both  osmotic  and  mechanical,  is  performed 
in  the  separation  of  the  fluid  from  the  blood  and  its  transference  in  the 
form  of  saliva  to  the  duct.  A  very  simple  experiment  will  suffice  to  show 
that  this  work  must  be  effected,  not  by  the  endothelial  cells  of  the  blood- 
vessels, but  by  the  gland  cells  themselves.  The  fluid  passes  from  the 
blood  vessels  first  into  the  lymphatic  spaces,  whence  it  is  taken  up  by 
the  secretory  cells.  If  the  first  act  in  secretion  consisted  in  an  increased 
exudation  of  fluid  from  the  blood  into  the  lymph  spaces,  the  first  effect  of 
exciting  the  chorda  tympani  nerve  should  be  to  cause  an  accumulation  of 
fluid  in  the  lymph  spaces,  some  increase  in  the  lymph  flow  from  the  gland, 
and  the  swelling  of  the  whole  gland.  By  placing  the  gland  in  a  plethysmo- 
graph  we  can  record  the  actual  changes  in  its  volume  which  ensue  on 
excitation  of  the  chorda  tympani.  If  all  secretion  be  prevented  by  the 
previous  administration  of  atropine,  stimulation  of  this  nerve  produces,  as 
might  be  anticipated,  an  increased  volume  of  the  gland  in  consequence  of  the 
dilatation  of  its  vessels  (Fig.  338).  If  however  the  gland  be  allowed  to 
secrete  we  obtain,  in  spite  of  the  simultaneous  increase  in  size  of  the  vessels, 
an  actual  diminution  in  the  size  of  the  gland  itself,  showing  that  the  first 
effect  of  the  stimulation  is  on  the  cells  of  the  alveoli  (Fig.  339).  Under  the 
stimulus  these  empty  themselves  of  the  fluid  they  contain,  replenishing  their 
loss  at  the  expense  of  the  fluid  in  the  lymph  spaces.  The  increased  passage 
of  fluid  from  blood  to  lymph  space  is  therefore  a  secondary  and  not  a  primary 
effect  of  the  nerve  stimulation,  and  the  first  effect  on  the  gland  is  a 
diminution  of  volume  and  not  an  increase,  as  one  would  expect  if  the  vascular 
endothelium  were  primarily  responsible  for  the  act  of  secretion. 

HISTOLOGICAL   CHANGES   DURING   SECRETION 

The  process  of  secretion  is  associated  with  marked  changes  in  the  structure 
of  the  cells  composing  the  secretory  alveoli.  The  changes  are  of  the  same 
general  character  whatever  class  of  glands  we  investigate,  though  the  ease 
with  which  they  are  to  be  demonstrated  varies  with  the  reactions  of  the 
various  glands  to  the  hardening  fluids  usually  employed.  If  a  small  frag- 
ment of  a  mucous  gland  be  teased  in  blood  serum  or  in  2  per  cent.  NaCl 
solution,  the  cells  are  found  to  be  packed  with  a  mass  of  coarse,  highly  refrac- 
tive granules.  (Fig.  310).  If  a  corresponding  specimen  be  made  from  a 
serous  gland  (Fig.  341)  the  cells  are  also  packed  with  granules,  which,  how- 
ever, are  much  finer  in  structure.  On  making  similar  specimens  from 
glands  which  have  been  forced  to  secrete  for  six  or  seven  hours,  the  individual 
cells  are  found  to  be  much  smaller  and  the  protoplasm  of  the  cell  is  absolutely 
or  relativelv  increased  in  amount,  white  the  granules  are  much  fewer  and  are 
now  confined  almost  entirely  to  the  inner  margin  of  the  cell.  Activity  is 
thus  associated  certainly  with  a  discharge  of  granules,  and  probably  with 
some  increased  building  up  of  protoplasm.    We  may  regard  the  act  of 


71G 


PHYSIOLOGY 


secretion  as  determined  by  the  alteration  of  the  pantiles  and  their  discharge, 
together  with  water  and  salts,  to  form  the  specific  secretion  of  the  gland. 
During  rest  the  granules  are  re-formed  by  precipitation  in  or  modification 
of  the  protoplasm  surrounding  the  nucleus.  We  have  evidence  that  although 
the  granules  form  the  secretion,  they  represent,  not  the  secretion  itself,  but 
a  precursor  of  some  at  any  rate  of  its  constituents.  Thus  if  acetic  acid  be 
added  to  the  saliva  obtained  from  the  submaxillary  gland,  the  mucin  is 
precipitated  as  threads  and  films.  If  the  granules  in  the  secreting  cells  also 
consist  of  mucin  we  should  expect  acetic  acid  to  have  a  coagulating  effect 
upon  them.  We  find,  on  the  contrary,  that  on  allowing  acetic  acid  to  flow 
over  a  section  of  the  fresh  gland  the  granules  at  once  swell  up  and  burst. 


Fig.  340.  Mucous  cells  from  a  fresh  sub- 
maxillary gland  of  a  dog.  (Langley.) 
a,  mucous  cell  examined  fresh  from 
a  resting  gland ;  a',  the  same  cell 
treated  with  weak  alcohol;  6  and  &', 
cells  from  a  discharged  gland  before  and 
after  treatment  with  weak  alcohol. 


Fig.    341.     Acini   of   a    serous   salivary 
gland.     (Langley.) 
a,   resting    condition;    B,    discharged 
condition. 


We  must  regard  these  granules  therefore,  not  as  mucin,  but  as  a  precursor 
of  mucin,  mucigen.  The  effect  of  ordinary  hardening  reagents,  such  as  dilute 
alcohol  up  to  70  per  cent,  or  Miiller's  fluid,  is  to  cause  these  granules  to  swell 
up  so  that  the  cells  become  filled  with  a  mass  of  mucin  giving  the  typical 
hyaline  appearance  of  ordinary  sections  of  these  glands.  In  the  case  of  the 
serous  glands  the  granules  (Fig.  342)  are  apparently  protein  in  nature.  Where 
ptyalin  is  a  constituent  of  the  saliva,  we  are  probably  justified  in  assuming 
that  it  is  contained  either  pre-formed  or  more  probably  as  a  precursor  in 
the  granules.  In  the  glands  of  the  stomach  we  have  evidence  that  the 
granules  are  not  pepsin — the  characteristic  ferment  of  gastric  juice — but  a 
precursor  of  this  substance,  namely,  pepsinogen.  It  is  very  customary, 
therefore,  to  speak  of  the  granules  in  a  secreting  gland  as  zymogen  granules, 
i.  e.  the  precursors  of  zymins  or  ferments.  It  is  probable  that  we  ought  to 
regard  these  granules  not  merely  as  material  precursors  of  the  constituents  of 
the  secretion,  but  as  little  machines  or  cell  laboratories  in  which  proceed  a 
whole  series  of  chemical  and  osmotic  changes  which  determine  the  production 
of  the  fully  formed  secretion  directly  from  the  protoplasm  and  indirectly 
from  the  ordinary  constituents  of  the  surrounding  lymph. 


DIGESTION  IN  THE  MOUTH 


717 


i 


Fig.  3i~.     Submaxillary  gland  of  rabbit. 
(Schafeb after  E.  MOller.) 
The  cells,  all  serous,  are  in  different  functional 
states:  o,  a  loaded  cell;  b,  a  discharged  cell;  c,  a 
secretory  canaliculus  penetrating  into  a  cell. 


From  an  examination  of  the  stained  specimens  of  glands  the  following 
stages  in  the  production  of  secretion  have  been  described  : 

(1)  In  the  neighbourhood  of  the  nucleus,  and  probably  with  its  active 
co-operation,  a  differentiation  of  the  protoplasm  occurs  with  the  production 
in  most  cases  of  a  basophile 
substance  which  in  hardened 
specimens  generally  takes  the 
appearance  of  filaments.  Since 
these  filaments  are  sometimes 
regarded  as  the  working  part 
of  the  protoplasm,  they  have 
been  given  the  name  of  ergas- 
loplasm  (Fig.  313,  c  and  e). 

(2)  By  a  modification  of 
the  ergastoplasm  granules  are 
formed.  After  their  first 
appearance  these  granules 
undergo  gradual  modification, 
as  is  shown  by  the  fact  that 
the  staining  reactions  of  the 
granules  near  the  base  of  the 
cell  differ  from  those  of  the  granules 
at  the  free  margin. 

(3)  When  the  secretion  is  ex- 
•cited,  the  fully  formed  granules 
take  up  water  and  salts  in  vary- 
ing proportions,  swell  up,  and 
discharge  their  contents  into  the 
lumen  of  the  alveolus  as  the 
secretion  proper  to  the  gland. 

ELECTRICAL   CHANGES 

Every  localised  chemical  change 
in  a  system  permeated  by  electro- 
lytes must  give  rise  to  electrical 
differences     of     potential.      It     is 

therefore  natural  that  electrical  changes  should  accompany  the  intense 
chemical  activity  which  is  associated  with  secretion.  The  interpretation  of 
these  changes  is  difficult,  owing  to  the  simultaneous  operation  of  another 
factor  which  may  .determine  electrical  differences  of  potential,  namely, 
the  movement  of  fluids  through  porous  membranes.  If  the  hilum  of 
the  "submaxillary  gland  and  its  outer  surface  be  connected  with  a 
galvanometer,  a  resting  difference  of  potential  is  nearly  always  found, 
generally  in  such  a  direction  that  the  outer  surface  is  positive  to  the 
hilum.  The  current  through  the  gland  is  therefore  from  within  out.  On 
exciting  the  chorda  tympani  nerve  a  diphasic  effect  is  generally  obtained, 


Fig.  343.  Celis  of  pancreas,  showing  suoees 
Bive  itages  in  activity,  l,b,c,d.  a,  resting; 
D,  discharged  gland.     (Mathews.) 


718  PHYSIOLOGY 

the  resting  difference  being  first  increased  and  later  on  diminished.  On 
excitation  of  the  sympathetic  nerve  we  generally  obtain  a  purely  negative 
variation  of  the  resting  difference.  These  results  were  interpreted  by 
Bayhss  and  Bradford  as  due  to  the  co-operation  of  the  two  factors,  chemical 
change  in  the  gland  cells  and  movement  of  fluid  through  the  cells.  The 
positive  variation,  i.  e.  the  current  from  within  out,  was  ascribed  to  the 
movement  of  fluid,  whereas  the  negative  variation  of  the  resting  difference 
was  thought  to  be  due  to  the  chemical  changes  in  the  gland  cells. 


THE   SIGNIFICANCE   OF   THE   DOUBLE   NERVE   SUPPLY 
TO    THE    GLANDS 

According  to  Heidenhain,  although  the  parotid  gland  gives  little  or  no  secretion 
on  stimulation  of  the  sympathetic  nerve,  prolonged  stimulation  of  this  nerve  causes 
histological  changes  in  the  gland  even  more  marked  than  those  produced  by  the  cranial 
nerve.  Similar  histological  changes  were  found  by  him  in  the  submaxillary  gland. 
He  was  therefore  led  to  put  forward  the  hypothesis  that  the  salivary  glands  are  supplied 
by  two  fundamentally  different  classes  of  fibres,  namely:  (1)  trophic  fibres,  which 
determine  the  chemical  changes  in  the  gland  responsible  for  the  production  of  the 
specific  constituents  of  the  secretion,  and  (2)  secreto-motor  fibres,  excitation  of  which 
causes  the  cells  to  take  up  water  and  salts  from  the  lymph  and  blood,  and  pass  them 
in  large  quantities  into  the  duct.  According  to  this  view  the  sympathetic  nerve 
supply  to  the  gland  would  consist  almost  entirely  of  trophic  fibres,  whereas  secreto- 
motor  fibres  would  predominate  in  the  cranial  nerve  supply.  The  action  of  atropine 
would  appear  at  first  sight  to  favour  tins  hypothesis.  In  minute  doses  it  entirely 
annuls  the  action  of  the  chorda  tympani  nerve  or  the  corresponding  nerve  to  the  parotid, 
while  it  is  without  effect  on  the  sympathetic  nerve  supply  unless  given  in  huge  doses. 
The  preponderating  effect  of  the  sympathetic  on  the  histological  structure  of  the  gland- 
cells  has  not  been  confirmed  by  later  observers,  and  the  varying  effects  of  atropine  on 
the  two  sets  of  nerve  fibres  may  be  conch tioned  by  morphological  rather  than  by 
functional  differences  between  their  nerve  endings.  According  to  Langley  and  Carlson, 
the  difference  in  the  action  of  the  chorda  tympani  and  of  the  sympathetic  on  the  sub- 
maxillary gland  is  due  to  the  synchronous  action  of  these  nerves. on  the  blood  supply 
to  the  gland,  the  sympathetic  causing  vaso-constriction,  while  the  chorda  tympani 
causes  vaso-dilatation.  In  confirmation  of  this  explanation  they  have  shown  that 
clamping  the  carotid  artery  during  chorda  stimulation  diminishes  the  amount  of  saliva 
secreted  but  increases  the  percentage  of  solids  in  the  fluid.  Tins  theory  is  however 
inadequate  to  explain  the  differences  observed  in  the  secretion  of  saliva  reflexly  aroused 
by  introduction  of  substances  into  the  mouth.  In  a  dog  with  a  permanent  submaxillary 
fistula  a  copious  flow  of  saliva  may  be  caused  by  the  introduction  of  025  per  cent,  hydro- 
chloric acid  or  of  meat  powder.  The  amount  of  saliva  secreted  under  the  two  circum- 
stances is  approximately  the  same,  but  that  evoked  by  the  introduction  of  meat  powder 
contains  about  twice  as  much  solid  contents  as  that  which  follows  the  introduction  of 
acid  into  the  mouth.  Babkin  has  shown  that  the  same  differences  are  found  after 
complete  section  of  the  sympathetic  and  that  there  is  the  same  acceleration  of  the 
circulation  through  the  gland  whether  the  secretion  is  aroused  by  introduction  of 
meat  powder  or  of  acid.  It  is  impossible  therefore  to  explain  the  difference  in  the 
composition  of  the  saliva  obtained  under  these  two  circumstances  as  due  to  differences 
in  the  blood  supply  to  the  gland,  and  we  must  conclude  either  that  the  chorda  tympani 
contains  different  kinds  of  fibres  which  are  excited  to  varying  extent  according  to  the 
nature  of  the  reflex  stimulations,  or  that  one  and  the  same  nerve  fibre  can  convey 
specifically  different  impulses.  The  latter  explanation  would  not  be  in  accord  with 
the  generally  accepted  ^fuller's  law  of  specific  irritability,  but  is  the  explanation  to 
which  Babkin  himself  inclines.  At  any  rate  it  is  certain  that  according  to  the  nature 
of  the  reflex  stimulus  either  the  secretion  of  water  and  salts  or  the  secretion  of  organic 


DIGESTION  IN  THE  MOUTH  719 

solids  may  preponderate,  altogether  apart  from  changes  in  the  circulation  simultaneously 
evoked. 

THE   ENERGY   INVOLVED   IN   THE   ACT   OF   SECRETION 

The  source  of  the  energy  must  be  sought  in  the  processes  of  oxidation 
occurring  in  the  cells  of  the  gland,  and  Barcroft  has  attempted  to  determine 
the  total  amount  of  energy  put  out  by  the  gland  in  the  act  of  secretion 
by  measuring  its  respiratory  exchanges  under  the  conditions  of  rest  and 
activity.  He  found  that  the  resting  submaxillary  gland  in  a  small  dog  took 
up  0-25  c.c.  of  oxygen  per  minute  and  put  out  0-17  c.c.  C02,  while  during 
active  secretion  it  absorbed  0'86  c.c.  02  and  gave  off  0-39  c.c.  C02.  Assum- 
ing that  the  total  oxygen  taken  up  is  employed  hi  the  oxidation  of  a  food 
substance,  such  as  glucose,  and  that  the  whole  of  the  energy  of  the  chemical 
changes  is  set  free  in  the  form  of  heat,  we  find  that  a  resting  gland  weighing 
about  six  grammes  produces  about  1-1  calories  per  minute.  We  know 
however  that  a  certain  amount  of  external  work  is  performed  in  the  secretion 
of  a  saliva  containing  less  salts  than  the  original  blood,  and  also,  when  there 
is  any  resistance  to  the  flow  of  saliva  through  the  duct,  in  raising  the  hydro- 
static pressure  of  the  saliva  in  the  duct  to  a  height  greater  than  that  in  the 
blood  capillaries. 

Can  we  from  all  these  data  form  a  conception  of  the  total  changes 
occurring  in  the  gland  and  involved  in  the  formation  of  the  secretion  ?  Even 
during  rest,  changes  are  going  on  in  the  gland  cells,  changes  which  involve 
the  taking  up  of  food  material  and  its  assimilation  under  the  influence  of 
the  nucleus,  perhaps  into  the  nucleus  itself,  and  certainly  into  the  undifferen- 
tiated cytoplasm.  In  this  cytoplasm  a  further  change  occurs,  leading  to  its 
transformation  into  granules.  When  activity  is  excited  by  the  stimulation  of 
secretory  nerves,  the  primary  change  appears  to  involve  simply  the  granules. 
These  structures  must  absorb  water,  apparently  against  osmotic  pressure. 
Those  nearest  the  lumen  swell  up,  become  converted  into  spheres  containing 
water  and  salts  in  smaller  proportion  than  exists  in  the  lymph  bathing 
the  cells  (and  presumably  in  the  protoplasm  surrounding  the  granules),  and 
in  this  swollen  form  are  discharged  or  ruptured  on  the  periphery  of  the  cell 
into  the  lumen,  so  giving  rise  to  secretion.  This  discharge  of  a  fluid  with 
a  smaller  molecular  concentration  than  the  cell  or  surrounding  blood  plasma 
must  lead  to  an  increased  concentration  in  the  remaining  parts  of  the  cell. 
The  increased  concentration  would  naturally  induce  a  flow  of  water  from 
lymph  into  cell,  and  the  consequent  concentration  of  the  lymph  would  in  the 
same  way  cause  a  flow  of  water  from  blood  to  lymph.  This  pull  of  water  by 
the  cell  from  the  blood  is  still  further  increased  in  another  way.  The  act 
of  secretion,  involving  as  it  does  the  expenditure  of  energy,  can  be  carried  out 
only  at  the  expense  of  chemical  changes  in  the  cell.  These  chemical  changes. 
as  in  all  other  metabolic  processes  of  the  body,  will  result  in  the  formation  of 
a  number  of  small  molecules  from  the  great  colloid  molecules  of  the  proto- 
plasm. The  products  of  metabolism,  or  metabolites,  will  therefore  accumulate 
in  the  cell,  pass  into  the  lymph,  and  increase  the  concentration  of  the  latter. 
The  increased  concentration  will  call  forth  an  increased  transudation  of 


720  PHYSIOLOGY 

fluid,  e.g.  water,  from  the  blood  vessels,  and  the  transudation  thus  evoked 
will  be  greater  than  that  necessary  to  provide  I  In1  water  of  the  saliva,  and 
will  therefore  produce  a  distention  of  the  lymphatic  spaces  of  the  gland  and 
an  increased  discharge  of  lymph  along  its  efferent  lymphatics.  As  a  second- 
ary result  of  the  activity,  perhaps  in  consequence  of  the  removal  of  the 
products  of  the  resting  metabolism  of  the  gland,  there  is  increased  growth  of 
protoplasm,  increased  activity  of  the  nucleus,  and  therefore  a  tendency  to 
increased  assimilatory  changes  and  a  preparation  of  the  cell  for  further 
secretory  changes  either  immediately  or  hereafter. 

In  the  gland  as  in  muscle,  when  we  attempt  to  form  a  conception  of  the  mechanism 
of  the  chemical  machine  in  the  living  cell,  we  are  brought  up  against  insuperable 
difficulties.  One  might  perhaps  conceive  of  the  secretory  granules  being  bounded  by 
a  membrane  impermeable  to  intermediate  metabolites  and  salts,  but  permeable  to 
carbon  dioxide.  If  the  lirst  effect  of  stimulation  of  the  secretory  nerves  were  to  pro- 
duce an  explosive  disintegration  of  the  complex  molecules  making  up  the  granules, 
we  should  have  a  sudden  multiplication  of  molecules  within  the  granules.  This  would 
cause  a  large  rise  of  the  osmotic  pressure  in  these  granules  and  the  consequent  absorp- 
tion of  water  from  the  surrounding  protoplasm.  This  process  however  could  only 
result  in  the  production  of  a  fluid  in  the  granules  having  the  same  osmotic  pressure 
as  the  surrounding  medium,  whereas  we  know  that  saliva  has  a  molecular  concen- 
tration which  is  only  one-half  that  of  the  blood  or  lymph.  We  should  therefore 
have  to  make  a  second  assumption,  namely,  that,  before  the  extrusion  of  the  solution 
from  the  granules,  there  is  a  further  breakdown  of  the  metabolites  by  a  process  of 
oxidation,  with  the  production  of  carbon  dioxide  which  diffuses  into  the  surrounding 
protoplasm.  We  have  however  no  evidence  of  either  of  these  processes  or  for  any 
of  these  assumptions,  and  I  have  only  adduced  them  in  order  to  show  how  far  we  are 
still  from  the  actual  comprehension  of  the  events  occurring  in  every  living  cell,  and 
underlying  its  conditions  of  rest  and  activity. 


SECTION  II 


THE    PASSAGE    OF    FOOD    FROM   THE    MOUTH 
TO    THE    STOMACH 

The  food  after  mastication  is  carried  to  the  stomach  by  a  complex  series 
of  co-ordinated  movements  involving  the  muscles  of  the  pharynx  and 
the  oesophagus  (Fig.  341).  Various 
methods  have  been  used  to  study 
the  process  of  deglutition  in  man 
and  the  higher  animals.  Important 
information  can  be  obtained  by 
allowing  a  man  or  animal  to  swallow 
either  a  fluid  or  solid  with  which 
bismuth  is  mixed,  and  observing  the 
passage  of  the  opaque  substance 
under  the  Kontgen  rays.  The  sub- 
nitrate  of  bismuth  may  be  mixed 
with  milk  for  a  fluid  or  with  bread 
and  milk  for  a  semi-solid  substance, 
or  may  be  enclosed  in  a  cachet  and 
swallowed  as  a  solid  bolus.  The 
time  of  entry  of  the  food  into  the 
stomach  may  be  determined  by  aus- 
cultating with  a  stethoscope  over  the 
region  of  the  car,diac  orifice.  Since 
a  certain  amount  of  air  is  always 
swallowed  at  the  same  time  as  the 
food,  the  escape  of  this  air  through 
the  small  cardiac  orifice  gives  rise 
to  a  bubbling  noise  which  can  be 
easily  heard.  In  the  horse  the  move- 
ment of  a  bolus  down  the  oesophagus 
can  be  seen  or  felt  from  the  outside 
of  the  neck.  The  relative  time- 
relations  of  the  events  at  different 
parts  of  the  oesophagus  may  be 
obtained  by  passing  sounds  provided  with  rubber  balloons  to  different 
levels  in  the  tube  and  connecting  these  sounds  with  recording  tambours 
46  721 


Fig.  344.  Dissection  to  show  muscles 
employed  iu  deglutition. 
b,  styloid  process,  from  which  ariso  I,  the 
styloglossus ;  2,  the  stylohyoid ;  3,  the  stylo- 
pharyngeal muscles  ;  c,  section  of  lower  jaw ; 
d,  hyoid  bone;  e,  thyroid  cartilago;  </.  isth- 
mus of  thyroid  gland ;  4,  cut  edge  of  mylo- 
hyoid muscle;  5,  6,  7,  8,  muscles  of  tongue; 
9,  10,  11,  superior,  middle,  and  inferior 
constrictors  of  pharynx;  12,  oesophagus. 
(Allen  Thomson.) 


722  PHYSIOLOGY 

or  piston  recorders.  This  method  has  been  employed  both  in  men  and 
in  animals. 

When  a  mouthful  of  water  is  taken  two  sounds  may  be  heard  on  ausculta- 
ting over  the  oesophagus.  The  first  sound  immediately  follows  the  beginning 
of  the  act  of  swallowing  and  is  probably  due  to  the  impact  of  the  fluid 
against  the  posterior  pharyngeal  wall,  brought  about  by  the  sudden  con- 
traction of  the  mylohyoid  and  other  muscles  which  throw  the  fluid  from  the 
back  of  the  tongue  across  the  pharynx.  The  second  sound  is  heard  best  by 
listening  over  the  epigastrium.  It  begins  from  four  to  ten  seconds  after  the 
first  sound,  and  lasts  for  two  or  three  seconds.  The  interval  between  the 
two  sounds  is  not  constant,  and  may  vary  in  the  same  individual.  If  the 
observation  be  carried  out  on  a  man  lying  on  his  back,  the  trickling  second 
sound  is  changed  into  a  series  of  sounds  which  have  been  described  as  squirts, 
which  vary  from  two  to  five  in  number,  each  lasting  about  one  second.  The 
second  sound  may  be  absent  when  a  solid  bolus  is  swallowed.  On  observing 
the  process  by  Rontgen  rays,  very  much  the  same  time-relations  are  obtained. 
If  a  mouthful  of  milk  mixed  with  bismuth  carbonate  be  swallowed,  it  will 
be  seen  passing  rapidly  down  the  oesophagus  to  the  cardiac  orifice  of  the 
stomach.  Here  the  passage  becomes  slow,  and  the  fluid  escapes  slowly  in  a 
narrow  stream  into  the  stomach.  The  average  time  which  elapses  between 
the  beginning  of  deglutition  and  the  disappearance  of  the  last  trace  of  fluid 
from  the  oesophagus  is  about  six  seconds.  The  same  course  of  events  is 
induced  when  the  food  swallowed  is  semi-solid.  If  however  the  bolus  be 
dry,  such  as  a  cachet  of  bismuth  carbonate,  it  may  pass  down  the  oesophagus 
with  extreme  slowness  and  may  take  as  much  as  fifteen  minutes  to  reach  the 
cardiac  orifice,  although  the  individual  who  has  swallowed  it  is  quite  unaware 
of  its  continued  presence  in  the  oesophagus.  If,  as  would  normally  be  the 
case,  the  cachet  be  well  moistened  with  saliva  or  water  before  swallowing, 
it  passes  much  more  rapidly,  the  total  time  taken  being  between  eight  and 
eighteen  seconds. 

It  has  been  customary  since  the  time  of  Magendie  to  divide  the  act  of 
swallowing  into  three  stages  :  during  the  first  the  bolus  of  food  is  carried 
past  the  anterior  pillars  of  the  fauces;  during  the  second  through  the 
pharynx,  past  the  openings  of  the  nasal  cavities  and  of  the  larynx;  and 
during  the  third  through  the  oesophagus  into  the  stomach.  There  is  how- 
ever no  pause  between  these  various  stages.  The  act  of  deglutition  is  one, 
and  the  initiation  of  the  first  stage  inevitably  involves  the  completion  of  the 
third.  The  food  is  masticated,  and  is  collected  as  a  bolus  on  the  dorsum 
of  the  tongue.  A  pause  then  takes  place  in  the  movements  of  mastication, 
a  slight  movement  of  the  diaphragm  usually  occurs  known  as  '  respiration  of 
swallowing,'  and  then  a  sudden  elevation  of  the  tongue  throws  the  bolus  back 
through  the  anterior  pillars  of  the  fauces.  In  this  movement  the  chief 
factor  is  the  contraction  of  the  mylohyoid  muscle,  which  presses  the  tongue 
against  the  palate  and  pushes  it  backwards.  The  backward  movement  of 
the  tongue  may  also  be  aided  by  the  contraction  of  the  styloglossus  and 
palatoglossus  muscles  which  pull  the  base  of  the  tongue  suddenly  backwards. 


PASSAGE  OF  FOOD   FROM  MOUTH  TO  STOMACH        723 

These  muscles,  especially  the  palatoglossi,  serve  to  close  the  isthmus  faucium, 
thus  preventing  any  return  of  the  food  towards  the  mouth. 

As  the  food  is  passing  through  the  upper  part  of  the  pharynx,  it  traverses 
a  region  common  to  the  respiratory  as  well  as  the  digestive  passages.  Its 
passage  through  this  region  is  therefore  rapid,  and  is  associated  with  a 
closure  of  the  two  openings  of  the  air  passages  into  the  pharynx.  The  nasal 
cavity  is  shut  off  by  a  simultaneous  contraction  of  the  levator  palati  and 
palato-pharyngeal  muscles  and  azygos  uvulae,  by  which  means  the  soft 
palate  is  raised  (Fig.  345)  and  the  posterior  pilars  are  approximated  to  the 


Fig.  345.     Diagram  (after  Tioerstedt)  to  show  the  position  of  the  soft  palato. 
I,  daring  rost;  II,  during  the  act  of  swallowing. 

uvula.    The  upper  and  back  wall  of  the  palate  is  thus  formed  into  a  tense 
sloping  roof  which  guides  the  bolus  down  the  pharynx. 

More  important  is  the  shutting  off  of  the  lower  air  passages.  The  con- 
traction of  the  mylohyoid  muscles,  which  initiates  deglutition,  is  followed 
almost  immediately  (at  an  interval  of  0-47  sec.)  by  an  elevation  of  the  larynx, 
and  this  elevation  is  accompanied  by  closure  of  the  glottis  as  well  as  of  the 
superior  opening  of  the  larynx.  The  laryngeal  opening  is  bounded  in  front 
by  the  epiglottis,  behind  by  the  tips  of  the  arytenoid  cartilages,  and  at  the 
sides  by  the  aryteno-epiglottidean  folds.  When  deglutition  takes  place  the 
arytenoid  cartilages,  which  normally  lie  against  the  posterior  wall  of  the 
pharynx,  are  rotated  and  move  inwards  and  forwards,  so  that  the  laryngeal 
opening  assumes  the  form  of  a  tri-radiate  fissure,  the  vertical  hmb  being 
short,  while  the  transverse  limb  is  rounded  owing  to  the  pulling  inwards  of  the 
margins  of  the  epiglottis.  At  the  same  time  both  the  true  and  false  vocal 
cords  come  together,  while  the  movement  of  the  dorsum  of  the  tongue 
backwards  enables  the  closed  laryngeal  orifice  to  lie  directly  under  the  back 
part  of  the  tongue.    The  muscles  which  are  actively  involved  in  this  closure 


724 


PHYSIOLOGY 


of  the    lower  air    passages  are  the  external   thyroarytenoid,   arytenoid; 

.aj^epiglottidean,  and  the  lateral  crico-arytcnoid  muscles.  Since  the 
approximation  of  the  posterior  to  the  anterior  boundary  of  the  laryngeal 
opening  is  only  rendered  possible  by  the  elevation  of  the  whole  larynx  under 
the  hyoid  bone,  the  act  of  deglutition  cannot  be  carried  out  unless  the  larynx 
is  free  to  move. 

The  two  openings  from  the  back  of  the  pharynx  into  the  air  passages 
being  thus  closed,  the  bolus  is  shot  rapidly  past  them  into  the  region  of  the 
middle  and  inferior  constrictors  of  the  pharynx.  If  the  bolus  be  liquid  or 
semi-fluid,  the  movement  of  the  back  part  of  the  tongue  may  be  sufficient  to 
propel  the  substance  past  the  constrictors  through  the  lax  oesophagus  to  its 
lower  end.  It  is  on  this  account  that,  when  corrosive  fluids  are  swallowed 
by  accident,  we  very  often  find  the  damage  to  the  oesophagus  limited 
to  the  three  points  where  it  is  narrowed  and  there  is  a  slight  hindrance 
to  the  onward  flow  of  fluid.  If  the  bolus  be  large  and  solid  or 
senii-solid,  it  is  seized  in  the  grasp  of  the  middle  constrictors  on  passing 
through  the  upper  part  of  the  pharynx,  and  is  thrust  by  successive  con- 
tractions of  this  muscle  and  of  the  inferior  constrictor  gradually  down  the 
oesophagus.  The  walls  of  the  cervical  part  of  the  oesophagus  are  composed 
of  striated  muscle.  In  the  thorax  striated  and  unstriated  muscles  are  asso- 
ciated together,  while  the  lower  third,  in  the  neighbourhood  of  the  stomach, 
consists  almost  entirely  of  unstriated  muscle.  Corresponding  to  these 
differences  in  structure,  Kronecker  and  Meltzer  have  found  differences  in  the 
duration  and  rapidity  of  propulsion  of  the  contractional  waves  in  each  part. 
The  following  Table  shows  the  time-relations  of  the  chief  muscles  engaged 
in  deglutition  as  determined  by  Kronecker  and  Meltzer  and  by  Marckwald  : 


Time  from 
commencement 

Interval 

Muscle  movement 

Duration  of 
contraction 

- 

- 

Mylohyoid 

0-6  sec. 

- 

0-03  sec. 

Respiration  of  swallowing 

- 

- 

0-07  sec. 

Elevation  of  larynx 

0-8  sec. 

03  sec. 

0-2  sec. 

Constrictors  of  pharynx 

1-0  to  20  sec. 

- 

0-9  sec. 

First  section  of  oesophagus 

2-0  to  2-5  sec. 

3-0  sec. 

1-8  sec. 

Second  section  of  oesophagus 

60  to  7-0  sec. 

6'0  sec. 

3-0  sec. 

Third  section  of  oesophagus 

about  .10  sec. 

The  free  passage  of  food  down  the  oesophagus  under  the  influence  of  the 
propulsive  force  exercised  by  the  mylohyoid  muscles  shows  that  the  walls 
of  this  tube  must  be  lax,  and  in  fact  one  must  assume  that  the  first  act  of 
deglutition,  so  far  as  concerns  the  oesophagus,  is  an  inhibition  initiated 


PASSAGE   OF  FOOD  FROM  MOUTH  TO  STOMACH        725 

reflexly  with  the  beginning  of  the  act  of  deglutition.  When  a  second  act 
of  deglutition  succeeds  the  first  with  a  sufficiently  short  interval,  the  reflex 
inhibition  due  to  the  second  act  may  prevent  the  development  of  any  wave 
of  contraction  in  the  oesophagus.    This  tube  thus  remains  in  a  lax  condition 


Fig.  340.  Curves  obtained  during  swallowing  by  placing  two  rubber  balloon?,  ono 
(the  upper  curve)  in  the  pharynx,  the  other  (lower  curve)  in  the  oesophagus. 
(Kronecker  and  Meltzer.) 

In  A  the  second  balloon  was  4  cm. ;  in  B  12  cm. ;  and  in  c  16  cm.  from  the 
upper  end  of  the  oesophagus.  In  each  curve  it  will  be  noticed  that  the  excursion 
of  the  upper  lever  is  followed  immediately  by  an  excursion  of  tho  lower  lever 
(due  to  passage  of  the  swallowed  fluid  and  transmitted  riso  of  pressure),  and 
then,  after  an  interval  of  timo  varying  with  the  distance  between  the  balloons, 
by  another  rise  due  to  tho  peristaltic  contraction  of  the  wall  of  the  oesophagus. 

and  allows  the  free  rapid  passage  of  the  food  downwards  until  the  movements 
of  deglutition  have  come  to  an  end,  when  a  peristaltic  contraction  occurs  and 
sweeps  all  remaining  adherent  particles  of  food  into  the  stomach.  The 
circular  fibres  of  the  lower  end  of  the  oesophagus  which  form  the  cardiac 
sphincter  of  the  stomach  are  normally  in  a  state  of  tonic  contraction.  When 
one  mouthful  of  food  is  swallowed,  it  may  be  either  squirted  directly  into  the 
stomach,  or  may  remain  at  the  lower  end  of  the  oesophagus  until  the  following 


72G 


PHYSIOLOGY 


peristaltic  wave  forces  it  through  the  orifice.  When  several  acts  of  deglu- 
tition succeed  one  another,  the  cardiac  sphincter  shares  in  the  inhibition 
of  the  oesophageal  walls,  and  offers  no  resistance  to  the  direct  propulsion 
of  food  from  the  mouth  to  the  stomach. 

Cannon  has  shown  that  the  relaxation  of  the  cardiac  orifice  which 
accompanies  swallowing  extends  also  to  the  cardiac  end  of  the  stomach. 
This  relaxation  lowers  tho  pressure  within  the  stomach,  and  makes  room  for 
the  incoming  food. 

If  the  stomach  be  filled  with  a  fluid  such  as  starch  solution,  the  cardiac 
sphincter  may  be  seen  to  relax  rhythmically,  allowing  of  the  regurgitation  of 


Fig.  347.     Tracings  of  respiratory  movements  to  show  the  effect  of  stimulating  the 

central  end  of  the  glossopharyngeal  nerve.     (Makckwald.) 

The  point  of  stimulation  is  marked  with  a  cross.     Note  that  the  stoppage 

may  occur  at  any  phase  of  the  respiratory  movement. 

the  stomach  contents  into  the  lower  part  of  the  oesophagus.  Their  entry 
into  this  tube  is  at  once  followed  by  a  peristaltic  contraction  of  this  part  of  the 
oesophagus  (apparently  entirely  unconscious),  which  drives  the  fluid  back 
into  the  stomach.  These  movements  of  regurgitation  become  more  and 
more  infrequent  as  the  gastric  contents  become  acid,  and  are  not  observed 
at  all  if  the  stomach  be  filled  with  a  fluid  already  acid.  This  phenomenon 
has  been  spoken  of  as  the  '  acid  control  of  the  cardia.' 


THE   NERVOUS   MECHANISM   OF   DEGLUTITION 

Deglutition  is  a  reflex  act.  When  we  swallow  voluntarily  we  supply  the 
necessary  initial  stimulus  either  by  touching  the  fauces  with  the  tongue  or 
by  forcing  a  certain  amount  of  saliva  into  the  fauces.  The  afferent  channels 
of  the  reflex  are  contained  in  the  second  division  of  the  fifth  nerve,  the  glosso- 
pharyngeal nerve,  and  the  pharyngeal  branches  of  the  superior  laryngeal 
nerve.  We  can  excite  a  single  act  or  a  whole  series  of  acts  of  deglutition  by 
electrical  stimulation  of  the  central  end  of  the  last-named  nerve.  The 
efferent  fibres  which  determine  the  contraction  of  muscles  engaged  in  the 
act  of  deglutition  travel  by  the  hypoglossal  nerve  to  the  muscles  of  the 


PASSAGE  OF  FOOD  FROM  MOUTH  TO  STOMACH        727 

tongue,  by  the  fifth  to  the  mylohyoid,  by  the  glossopharyngeal,  the  vagus, 
and  the  spinal  accessory  nerves  to  the  muscles  of  the  fauces  and  pharynx. 
The  closure  of  the  larynx  is  effected  by  impulses  which  travel  through  the 
superior  and  inferior  laryngeal  branches  of  the  vagus.  The  centre  for  the 
act  is  situated  in  the  medulla  oblongata,  and  can  be  considered  as  consisting 
of  a  chain  of  centres  stimulation  of  one  of  which  involves  the  firing  off  of  all 
the  others  in  orderly  sequence.  Thus,  as  Meltzer  has  shown,  the  propulsion 
of  the  contraction  down  the  oesophagus  is  determined  by  the  intracentral 
nervous  connections,  and  does  not  require  the  integrity  of  the  muscular  tube 
itself.  If  the  oesophageal  nerves  be  divided,  the  act  of  deglutition  is 
abolished,  the  upper  part  of  the  oesophagus  becoming  permanently  relaxed, 
while  the  lower  part,  including  the  cardiac  sphincter,  enters  into  a  state  of 
tonic  contraction.  On  the  other  hand,  the  oesophagus  may  be  ligatured  or 
cut  across  without  interfering  with  the  propulsion  of  the  wave  of  contrac- 
tion, started  in  the  pharynx,  from  one  end  of  the  tube  to  the  other. 
Stimulation  applied  to  the  mucous  surface  of  the  oesophageal  tube  is 
without  effect. 

There  is  an  important  interdependence  between  the  functions  of  respira- 
tion and  deglutition.  If  an  inspiratory  or  expiratory  movement  were 
going  on  during  the  act  of  deglutition,  food  might  be  drawn  into  the  lungs 
or  driven  into  the  nasal  cavities.  Such  an  accident  is  prevented  by  the 
fact  that  every  act  of  swallowing  inhibits  a  respiratory  movement.  This 
inhibition  is  effected  reflexly  through  the  glossopharyngeal  nerve.  Stimula- 
tion of  the  central  end  of  this  nerve  at  once  causes  cessation  of  respiration 
in  whatever  phase  it  may  happen  to  be  (Fig.  347).  This  cessation  lasts  for 
five  or  six  seconds,  i.  e.  a  sufficient  length  of  time  for  a  whole  series  of  acts 
of  deglutition.  Respiration  then  recommences,  and  the  inhibition  cannot  be 
prolonged  by  continuing  the  stimulation  of  the  glossopharyngeal  nerve.  This 
inhibition  of  the  activity  of  the  respiratory  centre  can  be  shown  on  oneself. 
If  the  breath  be  held  until  the  feeling  of  dyspnoea,  i.  e.  the  need  to  breathe, 
becomes  insistent,  relief  is  at  once  experienced  by  swallowing,  and  the  feeling 
of  relief  will  last  for  three  or  four  seconds. 


SECTION  III 

DIGESTION    IN    THE    STOMACH 

GASTRIC   JUICE 

Within  five  minutes  of  the  taking  of  food  into  the  mouth,  a  secretion  of 
gastric  juice  begins  from  the  multitude  of  tubular  glands  which  make  up  the 
greater  part  of  the  mucous  membrane  of  the  stomach.  As  the  food,  masti- 
cated and  thoroughly  mixed  with  saliva,  is  swallowed  in  successive  portions, 
it  accumulates  in  a  mass  in  the  fundus  of  the  stomach,  and  the  mass  thus 
formed  is  penetrated  with  difficulty  by  the  juice  which  is  continually  being 
poured  out  by  the  walls  of  the  stomach,  so  that  salivary  digestion  can  be 
continued  for  a  considerable  time. 

The  gastric  juice,  which  is  so  poured  out,  can  be  obtained  in  various 
ways,  most  of  them  yielding  it  mixed  more  or  less  with  the  foodstuffs.  In 
clinical  practice  it  is  the  custom  to  give  a  definite  meal,  and  then  at  a  given 
interval  after  the  meal  to  wash  out  the  stomach,  so  obtaining  a  mixture  of 
gastric  juice  and  partially  digested  food. 

A  method  of  obtaining  the  juice  in  a  perfectly  pure  condition  has  been 
devised  by  Pawlow.  A  case  had  been  previously  described  by  Richet  in 
which,  as  the  result  of  the  accidental  taking  of  a  corrosive  alkali,  the 
oesophagus  had  become  occluded  by  the  cicatrisation  of  the  ulcer  pro- 
duced. In  order  to  preserve  the  individual  from  starvation,  it  was  neces- 
sary to  perform  gastrostomy,  i.  e.  to  make  an  artificial  opening  into  the 
stomach  through  which  he  could  be  fed.  Although  in  this  patient  the 
passage  of  the  saliva  from  mouth  to  stomach  was  completely  prevented,  it 
was  observed  that  merely  taking  food  into  the  mouth  was  followed  by  the 
secretion  of  gastric  juice.  Pawlow  produced  this  condition  artificially  in 
dogs.  The  oesophagus  was  divided  and  the  two  ends  brought  to  the  surface 
of  the  neck.  At  the  same  time  an  opening  was  made  into  the  stomach.  The 
animals  could  be  fed  either  through  the  opening  of  the-  oesophagus  in  the 
neck,  or  with  solid  food  through  the  gastric  fistula.  They  could  eat  also 
and  swallow  food  as  usual,  but  the  food  thus  swallowed  simply  fell  out 
of  the  opening  in  the  neck  without  passing  into  the  stomach.  Under  these 
circumstances  it  is  found  that  the  talcing  of  food  is  quickly  followed  by  a 
secretion  of  gastric  juice,  which  can  be  collected  in  vessels  connected  with 
the  fistulous  opening.  If  taken  from  a  fasting  animal,  such  a  juice  is  per- 
fectly free  from  admixture  and  can  be  regarded  as  pure  gastric  juice.  It 
is  quite  clear,  strongly  acid,  without  smell.     It  contains  about  0-3  to  0-G 

72S 


DIGESTION  IN  THE  STOMACH  729 

per  cent,  total  solids;    it  contains  no  peptone,  but  traces  oi  protein.     The 
following  Table  represents  its  average  composition  : 

Hydrochloric  acid  .  .  .  0-46  to  0-58  per  cent. 

Chlorine         ....  0-49  „  0-62 

Total  solids    ....  0-43  „  0-60 

Ash 0-09  „  0-16 

If  the  juice  be  allowed  to  stand  in  the  ice  chest  for  a  day,  it  becomes  cloudy 
and  deposits  a  fine  granular  precipitate,  which  apparently  represents  the 
active  agent  of  the  juice  and  may  perhaps  be  regarded  as  pepsin  in  a  pure 
form. 

The  actions  of  gastric  juice  are  due  partly  to  the  acid,  partly  to  the 
combined  action  of  the  acid  and  the  ferments.  The  acid  of  the  gastric  juice, 
when  obtained  free  from  admixture,  is  entirely  hydrochloric  acid.  Dog's 
juice  contains  on  the  average  about  0-6  per  cent.  HC1;  human  gastric  juice 
probably  contains  less,  about  0-2  per  cent.  When  however  we  examine  the 
gastric  contents,  composed  of  a  mixture  of  gastric  juice  and  semi-digested 
food,  we  always  find,  besides  the  hydrochloric  acid,  other  acids  present, 
among  which  the  most  prominent  is  lactic  acid.  So  constantly  is  this  latter 
acid  present  that  it  was  formerly  thought  by  some  physiologists  to  be  the 
chief  acid  of  the  gastric  juice.  It  is  produced  by  processes  of  fermentation 
occurring  in  the  food.  Whenever  we  take  carbohydrates,  we  swallow  at  the 
same  time  micro-organisms,  and  these  in  the  warm  moist  mass  quickly 
attack  the  carbohydrates,  converting  them  into  sugar  and  then  into  lactic 
acid.  As  the  gastric  juice  gradually  soaks  into  the  food  and  renders  it  acid, 
it  stops  this  lactic  acid  fermentation,  so  that  whereas  in  the  early  stages  of 
gastric  digestion  both  acids  are  present  in  considerable  quantity,  towards 
the  end  of  gastric  digestion  lactic  acid  is  almost  entirely  absent. 

In  some  pathological  conditions  free  hydrochloric  acid  may  be  entirely  wanting  from 
the  gastric  juice,  and  the  detection  of  this  acid  in  gastric  juice  becomes  therefore  a 
matter  of  considerable  clinical  importance.  For  this  purpose  we  can  employ  various 
indicators,  which  change  colour  in  the  presence  of  a  free  strong  acid  such  as  HCI,  but 
are  unaffected  by  weak  acids  such  as  lactic  acids,  or  the  fatty  acids.  Chief  among 
these  indicators  are  Congo  red,  which  turns  blue  with  mineral  acids,  and  a  slaty  colour 
with  lactic  acid;  and  tropaolin  00,  which  turns  a  brilliant  red  in  the  presence  of  a  free 
mineral  acid,  but  is  unaltered  by  lactic  acid.  The  reagent  which  is  most  employed  is 
( Junzberg's  reagent.  This  is  a  mixture  of  phloroglucin  and  vanillin  dissolved  in  absolute 
alcohol.  A  drop  of  this  is  evaporated  to  dryness  in  a  porcelain  capsule.  A  drop  of 
the  fluid  suspected  to  contain  free  acid  is  then  added,  and  also  evaporated  to  dryness. 
If  free  HCI  be  present,  the  residue  on  drying  becomes  a  brilliant  red  colour,  an  effect 
which  is  not  produced  by  the  presence  of  free  lactic  or  free  fatty  acids. 

Great  stress  has  been  laid  on  the  determination  of  the  actual  amount  of 
free  H  ions  present,  and  for  this  purpose  the  acidity  of  gastric  juice  or  of 
digestive  mixtures  has  been  tested  by  determining  its  inverting  power  on 
cane  sugar,  or  its  power  to  hasten  the  saponification  of  ethyl  acetate.  The 
acidity  estimated  in  this  way  is  diminished  considerably  by  the  presence  of 
albumens,  and  still  more  by  the  presence  of  albumoses  or  peptones.  But 
it  does  not  seem  that  the  adjuvant  action  of  the  acid  on  the  proteolytic 


730  PHYSIOLOGY 

powers  of  the  gastric  ferment  is  in  any  way  affected  by  the  diminution  of 
its  acidity  caused  by  the  presence  of  peptone.  The  coloured  indicators 
mentioned  above  however  serve  as  trustworthy  guides  to  the  amount  of 
free  acid  present,  considered  with  regard  to  its  digestive  functions. 

Iu  order  to  determine  quantitatively  the  amount  of  free  HC1,  the  following  pro- 
cedure is  employed  (Morner  and  Sjoqvist) :  Ten  cubic  centimetres  of  the  gastric  juice 
are  neutralised  with  barium  carbonate  (litmus  being  employed  as  an  indicator).  The 
mixture  is  dried  in  a  platinum  dish,  incinerated,  and  the  ash  extracted  with  warm  water 
and  filtered.  In  this  process  the  organic  acids  are  destroyed  and  converted  into  barium 
carbonate.  The  solution  therefore  contains  merely  the  barium  which  was  taken  up  to 
combine  with  the  free  HC1.  Estimation  of  the  barium  in  the  filtrate  gives  the  amount 
of  BaCl  present,  and  therefore  the  amount  of  hydrochloric  acid  in  the  gastric  juice. 
The  barium  is  determined  by  titrating  in  presence  of  sodium  acetate  and  acetic  acid 
with  potassium  bichromate  solution,  '  tetra  paper  '.being  used  as  an  indicator.  This 
turns  deep  blue  in  the  presence  of  free  bichromate  in  solution. 

THE   ACTIONS   OF   GASTRIC   JUICE   ON   FOODSTUFFS 

By  the  action  of  the  hydrochloric  acid  certain  changes  are  induced  in  the 
foodstuffs.  Cane  sugar  is  inverted  to  glucose  and  fructose ;  some  proteins, 
such  as  blood  fibrin,  are  swollen  up  to  form  a  jelly-like  mass.  The  caseinogen 
of  milk  is  precipitated,  the  collagen  of  the  connective  tissues  is  swollen  up. 
It  is  possible  that  a  certain  amount  of  hydrolysis  also  takes  place  in  the 
dextrins  and  maltose  produced  by  the  action  of  ptyalin  on  starch. 

The  chief  digestive  function  of  the  gastric  juice  is  dependent  on  the 
action  of  the  ferment  pepsin.  This  substance,  which  is  inactive  in  neutral 
medium,  needs  the  co-operation  of  an  acid,  hydrochloric  acid  being  the 
most  effective,  though  its  place  may  be  taken  by  phosphoric,  sulphuric, 
or  lactic  acid.  Its  main  effect  is  on  the  proteins  of  the  food.  The 
stages  in  its  action  may  be  best  studied  on  blood  fibrin.  If  fibrin  be 
immersed  in  04  per  cent,  hydrochloric  acid,  it  swells  up  to  a  gelatinous 
mass.  On  then  stirring  in  an  extract  of  gastric  mucous  membrane,  or 
any  preparation  of  pepsin,  the  gelatinous  mass  rapidly  undergoes  solution. 
If  the  mixture  be  boiled  and  neutralised,  immediately  after  solution  has 
occurred,  nearly  the  whole  of  the  protein  is  thrown  down  in  a  coagulated 
form.  The  first  effect  therefore  is  the  production  of  coagulable  soluble 
proteins  from  the  insoluble  fibrin.  If  the  action  be  allowed  to  proceed  for 
some  hours,  a  whole  series  of  products  of  hydrolysis  are  found  in  the  mixture. 
On  neutralising  the  fluid,  a  precipitate  may  be  thrown  down  consisting  chiefly 
of  acid  albumen.  The  greater  proportion  of  the  protein  remains  in  solution. 
This  remainder  may  be  purified  from  any  unaltered  coagulable  protein  by 
boiling  in  slightly  acid  solution  and  filtering.  The  filtrate  contains  a 
mixture  of  bodies  belonging  to  the  class  of  hydrated  proteins,  viz.  proteoses 
and  peptones. 

By  means  of  fractional  precipitation  with  ammonium  sulphate  or  zinc 
sulphate,  these  mixtures  can  be  subdivided  into  various  substances,  although 
in  no  case  can  we  be  certain  that  we  are  dealing" with'chemical  individuals. 
The  Table  on  p.  731  represents  the  chief  bodies  obtained  by  Pick  by  this 


DIGESTION  IN  THE  STOMACH 


731 


Lead 
sulphide 
reaction 

Present 

Very 
strong 

Present 

3 

St 

< 

- 

; 

Carbo- 
hydrate 
reaction 

Absent 

s 

Very 
strong 

Absent 

S 

s 

Indol 

formed 

by  fusion 

with  KHO 

Very 
weak 
Very 
strong 
Present 

*              1 

Weak 
Strong 

8 

"3  § 

If* 

3 

r 

8              S         5 

1 

MiUon's 
test 

Very 

weak 
Strong 

Present 

s.        : 

S         ! 

3 
< 

If 

3 

3 

< 

3 

p. 
a 

c 

5 

o 

1907 
18-69 
25-15 

21-07 

49 

33-23 
23-79 

so 
-1 

00 
X  ^ 

— *'  "IT 

to 

1-22 
121 

2-97 

0-80 

30- 

1-63 
1-21 

fc 

17-98 
17-66 
16-02 

17-86 
16-94 

13-76 

14-25 
15-36 

6-61 

6-80 
6-90 

?          1 

7-03 

6-41 
7-32 

00 

o 

«3  M 

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55-12 
55-64 
48-93 

5311 

48-72 

43-98 

32-32 

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3. 

3 
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3-3 

i 

Insoluble  in 

32% 

Soluble  in 

80% 

Insoluble  in 

60-70% 

Soluble  in 
70% 

Insolublo  in 
35% 

Insoluble  in 
00-70% 

"  Soluble  in 

80% 

Soluble  in 

80% 

Soluble  in 
80-90% 

Soluble  in 
67-80% 

5 

Hetoro-albu- 

nioso 
Proto-albu- 

mose 
Thio-albu- 

mose 

A  Albumose 
poor  in  sul- 
phur 
BI  Albu- 
mose 

BII  Albu- 
mose, Gluco- 

albumose 
Bill  a  Albu- 
mose 
BUI  $  Albu- 
mose 

3 
0 

& 
p-l 

all 

o 

Sol 

O                    0   3 

7-      SI      «.S 
^     ■*       frTT 

neutral 

47-59  in  acid 

reaction 

ZnSOj 
54-08  in  acid 

reaction 
(NH4),S04 
70-95  in 
neutral 
63-77  in 

acid  reaction 
ZnS04 

68-80  in  acid 

3 
O 

a 

3 

be© 

S3 

£ 

Hetoro- 
and  proto- 
albumose 
fraction 
Deutero- 
albumose 

3 

1 

3 
1 

3 

T3S  O 

Absent 
Absent 

•2 11 
°^2 

3°    "3 
°>       S» 

•■g    o 

—    .3 

o-°5 

3 
J           1 

<! 

III 

3      § 
1    -1 

| 

Absent  or 

trace 

Present 

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SooS  so, 

3.~'3.~5 

■3  s  '3  M 

p,^  a, — 

o      o 
8     & 

5       o 

732 


PHYSIOLOGY 


method   from   '  Witte's    peptone,'   a    commercial    preparation    containing 
proteoses  and  peptones. 

The  following  careful  analysis  of  the  constituents  of  protoalbumose  and 
heteroalbumose  (or  protoproteose  and  heteroproteose)  respectively  shows 
that  the  different  proteoses  really  correspond  to  different  groupings  of  the 
amino-acids  making  up  the  original  protein  molecule  : 


Results  of  the  Complete  Hydrolysis  of  Hetero-  and  Protoalbumose 


Heteroalbumose 

Protoalbumose 

Glutaminic  acid          ..... 

9-51 

0-63 

Leucine    . 

305 

5-79 

Isoleucine 

2-96 

1-62 

Valine 

3-54 

0-76 

Alanine    . 

3-39 

2-50 

Valin,e-alanine  mixtu 

"e 

1-86 

000 

Proline     . 

4-27 

4-96 

Phenylalanine  . 

2-45 

4-35 

Aspartic  acid    . 

. 

4-73 

2-98 

Glycocoll 

0-15 

1-44 

Tyrosine 

3-48 

4-58 

Arginine  . 

7-30 

7-72 

Histidine 

3-90 

2-77 

Lysine 

8-90 

8-40 

Cystine    . 

1-36 

0-68 

Ammonia 

1             1-28 

0-92 

The  results  obtained  by  Pick  by  hydrolysis  of  these  different  bodies  show 
that,  in  the  breakdown  of  protein  by  gastric  juice,  there  is  really  a  division 
of  the  complex  molecule  into  smaller  molecules,  which  are  qualitatively 
different.  Thus  of  the  fractions  which  he  obtained,  some  contain  the 
greater  part  of  the  sulphur  originally  present  in  the  protein  molecule,  another 
contains  the  greater  part  of  the  carbohydrate  group,  while  others  are  free 
altogether  from  the  tryptophane  group  which  is  responsible  for  Hopkins' 
reaction  obtainable  in  the  original  protein. 

Proceeding  from  primary  through  secondary  albumoses  to  peptones,  there 
is  probably  a  continuous  diminution  in  the  size  of  the  molecule.  During 
the  time  which  gastric  juice  has  to  exert  its  influence,  a  maximum,  say,  of 
twelve- hours,  the  breakdown  of  proteins  never  passes  beyond  the  albumose 
and  peptone  stage,  and  it  is  in  this  form  that  the  proteins  of  the  food  pass  on 
through  the  pyloric  orifice  into  the  small  intestine. 


ACTION    ON    THE    CONNECTIVE   TISSUES    AND    OTHER 
FOODSTUFFS    ALLIED    TO   PROTEINS 

Collagen.  The  connective  tissues  are  made  up  chiefly  of  white  fibres 
more  or  less  modified,  which  consist  of  collagen.  This  substance  forms  the 
main  basis  of    areolar  tissue,  of  white  fibrous  tissue,  and  of  bone.      On 


DIGESTION  IN  THE  STOMACH  733 

prolonged  boiling,  it  is  converted  into  gelatin.  The  gastric  juice  dissolves 
collagen,  converting  it,  probably  through  the  stage  of  gelatin,  into  gelatoses 
and  gelatin  peptones,  bearing  the  same  relation  to  the  original  substance 
as  is  borne  by  the  proteoses  and  peptones  to  the  proteins.  On  account  of 
this  action,  adipose  tissue  (which  consists  of  protoplasmic  cells  distended 
with  fat  and  bound  together  by  connective  tissue)  is  broken  up  into  its 
constituent  cells.  The  protoplasmic  pellicle  is  dissolved,  and  the  fat  floats 
freely  in  the  gastric  juice. 

Elastin,  which  also  occurs  in  varying  amounts  as  the  chief  constituent 
of  the  elastic  fibres  of  connective  tissues,  is  slowly  acted  upon  by  gastric 
juice.  Under  the  conditions  of  natural  digestion  however,  it  may  be 
regarded  as  indigestible. 

Mucin,  which  forms  a  considerable  proportion  of  the  ground  substance 
of  connective  tissues,  is  converted  by  gastric  juice  into  peptone-like  sub- 
stances, and  into  reducing  bodies  probably  allied  to  glycosamine. 

The  nucleo-PROTEins,  the  chief  constituents  of  cells,  and  therefore 
ingested  in  large  amounts  with  foodstuffs  such  as  sweetbreads,  are  first 
dissolved  by  the  acid  of  the  gastric  juice,  and  are  then  broken  up  into  two 
moieties.  The  protein  half  is  converted  into  proteoses  and  peptones,  while 
the  nuclein  moiety  is  precipitated  in  an  insoluble  form. 

On  phospho-proteins  gastric  juice  acts  in  a  somewhat  similar  manner. 
The  protein  of  milk,  caseinogen,  undergoes  special  changes  in  the  stomach. 
The  first  effect  of  gastric  juice,  even  in  neutral  medium,  is  to  convert  the 
caseinogen  into  an  insoluble  casein.  This  action  is  generally  ascribed  to  the 
presence  of  a  distinct  ferment  of  the  gastric  juice,  named  rennin,  or  rennet 
ferment.  But,  according  to  some  authorities,  it  is  due  directly  to  the  pepsin, 
i.  e.  rennin  and  pepsin  are  identical.  For  the  conversion  of  caseinogen  into 
the  solid  clot  of  casein  the  presence  of  lime  salts  is  necessary.  The  addition 
of  rennet  to  an  oxalated  milk  apparently  produces  no  effect,  but  clotting 
ensues  if  a  soluble  linie  salt,  such  as  calcium  chloride,  is  then  added  to  the 
mixture.  Under  the  action  of  the  acid  gastric  juice  the  solid  clot  of  casein 
is  dissolved,  but  a  precipitate  is  left  containing  a  small  proportion  of  the 
original  phosphorus  of  the  caseinogen.  This  precipitate  is  sometimes 
spoken  of  as  para-nuclein,  or  pseudo-nuclein.  It  does  not  yield  purine 
bases  on  hydrolysis  with  acids,  but  contains  phosphoric  acid  in  organic  com- 
bination. By  prolonged  digestion  with  strong  gastric  juice  it  is  possible  to 
dissolve  the  whole  of  this  precipitate.  It  is  therefore  thought  that,  in  the 
clotting  of  milk,  the  caseinogen  under  the  action  of  the  rennet  first  undergoes 
a  conversion  into  a  soluble  casein,  or  perhaps  a  splitting  into  a  soluble  casein 
and  some  other  protein.  The  soluble  casein  then,  under  the  influence  of 
the  hme  salts,  forms  an  insoluble  casein,  which  is  precipitated  and  causes  the 
solidification  of  the  milk.  In  the  absence  of  lime  salts,  the  conversion  or 
splitting  of  caseinogen  takes  place,  but  the  second  stage  of  the  process  cannot 
occur  until  the  hme  salts  are  added. 


734  PHYSIOLOGY 

THE   EFFECT   OF   GASTRIC   JUICE   ON    CARBOHYDRATES 

On  account  of  the  fact  that  cane  sugar  undergoes  inversion  into  equal 
molecules  of  glucose  and  fructose  in  the  stomach,  it  has  been  sometimes 
thought  that  gastric  juice  contains  a  ferment,  invertase.  It  seems  however 
that  the  inversion  which  takes  place  in  the  stomach  can  be  completely 
accounted  for  by  the  action  of  hydrochloric  acid  present,  and  that  there  is 
no  need  to  assume  the  presence  of  a  special  ferment. 

In  the  same  way  inulin.  the  variety  of  starch  which  gives  rise  to  the 
laevorotatory  sugar,  fructose,  on  hydrolysis,  and  is  found  in  dahlia  tubers  and 
certain  other  reserve  structures  of  plants,  is  converted  by  the  acid  of  gastric 
juice  into  fructose.  The  inulin  is  therefore  completely  utilised  in  the 
alimentary  canal  of  animals,  although  there  is  no  definite  ferment  inulase 
provided  for  its  hydrolysis. 

THE   EFFECT   OF   GASTRIC   JUICE   ON   FATS 

The  chief  action  of  this  juice  on  fats  is  the  solution  of  their  connective 
tissue  framework  and  protoplasmic  envelopes,  so  as  to  set  the  fat  free  in 
the  gastric  contents.  After  a  fatty  meal  it.  is  found  moreover  that  a 
considerable  proportion  of  the  fat  in  the  stomach  has  undergone  hydrolysis 
and  conversion  into  free  fatty  acid.  In  this  hydrolysis  two  factors  are 
involved,  viz.  (1)  the  action  of  the  warm  dilute  hydrochloric  acid;  (2)  the 
action  of  a  special  fat-splitting  ferment  or  lipase,  which  is  secreted  by  the  walls 
of  the  stomach,  and  acts  especially  at  the  beginning  of  gastric  digestion 
before  the  contents  have  attained  a  high  degree  of  acidity.  The  action  of 
this  ferment  is  marked  only  if  the  fat  be  present  in  a  finely  divided  form, 
e.  g.  as  in  yolk  of  egg.  The  chief  digestion  of  fat  takes  place  in  the  next 
segment  of  the  alimentary  canal,  namely,  in  the  duodenum. 

THE   SECRETION   OF   GASTRIC   JUICE 

Pawlow  has  shown  that,  if  an  animal  provided  with  gastric  and  oesophageal 
fistulse  be  given  food  when  hungry,  it  will  eat  with  avidity,  and  since  the 
food  cannot  reach  the  stomach  and  so  satisfy  its  hunger,  it  will  continue  to 
eat  for  two  or  three  hours.  Five  minutes  after  the  beginning  of  this  sham 
feeding,  gastric  juice  begins  to  drop  from  the  fistulous  opening ;  and  in  this 
way  large  quantities  of  juice,  free  from  any  admixture  with  other  substances, 
can  be  easily  obtained.  By  this  means  we  obtain  a  secretion  of  gastric  juice, 
which  is  excited  by  the  presence  of  food  in  the  mouth.  This  method  does  not 
however  enable  us  to  determine  whether  the  character  of  the  juice  will  be 
altered  in  any  way  by  the  changes  which  the  food  undergoes  in  the  stomach 
itself.  In  order  to  form  an  idea  of  the  normal  course  of  secretion  of  gastric 
juice,  when  food  is  taken  into  the  stomach  in  the  ordinary  way,  Pawlow  has 
devised  another  procedure.  A  small  diverticulum  representing  about  one- 
tenth  of  the  whole  stomach  is  made  at  the  cardiac  or  pyloric  end,  in  direct 
muscular  and  nervous  continuity  with  the  rest  of  the  stomach,  but  shut  off 
from  the  main  part  of  the  viscus  by  a  diaphragm  of  mucous  membrane.  The 
method  in  which  this  operation  is  carried  out  will  be  evident  by  reference  to 


DIGESTION  IN  THE  STOMACH 


735 


the  diagram  (Fig.  348).  In  a  dog  treated  in  this  way  it  is  found  that  the 
amount  of  juice  secreted  by  the  small  stomach  bears  always  the  same  ratio 
to  the  amount  secreted  by  the  large  stomach,  while  the  digestive  power  of  the 
juice  obtained  from  the  small  stomach  is  equal  to  that  obtained  from  the 
larsre.    This  is  shown  in  the  folio  wins;  Table  : 1 


Secretion  from  Gastric  Fistula  after  Sham  Meal 


Hours 

Small  stomach 

Large  stomach 

Quantity 

Strength  * 

Quantity 

Strength 

1 

2 
3 

7-0  c.c. 
4-7  c.c. 
1-1  C.C. 

5-88  mm. 
5-75  mm. 
5-5    mm. 

68-25  c.c. 
41-5    c.c. 
140    c.c. 

5-5    mm. 
5-5    mm. 
5-38  mm. 

Total. 

13-4  c.c. 

- 

123-75  c.c. 

ITig.  348.     Diagram  to  show  Pawlow's  method  of  making  a  cul-de-sac  of  tho 
cardiac  end  of  the  stomach,  with  vascular  and  nerve  supply  intact. 
In  A  tho  line  of  the  incision  into  the  gastric  wall  is  shown.     B  represents 
the  operation  as  completed. 

In  A:  0,  oesophagus;  R.v,  L.v,  right  and  left  vagus  nerves;  P,  pylorus; 
6",  cardiac  portion  of  stomach;  A,  B,  line  of  incision. 

In  B  :  V,  main  portion  of  stomach;  S,  cardiac  cul-de-sac;  A,  abdominal 
wall;  e,  c,  mucous  membrane  reflected  to  form  diaphragm  between  the  two 
cavities. 


In  this  case  a  fistulous  opening  had  been  established  into  the  large 
stomach,  so  that  the  juice  could  be  obtained  simultaneously  from  both 
sections  of  this  organ.  Secretion  was  excited  by  a  sham  meal,  in  which  the 
food  taken  by  the  animal  was  not  allowed  to  reach  the  stomach,  but  dropped 
out  of  an  opening  in  the  neck.  It  will  be  seen  that  the  secretions  in  the  two 
sections  of  the  stomach  run  parallel  to  one  another,  while  there  is  an  almost 

1  Puwlow,  Tlie  Work  of  the  Digestive  Glands  (translated  by  Sir  W.  H.  Thompson, 
M.D.).  p.  80. 

a  The  strength  of  the  juice  was  determined  by  measuring  the  number  of  millimetres 
of  coagulated  egg-white  (in  Mett's  tubes)  which  were  digested  in  eight  hours. 


736 


PHYSIOLOGY 


exact  equivalence  between  the  strengths  of  the  juices  obtained  from  each 
section.  We  may  therefore  regard  the  secretion  obtained  from  the  small 
stomach  as  a  sample  of  that  produced  by  the  large,  and  from  the  changes  in 
this  small  stomach  judge  of  the  effects  occurring  in  the  whole  organ.  By 
this  method  it  is  possible  to  study  the  effects  of  a  normal  meal  in  which  the 
food  is  swallowed,  or  of  a  sham  meal  in  which  the  food  is  merely  masticated 
in  the  mouth,  or  of  a  meal  in  which  the  food  is  directly  introduced  into  an 
opening  into  the  large  stomach. 

The  method  which  we  must  adopt  for  the  collection  of  gastric  juice  shows 
that  we  have  to  do,  in  the  first  place,  with  a  reflex  nervous  mechanism, 
since  an  active  secretion  is  excited  by  the  presence  of  food  in  the  mouth  and 
by  its  mastication.  Moreover  a  secretion,  which  is  at  least  as  vigorous  as  that 
produced  by  a  sham  meal,  can  be  evoked  by  merely  arousing  in  the  dog  the 
idea  of  a  meal.  If  the  animal  be  hungry,  it  is  sufficient  to  show  it  the  food  to 
produce  a  secretion.  In  the  experiment  from  which  the  following  Table  is 
taken,  the  dog  was  continually  excited  by  showing  it  meat  during  a  period 
of  an  hour  and  a  half.  At  the  end  of  this  time  the  animal,  which  had  an 
oesophageal  fistula,  was  given  a  sham  meal.  It  will  be  observed  that  the 
psychical  secretion  obtaiued  during  the  first  period  of  the  experiment  was 
rather  greater  than  the  secretion  produced  by  the  introduction  of  food  into 
the  mouth. 


Psychical  Secretion  of  Gastric  Jdice  (Pawlow) 


Time 
8  minutes 
4 
4 

10 

10 


Quantity 

10  c.c. 
10  „ 
10  „ 
10  „ 
10  „ 

io  „ 

10  „ 
10  „ 
3  „ 


Sham  Feeding 


Time 
17  minutes 
9      „ 

8       „ 


Quantity 

10  c.c. 
10  „ 
10  „ 


The  afferent  ".hannels  for  this  reflex  may  be  therefore  either  the  afferent 
nerves  from  the  mouth  or,  when  the  idea  of  food  is  involved,  any  of  the  nerves 
of  special  sense,  such  as  sight,  smell,  or  hearing,  through  which  these  ideas 
are  called  forth.  The  efferent  channels  can  be  only  one  of  two  nerves,  viz. 
the  vagus  and  the  sympathetic,  since  these  are  the  only  two  which  are 
distributed  to  the  stomach.  That  it  is  the  former  of  these  nerves  which  is 
involved  is  shown  by  the  fact,  recorded  by  Pawlow,  that  psychical  secretion, 
as  well  as  the  results  of  a  sham  meal,  is  entirely  abolished  by  division  of  both 


DIGESTION  IN  THE  STOMACH  737 

vagi.  On  this  account  division  of  both  vagi  may  give  rise  to  entire  absence  of 
gastric  digestion,  and  death  of  the  animal  may  ensue  from  inanition,  or  from 
poisoning  by  the  products  of  decomposition  of  food  in  the  stomach,  even 
when  care  has  been  taken  to  avoid  injury  to  the  pulmonary  and  tracheal 
branches  of  these  nerves. 

The  converse  experiment  of  exciting  secretion  by  direct  stimulation  of  the  vagus 
presents  greater  difficulties.  Stimulation  of  the  vagus  in  the  neck  causes  stoppage 
of  the  heart,  and  consequent  anaemia  of  the  mucous  membrane  of  the  stomach.  More- 
over the  stomach  seems  to  be  much  more. susceptible  than  the  salivary  glands  to  the 
action  of  poisons,  such  as  anaesthetics.  Its  activity  is  also  easily  affected  by  inhibitory 
impulses  arising  in  the  central  nervous  system  as  the  result  of  either  painful  impressions 
or  emotional  states  of  the  animal.  In  order  to  avoid  these  disturbing  factors  Pawlow 
proceeded  as  follows  :  An  animal  with  fistula?  of  oesophagus  and  stomach  had  one 
vagus  nerve  divided.  A  thread  was  attached  to  the  peripheral  end  of  the  cut  vagus 
and  allowed  to  hang  out  through  the  wound.  Four  days  after  the  operation  the  vagus 
was  drawn  out  of  the  wound  by  carefully  pulling  on  the  thread,  so  as  not  to  hurt  or 
frighten  the  animal  in  any  way,  and  its  peripheral  end  stimulated  by  means  of  induc- 
tion shocks.  No  effect  was  produced  on  the  heart,  owing  to  the  degeneration  of  the 
cardio-inhibitory  fibres,  which  is  well  known  to  occur  within  this  period  after  section. 
Five  minutes  after  the  commencement  of  the  stimulation  the  first  drop  of  gastric  juice 
appeared  from  the  gastric  cannula,  and  a  steady  secretion  of  juice  was  obtained  with 
continuation  of  the  stimulation.  This  experiment  furnishes  the  decisive  and  final 
evidence  that  the  secretory  nerves  to  the  stomach  run  in  the  two  vagi.  There  is  one 
marked  difference  however  between  the  action  of  these  nerves  and  the  action  of  the 
chorda  tympani  nerve  on  the  submaxillary  gland,  namely,  the  great  length  of  the 
latent  period  before  gastric  secretion  begins.  The  length  of  this  latent  period  has 
not  yet  been  satisfactorily  explained.  It  cannot  be  due  to  delay  occurring  between 
the  vagus  fibres  and  the  local  nervous  mechanism  in  the  stomach.  It  may  be  that 
the  chemical  changes  finally  resulting  in  secretion  require  a  longer  period  for  their 
accomplishment  than  is  the  case  in  the  salivary  gland.  Physiologically  there  is  indeed 
no  special  need  for  a  rapid  secretion  of  gastric  juice,  whereas  in  the  mouth  it  is  essential 
that  the  introduction  of  food  should  be  immediately  followed  by  the  production  of 
saliva,  for  the  tasting  and  testing  of  the  food  and  for  its  subsequent  mastication  or 
rejection. 

These  experiments  show  conclusively  that  an  important— probably  the 
most  important — part  of  the  gastric  secretion  is  determined  by  a  nervous 
mechanism.  This  nervous  secretion  does  not  however  account  for  the  whole 
of  the  gastric  juice  obtained  as  the  result  of  a  meal.  If  an  animal  provided 
with  two  gastric  fistulse,  one  into  a  diverticulum  and  the  other  into  the 
main  stomach,  has  both  its  vagi  divided,  it  is  found  that  the  introduction  of 
meat  into  the  large  stomach  is  followed,  after  a  period  of  twenty  to  forty -five 
minutes,  by  the  appearance  of  a  secretion  of  gastric  juice  from  the  small 
stomach.  Moreover,  when  an  animal  is  given  a  normal  meal  and  is  allowed 
to  swallow  the  food  after  mastication,  the  total  amount  of  gastric  juice 
obtained  is  greater  than  that  produced  by  the  sham  feeding  alone  and  the 
flow  is  of  longer  duration.  In  fact,  we  may  say  that  the  gastric  juice  secreted 
in  response  to  a  normal  meal  consists  of  two  parts,  viz.  (1)  a  large  amount, 
the  secretion  of  which  begins  within  five  minutes  of  the  taking  of  the  food 
and  is  determined  by  the  reflex  nervous  mechanism  described  above ;  and 
(2)  a  smaller  portion,  the  secretion  of  which  is  excited  by  the  presence  of  the 
17 


738 


PHYSIOLOGY 


food  in  the  stomach.    This  combined  character  of  the  gastric  juice  produced 
by  a  normal  meal  is  shown  in  the  following  Table  (Pawlow) : 

Secretion  of  Gasteic  Juice 


Hours 

Normal  meal. 

200  grm.  meat  into 

stomach 

150  grm.  meat  direct 
Into  stomach 

Sham  meal 

Sum  of  two 
last  ex- 
periments 

Quantity 
c.c. 

Strength 
mm. 

Quantity 
c.c. 

Strength 

2-5 
2-75 
3-75 
3-75 

Quantity 
c.c. 

Strength 
mm. 

G-4 
5-3 
5-75 
0 

Quantity 
c.c. 

12-7 

12-3 

7-0 

5-0 

1 

3 
4 

12-4 
13-5 
7-5 

4-2 

5-43 
3-63 
3-5 
312 

50 

7-8. 
6-4 
50 

7-7 
4-5 
0-6 

0 

In  the  first  column  is  given  the  result  of  a  normal  meal  on  the  secretion 
from  the  gastric  diverticulum.  In  the  second  column  are  given  the  amount 
and  digestive  power  of  the  juice  which  is  excited  by  the  direct  introduction  of 
150  grm.  of  meat  into  the  large  stomach  of  the  animal,  care  being  taken  not 
to  excite  in  any  way  the  nervous  reflex  mechanism.  In  the  third  column 
are  given  the  amount  and  digestive  power  of  the  juice  which  is  evoked  by  a 
sham  meal  of  200  grm.  of  meat.  In  the  fourth  column  is  given  the  sum  of 
the  last  two  experiments.  It  will  be  seen  that  the  total  effect  of  the  sham 
meal  plus  the  direct  introduction  of  meat  into  the  stomach  is  almost  identical 
with  the  secretion  obtained  when  the  food  is  taken  in  a  normal  way  and 
allowed  to  pass  through  the  oesophagus  into  the  stomach. 

The  second  phase  of  the  gastric  secretion  cannot  be  ascribed  to  the  inter- 
vention of  the  reflex  vagal  mechanism.  Since  it  occurs  after  cutting  off  the 
stomach  from  its  connections  with  the  central  nervous  system,  it  must  have 
its  causation  in  the  gastric  walls  themselves.  That  it  cannot  be  due  to 
mechanical  stimulation  is  shown  by  the  fact,  previously  mentioned,  that 
it  is  impossible  by  local  stimulation  of  the  mucous  membrane,  by  rubbing, 
by  introduction  of  sand,  or  any  other  method,  to  evoke  a  secretion.  Moreover 
it  is  not  produced  by  all  sorts  of  food.  The  introduction  of  white  of  egg,  of 
starch,  or  of  bread  into  the  stomach  causes  no  secretion.  On  the. other  hand, 
if  bread  be  mixed  with  gastric  juice  and  allowed  to  digest  for  some  time,  the 
introduction  of  the  semi-digested  mixture  into  the  stomach  evokes  a  secre- 
tion. We  have  already  seen  that  meat  produces  a  secretion;  still  more 
potent  than  meat  however  is  a  decoction  of  meat,  or  bouillon,  or  Liebig's 
extract  of  meat,  or  certain  preparations  of  peptone.  Pure  albumoses  and 
peptones  have  no  effect,  so  that  the  exciting  mechanism  must  be  some 
chemical  substances  present  in  meat,  and  produced  in  various  other  foods 
under  the  action  of  the  first  gastric  juice  secreted  in  response  to_  nervous 
stimuli.  Popielski  has  shown  that  this  secretion  occurs  after  complete 
severance  of  the  stomach  from  the  central  nervous  system,  as  well  as  after 
destruction  of  the  sympathetic  nervous  plexuses  of  the  abdomen.    Since 


DIGESTION   IN   THE  STOMACH  739 

the  injection  of  bouillon  directly  into  the  circulation  has  no  effect,  this  author 
concludes  that  the  second  phase  of  secretion  is  determined  by  the  stimulation 
of  the  local  nerve  plexus,  and  that  we  have  here,  in  short,  a  peripheral  reflex 
action,  the  centres  of  which  are  situated  in  the  walls  of  the  stomach 
itself.  There  is  yet  another  possible  explanation  for  this  second  phase  of 
secretion.  Although  the  peptogenic  substances,  those  substances  which 
evoke  gastric  secretion  on  introduction  into  the  stomach,  have  no  effect  on 
the  gastric  glands  when  injected  directly  into  the  blood  stream,  it  is  possible 
that  they  may  have  an  influence  on  the  cells  which  line  the  cavity  of  the 
stomach,  and  that  they  may  produce,  in  these  cells,  some  other  substance 
which  is  absorbed  into  the  blood  and  acts  as  a  specific  excitant  of  the  gastric 
glands.  A  process  of  this  nature  is  known  to  occur  in  the  next  segment  of 
the  alimentary  canal,  viz.  the  duodenum,  where  it  determines  the  secretion 
of  the  pancreatic  juice  and  the  bile. 

Edkins  has  carried  out  a  series  of  experiments  to  determine  whether  such 
a  chemical  mechanism  may  not  also  account  for  the  secretion  of  gastric  juice, 
which  is  excited  by  the  introduction  of  substances  into  the  stomach.  Edkins' 
experiments  were  carried  out  in  the  following  way  :  The  animal,  dog  or  cat, 
having  been  anaesthetised,  the  abdominal  cavity  was  opened,  and  a  ligature 
passed  round  the  lower  end  of  the  oesophagus  so  as  to  occlude  the  cardiac 
orifice  and  effectually  crush  the  two  vagus  nerves.  A  glass  tube  was  then 
introduced  through  an  opening  in  the  abdomen  into  the  pyloric  part  of  the 
stomach,  and  fixed  in  this  position  by  a  ligature  tied  tightly  round  the 
pylorus.  The  glass  tube  was  connected  by  means  of  a  rubber  tube  with  a 
reservoir  containing  normal  salt  solution  at  the  temperature  of  the  body. 
By  means  of  this  reservoir,  a  certain  amount  of  fluid  was  introduced  into  the 
stomach  and  kept  there  at  a  constant  pressure ;  the  quantity  of  fluid  intro- 
duced vaiied  from  30  to  50  c.c.  It  has  been  shown  by  Edkins,  as  well  as  by 
von  Mering,  that  no  absorption  of  water  or  saline  fluid  occurs  in  the  stomach. 
It  is  therefore  possible  to  recover  the  whole  of  the  fluid  an  hour  after  it  has 
been  introduced,  by  simply  lowering  the  reservoir  below  the  level  of  the 
animal's  body.  If  secretion  of  gastric  juice  has  occurred  into  the  cavity  of 
the  stomach,  the  fluid  will  be  increased  in  amount  and  will  contain  hydro- 
chloric acid  as  well  as  pepsin.  In  a  series  of  control  observations  Edkins 
showed  that  the  mere  introduction  of  this  fluid  into  the  stomach  caused 
no  secretion  of  gastric  juice,  the  fluid  removed  at  the  end  of  an  hour  having 
the  same  bulk  and  the  same  neutral  reaction  as  the  fluid  which  had  been 
injected.  Edkins  then  tried  the  influence  of  injecting  substances  into  the 
blood  stream.  The  injection  of  peptone,  of  acid,  of  broth,  or  of  dextrin  into 
the  blood  stream  produced  no  secretion  of  gastric  juice.  If  however  in  the 
course  of  the  hour  during  which  the  fluid  was  allowed  to  remain  in  the 
stomach,  a  decoction  made  by  boiling  pyloric  mucous  membrane  with  acid, 
or  with  water,  or  with  peptones  was  introduced  in  small  quantities  every  ten 
minutes  into  the  jugular  vein,  the  fluid  removed  at  the  end  of  the  hour  was 
found  to  be  distinctly  acid  in  its  reaction  and  to  possess  proteolytic  properties. 
The  injection  of  these  substances  had  therefore  caused  the  secretion  of  a 


740  PHYSIOLOGY 

certain  amount  of  gastric  juice  containing  both  hydrochloric  acid  and 
pepsin.  In  order  to  produce  this  positive  effect,  it  was  necessary  to  employ 
pyloric  mucous  membrane,  extracts  made  by  infusing  or  boiling  cardiac 
mucous  membrane  with  any  of  these  substances  being  without  effect. 
Edkins  concludes  therefore  that  the  secondary  secretion  of  gastric  juice  is 
determined,  not,  as  Pawlow  and  Popielski  imagined,  by  a  local  stimulation 
of  the  reflex  nervous  apparatus  in  the  gastric  wall,  but  by  a  chemical 
mechanism.  The  first  products  of  digestion  act  on  the  pyloric  mucous 
membrane,  and  produce  in  tbis  membrane  a  substance  which  is  absorbed  into 
the  blood  stream,  and  carried  to  all  the  glands  of  the  stomach,  where  it  acts 
as  a  specific  excitant  of  their  secretory  activity.  This  substance  may  be 
called  the  gastric  secretin  or  gastric  hormone.  It  is  noteworthy  that  it  is 
produced  in  that  portion  of  the  stomach  where  the  process  of  absorption  is 
most  pronounced. 

The  normal  gastric  secretion  is  therefore  due  to  the  co-operation  of  two 
factors.  The  first  and  most  important  is  the  nervous  secretion,  determined 
through  the  vagus  nerves  by  stimulation  of  the  mucous  membrane  of  the 
mouth,  or  by  the  arousing  of  appetite  in  the  higher  parts  of  the  brain.  The 
second  factor,  which  provides  for  the  continued  secretion  of  gastric  juice 
long  after  the  mental  effects  of  a  meal  have  disappeared,  is  chemical,  and 
depends  on  the  production  in  the  pyloric  mucous  membrane  of  a  specific 
substance  or  hormone,  which  acts  as  a  chemical  messenger  to  all  parts  of  the 
stomach,  being  absorbed  into  the  blood  and  thence  exciting  the  activity  of 
the  various  secreting  cells  in  the  gastric  glands.  It  is  still  a  moot  point 
whether  this  gastric  hormone  is  formed  only  in  the  pyloric  mucous  membrane, 
or  whether  it  may  not  be  also  produced  in  the  lower  sections  of  the  gut. 
Popielski  has  stated  that  the  introduction  of  bouillon  into  the  small  intestine 
excites  a  secretion  of  gastric  juice  in  animals,  even  after  extirpation  of  the 
abdominal  sympathetic  plexuses  and  division  of  both  vagi.  On  the  other 
hand,  introduction  of  the  same  substance  into  the  large  intestine  has  no 
influence  on  gastric  secretion.  Popielski  ascribes  this  secretion  again  to  a 
local  reflex ;  but  it  is  more  probable  that  the  mechanism  in  this  case  is  the 
same  as  that  involved  in  the  secretion  which  is  excited  by  the  presence  of 
semi-digested  food  in  the  stomach  itself. 

Pawlow  has  shown  that  the  second  phase  of  the  gastric  secretion  is  largely 
influenced  by  the  character  of  the  contents  of  the  stomach.  Thus  the  inges- 
tion of  large  quantities  of  oil  diminishes  considerably  the  amount  of  gastric 
juice  secreted,  and  Pawlow  has  suggested  the  administration  of  oil  or  oily 
foods  as  a  possible  remedy  in  cases  where  the  production  of  gastric  juice, 
and  especially  of  hydrochloric  acid,  is  in  excess.  It  has  long  been  imagined 
that  the  secretion  of  gastric  juice  was  stimulated  by  the  taking  of  alkalies. 
This  idea  has  been  shown  by  Pawlow  to  be  erroneous.  Whereas  the  forma- 
tion of  gastric  juice  is  increased  by  the  administration  of  acids,  especially 
after  a  meal,  it  is  largely  diminished  by  the  administration  of  alkalies  such 
as  sodium  bicarbonate.  In  fact,  sodium  bicarbonate  diminishes  the  activity 
of  the  digestive  glands  throughout  the  alimentary  tract,  and  ca-u  be  used  as 


DIGESTION  IN  THE   STOMACH  741 

a  means  of  diminishing  the  secretion  of  gastric  juice  as  well  as  of  pancreatic 
juice. 

A  further  important  question  has  been  propounded  by  Pawlow,  namely, 
whether  there  is  any  alteration  in  the  constitution  and  amount  of  gastric 
juice  with  variations  in  the  character  of  the  food.  So  far  as  concerns,  the 
first  phase  of  secretion,  the  psychical  or  '  appetite  '  juice,  this  observer  has 
shown  that,  whatever  the  previous  diet  of  the  animal,  the  juice  always  has 
the  same  characters,  the  same  digestive  power,  and  the  same  percentage 
of  hydrochloric  acid.  He  finds,  however,  that  in  the  case  of  the  second,  or 
what  we  may  call '  chemical '  secretion,  i.  e.  that  produced  by  local  changes 
in  the  stomach,  there  is  considerable  variation  in  the  nature  of  the  juice. 
Whereas  the  secretion  of  juice  is  greatest  in  amount  after  a  meal  of  meat, 
the  digestive  power  of  the  juice  is  greatest  after  one  of  bread,  and  Pawlow 
regards  these  differences  in  the  juice  as  determined  by  the  variations  in  the 
stimulus  applied  to  the  gastric  mucous  membrane.  It  is  doubtful  however 
whether  these  results  justify  us  in  ascribing  a  number  of  specific  sensibilities 
to  the  gastric  mucous  membrane.  We  have  seen  that  the  psychical  juice 
depends  merely  on  appetite,  and  therefore  will  be  greater  in  amount  the  more 
welcome  the  food  is  to  the  animal.  On  the  other  hand,  the  juice  secreted  in 
the  second  phase  must  vary  according  to  the  quantity  of  gastric  hormone 
produced  in  the  pyloric  mucous  membrane,  and  therefore  with  the  nature 
and  amount  of  the  substances  produced  in  the  preliminary  digestion  of  the 
gastric  contents  by  .means  of  the  psychic  juice.  The  amount  of  juice  may 
vary  also  with  the  salts  contained  in  the  food,  according  to  their  alkaline  or 
acid  character,  and  the  percentage  of  pepsin  in  the  juice  may  vary  with  the 
intensity  of  stimulus  as  well  as  with  the  quantity  of  fluid  available  for  the 
formation  of  the  gastric  juice.  These  factors  will  co-operate  in  determining 
the  characters  of  the  whole  juice  secreted  after  any  given  meal,  and  it  seems 
possible  to  explain  the  variations,  observed  on  such  different  diets  as  meat 
and  bread,  without  having  recourse  to  the  difficult  assumption  of  a  specific 
sensibility  of  the  gastric  mucous  membrane  to  such  inert  substances  as 
dextrin  or  e<w  albumin. 


SECTION  IV 
THE   MOVEMENTS    OF   THE   STOMACH 


These  can  be  best  studied  by  Cannon's  method — that  is,  by  direct  observa- 
tion of  the  movements  in  a  living  unansesthetised  animal  by  means  of  the 
Rontgen  rays.  In  order  to  make  the  shape  of  the 
stomach  visible,  the  food — bread  and  milk — is 
mixed  with  a  quantity  of  bismuth  subnitrate  or 
bismuth  oxy  chloride  (Hertz).  The  presence  of 
this  salt  does  not  interfere  with  the  processes  of 
digestion,  but  renders  the  gastric  contents  opaque 
to  the  Rontgen  rays.  On  examining  by  this 
means  the  stomach  of  a  cat  which  has  just  taken 
a  meal,  the  whole  of  the  food  is  seen  to  be  lying 
in  the  fundus.  It  is  marked  off  by  a  strong 
constriction,  the  '  transverse  band,'  from  the 
pyloric  portion.  In  about  twenty  to  thirty 
minutes  faint  waves  of  contraction  begin  a  little  to 
the  cardiac  side  of  the  transverse  band  and  travel 
slowly  towards  the  pylorus.  These  waves  succeed 
one  another  so  that  the  pyloric  part  of  the  stomach 
may  present  a  series  of  constrictions.  Their  effect 
is  to  force  towards  the  pylorus  the  food  which  has 
been  digested  by  gastric  juice  and  detached  from 
the  surface  of  the  mass  in  the  fundus.  The 
pylorus  remaining  closed,  the  food  cannot  escape, 
and  therefore  is  squeezed  back,  forming  an  axial 
reflux  stream  towards  the  cardiac  end.  These 
contractions  last  throughout  the  whole  period  of 

Fig.  349.     Shadow  sketches  ,    .        n.        ,.  n     ,  ,      n 

of    the    outlines    of    the   gastric   digestion,   and    become    more    marked    as 
stomach  of  a  cat,  inmie-   digestion  proceeds.      By  their  action   the    whole 

diately  after  a  meal  (11.0),       ».,»,.,  ,  ,     ■         ,  •,, 

at  various  intervals  after-    01     the     food     IS     brought    in    close    CODtact    With 

every  particle  of  pyloric  mucous  membrane  and 
a  thorough  mixture  of  food  and  gastric  juice 
results.  At  varying  periods  after  a  meal,  accord- 
ing to  the  nature  of  the  food  taken,  the  arrival 
of  one  of  these  waves  of  contraction  at  the 
pylorus  causes  a  relaxation  of  the  orifice,  and  a  few  cubic  centimetres 
of  gastric  contents  are  squirted  into  the  first  part  of  the  duodenum.    While 

742 


wards  (12.0,  2.0,  3.30, 4.30). 
c,  situation  of  oesophageal 
opening ;  yz,  '  transverse 
band ' ;  wx,  junction  of 
cardiac  and  pyloric  por- 
tions.    (W.  B.  Gannon.) 


THE  MOVEMENTS  OF  THE  STOMACH 


743 


these  movements  of  the  pyloric  mill  are  going  on,  the  cardiac  portion  of 
the  stomach  is  exercising  a  steady  pressure  on  its  contents  in  consequence 
of  a  tonic  contraction  of  its  muscular  wall,  so  that  each  successive  portion  of 
the  food  mass  which  is  loosened  by  the  digestive  action  of  the  gastric  juice  is 
forced  on  into  the  pyloric  mill.  As  digestion  proceeds  the  opening  of  the 
pylorus  becomes  more  frequent.  The  stomach  empties  itself  more  and  more, 
until  finally  the  whole  of  the  viscus  has  the  shape  of  a  curved  tube  (Fig.  349). 


Fio.  350.     Sketch  of  human  stomach,  in  erect  position,  shortly  after  a 
bismuth  meal.     (Hertz.) 

t,  fundus;    V,  umbilicus;    ia,  incisura  angularis;    re,  pyloric  canal; 
o,  oesophagus. 

At  the  very  end  of  digestion  the  pylorus  may  open  to  allow  the  passage  even 
of  undigested  morsels  of  food. 

Very  similar  are  the  changes  in  the  human  stomach,  as  shown  by  Hertz. 
The  term  fundus  is  by  him  limited  to  that  part  of  the  stomach  situated 
above  the  cardiac  orifice  (in  the  erect  position).  The  body  of  the  stomach 
is  marked  off,  more  or  less,  by  the  incisura  angularis  on  the  lesser  curvature 
corresponding  to  what  we  have  called  the  transverse  band.  The  pyloric 
portion  consists  of  the  pyloric  vestibule  and  the  pyloric  canal,  the  latter 
being  a  tubular  portion  about  3-0  cm.  in  length,  especially  well  marked  in 
infants.  When  a  small  quantity  of  food  has  been  swallowed  (in  the  erect 
position)  its  weight  is  sufficient  to  overcome  the  resistance  of  the  contracted 
gastric  wall,  and  it  rapidly  passes  to  the  pyloric  part.  Peristalsis  begins 
almost  at  once,  each  constriction  starting  near  the  middle  of  the  stomach, 
and  deepening  as  it  slowly  progresses  towards  the  pylorus  (Fig.  350).  About 
one  inch  from  the  pyloric  canal  it  is  so  marked  that  part,  of  the  pyloric 
vestibule  becomes  almost  completely  separated  from  the  rest  of  the  stomach. 


744  PHYSIOLOGY 

The  part  thus  cut  off  then  diminishes  in  size  in  even'  direction,  part  of  its 
contents  being  forced  through  the  pyloric  canal,  while  the  remainder  escapes 
back  as  an  axial  reflux  stream  into  the  stomach.  The  waves  recur  at  regular 
intervals  of  fifteen  to  twenty  seconds,  and  three  or  four  are  present  simul- 
taneously. They  continue  without  cessation  until  the  stomach  is  empty — 
from  one  to  four  hours  after  the  meal  according  to  its  bulk  and  composition. 

The  foregoing  descriptions  apply  especially  to  the  events  wThich  succeed 
the  taking  of  a  considerable  meal.  If  warm  fluid  alone,  e.  g.  water,  be  swal- 
lowed, the  opening  of  the  pylorus  occurs  within  a  very  short  time  after 
the  fluid  has  reached  the  stomach.  Thus  if  a  large  draught  of  water  be  taken 
to  quench  thirst,  it  may  arrive  in  the  duodenum  within  a  minute  or  two  after 
being  swallowed,  and  it  is  from  the  duodenum  and  small  intestine  that  any 
absorption  takes  place.  When  a  meal  is  undergoing  digestion,  there  is  a  dis- 
tinct relation  between  the  amount  of  acid  present  in  the  gastric  contents  and 
the  opening  of  the  pylorus.  One  may  indeed  say  that  acidity  of  the  gastric 
contents  exercises  a  direct  inhibitory  stimulus  on  the  pyloric  sphincter. 

These  movements  of  the  two  portions  of  the  stomach  may  be  observed 
also  on  anaesthetised  animals  and  even  on  a  stomach  which  has  been  excised 
and  placed  in  warm  salt  solution.  They  must  therefore  have  their  origin  in 
the  walls  of  the  stomach  itself.  Although  the  co-ordination  between  the  two 
parts  of  the  stomach,  between  the  tonic  contractions  of  the  fundus  and  the 
rhythmic  contractions  of  the  pyloric  part,  may  be  carried  out  by  the  local 
nervous  system — Auerbach's  plexus — situated  between  the  layers  of  the 
muscular  coat,  it  is  probable  that  the  advancing  waves  of  contraction 
observed  in  the  antrum  are  myogenic,  i.  e.  directly  originated  in  and  deter- 
mined by  the  muscle  fibres  themselves.  Cannon  has  shown  that  these 
movements  persist  after  complete  division  of  Auerbach's  plexus  by  2  to  6 
circular  incisions  carried  through  the  entire  muscular  coat  of  the  stomach ; 
and  it  is  evident  that  they  do  not  partake  of  the  nature  of  a  true  peristalsis, 
since  they  are  not  preceded  by  a  wave  of  relaxation.  The  opening  of  the 
pylorus,  on  the  other  hand,  which  occurs  at  increasingly  frequent  intervals 
at  the  end  of  a  wave,  must  be  ascribed  to  a  nervous  mechanism.  Although 
the  local  mechanism  probably  plays  the  greater  part  in  this  act  of  relaxation, 
the  normal  emptying  of  the  stomach  is  also  largely  dependent  on  the  integrity 
of  the  connection  of  this  viscus  with  the  central  nervous  system.  If  both 
vagus  nerves  be  divided  in  a  dog  below  the  point  at  which  they  give  off  their 
branches  to  the  lungs  and  heart,  a  large  amount  of  food  may  remain  in 
the  stomach  in  an  undigested  condition.  The  secretion  of  gastric  juice  is 
deficient,  and  the  opening  of  the  pylorus  is  not  easily  carried  out.  Such  dogs 
therefore  tend  to  die  of  saprsemia,  being  poisoned  by  the  absorption  of 
products  of  putrefaction  from  the  gastric  contents.  Pawlow  has  shown  that 
animals  can  be  kept  alive  for  months  after  division  of  both  vagi  if  a  gastric 
fistula  be  made,  the  animals  be  carefully  fed,  and  care  be  taken  to  wash  out 
adherent  non-digested  portions  of  food  from  the  stomach. 

The  opening  of  the  pylorus  depends  not  only  on  intragastric  events  but 
also  on  the  condition  of  the  duodenum.     It  has  been  shown  by  Serdjukow 


THE  MOVEMENTS  OF  THE  STOMACH 


745 


that  the  pylorus  remains  firmly  closed  so  long  as  the  contents  of  the  duo- 
denum are  acid.  If  alkaline  fluid  be  introduced  into  the  stomach,  this  is 
rapidly  passed  into  the  duodenum.  If  however  some  acid  be  introduced  at 
the  same  time  into  the  duodenum  by  means  of  a  duodenal  fistula,  the  pylorus 
remains  firmly  closed,  and  no  fluid  passes  into  the  duodenum  until  the  acid 


Fig.  351.  Distribution  of  the  vagus  in  the  abdomen  of  the  dog. 
(M.  H.  Naylor.) 
RV,  LV,  right  and  left  vagi.  The  right  vagus  runs  behind  the  oesophagus 
(Oe)  and  stomach  (St),  and  in  those  places  is  represented  by  a  discontinuous 
line.  Cb,  connecting  branch  between  right  and  left  vagi ;  P,  pancreas ;  Dd, 
duodenum;  FT) J,  nexura  duodeno-jejunalis ;  I,  I,  I,  intestine;  L,  liver; 
K,  kidney ;  A,  suprarenal  capsule ;  R&,  LG,  right  and  left  cura  of  diaphragm ; 
L.Sy.Ch,  left  sympathetic  chain;  12  T>,  13  D,  twelfth  and  thirteenth  dorsal 
ganglia;  3  L,  third  lumbar  ganglion;  G.Sp.N,  L.Sp.N,  great  and  small 
splanchnic  nerves;  S.G,  left  semilunar  and  superior  mesenteric  ganglia; 
I).A,  dorsal  aorta. 

which  was  placed  there  has  been  neutralised  by  the  secretion  of  pancreatic 
juice  and  succus  entericus.  AVe  have  probably  in  the  walls  of  the  alimentary 
canal  a  local  nervous  mechanism  for  the  movements  of  the  pyloric  sphincter. 
This  may  be  played  upon  by  impulses  starting  either  in  the  stomach  or  in 
the  duodenum,  probably  by  the  contact  of  acid  with  the  mucous  membrane. 
Increasing  acidity  on  the  side  of  the  stomach  causes  relaxation  of  the  orifice, 
whereas  acidity  on  the  duodenal  side  causes  contraction  of  the  pyloric 


746  PHYSIOLOGY 

sphincter.  The  exact  parts  played  in  this  mechanism  by  the  local 
system  and  by  the  central  nervous  system  respectively  have  not  yet  been 
thoroughly  made  out,  though  there  is  no  doubt  that  these  movements  may 
proceed  independently  of  any  connection  with  the  central  nervous  system. 

Stimulation  of  the  peripheral  end  of  the  vagus  nerves  may  exercise  vary- 
ing effects  on  the  gastric  wall  as  well  as  on  its  sphincters.  In  the  normal 
animal  stimulation  of  the  peripheral  end  of  the  vagus  as  a  rule  causes  strong 
contractions  of  the  oesophagus  as  well  as  of  the  cardiac  sphincter.  After 
the  administration  of  atropine,  stimulation  of  the  same  nerve  will  occasion 
dilatation  of  the  cardiac  sphincter.  On  both  cardiac  and  pyloric  portions  of 
the  stomach  the  vagus  exercises  inhibitory  as  well  as  augmentor  effects.  So 
far  as  concerns  the  musculature  of  the  fundus  or  body  of  the  stomach,  the 
most  usual  result  is  an  inhibition  during  stimulation  of  the  vagus  succeeded 
by  an  augmented  tonus  immediately  the  stimulus  is  removed.  If  the  vagus 
be  excited  a  number  of  times,  the  tonus  of  the  muscular  wall  augments  with 
each  stimulus.  On  the  pyloric  portion  stimulation  of  the  vagus  also  causes 
inhibition,  followed  by  contraction.  The  inhibition  may  however  be  very 
short  and  in  rare  cases  altogether  absent,  so  that  during  the  excitation  this 
inhibition  is  followed  by  a  series  of  large  rhythmic  contractions.  The  pre- 
vailing motor  effect  of  the  vagus  therefore  is  in  the  fundus  increased  tonus, 
in  the  pyloric  portion  augmented  peristaltic  waves.  On  the  pylorus  itself 
we  may  obtain  from  vagal  stimulation  either  increased  or  diminished  con- 
traction. The  conditions  under  which  each  of  these  may  be  evoked  have  not 
yet  been  definitely  ascertained.  Whether  the  splanchnic  nerve,  i.  e.  the 
sympathetic  system,  has  a  direct  influence  on  the  movements  of  the  stomach 
has  been  disputed.  According  to  Page  May  any  effect  produced  by  stimula- 
tion of  this  nerve,  generally  consisting  in  diminished  motor  activity,  is 
probably  due  to  the  simultaneous  influence  on  the  vascular  supply  to  the 
organ ;  the  blood  vessels  being  constricted,  an  artificial  anaemia  is  produced 
which  in  itself  is  sufficient  to  account  for  diminished  activity.  Other 
observers  regard  the  splanchnic  as  having  an  influence  on  the  stomach  similar 
to  its  action  on  the  intestine,  and  regard  it  as  the  chief  inhibitory  nerve  to 
this  organ.  It  is  possible  that  the  extent  to  which  the  stomach  is  brought 
under  the  control  of  the  sympathetic  system  may  vary  in  different  species  of 
animals. 

Cannon  has  shown  that  the  'pangs  of  hunger'  are  associated  with  and  probably 
due  to  rhythmic  contractions  of  the  stomach  wall,  which  come  on  about  meal  time, 
especially  if  this  be  delayed. 

VOMITING 

Expulsion  of  the  stomach  contents  may  occur  as  a  result  of  over- 
distension of  this  organ,  of  the  presence  of  irritating  material  in  its  contents, 
or  from  abnormal  conditions  of  the  brain.  It  is  generally  preceded  by  a 
feeling  of  nausea,  which  is  associated  with  salivation.  The  large  quantities 
of  saliva  swallowed  still  further  distend  the  stomach  and  assist  the  opening 
of  the  cardiac  orifice.  In  the  act  of  vomiting  itself  the  first  event  is  a  deep 
inspiration.    The  glottis  is  then  closed,  and  this  is  followed  by  a  strong 


THE   MOVEMENTS  OF  THE  STOMACH  747 

contraction  of  the  diaphragm  and  of  the  abdominal  muscles.  At  the  same 
time  the  cardiac  orifice  is  relaxed.  By  means  of  X-rays  it  may  be  seen  that 
at  this  time  a  strong  contraction  occurs  at  the  incisura  angularis,  dividing 
the  stomach  into  two  separate  portions.  The  dilated  body  of  the  stomach 
is  pressed  between  the  abdominal  muscles  and  the  diaphragm,  so  that  its 
contents  are  expelled  through  the  relaxed  oesophagus  and  out  through  the 
mouth.  As  vomiting  proceeds  the  stomach  contracts  down  on  the  remaining 
contents,  but  the  main  factor  in  the  expulsion  is  the  contraction  of  the 
abdominal  muscles  and  diaphragm.  In  fact,  vomiting  may  be  excited  in  an 
animal  in  which  the  stomach  has  been  replaced  by  a  bladder. 

NERVOUS   MECHANISM   OF   VOMITING 

Normally  the  action  of  vomiting  is  reflex.  It  can  be  excited  by  tickling 
the  back  of  the  throat,  when  the  afferent  nerves  are  the  trigeninal  and  the 
glossopharyngeal,  or  by  irritation  of  the  stomach  through  the  afferent  fibres 
of  the  vagus.  But  it  may  be  excited  from  almost  any  of  the  abdominal 
viscera,  e.  g.  uterus,  kidney,  intestines,  etc.  It  may  also  be  excited  reflexly 
through  the  labyrinth  or  through  the  eyes,  as  in  vomiting  of  sea-sickness, 
and  is  a  marked  symptom  in  many  cases  of  disease  of  the  cerebrum  and 
cerebellum.  The  efferent  impulses  are  carried  by  the  vagi  to  the  stomach, 
by  the  phrenics  to  the  diaphragm,  and  by  the  various  spinal  nerves  to  the 
abdominal  muscles.  There  are  also  inhibitory  impulses  descending  the  vagi 
to  the  oesophagus  and  cardiac  sphincter.  The  reflex  act  depends  on  the 
integrity  of  the  medulla,  so  that  a  '  vomiting  centre  '  is  sometimes  said  to 
be  situated  in  the  medulla. 

Drugs  may  produce  vomiting  either  by  irritating  the  stomach,  e.g. 
mustard  and  water,  zinc  sulphate,  ipecacuanha,  or  by  direct  action  on  the 
medullary  centres,  e.g.  tartar  emetic,  apomorphine,  etc. 


INTESTINAL   DIGESTION 

The  products  of  gastric  digestion,  after  being  worked  up  in  the  pyloric 
half  of  the  stomach,  are  passed  at  intervals  into  the  first  part  of  the  duo- 
denum. Here  they  meet  the  secretions  of  three  glands,  namely,  the  pancreas, 
the  liver,  and  the  tubular  glands  of  the  intestine.  La  addition  to  these  must 
be  mentioned  the  secretion  of  Brunner's  glands,  which  are  situated  at  the 
very  beginning  of  the  duodenum.  The  glands  of  Brunner  extend  only  over 
about  half  to  one  and  a  half  inches  in  the  carnivora,  such  as  the  dog  or  cat, 
but  in  the  herbivora  they  may  be  found  occupying  the  upper  six  inches  of 
the  intestine.  The  secretion  of  these  various  juices  is  practically  simul- 
taneous and  is  aroused  by  the  very  act  of  entry  of  the  acid  chyme  into  the 
duodenum.  Although  they  co-operate  in  their  action  on  the  foodstuffs,  it 
will  be  convenient  to  deal  separately  with  each,  both  as  regards  their  action 
and  the  mechanism  of  their  secretion. 


SECTION  V 

THE    PANCREATIC   JUICE 

Pore  pancreatic  juice  can  be  obtained  either  from  an  animal  with  a  perma- 
nent fistula  or  from  one  with  a  temporary  fistula  by  the  injection  of  secretin 
into  the  animal's  veins.  A  flow  of  pancreatic  juice  may  also  be  produced 
by  the  administration  of  pilocarpine.  This  drug  acts  however  as  a  poison 
on  many  tissues  of  the  body,  not  confining  its  action  to  the  pancreas  or 
even  to  the  secreting  glands.  It  is  not  to  be  wondered  at  therefore  that  the 
pancreatic  juice  obtained  by  its  injection  differs  in  quality  from  that  obtained 
by  the  more  natural  method  of  injection  of  secretin.  The  average  com- 
position of  pancreatic  juice  is  shown  in  the  Table  on  p.  749. 

It  is  a  clear  or  slightly  opalescent  fluid,  strongly  alkaline  from  the  presence 

N  N 

of  sodium  carbonate,  its  alkalinity  varying  between  —  and  —  Na2C03.    It  is 

therefore  about  as  alkaline  as  gastric  juice  is  acid,  and  it  will  be  found  that 
equal  quantities  of  gastric  juice  and  pancreatic  juice,  when  added  together, 
practically  neutralise  one  another.  The  proteins  of  the  juice  may  be  roughly 
divided  into  three  groups,  a  small  amount  of  nucleo -protein  precipitated 
on  acidification,  a  protein  coagulating  at  55°  C,  and  another  at  about  75°  C. 
The  juice  tends  to  become  poorer  in  proteins  and  richer  in  alkali  as  secre- 

748 


THE   PANCREATIC  JUICE 


749 


A 

B 

c 

Alkalinity  : 

(a) 

(b) 

Number  of  c.c.        NaOH  equal  to  I 
10 

ll'-T 

12-4 

0 

5-5 

10  c.c.  juice     .          .          .          . ) 
J.  "..  in  terms  of  Na  in  100  c.c. 

Total  solids  in  100  c.c.           .          .  \ 

0-2921 
1-6        \ 

1-5G       J 

0-2852 
2-25 

0-2587 

„    ( 

0-116o 

6-38 

6-10 

Total  proteins  in  100  c.c. 

0-5 

— 

— 

4-8 

( 
Ash  in  100  c.c j 

1-00       | 
0-92       | 

100 

1-00 

1-3 

Chlorides  in  100  c.c.     . 

0-280S  1 
0-2966  I 

— 

— 

ii  2695 

Total  nitrogen     .... 

— 

— 

0-735 

A.  Secretin  juice  from  three  dogs.     Sp.  gr.  1014. 

B.  Secretin  juice,  specimen  collected  at  beginning  (a),  and  at  end  (6). 

C.  Pilocarpine  juice. 

tion  proceeds.  The  concentrated  juice  obtained  by  injection  of  pilocarpine, 
which  may  contain  as  much  as  6  per  cent,  total  solids,  is  always  considerably 
less  alkaline  than  the  more  dilute  juice  got  by  injection  of  secretin.  The 
most  interesting  and  important  constituents  of  the  juice  are  its  ferments 
or  precursors  of  ferments.  The  juice  on  arrival  in  the  intestine  has,  or 
develops,  an  effect  on  all  three  classes  of  foodstuffs,  namely,  proteins,  fats, 
and  carbohydrates,  due  to  the  presence  of  distinct  ferments,  viz.  trypsin, 
steapsin  or  lipase,  and  amylopsin. 


/ 


ACTION    ON    PROTEINS 


Although  the  digestive  action  of  pancreatic  juice  on  proteins  was  pointed 
nut-  by  Corvisart,  little  attention  was  paid  to  this  effect  either  by  Claude 
Bernard  or  subsequent  authorities,  until  Kiilme  subjected  the  action  of 
extracts  of  the  gland  to  a  thorough  investigation.  The  neglect  of  this 
action  by  Claude  Bernard  mast  be  ascribed  to  the  fact  that  he  worked  with 
pancreatic  juice.  It  has  been  shown  more  recently  that  pancreatic  juice  as 
secreted  is  free  from  proteolytic  effects,  and  that  for  the  development  of  this 
power  it  is  necessary  that  some  change  should  be  brought  about  in  the  juice 
itself,  namely,  a  conversion  of  trypsinogen  into  trypsin.  This  change  under 
normal  circumstances  is  brought  about  directly  the  juice  enters  the  gut,  by 
the  action  of  a  substance — enterokinase — contained  in  the  succus  entericus. 
The  pancreatic  juice  thereby  acquires  a  proteolytic  activity  superior  to  that 
of  any  other  digestive  juice,  so  that  the  proteins  of  the  food  undergo  a  very 
thorough  disintegration.  The  different  constituents  of  the  protein  molecule 
show  a  varying  resistance  to  the  action  of  trypsin.  The  greater  part  of  the 
molecule  is  rapidly  broken  down  into  its  proximate  constituents,  namely, 
amino-acids,  and  the  same  change  is  undergone  by  the  proteoses  and  pep- 
tones resulting  from  the  gastric  digestion  of  proteins.  Within  a  few  minutes 
therefore  after  the  chyme  has  reached  the  small  intestine,  a  certain  amount 


750  PHYSIOLOGY 

of  ammo-acids  will  have  been  formed.  Some  of  the  groups  present  a 
resistance  to  disintegration.  After  tryptic  digestion  for  a  few  hours,  the 
mixture  will  be  found  still  to  contain  a  considerable  quantity  of  peptone, 
which  in  consequence  of  its  resistance  to  further  alteration  was  designated  by 
Kiilme  '  antipeptone.'  The  autipeptone  of  Kiihne  certainly  included  some 
of  the  diamino-acids,  which  at  that  time  had  not  been  isolated.  There  is 
always  a  part  however  which  gives  the  biuret  reaction  and  is  only  slightly 
broken  down  after  the  prolonged  action  of  trypsin.  Even  when  the  trypsin 
has  acted  for  weeks  and  the  biuret  reaction  has  entirely  disappeared,  the 
mixture  will  be  found  to  contain,  in  addition  to  the  separate  amino-acids, 
some  members  of  the  polypeptide  class,  composed  of  two  or  more  molecules 
of  amino-acid  united  together.  One  of  these  polypeptides  has  been  isolated 
by  Fischer  and  Abderhalden  from  the  products  of  tryptic  digestion  of  the 
protein  of  silk,  and  has  been  found  to  contain  glycine,  alanine,  and  proline. 
The  stages  in  tryptic  digestion,  e.g.  of  fibrin,  may  be  set  out  as  follows  : 

(1)  After  one  hour's  digestion — soluble  coagulable  protein,  deutero- 
albumose,  peptone,  amino-acids,  with  a  small  amount  of  alkali  metaprotein 
produced  by  the  action  of  the  alkali  of  the  juice. 

(2)  After  digestion  for  one  day — deutero-albumose,  '  antipeptone,' 
a  mil  i  u-acids,  polypeptides. 

(3)  After  digestion  for  one  month — amino-acids,  polypeptides. 
Among  the  amino-acids  tyrosine  is  one  of  the  first  to  be  split  off,  and  this 

substance,  with  leucine,  was  among  the  earliest  known  products  of  pancreatic 
digestion.  The  action  of  trypsin  is  thus  seen  to  resemble  very  closely  the 
action  of  boiling  concentrated  hydrochloric  acid.  Like  the  latter  it  attacks 
the  protein  molecule  at  the — CO— NH — coupling,  introducing  water  at 
this  point  and  therefore  breaking  up  the  polypeptide  groupings  into  simple 
amino-acids.  Why  it  always  leaves  a  certain  remnant  of  the  polypeptides 
unattached  is  not  at  present  explained.  The  investigation  of  its  action  on 
the  polypeptides  has  shown  that  very  minute  differences  in  the  grouping 
of  the  molecule  may  determine  whether  or  not  the  molecule  is  attacked  by 
trypsin.  Apparently  it  will  only  attack  such  molecules  as  are  present  in 
the  naturally  occurring  proteins.  Thus  under  the  action  of  trypsin  the 
following  polypeptides  undergo  hydrolytic  dissociation :  alanyl  glycine, 
alanyl  alanine,  alanyl  leucine  A;  while  the  closely  similar  polypeptides, 
glycyl  alanine,  glycyl  glycine,  alanyl  leucine  B  are  left  untouched. 


CONDITIONS   OF   TRYPTIC   ACTIVITY 

Since  the  pancreatic  juice  is  strongly  alkaline,  it  might  be  expected  that 
trypsin  would  be  most  effective  in  an  alkaline  medium.  It  must  be  remem- 
bered however  that  the  alkaline  juice,  when  secreted,  meets  the  correspond- 
ingly acid  contents  discharged  from  the  stomach,  and  that  the  resulting 
mixture  is  practically  neutral.  This  neutrality  exists  throughout  the  small 
intestine,  the  reaction  of  the  contents  of  the  gut  being  similar  to  that  of  a 
fluid  containing  alkali  which  has  been  saturated  by  the  passage  of  carbonic 


THE  PANCREATIC  JUICE  751 

acid,  viz.  alkaline  to  such  indicators  as  methyl  orange,  and  acid  to  such 
indicators  as  phenolphthalein.  On  investigating  the  action  of  trypsin  out- 
side the  body,  it  is  found  that,  at  any  rate  as  concerns  its  earlier  stages,  t  his 
ferment  is  more  active  in  the  presence  of  sodium  carbonate.  It  is  usual  to 
make  up  an  artificial  digestive  mixture  by  dissolving  commercial  trypsin  in 
0-2  to  0-3  per  cent,  sodium  carbonate.  The  optimum  amount  of  sodium 
carbonate  depends  on  the  strength  of  the  solution  in  trypsin  :  the  more 
trypsin  present  the  higher  is  the  optimum  amount  of  sodium  carbonate.  It 
is  stated  that,  although  an  alkaline  reaction  is  more  advantageous  for  the 
earlier  stages  of  tryptic  activity,  the  later  stages  take  place  best  in  a  neutral 
medium.  This  result  is  probably  due  to  the  fact  that  trypsin  in  alkaline 
medium  is  extremely  unstable  so  that,  when  prolonged  digestions  are  carried 
out,  the  trypsin  would  be  rapidly  destroyed  if  the  medium  were  strongly 
alkaline.  The  destructibility  of  trypsin,  as  well  as  its  action,  is  largely 
affected  by  the  presence  of  proteins  or  their  digestion  products  in  solution. 
Eayliss  has  adduced  evidence  to  show  that,  when  trypsin  acts  upon  protein, 
it  enters  into  some  form  of  combination  with  the  protein  molecule.  This 
combination  protects  the  trypsin  from  the  destructive  action  of  alkali.  The 
velocity  of  the  reaction,  which  takes  place  under  the  influence  of  trypsin, 
gradually  diminishes,  owing  probably  to  a  combination  of  the  trypsin  with 
the  products  of  digestion,  e.g.  with  the  peptones  or  amino-acids,  and  its 
consequent  removal  from  the  sphere  of  action.  If  by  any  means  the  amino- 
acids  be  removed  the  action  of  the  trypsin  is  renewed.  Destruction  of  the 
ferment  occurs  in  the  intestine  itself.  If  the  intestinal  contents  be  collected 
by  means  of  a  fistula  at  the  lower  end  of  the  ileum,  they  show  little  or  no 
proteolytic  activity.  Trypsin  is  therefore  an  extremely  active  ferment, 
which  carries  out  its  function  of  protein  hydrolysis  at  the  upper  part  of  the 
gut  and  is  destroyed  before  reaching  the  lower  end. 

THE   ACTIVATION   OF   PANCREATIC   JUICE 

It  was  observed  by  Kuhne  that  extracts  of  the  fresh  pancreas  did  not 
develop  their  full  activity  for  some  considerable  time,  the  development 
being  aided  by  preliminary  treatment  with  a  weak  acid.  When  a  pancreatic 
fistula  is  made  according  to  Pawlow's  •  method,  the  juice  obtained  always 
presents  some  proteolytic  activity.  It  was  shown  by  Pawlow  and  Chepo- 
walnikoff  that  the  development  of  the  activity  of  the  juice  was  due  to  the 
action  of  a  constituent  of  the  succus  entericus  which  they  named  enterokinase, 
and  it  has  since  been  found  that,  if  care  be  taken  to  avoid  contact  of  the 
juice  with  the  mucous  membrane  surrounding  the  orifice  of  the  duct,  it  is, 
when  secreted,  entirely  inactive.  The  enterokinase  acts  like  a  ferment 
on  a  body,  trypsinogen,  present  in  the  juice  as  secreted,  converting  this  into 
trypsin.     Pawlow  therefore  called  this  body  the  '  ferment  of  ferments.' 

This  view  of  the  action  of  enterokinase  has  been  challenged,  especially  by  Delczenne, 
according  to  whom  there  is  an  actual  combination  between  the  enterokinase  and  (lie 
trypsinogen,  trypsin  itself  being  a  mixture  or  combination  of  the  two  bodies.  He 
compared  the  reaction  to  that  of  the  hemolysins,  which,  as  is  well  known,  involve  in 


752  PHYSIOLOGY 

their  action  the  co-operation  of  two  bodies,  the  amboceptor  and  the  complement. 
If  (liis  were  correct,  there  should  always  be  a  proportionality  between  the  quantities 
of  trypsinogen  and  enterokinase  respectively  which  are  necessary  to  form  trypsin.  It 
lias  been  shown  by  Bayliss  and  Starling  that  this  proportionality  is  not  present.  The 
smallest  quantity  of  enterokinase  is  sufficient  to  activate  any  amount  of  trypsinogen 
if  sufficient  time  be  allowed.  The  effect  of  increasing  or  diminishing  the  amount  of 
enterokinase  is  not  to  alter  the  total  amount  of  trypsin  finally  produced,  but  merely 
the  time  taken  for  its  production.  This  behaviour  characterises  a  ferment,  and  we  may 
therefore  conclude  that  the  view  originally  put  forward  by  Pawlow  is  correct,  namely, 
that  trypsin  is  produced  from  trypsinogen  under  the  action  of  a  ferment,  enterokinase. 
If  pancreatic  juice  be  allowed  to  stand,  even  with  the  addition  of  toluol  to  prevent 
bacterial  infection,  it  gradually  acquires  a  certain  degree  of  activity.  If  however 
sochum  fluoride  be  used  as  an  antiseptic,  the  juice  remains  permanently  inactive.  The 
spontaneous  activation  of  the  juice  may  be  hastened  by  neutralisation.  The  most 
potent  means  next  to  enterokinase  is  the  addition  of  lime  salts.  If  a  few  drops  of 
10  per  cent,  calciiun  chloride  solution  be  added  to  fresh  pancreatic  juice,  the  calcium 
being  in  such  a  quantity  as  to  suffice  to  combine  with  all  the  carbonate  present  in  the 
juice,  complete  activation  of  the  juice  occurs  within  a  couple  of  days,  no  further  increase 
in  its  digestive  powers  being  obtained  on  subsequent  addition  of  enterokinase.  It  has 
been  suggested  that  the  action  of  calcium  is  in  some  way  to  assist  in  the  production 
of  an  enterokinase  from  some  precursor  of  this  body  already  present  in  the  juice. 
According  to  Mellanby,  the  calcium  acts  simply  by  neutralising  the  juice  and  thus 
allowing  minute  traces  of  enterokinase  already  present  in  the  juice  to  exert  their  effect. 
It  is  not  likely  that  this  calcium  activation  plays  any  part  in  the  normal  processes 
of  digestion,  since  for  its  completion  it  needs  twelve  to  sixteen  hours,  whereas  the 
enterokinase  present  in  the  succus  entericus  will  effect  the  activation  of  the  juice  within 
a  few  minutes. 

THE   ACTION   OF   PANCREATIC   JUICE   ON   MILK 

On  the  addition  of  pancreatic  juice  to  milk  a  clot  is  produced  which 
speedily  redissolves.  If  re-solution  takes  place  too  rapidly  the  production 
of  a  formed  clot  may  be  missed.  In  every  case  however,  on  heating  the 
milk  a  few  minutes  after  the  addition  of  the  trypsin,  a  clot  is  obtained.  How 
far  this  action  is  to  be  ascribed  to  the  proteolytic  ferment  trypsin,  or  how 
far  it  is  due  to  the  presence  of  a  free  rennet-like  ferment  in  the  juice,  is  not 
yet  definitely  settled.  Since  the  rennet  action  is  parallel  to  the  proteolytic 
activity  of  the  juice,  it  is  probable  that  we  must  regard  the  clotting  of  milk 
as  the  first  stage  in  its  proteolysis. 

THE   ACTION   OF   PANCREATIC   JUICE   ON   CARBOHYDRATES 

The  pancreatic  juice,  as  well  as  fresh  extracts  of  the  pancreas  itself, 
contains  a  strong  amylolytic  ferment,  diastase,  amylase,  or  amylopsin.  If 
a  few  drops  of  pancreatic  juice  be  added  to  a  1  per  cent,  solution  of  boiled 
starch,  within  a  few  seconds  the  solution  clears,  and  in  half  a  minute,  on  the 
addition  of  iodine,  a  red  colour  is  obtained,  showing  the  presence  of  erythro- 
dextrin.  At  the  end  of  a  few  minutes  no  colour  is  produced  with  iodine, 
and  the  solution  contains  maltose.  The  stages  in  the  hydrolysis  of  starch 
brought  about  with  pancreatic  juice  are  exactly  similar  to  those  effected 
by  ptyalin.  If  the  juice  be  neutralised,  the  process  of  hydrolysis  goes  on 
to  the  formation  of  dextrose  or  glucose.  This  further  conversion  is  due  to 
the  presence  in  the  juice  of  a  second  ferment — maltase — which  converts 


THE  PANCREATIC  JUICE  753 

the  disaccharide  maltose  into  the  monosaccharide  glucose.  The  juice  in 
the  gut  is  therefore  able  to  effect  the  further  digestion  of  the  products  of 
salivary  digestion.  On  the  other  disaccharides  pancreatic  juice  is  without 
effect.  It  contains  no  invertase,  nor  does  it,  in  spite  of  certain  statements 
to  the  contrary,  ever  contain  lactase.  It  has  therefore  no  effect  on  either 
cane  sugar  or  milk  sugar. 

'     THE  ACTION   OF  PANCREATIC  JUICE   ON   FATS 

Fresh  pancreatic  juice  contains  a  strong  lipase  or  fat-splitting  ferment,  by 
means  of  which,  in  the  presence  of  water,  neutral  fats,  e.  g.  the  triglycerides 
of  palmitic,  stearic,  and  oleic  acids,  are  broken  up  into  glycerin  and  the 
corresponding  fatty  acids.  This  ferment  is  active  either  in  alkaline,  neutral, 
or  very  slightly  acid  reaction.  If  the  reaction  be  alkaline,  the  fatty  acids 
produced  by  the  lipolysis  combine  with  the  alkali  present  with  the  formation 
of  soaps.  The  ferment  may  be  obtained  from  extracts  of  the  fresh  gland, 
but  is  rapidly  destroyed  if  active  trypsin  be  present.  It  is  also  contained  in 
some  of  the  dried  commercial  preparations  of  trypsin.  It  is  apparently 
insoluble  in  distilled  water,  and  is  therefore  found  in  the  residue  after  extract- 
ing these  commercial  preparations  with  water.  It  is  easily  soluble  in  glycerin. 
The  velocity  with  which  iipolysis  occurs  is  much  increased  (four  to  five  times) 
by  the  addition  of  bile.  This  adjuvant  action  of  bile  is  not  destroyed  by 
boiling,  and  is  due  entirely  to  the  bile  salts.  These  act  in  two  ways.  In 
the  first  place,  by  their  physical  qualities  they  diminish  the  surface  tension 
between  water  and  oil,  so  enabling  a  closer  contact  to  be  effected  between 
the  watery  solution  contained  in  the  juice  and  the  oil  which  is  presented 
to  it.  Moreover  they  may  aid  in  the  solution  of  the  ferment  itself.  In  the 
second  place,  bile  salts  have  a  solvent  action  on  soaps  as  well  as  on  fatty 
acids  in  slightly  acid  medium.  Bile  may  be  regarded  therefore  as  a  favour- 
able excipient  or  medium  for  the  interaction  of  the  lipase  and  the  neutral 
fats.  The  lipase  of  pancreatic  juice  will  also  hydrolyse  the  esters  of  the 
fatty  acids,  such  as  ethyl  butyrate  or  monobutyrin.  On  the  phosphorised 
fats  or  phosphatides,  such  as  lecithin,  its  action  is  still  a  subject  of  doubt. 
According  to  certain  authors  extracts  of  the  pancreas  have  the  power  of 
splitting  off  choline  from  lecithin.  It  is  not  known  whether  the  same 
property  is  present  in  pancreatic  juice  itself,  or  whether  any  other  dissocia- 
tions are  brought  about  in  the  complex  molecule  of  lecithin  under  the  action 
of  this  digestive  fluid. 

THE  SECRETION   OF   PANCREATIC   JUICE 

In  order  to  study  the  relation  of  the  secretion  of  pancreatic  juice  to  the 
other  processes  of  digestion,  observations  must  be  carried  out  on  an  animal 
with  a  permanent  pancreatic  fistula. 

Such  a  fistula  was  established  by  Claude  Bernard  by  bringing  the  duct  of  the  pancreas 

to   the  surface  and  inserting  into  it  a  lead  or  silver  tube.     The  arrangement  was 

unsatisfactory,  since  after  a  few  days  the  tube  dropped  out  and  the  natural  course  of 

the  duct  from  pancreas  to  intestine  was  restored.     In  order  to  avoid  the  disadvantages 

48 


754  PHYSIOLOGY 

of  this  proceeding  Heidenhain  and  Pawlow  independently  devised  another  method 
to  enable  us  to  determine  the  causes  of  pancreatic  secretion.  The  pancreas  in  most 
cases  possesses  two  ducts,  the  upper  one  opening  along  with  the  bile  duct,  the  lower  one 
a  short  way  down.  The  relative  sizes  ot  these  two  ducts  vary  in  different  animals, 
the  lower  one  being  larger  in  the  dog,  while  in  man  and  the  eat  the  upper  one  is  larger. 
In  order  to  establish  a  pancreatic  fistula  in  a  dog,  a  small  quadrilateral  piece  of  the 
duodenal  wall  is  exsected,  having  the  papilla  of  the  lower  duct  opening  in  the  middle 
of  its  mucous  surface.  The  integrity  of  the  gut  is  restored  by  suturing  in  a  single  line 
of  stitches  the  margins  of  the  wound  in  the  duodenum,  and  the  exsected  piece  is  brought 
to  the  surface  and  stitched  in  the  middle  of  the  abdominal  wound.  The  greater  part 
of  the  pancreatic  secretion  will  escape  by  the  fistula,  and  can  be  collected  either  by  the 
insertion  of  a  cannula  into  the  duct  or  by  attaching  a  glass  funnel  below  its  orifice. 
Great  care  has  to  be  taken  in  the  after  treatment  of  such  animals.  The  pancreatic 
juice,  which  flows  over  the  papilla,  acquires  in  so  doing  strong  proteolytic  powers, 
and  tends  therefore  to  dissolve  and  irritate  the  adjacent  abdominal  wall.  This  can  be 
prevented  by  taking  care  to  collect  all  the  juice,  and  to  allow  none  to  flow  away  over 
the  surface  of  the  body.  Another  drawback  is  that  the  continual  loss  of  pancreatic 
juice  in  many  cases  seriously  affects  the  animal's  health.  This  may  be  obviated  to  a 
certain  extent  by  keeping  the  animal  on  a  milk  diet  with  the  addition  of  sodium  bicar- 
bonate to  replace  the  loss  of  this  salt  by  the  juice.  With  great  care  Pawlow  has  succeeded 
in  keeping  such  animals  in  a  perfectly  healthy  condition. 

In  the  fasting  condition  there  is,  as  a  rule,  no  secretion  of  juice,  though 
the  escape  of  a  few  drops  may  be  observed  at  long  intervals.  If  a  meal  be 
administered  to  the  animal,  a  flow  of  juice  begins  in  one  to  one  and  a  half 
minutes.  From  this  time  there  is  a  steady,  slow  rise  of  the  rate  of  secre- 
tion, which  lasts  for  two  to  three  hours,  and  then  gradually  diminishes.  The 
greatest  increase  in  flow  is  observed  at  the  time  when  the  first  portions  of 
digested  food  escape  from  the  stomach  into  the  duodenum.  The  secretion 
must  therefore  be  determined  in  some  way  by  the  entry  of  this  food  into 
the  duodenum.  By  experiments  on  dogs  possessing  a  gastric  as  well  as  a 
pancreatic  fistula,  it  has  been  shown  that  the  introduction  of  acid,  e.  g. 
0-4  per  cent.  HC1,  into  the  stomach  evokes,  as  soon  as  it  passes  into  the 
duodenum,  a  rapid  flow  of  pancreatic  juice.  A  similar,  but  smaller,  effect 
is  produced  by  the  passage  of  oil  from  the  stomach  into  the  duodenum. 
The.  introduction  of  alkalies  is  without  effect.  Weak  acids  are  also  effective 
exciters  of  secretion  if  they  be  introduced  directly  into  the  duodenum  itself 
or  into  a  loop  of  small  intestine.  The  effect  gradually  diminishes  as  the 
loop  which  is  chosen  comes  nearer  to  the  csecum,  and  as  a  rule  the  injection 
of  dilute  acid  into  the  lower  foot  or  eighteen  inches  of  ileum  is  without  effect 
on  the  pancreas.  The  striking  resemblance  between  the  secretion  thus 
evoked  and  that  produced  in  the  salivary  glands  by  injection  of  acid  into 
the  mouth  suggests  that  we  have  here  to  do  with  a  reflex  of  the  same  kind 
as  that  which  affects  the  sab  vary  glands.  In  the  search  for  the  channels 
of  this  reflex  Heidenhain  showed  that  stimulation  of  the  medulla  oblongata 
occasionally  produced  a  flow  of  pancreatic  juice.  He  was  unable  however 
to  obtain  any  secretion  on  stimulation  of  the  vagus  nerve.  The  pancreas 
receives  fibres  from  the  vagi  as  well  as  from  the  splanchnic  nerves  (sym- 
pathetic system).  According  to  Pawlow  the  ill  success  of  Heidenhain's 
experiments  was  due  to  the  fact  that  in  any  operation  a  gland  is  played 
upon  by  reflex  impulses  partly  of  an  inhibitory,  partly  of  a  secretory  nature, 


THE  PANCREATIC  JUICE  755 

in  which  the  inhibitory  predominate,  and  by  the  further  fact  that  the 
pancreas  is  extremely  susceptible  to  alterations  in  its  blood  supply,  so  that 
any  stimulation  of  the  vagus  which  caused  inhibition  of  the  heart  would 
ipso  facto  prevent  the  effect  of  simultaneous  excitation  of  secretory  fibres 
from  making  its  appearance.  Pawlow  noticed  that  if  in  an  animal  with  a 
permanent  fistula  the  vagus  on  one  side  were  cut  and  left  for  four  days  in 
order  to  allow  the  cardio-inhibitory  fibres  to  degenerate,  repeated  stimula- 
tion of  the  peripheral  end  of  the  nerve  evoked  a  flow  of  pancreatic  juice. 
He  obtained  the  same  results  by  stimulating  this  nerve  below  the  point  at 
which  it  had  given  off  its  cardio-inhibitory  fibres,  in  animals  in  which  the 
reflex  inhibitions  from  the  operation  itself  were  prevented  by  total  section 
of  the  medulla.  Under  certain  circumstances  he  obtained  also  secretion 
on  stimulation  of  the  splanchnic  nerves,  and  therefore  concluded  that  these 
two  nerves — splanchuics  and  vagi — were  the  efferent  channels  in  the  reflex 
secretion  set  up  by  the  introduction  of  the  acid  into  the  duodenum.  It 
was  shown  later  however  independently  both  by  Popielski,  a  pupil  of 
Pawlow,  and  by  Wertheimer,  that  the  injection  of  acid  into  a  loop  of  small 
intestine  was  followed  by  secretion  of  juice  even  after  section  of  both  vagi 
and  destruction  of  the  sympathetic  ganglia  at  the  back  of  the  abdominal 
cavity.  On  repeating  these  experiments  Bayliss  and  Starling  found  that  a 
secretion  of  juice  was  produced  even  when  the  acid  was  introduced  into  a 
loop  of  the  small  intestine  entirely  freed  from  any  possible  nervous  connec- 
tions with  the  rest  of  the  body.  It  was  evident  therefore  that  the  stimulus 
or  message  from  the  intestine  to  the  pancreas  which  causes  the  secretion  of 
the  latter  must  be  carried,  not  by  the  nervous  system,  but  by  the  blood 
stream.  Since  the  injection  of  acid  into  the  portal  vein  was  without  effect 
on  the  pancreas,  it  was  concluded  that  something  must  be  produced  in  the 
epithelial  cells  of  the  gut  under  the  influence  of  acid,  and  that  this  product 
of  the  epithelial  cells  was  absorbed  in  the  blood  stream  and  was  the  active 
agent  in  exciting  the  pancreas.  On  pounding  up  some  scrapings  of  the 
intestinal  mucous  membrane  with  dilute  hydrochloric  acid  and  filtering,  and 
injecting  the  filtrate,  a  copious  flow  of  pancreatic  juice  was  produced.  This 
chemical  messenger  or  hormone  from  the  intestine  to  the  pancreas  is  called 
1  secretin,'  or  '  pancreatic  secretin '  to  distinguish  it  from  possible  other 
members  of  the  same  class.  It  is  produced  in  the  mucous  membrane  from 
a  precursor — pro-secretin.  The  latter  has  not  been  isolated,  but  that  it  is 
present  in  the  mucous  membrane  is  shown  by  the  fact  that  secretin  can  be 
extracted  by  the  action  of  acids  from  mucous  membrane  which  has  been 
killed  by  heat  or  by  the  prolonged  action  of  alcohol. 

Secretin  itself  is  not  a  ferment.  In  order  to  prepare  it  the  mucous 
membrane  is  groimd  up  with  sand,  boiled  wath  04  per  cent,  hydrochloric 
acid,  and  then  neutralised  while  boiling  by  the  cautious  addition  of  sodium 
hydrate.  The  coagulable  proteins  are  in  this  way  precipitated,  and  the 
filtered  solution  contains  the  secretin.  It  is  not  precipitated  by  the  ordinary 
alkaline  reagents,  and  diffuses  slowly  through  animal  membranes  Though 
stable  in  acid  solutions,  it  is  very  rapidly  destroyed  in  alkaline  or  neutral 


756  PHYSIOLOGY 

solutions,  especially  under  the  influence  of  bacteria.  It  is  apparently 
oxidised  with  extreme  ease.  A  similar,  or  more  probably  the  same,  body 
may  be  produced  from  intestinal  mucous  membrane  by  treating  this  with 
solutions  of  soap. 

Li  this  secreting  mechanism  we  have  a  very  striking  example  of  a 
correlation  between  the  activities  of  two  different  portions  of  the  body  effected 
by  chemical  means.  The  strongly  acid  chyme  enters  the  first  part  of  the 
duodenum.  Immediately  a  certain  amount  of  secretin  is  produced  by 
the  acid  in  the  cells  of  the  mucous  membrane.  The  secretin  is  carried  by 
the  blood  stream  to  the  cells  of  the  pancreas  and  excites  there  the  secretion 
of  strongly  alkaline  pancreatic  juice.  As  soon  as  sufficient  juice  has  been 
secreted  to  neutralise  the  acid  chyme,  the  formation  of  secretin  and  there- 
fore the  further  secretion  of  pancreatic  juice,  comes  to  an  end.  If  the  stomach 
still  contains  food,  the  process  is  however  renewed,  in  virtue  of  the  local 
reflex  mechanism  which  we  have  just  studied  regulating  the  opening  and 
closure  of  the  pylorus.  So  long  as  the  contents  of  the  duodenum  are  acid, 
the  pylorus  remains  firmly  closed.  As  soon  as  these  are  neutralised,  the 
pylorus  relaxes  and  allows  the  entrance  of  a  further  portion  of  acid  chyme. 
Thus  the  formation  of  secretin  proceeds  afresh,  and  the  whole  chain  of 
processes  goes  on  until  the  stomach  is  empty  and  all  its  contents  have 
passed  into  the  intestine. 

In  view  of  the  efficacy  of  this  chemical  reflex  mechanism,  the  question 
arises  whether  the  results  first  obtained  by  Pawlow  were  really  due  in  some 
way  to  the  formation  of  secretin.  Stimulation  of  the  vagus  may  cause 
contraction  of  the  stomach,  opening  or  closing  of  the  pylorus,  and  it  seems 
possible  that  under  its  action  there  might  have  been  an  escape  of  acid  gastric 
contents  into  the  intestine,  and  therefore  the  formation  of  secretin,  which 
would  suffice  to  arouse  the  pancreatic  secretion.  Later  experiments  by  this 
observer,  in  which  the  escape  of  any  gastric  contents  was  effectively  pre- 
vented by  ligature  of  the  pylorus  while  the  stomach  itself  contained  an 
alkaline  solution,  have  shown  that  even  with  these  precautions  a  flow  of  juice 
may  be  obtained  on  stimulation  of  the  vagus  nerve.  The  flow  however 
is  very  small  in  comparison  with  that  obtained  by  injection  of  secretin,  and 
one  must  conclude  that,  although  the  nervous  system  may  play  a  small 
part  in  the  excitation  of  the  activity  of  this  gland,  the  main  factor  involved 
is  the  chemical  mechanism  which  has  just  been  described. 

The  amount  of  pancreatic  juice  obtained  after  a  meal  varies  with  the 
nature  of  the  latter.  The  Table  on  p.  757  represents  the  results  obtained  on 
an  animal  fed  with  600  c.c.  of  milk,  250  grm.  of  bread,  and  100  grm.  of  meat 
respectively. 

The  differences  between  these  results  seem  largely  determined  by  the 
duration  of  gastric  digestion,  and  therefore  the  amount  of  acid  secreted 
in  the  stomach  and  passed  on  to  the  duodenum.  It  was  suggested  by 
Walther  that,  apart  from  this  quantitative  adaptation,  there  was  a  qualitative 
alteration  in  the  constitution  of  the  juice  according  to  the  nature  of  the 
food  ingested,  that,  e.g.,  excess  of  protein  causes  an  increase  of  the  trypsin, 


THE  PANCREATIC  JUICE 


757 


while  excess  of  carbohydrate  would  cause  an  increase  in  the  amylase  of  the 
juice.  Later  researches  have  failed  to  confirm  this  view.  Apparently  when 
the  pancreas  is  excited  to  secrete,  it  turns  oat  its  various  ferments  in  constant 
proportion,  depending  on  the  amounts  of  these  already  present  and  stored 
up  in  the  gland. 

Secretion  of  Pancreatic  Juice  (Walther) 


Hours  after  meal 

600  c.c.  milk 

250  grm.  bread 

100  grm.  meat 

1 

8-5  c.c. 

36-5  c.c. 

38-75  c.c. 

2 

7-6  c.c. 

50-2  c.c. 

44-6    c.c. 

3 

14-6  c.c. 

20-9  c.c. 

304    c.c. 

4 

11-2  c.c. 

14-1  c.c. 

16-9    c.c. 

5 

3-2  c.c. 

16-4  c.c. 

0-8    c.c. 

6 

1-0  c.c. 

12-7  c.c. 

— 

7 

— 

J0-7  c.c. 

— 

S 

— 

6-9  c.c. 

— 

THE   STRUCTURAL   CHANGES    IN   THE   PANCREAS 
ACCOMPANYING   SECRETION 

The  ease  with  which  secretin  may  be  prepared  and  used  to  arouse  the 
activity  of  the  pancreas  has  rendered  it  possible  to  study  more  closely  the 
changes  which  in  this  gland  accompany  activity.  Kuhne  and  Sheridan 
Lea  succeeded  in  observing  the  gland  of  the  rabbit  in  a  living  state  under  the 


Fio.  352.     A  terminal  lobulo  of  the  pancreas  of  the  rabbit.     (Kuhne  and 

Sheridan  Lea.) 

a,  in  resting  condition;   B,  after  active  socretion. 

microscope.  They  noted  that  activity,  excited  by  pilocarpine,  was  asso- 
ciated with  a  discharge  of  granules,  a  clearing  up  of  the  cells,  and  a  diminu- 
tion in  size  and  the  appearance  of  a  lumen  to  the  gland  alveoli  (Fig.  352). 
A  normal  resting  gland  is  of  an  opaque,  yellowish-white  colour  and  of  firm 
consistence.  On  section  it  is  seen  to  consist  of  numerous  secreting  alveoli 
which  open  into  narrow  intercalary  tubules,  and  these  in  their  turn  into  wide 
collecting  tubules.  The  lining  epithelium  of  the  intercalated  tubules  is 
often  continued  into  the  secreting  part,  where  they  he  internal  to  the  secret- 
ing cells,  as  the  so-called  centro-acinar  cells.    The  secreting  cells  themselves 


758 


PHYSIOLOGY 


present  two  well-marked  zones,  a  narrow  peripheral  zone  in  which  the 
nucleus  is  embedded,  which  is  strongly  basophile,  and  a  central  part  which 
is  turned  towards  the  lumen,  occupying  two-thirds  or  three-quarters  of  the 
cell,  and  is  closely  packed  with  highly  refractive  gramiles  strongly  acidophile 
and  presumably  containing  or  composed  of  the  precursors  of  the  various 
constituents  of  the  pancreatic  juice  (Fig.  353).  If  the  activity  of  the  gland 
be  aroused  by  injection  of  secretin  and  the  injection  be  continued  until  the 


Fig.  353.     Alveoli  of  dog's  pancreas.     (Babkin,  Rubaschkin  and  Sawitsch.) 
a,  resting ;  B,  after  moderate  secretion  with  discharge  of  granules. 

rate  of  secretion  evoked  by  each  injection  diminishes  considerabty,  i.  e.  the 
gland  shows  signs  of  fatigue,  marked  changes  are  observed  both  macro- 

«;ally  and  under  the  microscope.  The  gland  is  now  pink  and  trans- 
t  in  appearance,  moist  and  soft  in  consistence.  On  section  the  lumen 
3h  alveolus  is  enlarged,  the  cells  are  shrunken,  and  the  granules  are 
found  to  he  only  along  the  border  of  the  cell  turned  towards  the  lumen,  the 
rest  of  the  cell,  which  is  much  reduced  in  size,  being  made  up  of  the 
basophile  protoplasm.  Similar  effects  are  observed  after  long  continued 
stimulation  of  the  vagus  (Fig.  353  B). 


V 


SECTION  VI 
LIVER   AND    BILE 


The  liver,  the  largest  gland  in  the  body,  is,  like  the  other  glands  associated 
with  the  alimentary  tract,  formed  in  the  embryo  by  an  outgrowth  of  the 
hypoblast  lining  the  alimentary  canal.  At  first  it  resembles  in  structure 
other  secreting  glands,  such  as  the  pancreas,  being  composed  of  branch 
tubules  which  pour  their  secretion  into  a  common  duct.  In  the  adult 
however,  the  relation  of  the  hver  cells  to  the  ducts  is  entirely  subordinated 
to  their  relation  to  the  blood  vessels  of  the  liver,  and  it  requires  special 
histological  methods  to  make  out  the  relations  between  the  liver  cells  and 
the  bile  ducts.  The  hver,  on  section,  is  seen  to  be  divided  oft  into  lobules 
composed  of  columns  of  polygonal  cells,  radiating  from  the  centre  like  the 
spokes  of  a  cart-wheel.  The  portal  vein,  which  drains  the  blood  from  the 
alimentary  canal,  breaks  up  into  branches  which  he  at  the  periphery  of 
the  lobules,  forming  the  interlobular  veins,  and  send  off  numberless  capillaries 
which  pass  inwards  between  the  columns  of  cells  to  join  the  intralobular  vein 
lying  at  the  centre  of  the  lobule.  From  the  intralobular  the  blood  passes 
by  the  large  sublobular  vein  into  the  hepatic  veins  and  inferior  vena  cava. 
In  an  injected  specimen  it  is  easy  to  see  that  every  liver  cell  is  comiected 
with  at  least  one  blood  capillary,  and  the  liver  thus  forms  a  blood  gland, 
lying  as  it  does  at  the  gate  of  entrance  of  blood  from  the  alimentary  canal 
into  the  general  circulation.  The  portal  vein  conveys  only  venous  bloo^l 
to  the  liver.  In  order  to  supply  oxygen  to  the  working  hver  cells,1 
organ  receives  a  second  supply  of  arterial  blood  by  the  hepatic  artery  derr 
from  the  cceliac  branch  of  the  aorta.  The  branch  of  the  hepatic  artery  runs 
with  the  branches  of  the  portal  vein  in  the  connective  tissue  pf  Glisson's 
capsule  surrounding  the  lobules,  and  breaks  up  into  capillaries  which  are.  in 
free  communication  with  the  capillaries  derived  from  the  portal  system 
and  pour  their  blood  finally  into  the  hepatic  vein. 

As  might  be  expected  from  its  structure,  the  secretory  functions  of  the 
hver  represent  but  a  small  proportion  of  its  activities  in  the  body.  The 
liver  is,  in  fact,  the  greatest  chemical  factory  of  the  body,  receiving  by 
the  portal  vein  the  products  of  digestion  as  they  are  absorbed  from  the 
alimentary  canal.  It  converts  these  into  other  substances,  breaking  them 
down  or  building  them  up  according  to  the  needs  of  the  body  as  a  whole. 
Thus,  when  carbohydrates  are  being  absorbed  in  quantity,  it  converts  the 
glucose  contained  in  the  portal  blood  into  glycogen  which  it  stores  up, 

769 


blood 

2lW 


7G0 


PHYSIOLOGY 


reconverting  the  latter  into  glucose  and  letting  it  loose  into  the  circulation 
when  this  substance  is  required  by  the  body  tissues.    In  the  complete 
absence  of  carbohydrate  from  the  food,  the  liver  may,  as  we  shall  see  later, 
actually  convert  the  products  of  protein  digestion  into  sugar.    In  the  same 
way  the  liver  plays  an  important  part  in  the  metabolism  of  proteins  and 
of  fats,  so  that  its  functions  will  have  to  be  dealt  with  in  the  various  chapters 
concerned  with  the  fate  of  the  different  foodstuffs  and  different  constituents 
of  the  animal  body.    In  this  chapter  we  are  merely  concerned  with  its  action 
as  a  secreting  gland.    The  fact  that  its  secretion  is  in  so  many  animals 
poured  into  the  intestine  by  an  orifice  common  to  it  and  the  pancreatic  juice 
suggests  that  these  two  fluids  co-operate  in  their  actions  on  the  ingested 
foodstuffs,  and  points  to  a  direct  use  of  the  bile  in  the  processes  of  digestion. 
In  addition  to  this  function,  the  bile  must  also  be  regarded  as  an  excretion, 
representing  as  it  does  the  channel  by  which  the  products  of  disintegration 
of  haemoglobin — the  red  colouring-matter  of  the  blood — are  got  rid  of  from 
the  organism.    As  an  excretion  the  production  of  bile  must  be  continuous 
and  related,  not  to  the  processes  of  digestion,  but  to  the  intensity  of  destruc- 
tion of  the  red  corpuscles.     On  the  other  hand,  bile  as  a  digestive  fluid  is 
needed  in  the  gut  only  during  the  period  that  digestion  is  going  on.    The 
exigencies  of  the  body  therefore  require  a  continuous  excretion  of  bile  by  the 
liver,  but  a  discontinuous  entry  of  this  fluid  into  the  small  intestine.    This 
discontinuity  in  the  entry  of  a  continuous  secretion  into  the  intestine  is 
secured,  in  the  majority  of  animals,  by  the  existence  of  the  gall  bladder,  a 
diverticulum  from  the  bile  ducts,  in  which  all  bile,  secreted  during  the 
intervals  between  the  periods  of  digestive  activity,  is  stored  up.    In  the 
horse,  where  the  gall  bladder  is  absent,  its  place  is  taken  to  some  extent  by 
the  great  size  of  the  bile  ducts.    Moreover  in  such  an  animal  the  process  of 
digestion  is  much  more  continuous  in  character  than  it  is  in  carnivora. 
Since  the  bile  accumulates  in  the  gall  bladder  during  the  whole  time  that 
digestion  is  not  going  on,  and  is  only  poured  into  the  gut  during  digestion, 
ia^a  fasting  animal  the  gall  bladder  is  distended,  whereas  in  an  animal 
^Kb  hours  after  a  meal  the  gall  bladder  is  practically  empty. 
^^T>uring  the  period  that  the  bile  remains  in  the  gall  bladder  it  under- 
goes certain  changes,  as  is  shown  by  comparison  of  the  composition  of  bile 
obtained  fr,om  the  gall  bladder  with  that  obtained  from  a  fistula  of  the 
bile  duct. 


Analyses  of  Bile  (Human) 


From  a  biliary  fistula  (Yco  and  Herroun)  in  100  parts 

Mucin  and  pigments        .  .  0-148 

Sodium  taurocholate 

Sodium  glycocholate 

Cholesteriu    . 

Lecithin 

Fats   . 

Inorganic  salts 

Water  . 


From  the  gall  bladder  (Hoppe-Peyler)  in  100  pnrts 
Mucin 1-29 


0-055     Sodium  taurocholate 

0-87 

0-165      Sodium  glycocholate 

303 

Soaps 

1-39 

0038     Cholesterin 

0-35 

Lecithin 

053 

0-840     Pats    . 

0-73 

98-7 

THE   LIVER  AND  BILE  761 

During  its  stay  in  the  bladder  the  bile  is  concentrated  by  the  loss  of 
water  and  by  the  addition  to  it  of  mucin  or  nucleo-albumen,  derived  from 
the  cells  lining  the  bladder.  Of  the  other  constituents  of  bile,  the  pigments 
must  be  regarded  simply  as  waste  products,  and  an  index  to  the  disintegra- 
tion of  haemoglobin.  Their  mode  of  origin  will  be  discussed  in  dealing  with 
the  history  of  the  red  blood  corpuscles.  They  pass  into  the  intestine  and 
are  there  converted  by  the  processes  of  bacterial  reduction  into  stercobilin, 
which  is  excreted  for  the  most  part  with  the  faeces,  a  small  proportion  being 
absorbed  into  the  blood  vessels  and  turned  out  in  a  more  or  less  altered 
condition  as  the  pigments  of  the  urine.  From  the  point  of  view  of  digestion, 
the  important  constituents  of  bile  are  the  bile  salts,  with  the  lecithin  and 
cholesterin  held  in  solution  by  these  salts.  The  time  relations  of  the  secre- 
tion, as  well  as  of  the  flow  of  bile  into  the  intestine  in  connection  with  the 
processes  of  digestion,  can  be  learnt  from  animals  in  which  the  bile  is 
conducted  to  the  outside  of  the  body  by  means  of  a  permanent  fistula. 

For  this  purpose  Pawlow  has  devised  the  following  operation  :  In  the  dog  the 
abdomen  is  opened,  and  the  common  bile  duct  sought  as  it  passes  through  the  intestinal 
wall.  The  orifice  of  the  duct,  with  a  piece  of  the  surrounding  mucous  membrane, 
is  cut  out  of  the  wall  of  the  intestine,  and  the  aperture  thus  made  sutured.  The 
excised  portion  of  mucous  membrane,  with  the  opening  of  the  duct,  is  then  sewn  on  to 
the  surface  of  the  duodenum,  and  the  loop  of  duodenum  at  this  point  is  stitched  into 
the  abdominal  wound.  After  healing,  the  natural  orifice  of  the  bile  duct  is  thus  made 
to  open  on  the  surface  of  the  abdomen. 

In  an  animal  treated  in  this  way  the  flow  of  bile  from  the  fistula  is  found 
to  run  parallel  to  the  pancreatic  secretion.  Although  smaller  in  amount,  it 
rises  and  falls  with  the  latter.  Thus  a  meal  of  meat  produces  a  large  flow  of 
bile,  a  meal  of  carbohydrates  only  a  small  flow.  Moreover,  beginning  almost 
immediately  after  taking  food,  it  attains  its  maximum  with  the  pancreatic 
juice  in  the  third  hour  and  then  rapidly  declines. 

In  the  production  of  this  flow  of  bile  two  factors  may  be  involved  :  (1)  the 
emptying  of  the  gall  bladder;  (2)  an  increased  secretion  of  the  bile.  In 
order  to  determine  the  relative  importance  to  be  ascribed  to  each  factor, 
we  must  compare  the  results  obtained  on  an  animal  possessing  a  Pawlow 
fistula  with  those  obtained  on  an  animal  provided  with  a  fistulous  opening 
into  the  gall  bladder,  the  common  bile  duct  in  the  latter  having  been  ligatured 
to  ensure  that  the  total  secretion  of  bile  passes  out  by  the  fistula.  In  such 
animals  we  find,  as  we  should  expect,  that  the  secretion  of  bile  is  a  con- 
tinuous process,  but  that,  synchronously  with  the  great  outpouring  of  bile 
into  the  intestine  during  the  third  hour  after  a  meal,  there  is  an  increased 
secretion  of  tins  fluid.  The  passage  therefore  of  the  semi-digested  food 
from  the  stomach  into  the  duodenum  causes  not  only  a  slow  contraction 
and  emptying  of  the  gall  bladder  but  also  an  increased  secretion  of  bile  by 
the  liver.  What  is  the  mechanism  involved  in  the  production  of  these  two 
effects  ?  The  muscular  wall  of  the  gall  bladder,  as  has  been  shown  by  Dale, 
is  under  the  control  of  nerves  derived  both  from  the  vagus  and  from  the 
sympathetic,  the  former  conveying  motor  and  the  latter  inhibitory  impulses. 
It  is  usual  to  suppose  that  the  entry  of  acid  chyme  into  the  duodenum 


7G2  PHYSIOLOGY 

provokes  reflexly  the  concentration  of  the  gall  bladder,  but  the  exact  paths 
and  steps  in  this  reflex  act  have  not  yet  been  fully  determined.  The  increased 
secretion  of  bile,  which  is  produced  by  the  passage  of  the  acid  chyme  through 
the  pylorus,  can  be  also  evoked  by  the  introduction  of  acid,  such  as  0-4  per 
cent.  HC1,  into  the  duodenum,  and  occurs  even  after  division  of  all  con- 
nection between  the  liver  and  the  central  nervous  system.  Since  the 
presence  of  bile  is  necessary  for  the  full  development  of  the  activities  of  the 
pancreatic  juice,  and  its  secretion  is  initiated  by  the  same  sort  of  stimulus, 
i.  e.  acid  applied  to  the  mucous  membrane  of  the  gut,  the  question  naturally 
arises  whether  the  mechanism  for  the  secretion  of  bile  may  not  be  identical 
with  that  for  the  secretion  of  pancreatic  juice.  In  order  to  decide  this 
point  we  must  make  a  temporary  biliary  fistula  by  inserting  a  cannula  into 
the  hepatic  duct.  A  solution  of  secretin  is  then  prepared  from  an  animal's 
intestine.  In  making  this  solution  we  must  be  careful  to  avoid  any  con- 
tamination by  bile  salts,  which  may  possibly  be  adherent  to  the  mucous 
membrane  of  the  gut  and  would  in  themselves,  on  injection,  evoke  an  increased 
secretion  of  bile.  It  is  therefore  better  to  extract  the  pounded  mucous 
membrane  with  boiling  absolute  alcohol,  until  this  fluid,  evaporated  into 
a  small  bulk,  shows  no  trace  of  bile  salts.  The  dried  and  powdered  gut  is 
then  boiled  with  dilute  acid.  On  injecting  the  solution  of  secretin  so  obtained 
into  the  animal's  veins,  an  increased  flow  of  bile  is  at  once  produced.  In 
one  experiment,  for  instance,  the  injection  into  the  veins  of  5  c.c.  of  a  solu- 
tion of  secretin,  prepared  in  this  way,  increased  the  secretion  of  bile  by  the 
liver  from  twenty-seven  drops  in  fifteen  minutes  to  fifty-four  drops  in 
fifteen  minutes.  The  rate  of  secretion  was  therefore  doubled.  We  may 
conclude  that  the  mechanism,  by  which  the  increased  secretion  of  bile  is 
produced  at  the  time  when  this  fluid  is  required  in  the  intestine,  is  identical 
with  that  for  the  secretion  of  pancreatic  juice,  and  that  in  each  case  one 
and  the  sam^  substance — secretin — is  formed  by  the  action  of  the  acid  on 
the  cells  of  the  mucous  membrane  and,  on  absorption  into  the  blood  stream, 
excites  both  the  fiver  and  the  pancreas  to  increased  activity. 

THE   DIGESTIVE   FUNCTIONS   OF   THE   BILE 

Bile  contains  a  weak  amylolytic  ferment.  Its  uses  in  digestion  are 
dependent  however,  not  on  the  presence  of  this  ferment,  but  on  the  peculiar 
action  of  the  bile  salts  on  the  fermentative  powers  of  the  pancreatic  juice. 
It  was  shown  long  ago  by  Williams  and  Martin  that  the  amylolytic  power 
of  pancreatic  extracts  is  doubled  by  the  addition  of  bile  or  of  bile  salts. 
Pawlow  has  stated  that  the  same  holds  good  of  the  proteolytic  power  of  this 
juice.  Most  important  however  is  the  part  played  by  the  bile  in  the  diges- 
tion and  absorption  of  fats.  The  fat-splitting  action  of  pancreatic  juice  is 
trebled  by  the  addition  of  bile,  whether  boiled  or  unboiled.  This  quickening 
action  of  the  bile  probably  depends,  like  its  function  in  the  absorption  of 
fats,  on  the  peculiar  physical  properties  of  the  bile  salts,  with  those  of  the 
lecithin  and  cholesterin  which  they  hold  in  solution.  Not  only  does  such 
a  solution  diminish  the  surface  tension  between  watery  and  oily  fluids,  so 


THE  LIVER   AND   BILE  763 

promoting  the  closer  approach  of  the  lipase  of  the  pancreatic  juice  to  the 
fats  on  which  it  is  to  act,  but  it  has  also  the  power  of  dissolving  fatty  acids 
and  soaps,  including  even  the  insoluble  calcium  and  magnesium  soaps. 
It  is  probable  that  it  aids  also  in  holding  in  solution,  and  bringing  in  con- 
tact with  the  fat,  the  lipase  of  the  pancreatic  juice.  It  has  been  shown  by 
Nicloux  that  the  lipase  contained  in  oily  seeds,  such  as  those  of  the  castor 
plant,  is  insoluble  in  water,  but  soluble  in  fatty  media.  The  dried  ferment 
obtained  from  the  pancreas  in  many  cases  yields  no  lipase  to  water,  but 
gives  a  strongly  lipolytic  solution  when  extracted  with  glycerin.  The 
digestive  function  of  bile  therefore  lies  in  its  power  of  serving  as  a  vehicle 
for  the  suspension  and  solution  of  the  interacting  fats,  fatty  acids,  and 
fat-splitting  ferment.  This  vehicular  function  plays  an  important  part 
in  the  absorption  of  fats.  These  pass  through  the  striated  basilar  mem- 
brane bounding  the  intestinal  side  of  the  epithelium,  not,  as  was  formerly 
thought,  in  a  fine  state  of  suspension  (an  emulsion),  but  dissolved  in  the 
bile  in  the  form  of  fatty  acids  or  soaps  and  glycerin.  On  the  arrival  of 
these  products  of  digestion  in  the  epithelial  cells,  a  process  of  resynthesis 
is  set  up.  Droplets  of  neutral  fat  make  their  appearance  in  the  cells,  whence 
they  are  passed  gradually  into  the  central  lacteal  of  the  villus  and  so  into 
the  lymphatics  of  the  mesentery  and  into  the  thoracic  duct.  The  bile 
salts  thus  released  from  their  function  as  carriers  are  absorbed  by  the  blood 
circulating  through  the  capillaries  of  the  villi,  and  carried  by  the  portal 
vein  to  the  liver.  On  arrival  they  are  once  more  taken  up  by  the  liver 
cells  and  turned  out  into  the  bile.  Owing  to  the  fact  of  their  ready  excre- 
tion by  the  liveT  cells,  bile  salts  are  the  most  reliable  cholagogues  with 
which  we  are  acquainted .  By  this  circulation  of  bile  between  liver  and  intes- 
tine, the  synthetic  work  of  the  liver  in  the  production  of  the  bile  salts  is 
reduced  to  a  minimum,  and  it  has  only  to  replace  such  of  the  bile  salts  as 
undergo  destruction  in  the  alimentary  canal  under  the  influence  of  micro- 
organisms, and  are  lost  to  the  organism  by  passing  out  in  the  faeces  as  a 
gummy  amorphous  substance  known  as  dyslysin.  Further  investigation  is 
still  wanted  as  to  the  exact  method  in  which  secretin  acts  on  the  liver  cells, 
and  especially  as  to  whether  it  actually  excites  in  them  the  manufacture  of 
fresh  bile  salts,  or  whether  it  simply  hastens  the  excretion  of  such  bile  salts 
as  have  been  formed  by  the  spontaneous  activity  of  the  liver  cells  or  have 
arrived  at  them  after  absorption  from  the  alimentary  canal.  Such  questions 
can  be  decided  only  by  studying  the  action  of  secretin  on  animals  possessing 
a  permanent  biliary  fistula. 

The  eSect  of  various  diets  on  the  secretion  of  bile  has  been  studied  by  Barbera. 
He  finds  that,  whereas  the  secretion  of  bile  is  greatest  on  a  meat  diet,  it  is  somewhat 
less  on  a  diet  of  fat,  and  is  insignificant  on  a  purely  carbohydrate  diet.  That  is  to  say, 
l  In-  secretioD  of  bile  is  greatest  on  those  diets  the  digestion  of  which  is  attended  by  the 
passage  of  a  large  amount  of  acid  chyme  or  of  oil  into  the  duodenum.  Oil  is  almost 
as  efficacious  as  acid  in  promoting  the  production  of  secretin  in  the  living  duodenum, 
the  production  in  this  case  being  probably  determined  by  the  formation  of  soap  from 
the  oil  and  the  direct  action  of  the  soap  on  the  prosecretin  in  the  epithelial  cells  of 
the  gut. 


*s 


SECTION  VII 

THE    INTESTINAL   JUICE 

For  the  development  of  one  of  its  most  important  properties,  namely,  that 
of  proteolysis,  the  pancreatic  juice  is  dependent  on  the  co-operation  of  the 
intestinal  juice  or  succus  entericus.  Besides  this  activating  power  on  the 
pancreatic  juice,  the  intestinal  juice  has  numerous  other— functions  to 
discharge  in  the  digestion  of  the  foodstuffs.  In  spite  of  the  great  similarity 
which  obtains  between  the  microscopic  structure  of  the  wall  of  the  gut  at 
different  levels  from  duodenum  to  ileocolic  valve,  functionally  there  are  many 
differences  between  the  upper,  middle,  and  lower  portions  of  the  gut. 
Speaking  generally,  we  may  say  that,  whereas  the  processes  of  secretion  are 
better  marked  in  the  upper  portions  of  the  gut,  the  processes  of  absorption 
predominate  in  the  lower  sections,  i.  e.  in  the  ileum.  Much  of  the  divergence 
in  the  statements  which  have  been  made  with  regard  to  the  factors  determin- 
ing secretion  and  absorption  in  the  small  intestine  is  due  to  the  failure  to 
appreciate  this  great  difference  between  the  activity  of  the  mucous  membrane 
at  various  levels. 

The  process  of  secretion  in  the  small  intestine  may  be  studied  by  isolating  loops  by 
means  of  ligatures,  and  determining  the  amount  of  secretion  formed  in  these  loops  in 
the  course  of  a  few  hours'  experiment  on  an  anaesthetised  animal.  Better  results 
however  may  be  obtained  by  establishing  permanent  fistulse.  These  fistulas  are  of 
two  kinds.  Thiry's  original  method  of  establishing  a  fistula  consisted  in  cutting  out 
a  loop  of  intestine,  and  restoring  the  continuity  of  the  gut  by  suturing  the  two  ends 
from  which  the  loop  had  been  severed.  The  upper  end  of  the  loop  itself  is  closed  and 
the  lower  end  is  sutured  into  the  abdominal  wound.  For  some  purposes  it  is  better 
to  make  a  Thiry-Vella  fistula.  In  this  case  the  continuity  of  the  gut  is  restored  as  in 
the  simple  Thiry  fistula,  but  both  ends  of  the  excised  loop  are  left  open  and  brought 
into  the  abdominal  wound.  In  such  a  fistula  it  is  easy  to  introduce  substances  into 
the  upper  end  and  determine  the  flow  of  juice  from  the  lower  end,  the  constant  empty- 
ing of  the  loop  being  provided  for  by  the  peristaltic  contractions  of  its  muscular  coat. 

In  animals  with  intestinal  fistulae  a  number  of  different  conditions  have 
been  found  to  give  rise  to  a  flow  of  succus  entericus,  and  so  far  no  qualitative 
difference  has  been  recorded  between  the  upper  and  lower  ends  of  the  gut. 
A  condition  which  will  cause  a  free  flow  of  juice  from  a  fistula  high  up  in  the 
intestine  will  generally  cause  a  scanty  flow  from  a  fistula  made  from  the 
ileum.  In  all  cases  it  is  found  that  a  flow  of  juice  is  produced  in  consequence 
of  a  meal.  If  a  dog  with  a  fistula,  which  has  been  starved  for  twenty-four 
hours,  be  given  a  meal  of  meat,  a  flow  of  juice  may  begin  within  the  next 

7G4 


THE  INTESTINAL5  JUICE  765 

ten  minutes.  The  flow  remains  very  slight  for  about  two  hours  and  then 
suddenly  increases  in  amount  during  the  third  hour,  corresponding  thus 
very  nearly  to  the  flow  of  pancreatic  juice  excited  by  the  same  means.  In 
this  post-prandial  secretion  of  juice  it  is  not  probable  that  the  nervous  system 
takes  any  very  large  share,  though  its  intervention  in  the  secretion  has  not 
been  excluded  by  direct  experiment. 

There  are  certain  facts  which  seem  indeed  to  speak  for  an  action  of  the  central 
nervous  system  on  the  process  of  intestinal  secretion,  not  in  the  direction  of  augmenta- 
tion, but  in  the  direction  of  inhibition  of  secretion.  Thus  it  has  been  observed,  on 
many  occasions,  that  extirpation  of  the  nerve  plexuses  of  the  abdomen  or  section  of 
the  splanchnic  nerves  causes  a  condition  of  diarrhoea  which  may  last  for  two  or  three 
days.  This  condition  might  be  determined  either  by  an  increased  motor  activity  of 
the  gut,  or  by  removal  of  inhibitory  impulses  normally  arriving  at  the  intestinal  glands. 
Such  a  view  receives  support  from  an  experiment  first  performed  by  Moreau.  The 
abdomen  of  a  dog  is  opened  under  an  anaesthetic,  and  three  contiguous  loops  of  small 
intestine  are  separated  by  means  of  ligatures  from  the  rest  of  the  gut.  The  middle 
loop  is  then  denervated  by  destruction  of  all  the  nerve  fibres  lying  on  its  blood  vessels, 
as  they  course  through  the  mesentery,  care  being  taken  not  to  injure  the  blood  vessels 
themselves.  The  loops  are  then  replaced  in  the  abdomen  and  the  animal  left  from 
four  to  sixteen  hours.  On  killing  the  animal  at  the  end  of  this  time,  it  is  often  found 
that  the  middle  loop,  i.  e.  the  denervated  loop,  is  distended  with  fluid  having  all  the 
properties  of  ordinary  intestinal  juice,  whereas  the  other  two  loops  are  empty.  A 
series  of  comparative  experiments  by  Mendel  and  by  Falloise  have  shown  that  the 
secretion  begins  about  four  hours  after  the  operation,  increases  for  about  twelve  hours, 
and  then  rapidly  declines,  so  that  at  the  end  of  two  days  all  three  loops  will  be  found 
empty.  This  has  often  been  interpreted  as  due  to  the  removal  of  inhibitory  impulses 
passing  from  the  central  nervous  system  to  the  local  secretory  mechanism,  and  we  have 
no  direct  evidence  which  can  be  adduced  against  such  a  view.  It  is  possible  however 
that  the  hyperemia  of  the  gut,  which  is  produced  by  the  process  of  denervation, 
may  be  sufficient  to  account  for  the  increased  formation  of  intestinal  juice,  since  the 
hyperemia  will  tend  to  pass  off  as  the  vessels  recover  a  local  tone. 

It  is  not  possible  to  explain  the  flow  of  intestinal  juice  which  follows  a 
meal  by  any  assumption  of  nervous  impulses  transmitted  through  the  local 
nerve  plexuses  of  the  gut,  since  these  have  been  divided  in  the  making 
of  the  fistula.  If  we  exclude  a  nervous  reflex  action  by  the  long  paths, 
namely,  through  the  spinal  cord  and  the  sympathetic  or  vagus  nerves,  the 
flow  which  attends  the  passage  of  food  into  the  first  part  of  the  duodenum 
must  be  excited  by  the  formation  of  some  chemical  messenger.  As  to  the 
existence  of  such  a  chemical  messenger  or  hormone  for  the  intestinal  secretion 
there  can  be  no  doubt,  bat  the  evidence  as  to  its  precise  nature  is  at  present 
conflicting.  It  is  stated  by  Pawlow  that  the  most  effective  stimulus  to  the 
flow  of  succus  entericus  is  the  presence  of  pancreatic  juice  in  the  loop  of 
gut.  No  evidence  has  yet  been  brought  forward  that  injection  of  pancreatic 
juice  into  the  blood  stream  will  cause  any  flow  of  intestinal  juice.  On  the 
other  hand,  Delezenne  and  Frouin  have  shown  that,  in  animals  provided 
with  a  permanent  fistula  involving  the  duodenum  or  upper  part  of  the 
jejunum,  intravenous  injection  of  secretin  always  causes  a  secretion  of 
intestinal  juice.  In  the  upper  part  of  the  gut  therefore,  the  simultaneous 
presence  of  the  three  juices  necessary  for  complete  duodenal  digestion,  is 
ensured  by  one  and  the  same  mechanism,  namely,  by  the  simultaneous 


766  PHYSIOLOGY 

activity  of  the  secretin,  produced  in  the  intestinal  cells  by  the  action  of  the 
acid  chyme,  on  pancreas,  liver,  and  intestinal  glands.  A  further  chemical 
mechanism  for  the  arousing  of  intestinal  secretion  has  been  described 
by  Frouin.  According  to  this  observer,  the  flow  of  juice  can  be  excited  by 
intravenous  injection  of  intestinal  juice  itself.  Since  this  juice  is  alkaline 
and  does  not  produce  any  effect  on  the  pancreas,  it  must  be  free  from  pan- 
creatic secretin.  It  would  seem  therefore  that  the  flow  of  juice  in  the  upper 
part  of  the  gut,  excited  by  the  pancreatic  secretin,  causes  also  a  production  of 
a  different  secretin  or  hormone,  which  can  be  absorbed  from  the  lumen  of  the 
gut,  travel  by  the  blood  stream  to  other  segments  of  the  small  intestine,  and 
there  excite  a  secretion  in  preparation  for  the  on-coming  food.  Further 
experiments  are  however  necessary  on  this  point. 

The  glands  of  the  small  intestine  can  also  be  excited  by  direct  mechanical 
stimulation  of  the  mucous  membrane.  The  easiest  method  of  exciting  a 
flow  of  intestinal  juice  from  a  permanent  fistula  is  to  introduce  into  the 
intestine  a  rubber  tube.  The  presence  of  the  solid  object  in  the  gut  causes 
a  secretion,  and  within  a  few  minutes  drops  of  juice  can  be  obtained  from 
the  free  end  of  the  tube.  The  object  of  such  a  sensibility  to  mechanical 
stimuli  is  obvious;  it  is  of  the  highest  importance  that  the  onward  passage 
of  any  solid  object,  especially  if  it  .be  indigestible,  shall  be  aided  by  the 
further  secretion  of  juice  in  the  portions  of  gut  which  are  immediately 
stimulated.  This  mechanical  stimulation  probably  acts  on  the  tubular 
glands  of  the  intestine  through  the  intermediation  of  the  local  nervous 
system,  the  plexus  of  Meissner.  It  is  stated  by  Pawlow  that  a  juice  obtained 
by  mechanical  stimulation  differs  from  that  produced  by  the  introduction  of 
pancreatic  juice  into  the  loop  in  containing  little  or  no  enterokinase,  so  that 
the  pancreatic  juice  excites  the  secretion  of  the  substance  which  is  necessary 
for  its  own  activation. 


CHARACTERS   OF   INTESTINAL   JUICE 

The  intestinal  juice  obtained  from  a  permanent  fistula  has  a  specific 
gravity  of  about  1010.  It  is  generally  turbid  from  the  presence  in  it  of 
migrated  leucocytes  and  disintegrated  epithelial  cells.  It  contains  about 
1-5  per  cent,  total  solids,  of  which  0-8  per  cent,  are  inorganic  and  consist 
chiefly  of  sodium  carbonate  and  sodium  chloride.  It  is  markedly  alkaline  in 
reaction,  but  less  so  than  the  pancreatic  juice.  The  organic  matter,  besides 
a  small  amount  of  serum  albumin  and  serum  globulin,  includes  a  number  of 
ferments,  all  of  which  are  adapted  to  complete  the  processes  of  digestion 
of  the  foodstuffs  commenced  in  the  stomach  and  duodenum.  Of  these 
ferments  two  are  concerned  in  proteolysis.  Enterokinase  we  have  already 
studied  in  detail.  Possessing  itself  no  action  on  proteins,  its  presence  is 
necessary  for  the  development  of  the  full  proteolytic  powers  of  the  pancreatic 
juice.  In  addition  to  this  ferment  another  ferment  has  been  described  by 
Cohnheim  under  the  name  '  erepsin.'  Erepsin  or  some  similar  ferment  is 
present  in  the  fresh  pancreatic  juice  and  in  almost  all  tissues  of  the  body.     It 


THE  INTESTINAL  JUICE  767 

i.s  distinguished  by  the  fact  that,  although  it  has  no  power  of  digesting  coagu- 
lated protein  or  gelatin,  and  only  slowly  dissolves  caseinogen  and  fibrin,  it 
has  a  rapid  hydrolytic  effect  on  the  first  products  of  proteolysis,  converting 
alburnoses  and  peptones  into  amino-  and  diamino-acids — their  ultimate 
cleavage  products. 

The  other  ferments  of  the  intestinal  juice  are  connected  with  the  digestion 
of  carbohydrates.  In  all  mammals  the  intestinal  jaice  is  found  to  contain 
inverlase,  which  transforms  cane  sugar  into  glucose  and  lsevulose  or  fructose, 
and  maltose,  which  converts  maltose  into  glucose.  In  mammals  the 
intestinal  mucous  membrane  also  contains  lactase,  i.  e.  a  ferment  converting 
milk  sugar  into  galactose  and  glucose.  Such  a  ferment  can  be  extracted 
from  the  mucous  membrane  of  all  young  animals,  but  may  be  very  slight  or 
even  absent  in  the  intestines  of  older  animals,  when  it  is  no  longer  needed  for 
the  ordinary  processes  of  nutrition.  By  means  of  these  three  ferments, 
coming  as  they  do  after  the  digestion  of  the  starches  by  the  amylase  of  the 
saliva  and  pancreatic  juice,  it  is  provided  that  all  the  carbohydrate  food  of 
the  animal  is  transformed  into  a  hexose,  in  which  form  alone  carbohydrate 
can  be  taken  up  and  assimilated  by  the  cells  of  the  body.  The  seat  of  origin 
of  these  various  ferments  has  been  the  subject  of  special  investigations  by 
Falloise.  Whereas  secretin  can  be  obtained  from  the  whole  thickness  of  the 
mucous  membrane,  and  is  probably  therefore  contained  in  the  form  of 
prosecretin  in  the  epithelial  cells  covering  the  villi  as  well  as  in  those  lining 
the  follicles  of  Lieberkiihn,  a  superficial  scraping  of  the  mucous  membrane, 
which  removes  only  the  epithelial  cells  covering  the  villi  with  the  adherent 
mucus  and  intestinal  secretion,  gives  a  much  more  active  solution  of  entero- 
kinase  than  a  deeper  scraping.  The  most  active  solutions  of  enterokinase 
are  however  to  be  obtained  from  the  fluid  found  in  the  cavity  of  the  intestine 
after  the  injection  of  secretin.  It  seems  therefore  that  enterokinase  is  not 
present  as  such  in  the  epithelial  cells,  but  is  first  produced  in  the  process  of 
secretion  and  formation  of  the  intestinal  juice.  The  other  ferments,  namely, 
erepsin,  maltose,  inverlase,  and  lactase,  probably  pre-exist  as  such  in  the 
epithelial  cells,  especially  in  those  lining  the  tubular  glands  of  the  gut,  since 
pounded  mucous  membrane  in  water  yields  a  solution  of  these  ferments  which 
is  generally  more  powerful  in  its  action  than  the  succus  entericus  itself.  So 
great  is  the  difference,  in  fact,  that  many  physiologists  have  suggested  that 
the  chief  action  of  these  ferments  occurs,  not  in  the  lumen  of  the  gut,  but  in 
the  passage  of  the  foodstuffs  through  the  epithelial  cells  of  the  small  intestine 
on  their  way  to  the  blood  vessels. 


SECTION  VIII 

FUNCTIONS    OF   THE   LARGE    INTESTINE 

Grkat  differences  are  found  in  the  structure  of  the  large  intestine  of  different 
animals,  differences  which  depend,  not  on  the  zoological  position  of  the 
animal,  but  entirely  on  the  nature  of  its  food.  In  the  carnivora  the  large 
intestine  is  short  and  narrow  and  possesses  little  or  no  caecum.  In  herbivora 
the  large  intestine  is  well  developed  with  sacculated  walls,  and  the  caecum — - 
i.  e.  that  part  of  the  large  gut  distal  to  the  opening  of  the  ileum  into  the 
colon— is  very  large.  Man  occupies  a  somewhat  intermediate  position  be- 
tween these  two  classes.  The  differences  between  the  total  length  of  the 
alimentary  canal  in  various  animals  are  largely  determined  by  the  varying 
development  of  the  large  intestine.  The  relation  of  these  differences  to  the 
diet  is  seen  if  we  compare  the  length  of  the  intestine  with  the  length  of  the 
animal.  Thus  in  the  cat  the  intestine  is  three  times  the  length  of  the  animal, 
in  the  dog  from  four  to  six  times,  in  man  from  seven  to  eight  times,  in  the 
pig  fourteen  times,  and  in  the  sheep  twenty-seven  times.  The  great  develop- 
ment of  the  large  intestine  in  vegetable  feeders  is  due  to  the  fact  that,  in  this 
class  of  food,  all  the  nutritious  material  is  enclosed  in  cells  surrounded  by 
cellulose  walls.  In  order  that  the  foodstuffs — e.g.  proteins,  starch,  etc. — • 
may  be  dissolved  by  the  digestive  juices  and  absorbed  by  the  wall  of  the 
gut,  these  cellulose  walls  must  be  disintegrated.  In  none  of  the  higher  verte- 
brates do  we  find  any  cellulose-digesting  ferment,  cytase,  produced  in  the 
alimentary  canal.  The  cellulose  has  therefore  to  be  dissolved  either  by  the 
agency  of  bacteria  or  by  means  of  cellulose-dissolving  ferments  which  may  be 
present  in  the  vegetable  cells  themselves.  Thus  in  ruminants  the  masses  of 
grass  and  hay  are  first  received  into  the  paimch,  where  they  are  kept  warm 
and  moist  with  saliva.  In  the  paunch  opportunity  is  thus  given  for  the 
development  of  huge  numbers  of  micro-organisms  which  can  dissolve  cellu- 
lose. From  time  to  time  portions  of  the  sodden  mass  are  returned  to 
the  mouth,  chewed  and  then  swallowed  again  to  be  subjected  to  the  action 
of  the  proper  digestive  juices.  In  the  horse  and  rabbit  the  chief  part  of  the 
digestion  of  the  cellulose  occurs  in  the  C33cum.  Even  after  abstinence  from 
food  for  some  time  the  caecum  is  still  found  to  contain  food  material.  In  the 
caecum,  under  the  action  of  bacteria,  the  cellulose  is  dissolved  and  the  cells 
are  opened  up  so  as  to  allow  their  contents  to  escape.  The  products  of 
digestion  of  cellulose  include  a  number  of  organic  acids,  chiefly  of  the  lower 
fatty  acid  series,  as  well  as  methane,  carbon  dioxide,  and  hydrogen.  In  the 
paunch  the  acids  accumulate  so  that  fermentation  occurs  in  an  acid  medium, 

768 


FUNCTIONS  OF  THE  LARGE  INTESTINE  769 

whereas  in  the  caecum  the  acids  are  neutralised  by  the  secretion  of  alkalies 
and  the  reaction  remains  practically  neutral.  The  products  of  digestion 
of  cellulose,  as  well  as  the  contents  of  the  vegetable  cells  set  free  by  the 
solution  of  the  cell  walls,  are  gradually  absorbed  by  the  walls  of  the  large  gut. 
In  carnivora  the  large  intestine  has  very  unimportant  functions  to  discharge 
in  digestion  and  absorption.  The  proteins  of  meat  are  practically  entirely 
absorbed  by  the  time  that  the  food  has  arrived  at  the  ileocolic  valve,  and  the 
same  applies  to  fat.  In  man  the  importance  of  the  large  intestine  will  vary 
with  the  nature  of  his  food.  Under  the  conditions  of  civilised  life  the  food 
material  is  almost  entirely  absorbed  by  the  time  that  it  reaches  the  lower  end 
of  the  ileum.  If  however  a  large  quantity  of  vegetable  food  be  taken,  such 
as  fruit  or  green  vegetables,  or  cereals  roughly  prepared  and  coarsely  ground, 
a  considerable  amount  of  material  may  reach  the  large  intestine  unabsorbed. 
A  certain  proportion  of  this  may  undergo  absorption  in  the  large  intestine, 
while  the  rest  will  pass  oat  with  the  faeces,  increasing  their  bulk. 

It  is  hardly  possible  to  speak  of  a  secretion  by  the  mucous  membrane 
of  the  large  intestine.  In  herbivora  alkaline  carbonates  are  secreted  to 
neutralise  the  acids  produced  in  the  bacterial  fermentation  of  the  food,  but 
the  processes  of  absorption  and  secretion  keeping  pace,  there  is  no  accumu- 
lation of  the  products  of  secretion  in  the  intestine.  A  section  of  the  mucous 
membrane  shows  a  number  of  simple  tubular  glands.  The  greater  number  of 
the  cells  liniug  these  glands  are  typical  '  goblet '  cells  and  contain  plugs  of 
mucin.  The  secretion  of  mucus  not  only  aids  the  passage  of  the  faeces 
along  the  gut,  but  probably  impedes  the  propagation  of  the  bacteria  which 
are  present  in  countless  numbers  in  the  faeces.  This  may  account  for  the 
fact  that  although  bacteria  are  so  numerous  in  the  faeces,  it  is  difficult  to 
cultivate  any  large  numbers,  most  of  them  being  dead. 

As  an  absorbing  organ  the  large  intestine  of  man  is  of  little  importance. 
From  observations  on  fistulae  in  man  it  has  been  calculated  that  about  500 
c.c.  of  water  pass  the  ileocolic  valve  in  the  twenty-four  hours.  Of  these  about 
400  c.c.  undergo  absorption  in  the  large  intestine.  The  absorption  of  any 
of  the  food  substances  by  this  part  of  the  gut  is  much  slower  than  that  which 
takes  place  on  introduction  by  the  mouth.  Feeding  by  nutrient  enemata 
is  thus  always  very  inadequate.  In  some  cases  after  the  introduction  of 
large  enemata  into  the  large  intestine,  a  certain  amount  may  escape  back- 
wards into  the  ileum  and  may  there  undergo  absorption.  The  isolated  large 
intestine  of  man  is  able  to  absorb  only  about  6  grm.  of  dextrose  per 
hour  and  about  80  c.c.  of  water.  If  egg  albumin  or  caseinogen  solutions 
be  introduced  by  the  rectum,  no  absorption  can  be  detected  after  several 
hoars.  In  observations  extending  over  a  considerable  time,  some  disappear- 
ance has  been  observed  of  proteins  and  emulsified  fats,  as  well  as  of  boiled 
starch.  This  was  due  however  to  the  action  of  bacteria  on  these  substances, 
and  was  probably  of  very  little  value  for  the  nourishment  of  the  individual. 
Feeding  by  nutrient  enemata  is  thus  merely  a  method  of  slow  starvation. 
If  it  is  employed  it  should  be  limited  to  administration  of  water,  salines, 
or  solutions  of  glucose. 
49 


770  PHYSIOLOGY 

The  chief  value  of  the  large  intestine  in  carnivora  and  in  civilised  man 
would  seem  to  be  as  an  excretory  organ,  since  it  plays  an  important  part  in 
the  excretion  of  lime,  magnesium,  iron,  and  phosphates.  Lime  salts  are 
excreted  partly  with  the  faeces,  partly  in  the  urine.  The  path  taken  by  the 
lirne  under  different  conditions  varies  with  the  character  of  the  other  con- 
stituents of  the  food.  If  phosphates  are  present  in  large  quantities,  the 
greater  part  of  the  lime  will  be  excreted  by  the  large  intestine  and  escape 
with  the  faeces  as  insoluble  calcium  phosphate.  If  acids  be  administered, 
such  as  hydrochloric  acid,  the  amount  of  lime  in  the  urine  will  increase,  that 
in  the  faeces  will  diminish.  Thus  in  herbivora  normally  only  about  3  to  6 
per  cent,  of  the  lime  is  excreted  with  the  urine,  whereas  in  carnivora  with 
an  acid  urine  the  proportion  leaving  the  body  by  this  channel  rises  to 
27  per  cent.  The  excretion  of  magnesium  is  determined  by  very  similar 
conditions.  Its  phosphates  are  somewhat  more  soluble  than  those  of  lime. 
In  man  about  50  per  cent,  of  the  magnesium  leaving  the  body  is  contained  in 
the  urine,  whereas  the  amount  of  lime  in  the  faeces  is  ten  to  twenty  times 
as  much  as.  that  contained  in  the  urine.  It  must  be  remembered  that  the 
whole  of  this  difference  is  not  due  to  excretion  of  lime  into  the  gut,  since  a 
certain  proportion  of  this  substance  may  be  precipitated  as  an  insoluble 
phosphate  or  carbonate  in  the  upper  part  of  the  small  intestine  and  pass 
through  the  gut  without  undergoing  absorption. 

The  absorption  of  iron  takes  place  in  the  duodenum  and  upper  part  of 
the  jejunum.  Only  1  or  2  milligrammes  appear  in  the  urine,  all  the  rest 
being  excreted  in  the  large  gut  and  appearing  in  the  faeces,  chiefly  as  sulphide 
of  iron. 

Of  the  acid  radicals  phosphates  may  pass  out  either  with  the  urine  or  with 
the  faeces,  the  exact  path  taken  being  determined  by  the  relative  amount  of 
calcium  and  alkaline  metals  present  in  the  food.  If  there  is  an  excess  of 
calcium  most  of  the  phosphates  will  leave  with  the  faeces. 

The  large  intestine  is  the  main  channel  of  excretiou  for  certain  substances 
which  cannot  be  regarded  as  normal  constituents  of  the  food,  e.  g.  the  heavy 
metals,  such  as  bismuth  and  mercury.  If  bismuth  be  administered  sub- 
cutaneously,  the  faeces  will  be  found  to  contain  this  substance,  and  the  wall 
of  the  large  intestine  will  be  stained  black  from  a  deposit  of  sulphide  of 
bismuth.  This  deposit  stops  short  at  the  ileocolic  valve.  The  excretion 
of  mercury  by  the  wall  of  the  large  intestine  may  account  for  the  frequent 
presence  of  ulceration  of  +his  part  of  the  gut  in  cases  of  poisoning  by  mercury. 


SECTION  IX 

MOVEMENTS    OF   THE    INTESTINES 

The  movements  of  the  intestines  can  be  investigated  either  by  observation 
of  the  exposed  gut,  or  by  the  shadow  method  introduced  by  Cannon,  in  which 
the  nature  of  the  movements  is  judged  from  the  shadows  of  food  containing 
bismuth  which  are  thrown  on  a  sensitive  screen  by  means  of  the  Rontgen 
rays.     These  movements  have  been  the  subject  of  experimental  investigation 
for  many  years,  but  with  varying  results.    The  great  discrepancy  which 
obtained  between  the  statements  of  earlier  observers  is  due  to  the  fact  that 
they  failed  to  exclude  the  many  disturbing  impulses  which  can  play  on  any 
segment  of  the  gut,  either  reflexly  through  the  central  nervous  system,  or 
from  other  parts  of  the  alimentary  canal  itself  through  the  local  nervous 
system.     In  order  to  observe  the  normal  movements  of  the  gut,  it  is  neces- 
sary to  exclude  the  disturbing  influences  due  to  reflexes  through  the  central 
nervous  system,  either  by  extirpation  of  the  whole  of  the  nerve  plexuses  in 
the  abdomen,  or  by  division  of  the  splanchnic  nerves,  or  by  destruction  of  the 
lower  part  of  the  spinal  cord  from  about  the  middle  dorsal  region.     If  the 
abdomen  of  an  animal,  which  has  been  treated  in  this  way,  be  opened  in  a 
bath  of  warm  normal  salt  solution,  so  as  to  exclude  the  disturbing  influence 
of  drying  and  cooling  of  the  gut,  the  small  intestine  will  be  seen  to  present 
two  kinds  of  movements.     In  the  first  place,  all  the  coils  of  gut  undergo 
swaying  movements  from  side  to  side — the  so-called  pendular  movements. 
( lareful  observation  of  any  coil  will  show  that  these  movements  are  attended 
with  slight  waves  of  contraction  passing  rapidly  over  the  surface.     If  a 
rubber  balloon,  filled  with  air  and  connected  with  a  tambour,  be  inserted 
into  any  part  of  the  gut,  it  will  reveal  the  existence  of  rhythmic  contractions 
of  the  circular  muscle  repeated  from  twelve  to  thirteen  times  per  minute. 
By  means  of  a  special  piece  of  apparatus  (the  '  enterograph  ')  it  is  possible 
without  opening  the  gut  to  record  the  movements  of  either  circular  or 
Longitudinal  muscular  coats;  and  it  is  then  found  that  both  coats  present 
rhythmic  contractions  at  the  same  rate,  the  two  coats  at  any  point  con- 
tracting synchronously.     When  the  contractions  are  recorded  by  means  of  a 
balloon,  the  constriction  which  accompanies  each  contraction  is  seen  to 
be  most  marked  at  the  middle  of  the  balloon,  i.  e.  at  the  point  of  greatest 
tension,  and  the  amplitude  of  the  contractions  is  augmented  by  increasing 
the  tension  on  the  walls  of  the  gut.     These  movements  are  unaffected  by 
the  direct  application  of  drags  such  as  nicotine  or  cocaine,  which  we  might 

771 


772  PHYSIOLOGY 

expect  to  paralyse  any  local  nervous  structures  in  the  wall  of  the  gut. 
Bayliss  and  Starling  concluded  that  these  rhythmic  contractions  were 
myogenic,1  that  they  were  propagated  from  muscle  fibre  to  muscle  fibre,  and 
that  they  coursed  down  the  gut  at  the  rate  of  about  5  cm.  per  second.  Since 
however  they  may  apparently  arise  at  any  portion  of  the  gut  which  is  subject 
to  any  special  tension,  it  is  not  easy  to  be  certain  that  a  contraction  recorded 
at  any  point  is  really  propagated  from  a  point  two  or  three  inches  higher  up. 
These  contractions  must  cause  a  thorough  mixing  of  the  contents  of  the  gut 
with  the  digestive  fluids.  On  examining  under  the  Rontgen  rays  the 
intestines  of  a  cat  which  has  taken  a  large  meal  of  bread  and  milk  mixed  with 
bismuth  some  hours  previously,  a  length  of  gut  may  be  seen  in  which  the 
food  contents  form  a  continuous  column.     Suddenly  movements  occur  in  this 


i  v -  — — -~^j 

'  CD  CD  CD  CD  CD  M  ' 

FlG.  354.     Diagram  of  the  '  segmentation  '  (pendular)  movements  of  the  intestines  as 

observed  by  the  Rontgen  rays,  after  administration  of  bismuth.     (Cannon.) 

I.  A  continuous  column,  intestinal  movements  being  absent.     2.     The  column 

broken  up  into  segments.     3.  Five  seconds  later,  each  segment  divided  into  two, 

the  halves  joining  the  corresponding  halves  of  adjacent  segments.     4.  Condition 

(2)  repeated  five  seconds  later. 

column,  which  is  split  into  a  number  of  equal  segments.  Within  a  few 
seconds  each  of  these  segments  is  halved,  the  corresponding  halves  of  adja- 
sent  segments  uniting.  Again  contractions  recur  in  the  original  positions, 
dividing  the  newly  formed  segments  of  contents  and  re-forming  the  segments 
in  the  same  position  as  they  had  at  first  (Fig.  354).  If  the  contraction  is  a 
continuous  propagated  wave,  it  is  evidently  reinforced  at  regular  intervals 
down  the  gut,  so  as  to  divide  the  column  of  food  into  a  number  of  spherical 
or  oval  segments.  The  points  of  greatest  tension  immediately  become  the 
points  which  are  midway  between  the  spots  where  the  first  contractions 
were  most  pronounced.  The  second  contractions  therefore  start  at  these 
points  of  greatest  tension,  and  divide  the  first  formed  segments  into  two  parts, 
which  join  with  the  corresponding  halves  of  the  neighbouring  segments.  In 
this  way  every  particle  of  food  is  brought  successively  into  intimate  contact 
with  the  intestinal  wall.     These  movements  have  not  a  translatory  effect,  and 

1  Magnus  has  shown  that  strips  of  the  longitudinal  coat,  pulled  off  from  the  small 
intestine  of  the  cat,  may  continue  to  beat  regularly  in  oxygenated  Ringer's  solution.  He 
stated  that  these  contractions  occurred  only  if  portions  of  Auerbach's  plexus  were  still 
adherent  to  the  muscle  fibres,  and  concluded  therefore  that  the  rhythmic,  like  the 
peristaltic,  contractions  were  neurogenic.  Gun  and  Underhill  however  have  obtained 
well-marked  rhythmic  contractions  from  strips  of  muscle  entirely  free  from  any  remains 
of  the  nerve  plexus,  thus  confirming  the  view  enunciated  above. 


MOVEMENTS  OF  THE  INTESTINES  773 

a  column  of  food  may  remain  at  the  same  level  in  the  gut  for  a  considerable 
time. 

The  onward  progress  of  the  food  is  caused  by  a  true  peristaltic  contrac- 
tion, i.  e.  one  which  involves  contraction  of  the  gut  above  the  food  mass  and 
relaxation  of  the  gut  below.  If  a  balloon  be  inserted  in  the  lumen  of  the. 
exposed  gut,  it  will  be  found  that  pinching  the  gut  above  the  balloon  causes 
an  immediate  relaxation  of  the  muscular  wall  in  the  neighbourhood  of  the 
balloon.  This  inhibitory  influence  of  the  local  stimulus  may  extend  as 
much  as  two  feet  down  the  intestine  towards  the  ileocaecal  valve.  On  the 
other  hand,  pinching  the  gut  half  an  inch  below  the  situation  of  the  balloon 
causes  a  strong  continued  contraction  to  occur  at  the  balloon  itself  (Fig.  355). 


Fig.  355.  Intestinal  contraptions  (balloon  method).  In  this  dog  all  the  abdominal 
ganglia  had  been  excised,  and  both  vagi  cut.  Showing  propagated  effects  of 
mechanical  stimulation  above  and  below  the  balloon. 

(1)  pinch  above,  (2)  pinch  below,  (3)  pinch  below  balloon. 

Stimulation  at  any  portion  of  the  gut  causes  contraction  above  the  point  of 
stimulus  and  relaxation  below  the  point  of  stimulus  (the  '  law  of  the  intes- 
tines ').  The  same  effect  is  produced  by  introduction  of  a  bolus  of  food, 
especially  if  it  be  large  or  have  a  direct  irritating  effect  on  the  wall  of  the  gut 
(Fig.  356).  In  this  case  the  contraction  above  and  the  inhibition  below 
cause  an  onward  movement  of  the  bolus,  which  travels  slowly  down  the 
whole  length  of  the  gut  until  it  passes  through  the  ileocaecal  opening  into 
the  large  intestine.  The  peristaltic  contraction  involves  the  co-operation  of 
a  nervous  system.  Whereas  in  the  oesophagus  it  is  the  central  nervous 
system  which  is  involved,  the  peristaltic  contractions  in  the  small  intestine 
occur  after  severance  of  all  connection  with  the  brain  and  spinal  cord.  On 
the  other  hand,  they  aTe  absolutely  abolished  by  painting  the  intestine  with 
nicotine  or  with  cocaine.  They  must  therefore  be  ascribed  to  the  local 
nervous  system  contained  in  Auerbach's  plexus,  which  we  can  regard 
as  a  lowly  organised  nervous  system  with  practically  one  reaction, 
namely,  that  formulated  above  as  the  'law  of  the  intestines.'  An  anti- 
peristalsis  is  never  observed  in  the  small  intestine.  Mall  has  shown  that, 
if  a  short  length  of  gut  be  cut  out  and  reinserted  in  the  opposite  diredion,  a 
species  of  partial  obstruction  results,  in  consequence  of  the  fact  that  the  peri- 
staltic waves,  started  above  the  point  of  operation,  cannot  travel  downwards 


774  PHYSIOLOGY 

over  the  reversed  length  of  gut.  The  intestine  above  this  point  therefore 
becomes  dilated.  If  however  the  reactions  of  the  local  nervous  system 
be  paralysed  or  inhibited,  a  reflux  of  intestinal  contents  is  quite  possible,  since 
the  contractions  excited  at  any  spot  by  local  stimulation  (if  the  muscle  have 
the  effect  of  driving  the  food  either  upwards  or  down  wards ;  the  direction  of 
movement  of  tke  food  will  be  that  of  least  resistance. 

The  movements  of  the  small  intestine,  are  also  subject  to  the  central 
nervous  system.  Stimulation  of  the  vagus  has  the  effect  of  producing  an 
initial  inhibition  of  the  whole  small  intestine,  followed  by  increased  irrita- 
bility and  increased  contractions  (Fig.  357).  On  the  other  hand,  stimulation 
of  the  splanchnic  nerves  causes  complete  relaxation  of  both  coats  of  the  small 
gut  (Fig.  358).    It  seems  that  the  splanchnics  normally  exercise  a  tonic 


Fie:.  356.  Passage  of  bolus.  Contractions  of  longitudinal  coat  (enterograph).  The 
bolus  (of  soap  and  cotton-wool)  was  inserted  into  the  intestine  four  inches  above  the 
recorded  spot  at  A.  The  figures  below  the  tracing  indicate  the  distance  of  the  middle 
of  the  bolus  from  the  recording  levers.  As  the  bolus  arrives  two  inches  above  the 
levers,  there  is  cessation  of  the  rhythmic  contractions  and  inhibition  of  the  tone  of 
the  muscle.  This  is  followed,  as  the  bolus  is  forced  past,  by  a  strong  contraction  in 
the  rear  of  the  bolus. 

inhibitory  influence  on  the  intestinal  movements,  which  can  be  increased  by 
all  manner  of  peripheral  stimuli.  On  this  account  it  is  often  impossible  to 
obtain  any  movements  in  the  exposed  intestine  so  long  as  these  remain  in 
connection  with  the  central  nervous  system  through  the  splanchnic  nerves. 
The  relaxed  condition  of  the  gut  which  obtains  in  many  abdominal  affections 
is  probably  also  reflex  in  origin,  and  is  due  to  reflex  inhibition  through  the 
splanchnic  nerves. 

As  a  result  of  the  two  sets  of  movements  described  above,  the  food  is 
thoroughly  mixed  with  the  digestive  juices,  and  the  greater  part  of  the 
products  of  digestion  are  brought  into  contact  with  the  intestinal  wall  and 
absorbed.  What  is  left — a  proportion  varying  in  different  animals  according 
to  the  nature  of  the  food — is  passed  on  by  occasional  peristaltic  contractions 
through  the  lower  end  of  the  ileum  into  the  colon,  or  large  intestine.  The 
lowest  two  centimetres  of  the  ileum  present  a  distinct  thickening  of  the 
circular  muscular  coat,  forming  the  ileocolic  sphincter.  This  sphincter  relaxes 
in  front  of  a  peristaltic  wave  and  so  allows  the  passage  of  food  into  the  colon. 
On  the  other  hand,  it  contracts  as  a  rule  against  any  regurgitation  which 
might  be  caused  by  contractions  in  the  colon.  Although  thus  falling  into 
line  with  the  rest  of  the  muscular  coat  as  concerns  its  reaction  to  stimuli 


MOVEMENTS  OF  THE  INTESTINES  775 

arising  in  the  gut  above  or  below,  it  presents  a  marked  contrast  to  the  rest  of 
the  gut  in  its  relation  to  the  central  nervous  system.  It  is  unaffected  by 
stimulation  of  the  vagus.      Stimulation  of  the  splanchnic  however,  which 


Fig.  357.     Effect  of  stimulation  of  right  vagus  on  intestinal  contractions. 


Fig.  358.    Excitation  of  both  splanchnic  nerves.    Balloon  method.     Intestine 
returned  to  abdomen. 

causes  complete  relaxation  of  the  lower  part  of  the  ileum  with  the  rest  of  the 
small  intestine,  produces  a  strong  contraction  of  the  muscle  fibres  forming  the 
ileocolic  sphincter  (Elliott). 

MOVEMENTS  OF  THE  LARGE  INTESTINE 
By  means  of  the  occasional  peristaltic  contractions,  accompanied  by 
relaxation  of  the  ileocolic  sphincter,  the  contents  of  the  small  intestine 
are  gradually  transferred  into  the  large.  In  man  these  contents  are 
considerable  in  bulk,  are  semi-fluid,  and  probably  fill  the  ascending  as  well 
as  the  transverse  colon. 


776  PHYSIOLOGY 

The  large  intestine  is  supplied  with  nerves  from  the  central  nervous 
system.    These  run  partly  in  the  sympathetic  system  along  the  colonic 
and  inferior  mesenteric  nerves,  partly  in  the  pelvic  visceral  nerves  or  nervi 
erigentes,  which  come  off  from  the  sacral  cord  and  pass  direct  to  the  pelvic 
viscera.    In  addition  it  possesses  a  local  nervous  system,  presenting  the 
same  structure  as  that  found  in  the  small  intestine.    The  movements  of  the 
large  intestine  differ  considerably  in  various  animals,  as  has  been  shown  by 
Elliott,  according  to  the  nature  of  the  food  and  the  part  played  by  this 
portion  of  the  gut  in  the  processes  of  absorption.     In  the  dog  absorp- 
tion is  almost  complete  at  the  ileocolic  valve,  whereas  in  the  herbivora  a  very 
large  part  of  the  processes  of  digestion  and  absorption  occurs  in  the  colon  and 
csecum.    Man  takes  an  intermediate  position  as  regards  his  large  intestine 
between  these  two  groups  of  animals.    Elliott  and  Barclay  Smith  divide 
the  large  intestine  into  four  parts,  according  to  their  functions,  viz.  the 
csecum,  and  the  proximal,  intermediate,  and  distal  portions  of  the  colon. 
Of  these  the  dog  possesses  practically  only  the  distal  colon.    We  may  take 
Elliott's  account  of  the  movements  as  they  probably  occur  in  man.    They 
agree  very  closely  with  those  observed  by  Cannon  under  normal  circum- 
stances in  the  cat  by  means  of  the  Kontgen  rays.     The  food  as  it  passes  from 
the  ileum  first  fills  up  the  proximal  colon.    The  effect  of  this  distension  is  to 
cause  a  contraction  of  the  muscular  wall  at  the  junction  between  the  ascend- 
ing and  transverse  colon.      This  contraction  travels  slowly  over  the  tube 
in  a  backward  direction  towards  the  cascum,  and  is  quickly  succeeded  by 
another,  so  that  the  colon  may  present  at  the  same  time  several  of  these 
advancing  waves.    These  waves  are  spoken  of  as  anti-peristaltic;  but  as 
they  do  not  involve  also  an  advancing  wave  of  inhibition,  they  must  not 
be  regarded  as  representing  the  exact  antithesis  of  a  peristaltic  wave,  as  we 
have  defined  it.    The  effect  of  these  waves  is  to  force  the  food  up  into  the 
csecum,  regurgitation  into  the  ileum  being  prevented  partly  by  the  obliquity 
of  the  opening,  partly  by  the  tonic  contraction  of  the  ileocolic  sphincter. 
As  the  whole  of  the  contents  cannot  escape  into  the  caecum,  a  certain  portion 
will  slip  back  in  the  axis  of  the  tube,  so  that  these  movements  have  the  same 
effect,  as  the  similar  contractions  in  the  pyloric  end  of  the  stomach,  causing  a 
thorough  churning  up  of  the  contents  and  its  close  contact  with  the  intestinal 
wall.    The  movements  are  rendered  still  more  effective  by  the  sacculation  of 
the  walls  of  this  part  of  the  large  intestine.    The  distension  of  the  csecum 
paused   by  this  anti-peristalsis  excites   occasionally  a  true   co-ordinated 
peristaltic  wave  which,  starting  in  the  csecum,  drives  the  food  down  the 
intestine  into  the  transverse  part.    These  waves  die  away  before  they  reach 
the  end  of  the  colon,  and  the  food  is  driven  back  again  by  waves  of  anti- 
peristalsis.     Occasionally  more  food  escapes  through  the  ileocolic  sphincter 
from  the  ileum,  so  that  the  whole  ascending  and  transverse  colon  may  be  filled 
with  the  mass  undergoing  a  constant  kneading  and  mixing  process.     The 
result  of  this  process  is  the  absorption  of  the  greater  part  of  the  water  of  the 
intestinal  contents,  as  well  as  of  any  nutrient  material ;  and  the  drier  part  of 
the  intestinal  mass  collects  towards  the  splenic  flexure,  where  it  may  be 


MOVEMENTS  OF  THE  INTESTINES  777 

separated  by  transverse  waves  of  constriction  from  the  more  fluid  parts 
which  are  being  driven  to  and  fro  in  the  proximal  and  intermediate  portions. 
By  means  of  occasional  peristaltic  waves  these  hard  masses  are  driven  into 
the  distal  part  of  the  colorr.  The  distal  colon  must  be  regarded  as  a  place 
for  the  storage  of  the  faeces  and  as  the  organ  of  defsecation.  In  the  transverse 
colon,  in  the  descending  and  iliac  colon,  the  anti-peristaltic  movements  and 
consequent  churning  of  the  contents  are  probably  slight.  These  therefore 
represent  the  intermediate  colon,  with  propulsive  peristalsis  as  its  chief 
activity.    The  descending  colon  is  never  distended,  and  Elliott  therefore 


Fia.  359.  Skiagram  to  show  normal  position  of  colon  in  man,  and  the  position  attained 
by  its  contents  at  different  periods  after  a  meal  containing  bismuth.  The  bismuth 
meal  was  taken  at  8  a.m.  The  timos  of  arrival  at  different  leveLs  are  marked  on  tho 
colon.     (Hertz.  ) 

regards  it  as  a  transferring  segment  of  exaggerated  irritability.  The 
storage  of  the  waste  matter  takes  place  chiefly  in  the  sigmoid  flexure. 
This  with  the  rectum  represents  the  distal  portion  of  the  colon.  The  dis- 
tinguishing feature  of  the  distal  colon  is  its  complete  subordination  to  the 
spinal  centres.  It  probably  remains  inactive  until  an  increasing  distension 
excites  reflexly  through  the  pelvic  visceral  nerves  a  complete  evacuation  of 
this  portion  of  the  gut.  Stimulation  of  these  nerves  in  an  animal,  such  as  the 
cat,  produces  a  rapid  shortening  of  the  distal  part  of  the  colon,  due  to 
contraction  of  the  recto-coccygeus  and  longitudinal  fibres  of  the  gut,  followed 
after  some  seconds  by  a  contraction  of  the  circular  coat.  This  originates 
at  the  lower  limit  of  the  area  of  anti-peristalsis,  i.  e.  probably  at  the  upper  end 
of  the  sigmoid  flexure,  and  spreading  rapidly  downwards  empties  the  whole 
of  this  segment  of  the  gut.  In  man  the  emptying  of  the  rectum  itself  is 
largely  assisted  by  the  contractions  of  the  voluntary  muscles  of  the 
abdominal  walls  and  pelvic  floor. 

The  last  section  of  the  rectum  is  emptied  at  the  close  of  the  act,  by  a 


778  PHYSIOLOGY 

forcible  contraction  of  the  levator  ani  and  the  other  perineal  muscles,  and 
I  his  contraction  also  serves  to  restore  the  everted  mucous  membrane. 

The  carrying  out  of  this  reflex  act  is  dependent  on  the  integrity  of  a  certain 
part  of  the  lumbar  spinal  cord.  If  this  'centre'  be  destroyed,  the  tonic 
contraction  of  the  sphincter  muscles  disappears.  This  centre  may  be  either 
excited  to  increased  action,  or  be  inhibited  by  peripheral  stimulation  of 
various  nerves  or  by  emotion  such  as  fear.  Application  of  warmth  to  the 
region  of  the  anus  causes  reflex  relaxation  of  the  sphincter;  application  of 
cold  increases  its  tonic  contraction. 

In  man,  as  Hertz  has  shown  by  the  skiagraphic  method,  the  pelvic 
colon  becomes  filled  with  faeces  from  below  upwards,  the  rectum  remaining 
empty  till  just  before  defalcation.  In  individuals  whose  bowels  are  opened 
regularly  every  morning  after  breakfast,  the  entry  of  faeces  into  the  rectum 
gives  rise  to  a  sensation  of  fulness  and  acts  as  the  call  to  defalcation.  If 
no  response  be  made,  the  desire  to  defaecate  passes  away,  since  the  rectum 
relaxes  and  the  faecal  mass  no  longer  exercises  pressure  on  its  wall. '  Hertz 
has  shown  that  the  minimal  pressxire  required  to  produce  the  call  to  defaecate 
varies  from  30  to  40  mm.  Hg.,  according  to  the  length  of  the  gut  which  is  the 
seat  of  distension. 


SECTION  X 
THE   ABSORPTION    OF    THE    FOODSTUFFS 

THE   ABSORPTION   OF   WATER   AND   SALTS 

The  intake  of  water  and  probably  of  salts  by  the  alimentary  canal,  in 
accordance  with  the  requirements  of  the  organism  as  a  whole,  seems  to 
be  regulated  almost  entirely  by  the  central  nervous  system,  the  higher  parts 
of  this  system,  viz.  those  concerned  with  appetite,  being  particularly 
involved  in  the  process.  Thus  in  man  any  large  loss  of  fluid  to  the  body, 
as  by  sweating,  diarrhoea,  haemorrhage,  gives  rise  to  an  intense  thirst  that 
has  its  natural  reaction  in  increased  intake  of  water  by  the  mouth.  On  the 
other  hand,  the  property  possessed  by  the  alimentary  canal  of  absorbing 
water  and  weak  saline  fluids  contained  in  its  interior  is  veiy  little  influenced 
by  the  state  of  depletion,  or  otherwise,  of  the  water  depot's  of  the  body. 
It  is  practically  impossible,  however  large  the  quantities  of  fluid  ingested, 
to  evoke  the  production  of  fluid  motions,  the  greater  part  of  the  ingested 
fluid  being  absorbed  on  its  way  through  the  alimentary  canal.  Thus  a 
man  may  keep  himself  in  perfect  health  and  maintain  the  water  content  of 
his  body  constant  whether  he  take  one  litre  or  six  litres  of  water  daily. 
The  whole  process  of  regulation ,  apart  from  that  determined  by  appetite,  is 
carried  out  at  the  other  end  of  the  cycle,  viz.  by  the  kidneys.  As  concerns 
absorption  of  water  there  is  no  chemical  solidarity  between  the  alimentary 
surface  and  the  rest  of  the  body.  Whenever  water  is  presented  to  this 
surface  it  is  absorbed  and  passes  into  the  circulation. 

The  absorption  of  water  in  the  stomach  may  be  regarded  as  nil. 
Although  from  this  viscus  alcohol  and  possibly  peptone  and  sugar  may 
be  absorbed  to  a  slight  extent,  water  or  saline  fluids  introduced  into  it 
are  passed  through  the  pylorus  either  without  change  or  increased  by  the 
secretion  of  fluid  from  the  gastric  glands.  In  no  case  is  there  a  diminution 
of  fluid  in  the  stomach. 

The  chief  absorption  of  water  occurs  in  the  small  intestine.  It  is  on 
this  account  that  the  salient  features  of  cases  of  dilatation  of  the  stomach 
with  stenosis,  absolute  or  relative,  of  the  pyloric  orifice  can  be  nearly  all 
referred  to  the  starvation  of  the  body  in  water,  and  can  be  often  relieved 
by  the  administration  of  water  either  subcutaneously  or  by  the  rectum,  i.  e. 
by  the  channels  through  which  absorption  is  still  possible.  The  introduction 
of  water  into  the  stomach  simply  increases  the  dilatation,  but  does  not 
relieve  the  intense  thirst  of  the  patient.     Water  that  has  been  swallowed 

779 


780 


PHYSIOLOGY 


to  quench  thirst  has  first  to  be  passed  from  the  stomach  into  the  small 
intestine  before  it  can  be  absorbed  and  relieve  the  needs  of  the  tissues.  The 
intestinal  contents  at  tin-  ileocaecal  valve  contain  relatively  nearly  as  much 
water  as  they  do  at  the  upper  part  of  the  jejunum.  Their  absolute  bulk  is 
however  much  smaller,  so  that  only  a  small  proportion  of  the  water  that 
has  been  taken  in  by  the  mouth  remains  to  be  absorbed  in  the  large  gut— 
an  amount  probably  much  less  than  that  which  has  been  added  to  the 
contents  of  the  small  intestine  in  the  form  of  secretion  by  the  stomach, 
liver,  pancreas,  and  intestinal  tubules. 

The  main  problem  before  us  is  therefore  the  mechanism  of  absorption 
of  water  and  saline  fluids  by  the  villi  of  the  small  intestine.     By  means 


i  lentra]  lactea  I 


-  Submucosa 
Lymphatic  plexus 
Circular  muscle 

Lymphatic  plexus 
Longitudinal  muscle 


300.     Diagrammatic  section  through  wall  of  small  intestine  to  show  vascular  and 
lymphatic  arrangements  of  mucous  membrane.     (After  Mall.) 


of  these  structures  the  absorbing  surface  of  the  intestine  is  largely  increased. 
It  has  been  calculated  that  each  square  milhmetre  of  intestine  represents 
an  absorbing  surface  of  3  to  12  mm.2  Each  villus  (Fig.  360)  consists  of  a 
framework  of  reticular  tissue  containing  many  leucocytes  in  its  meshes, 
separated  from  the  lumen  of  the  gut  by  a  continuous  layer  of  columnar 
epithelial  cells.  These  cells  rest  on  an  incomplete  basement  membrane  aud 
present  on  the  side  turned  towards  the  lumen  of  the  gut  a  striated  border. 
The  villus  offers  two  channels  by  means  of  which  material,  which  has  passed 
through  the  epithelium,  may  be  carried  into  the  general  circulation.  In 
the  centre  of  the  villus  is  the  central  lacteal,  a  club-shaped  vessel  bounded 
by  a  complete  layer  of  delicate  endothelial  cells.  This  leads  into  a  plexus 
of  lymphatics  placed  superficially  to  the  muscularis  mucosa?.  From  the 
superficial  plexus  communicating  branches  pass  vertically  to  a  correspond- 
ing plexus  lying  in  the  submucosa.  The  central  lacteal  and  the  superficial 
plexus  are  free  from  valves,  which  however  are  present  in  abundance 
in  the  deeper  plexus,  so  that  fluid  can  pass  easily  from  the  lacteal  to  the 


THE  ABSORPTION   OF  THE  FOODSTUFFS  781 

deeper  plexus,  but  not  in  the  reverse  direction.  From  the  muscularis 
mucosa  unstriated  muscle  fibres  pass  up  through  the  villus  to  be  attached 
partly  to  the  other  surface  of  the  central  lacteal,  partly  by  expanded 
extremities  to  the  basement  membrane  covering  the  surface  of  the  villus. 
Contraction  of  these  muscle  fibres  will  tend  to  empty  the  central  lacteal 
into  the  deep  plexus  of  lymphatics  and  may  also  cause  an  expulsion  of 
the  contents  of  the  spaces  of  the  retiform  tissue  of  the  villus  into  the  central 
lacteal.  The  alimentary  canal  represents  one  of  the  few  localities  where  a 
formation  of  lymph  is  constantly  proceeding,  even  in  a  condition  of  com- 
plete rest.  On  placing  a  cannula  in  the  thoracic  duct  of  a  dog  an  outflow  of 
lymph  is  obtained  which  may  vary  in  different  animals  between  1  c.c.  and 
10  c.c.  in  the  ten  minutes.  The  greater  part  of  this  lymph  is  derived  from 
the  alimentary  canal,  so  that  any  of  the  intestinal  contents  which  have 
made  their  way  into  the  spaces  of  the  villus  might  be  entrained  in  this 
lymph  current  and  carried  away  with  it  into  the  thoracic  duct  and  so  into 
the  general  blood  system. 

The  other  possible  channel  of  absorption  is  by  the  capillary  blood 
vessels  of  the  villus.  Each  villus  is  supplied  with  blood  from  one  or  two 
arterioles  which  break  up  into  a  rich  plexus  of  capillaries  lying  close  under 
the  basement  membrane  of  the  villus.  The  return  blood  is  collected  into 
one  or  two  veins,  which  join  the  radicles  of  the  portal  vein  in  the  submucosa 
and  in  the  mesentery.  In  these  capillaries  the  blood  is  circulating  rapidly, 
so  that  a  considerable  amount  of  material  may  pass  into  them  from  the 
spaces  of  the  villus  within,  say,  one  hour  without  altering  appreciably  the 
percentage  composition  of  the  blood.  On  the  other  hand,  it  must  be  remem- 
bered that  the  blood  in  these  vessels  is  at  a  high  pressure,  probably  not  less 
than  30  mm.  Hg.,  so  that  any  absorption  into  the  blood  stream  must  occur 
against  this  pressure.  It  is  probable  therefore  that,  in  explaining  any 
absorption  by  the  blood  vessels,  we  shall  have  to  place  out  of  court  any 
possibility  of  the  passage  occurring  in  consequence  of  hydrostatic  differences 
of  pressure,  i.  e.  by  a  process  of  filtration'. 

When  salt  solutions  are  introduced  into  the  small  intestine,  they  are 
rapidly  absorbed  without  the  production  of  any  corresponding  increase  in 
the  rate  of  lymph  flow  from  the  thoracic  duct.  On  the  other  hand,  the 
absorption  of  large  amounts  of  fluid  may  cause  an  actual  diminution  of 
the  solids  of  the  plasma,  so  that  we  are  justified  in  regarding  the  capillary 
network  of  blood  vessels  at  the  surface  of  the  villi  as  solely  responsible  for 
the  absorption. 

What  are  the  forces  which  cause  this  transference  of  fluid  and  dissolved 
substances  from  one  side  to  the  other  of  the  membrane  composed  of  epithelial 
cells  plus  capillary  endothelium  ?  Like  other  cells,  those  of  the  intestinal 
epithelium  are  bounded  on  their  free  surface  by  a  '  lipoid '  membrane, 
i.  e.  one  containing  some  complex  of  lecithin  and  cholesterin  and  permeable 
only  by  such  substances  as  are  soluble  in  lipoids.  On  the  other  hand,  the 
cement  substance  between  the  cells  may  be  of  a  different  character  and 
possibly  permeable  to  water-soluble  substances.     The  question  has  been 


7«2  PHYSIOLOGY 

propounded  whether  the  greater  part  of  the  substances,  which  enter  the 
blood  plasma  from  the  gut,  pass  between  the  cells  or  through  the  cells.    Water 
could  of  course  pass  in  either  way.     Most  of  the  inorganic  salts  such  as 
sodium  chloride,  as  well  as  the  very  important  constituents  of  the  food, 
the  sugars,  are  insoluble  in  lipoids  and  would  have  to  pass    between  the 
cells.     When  the  question    is  investigated  by  the  use  of  dyestuffs,  soluble 
or  insoluble  in  lipoids,  it  is  found  that  the   lipoid-soluble  dyestuffs,  such 
as  neutral  red  or  tohiidin  blue,  pass  into  the  cells,  whereas  the  dyestuffs 
which  are  insoluble  in  such  substances  pass  into  the  intercellular  spaces. 
Too  much  stress  however  must  not  be  laid  on  these  experiments.     All  these 
dyestuffs  are  abnormal  so  far  as  the  body  is  concerned.     We  cannot  imagine 
that,  at  any  time  in  the  course  of  evolution  of  the  properties  of  the  intestinal 
epithelium,  the  cells  were  ever  presented  with  or  had  to  discriminate  between 
different  dyestuffs.     The  fact  that  absorption  of  these  dyestuffs  is  deter- 
mined by  the  physical  conditions  of  the  cell  membrane  is  no  proof  that  the 
absorption  of  the  normal  food  constituents  is  determined  in  the  same  way. 
In  fact,  it  is  quite  legitimate  to  assume  that  the  lipoid  membrane  or  limiting 
layer  round  every  cell  has  as  its  main  office,  not  the  regulation  of  the  access 
of  foodstuffs  to  the  cell,  but  its  protection  from  any  of  the  foodstuffs  which 
it  does  not  require  for  its  metabolism.     If  it  were  not  for  such  a  membrane 
the  assimilation  of  a  salt  would  be  determined  entirely  by  its  concentration 
in  the  immediate  surroundings  of  the  cell,  whereas  we  know  that  assimila- 
tion by  any  living  organism,  whether  uni-  or  multi-cellular,  is  regulated 
in  the  first  place  by  the  activity  of  the  organism  itself.     According  to  this 
activity  and  the  needs  thereby  induced,  the  uptake  of  food  material  may 
be  large  or  small  whatever  its  concentration  in  the  surrounding  medium. 
It  would  indeed  be  strange  that  the  whole  absorbing  surface  of  the  intestine 
should  be  covered  by  a  membrane,  of  which  the  greater  part  was  useless 
for  the  absorption  of  the  common  foodstuffs,  as  would  be  the  case  if  these 
could  only  penetrate  the  membrane  by  the  narrow  chinks  between  the 
cells.     It  seems  more  probable  that  the  absorption  of  the  different  food- 
stuffs, and  probably  also  of  the  normal  salts  of  the  body,  is  effected  by 
the  cells  themselves,  in  accordance  with  their  nutritional  needs,  and  this 
view  is  strengthened  when  we  come  to  examine  into  the  absorption  even 
of  normal  saline  solutions.     If  50  c.c.  of  normal  sodium  chloride  solution 
be  introduced  into  a  loop  of  intestine,  it  is  absorbed  steadily,  so  that  at 
the  end  of  an  hour  not  more  than  about  20  c.c.  may  be  recoverable.    The 
absolute  amounts  absorbed  differ  in  various  experiments,  but  are  fairly 
uniform   for  repeated   observations   on   one   and   the  same   animal.     The 
absorption  of  such  a  solution  could  be  ascribed  to  the  osmotic  pressure  of 
the  colloids  in  the  blood  plasma  or  lymph  within  the  spaces  of  the  villi. 
If,  instead  of  using  isotonic  solutions,  hypertonic  solutions  are  employed, 
e.  g.  a  2  or  3  per  cent.  NaCl  solution,  absorption  still  takes  place,  but  may 
be  preceded  by  an  interval  in  which  there  is  an  actual  increase  of  the  fluid 
contained  in  the  gut.     Here  again  we  might  ascribe  the  absorption  to  the 
physical  factors  present,  were  it  not  that  absorption  is  found  to  commence 


THE  ABSORPTION   OF   THE  FOODSTUFFS  783 

before  the  fluid  in  the  gut  has  attained  isotonicity  with  the  blood.  In  fact, 
employing  a  1-5  per  cent,  salt  solution,  absorption  may  occur  from  the 
very  beginning  of  the  experiment.  If  such  a  solution  is  passed  through 
the  epithelial  membrane  into  the  blood  plasma  with  a  smaller  tonicity, 
it  is  evident  that  work  must  be  done  in  the  process,  work  which  can  only 
be  furnished  by  the  cells  of  the  epithelium.  When  sugar  solutions  are 
employed  they  behave  in  somewhat  similar  fashion  to  sodium  chloride 
solutions,  provided  that  the  sugar  is  one  of  the  absorbable  hesoses,  both 
sugar  and  water  being  rapidly  absorbed.  It  is  important  to  note  that 
dextrose  is  absorbed  from  the  gut  almost  as  rapidly  as  sodium  chloride,  and 
quite  as  rapidly  as  sodium  iodide,  although  its  diffusibility  is  very  consider- 
ably less  than  either  of  these  salts.  Moreover,  great  differences  are  found 
between  the  rate  at  which  different  sugars  are  absorbed,  differences  which 
are  not  referable  to  the  diffusibility  of  the  sugars  in  question.  Thus  the 
monosaccharides  glucose,  fructose,  galactose  are  absorbed  with  double 
the  rapidity  of  solutions  of  cane  sugar  and  maltose,  and  it  seems  that,  in 
the  absence  of  hydrolytic  splitting  of  the  disaccharides,  absorption  from  the 
gut  would  be  entirely  abolished.  Lactose  disappears  from  the  intestine 
much  more  slowly  than  either  of  the  other  two  disaccharides,  so  that  large 
doses  may  give  rise  to  a  laxative  effect.  In  animals  devoid  of  lactase,  the 
lactose-splitting  ferment,  in  their  intestinal  epithelium  milk  sugar  is  apparently 
not  absorbed  at  all. 

The  most  cogent  argument,  perhaps,  in  favour  of  an  active  intervention 
of  the  cells  of  the  gut  in  the  process  of  absorption  is  furnished  by  the  study 
of  the  absorption  of  blood  serum.  It  has  been  shown  that  if  an  animaFs 
own  serum  be  introduced  into  a  loop  of  its  intestine  the  serum  undergoes 
absorption.  This  absorption  affects  the  water  and  salts  more  than  the 
protein,  so  that  the  percentage  of  the  proteins  in  the  fluid  remaining  in  the 
intestine  is  increased.  Finally  however  the  whole  of  the  serum  is  absorbed. 
In  this  case  the  fluid  within  the  gut  is  identical  with  the  fluid  within  the 
blood  vessels.  There  are  no  differences  in  concentration,  quality  of  salts, 
or  osmotic  pressure  of  proteins.  Nevertheless  water  passes  through  the 
cells  of  the  gut  from  their  inner  to  their  outer  sides,  entraining  with  it  the 
salts  of  the  serum  and  a  certain  proportion  of  the  indiffusible  proteins.  It 
is  impossible  to  explain  this  result  as  due  to  the  digestion  of  the  proteins 
and  their  conversion  into  diffusible  products,  since  the  intestinal  loops 
were  washed  free  of  any  trypsin  that  they  contained,  and  serum  has  itself 
'  a  strong  antitryptic  action  which  would  prevent  its  being  attacked  by  a 
solution  of  trypsin. 

The  active  intervention  of  the  cells  in  the  absorption  of  salt  solutions 
and  serum  can  be  abolished  by  any  means  which  diminishes  or  destroys 
their  vitality,  such  as  the  addition  of  sodium  fluoride  to  the  fluid  to  be 
absorbed,  or  destruction  of  the  epithelium  by  previous  temporary  occlusion 
of  the  blood  vessels  supplying  the  loop  of  intestine. 

We  must  conclude  that,  when  a  fluid  is  introduced  into  the  intestine,  an 
active  transference  of  water  from  the  lumen  into  the  blood  stream  is  effected 


784  PHYSIOLOGY 

by  the  intermediation  of  forces  having  their  origin  in  the  metabolism  of  the 
cells  themselves.  This  work  of  absorption  of  the  cells  may  be  aided  or 
hindered  according  to  the  physical  conditions  present.  If  these  act  against 
the  cells,  e.g.  if  the  fluid  be  hypertonic,  the  absorption  is  effected  more 
slowly,  while  with  hypotonic  solutions  the  physical  conditions  concur  with 
the  vital  activity  of  the  cells  in  bringing  about  a  very  rapid  transference  of 
fluid  from  the  gut  into  the  blood  vessels.  Among  these  physical  conditions 
we  must  reckon  the  nature  of  the  salts  present  in  the  solution.  If  these 
can  pass  easily  into  and  through  the  cells,  e.g.  ammonium  salts,  sodium 
chloride,  absorption  is  carried  out  rapidly.  If  on  the  other  hand  the  salts 
in  the  intestinal  contents  are  but  shghtly  diffusible  or  have  very  little  power 
of  penetrating  into  the  cells,  the  absorption  of  water  by  the  cells  causes  an 
increased  concentration  of  the  salts,  and  therefore  an  increased  osmotic 
pressure  which  offers  a  resistance  to  any  further  absorption;  and  the 
process  comes  to  an  end  when  the  absorptive  power  of  the  cells  is  exactly 
balanced  by  the  increased  osmotic  pressure,  or  attraction  for  water,  of  the 
intestinal  contents. 

Cushny  and  Wallace,  as  the  result  of  their  experiments  on  the  relative  absorbability 
of  salt  solutions  from  the  gut,  divide  the  salts  into,  four  main  classes  as  follows  : 


I 

II 

Ill 

IV 

Sodium  chloride, 

Ethyl  sulphate, 

Sulphate,  phosphate, 

Oxalate, 

bromide,  iodide, 

nitrate,  lactate,  sali- 

ferrocyanide,   capry- 

fluoride. 

formate,  acetate, 

cylate,  phthalate. 

late,  malonate,  succi- 

propionate, butyrate, 

nate,  malate,  citrate, 

valerianate,  caprate. 

tartrate. 

Of  these  the  first  class  contains  those  salts  which  are  absorbed  with  great  ease 
from  the  intestine.  The  second  group  of  salts  are  absorbed  with  somewhat  greater 
difficulty.  The  third  group  are  absorbed  so  slowly,  i.  e.  the  salts  retain  the  water  in 
which  they  are  dissolved  so  long  that  they  increase  peristalsis  and  act  as  laxatives  or 
purgatives.  The  members  of  the  fourth  class  are  not  absorbed  at  all.  It  is  evident 
that  this  classification  is  independent  of  the  diffusibility  of  the  salts.  Sodium  acetate 
has  a  much  smaller  dissociation  value  and  a  lower  diffusibility  than  sodium  chloride 
or  iodide,  and  yet  is  absorbed  at  approximately  the  same  rate  as  these  two  salts.  There 
is  however,  as  Cushny  pointed  out,  one  physical  or  chemical  character  which  apparently 
determines  the  non-absorbability  (relative  or  absolute)  of  the  members  of  the  tliird 
and  fourth  classes.  All  these  salts  form  insoluble  compounds  with  calcium.  This 
common  character  is  not  an  explanation  of  the  permeability  of  the  cell  wall,  but  is 
simply  a  general  statement  of  one  of  the  conditions  which  affect  the  power  of  the  cells 
to  take  up  salts  from  their  solutions,  this  power  being  absent  in  the  case  of  salts  which 
furnish  an  insoluble  calcium  compound. 

THE   ABSORPTION   OF  FATS 

Fats  administered  to  an  animal  in  excess  of  its  diurnal  requirements 
are  stored  up  in  the  body  in  the  form  in  which  they  are  administered.  Each 
cell  of  the  body  probably  possesses  in  itself  the  mechanism  for  the  utilisation 
of  these  neutral  fats,  and  for  effecting  in  them  the  various  changes  involved 
in  the  successive  stages  of  their  disintegration  and  oxidation  through  which 
they  are  finally  converted  to  C02  and  water.    The  problem  therefore  of  fat 


THE  ABSORPTION  OF  THE  FOODSTUFFS  785 

absorption  is  ultimately  one  of  the  simplest  with  which  we  have  to  deal, 
and  involves  merely  the  transference  of  the  neutral  fat  of  the  food  to  the 
circulating  fluids  in  such  a  form  that  it  can  be  carried  by  them  to  the  place 
where  it  is  required  for  the  metabolism  of  the  body  or  where  it  may  be 
stored  up  as  a  reserve  substance. 

The  processes  of  digestion  of  fat  result  in  the  production  of  glycerin  and 
fatty  acids,  if  the  reaction  be  neutral  or  slightly  acid.  If  the  reaction  of  the 
gut  be  alkaline,  the  alkali  will  combine  with  the  fatty  acids  to  produce  soaps. 
Analyses  of  the  contents  of  the  gut  after  a  fatty  meal  show  that  the  greater 
proportion  of  the  fats  are  present  as  a  mixture  of  fatty  acids  and  soaps,  the 
amount  of  these  substances  as  compared  with  unchanged  fat  increasing  as  we 
descend  the  gut. 

In  studying  the  absorption  of  fats  the  investigator  is  able  to  take  advantage  of  tho 
fact  that  the  micro-chemical  detection  of  this  substance  is  usually  very  easy.  Globules 
of  fats  or  fatty  acids  containing  any  proportion  of  the  unsaturated  fatty  acids  have 
the  property  of  reducing  osmic  acid,  and  therefore  of  being  stained  black  by  this  reagent. 
Practically  all  the  fats  which  occur  in  the  food  or  in  the  cells  of  the  body  contain  oleic 
acid  or  the  glyeende  of  this  acid  in  association  with  palmitic  or  stearic  acid,  and  therefore 
give  the  typical  micro-ohemical  fat  reactions.  In  many  cases  it  is  useful  to  employ  the 
specific  stains  for  fats,  such  as  Sudan  red  or  alkanna  red.  It  is  important  to  remember 
that  the  intensity  of  the  fat  reaction  given  by  a  cell  is  only  an  expression  of  the  fat  or 
fatty  acid  contained  in  a  free  state  in  the  cell,  and  is  no  criterion  of  the  total  amount  of 
fat  which  may  be  present.  Thus  a  normal  heart  muscle  in  section  gives  only  a  diffuse 
light  brown  coloration  with  osmic  acid.  After  poisoning  by  phosphorus  or  by  diphtheria 
toxin,  every  muscle  cell  may  be  found  studded  with  minute  black  granules  of  fat. 
Chemical  analysis  shows  however  that  the  normal  heart  muscle  contains  as  much  fat 
as  the  degenerated  muscle.  Our  micro-chemical  methods  will  therefore  throw  no  light 
on  the  amount  of  fat  which  is  actually  in  combination  with  the  cell  protoplasm. 

If  an  animal  be  examined  a  few  hours  after  the  administration  of  a 
meal  rich  in  fats,  the  lymphatics  of  the  intestine  are  seen  to  be  distended 
with  a  milky  fluid — chyle — and  the  same  fluid  is  found  filling  the  cistema 
lymphatica  magna  and  the  thoracic  duct.  The  lymph  from  the  thoracic 
duct  will  also  be  niilky,  and  chemical  analysis  shows  that  the  opacity  is  due 
to  the  presence  of  minute  granules  of  neutral  fat.  The  fat  in  such  chyle 
may  amount  to  over  6  per  cent.,  so  that  in  a  moderate-sized  dog  12  grammes 
of  fat  may  be  carried  in  the  course  of  au  hour  from  the  intestine  to  the  blood 
by  this  means.  This  great  access  of  fat  to  the  blood  during  fat  absorption 
introduces  corresponding  changes  in  the  blood.-  The  plasma  itself  becomes 
milky,  and  if  the  blood  be  allowed  to  clot,  the  serum  expressed  from  the  clot 
is  also  milky.  On  standing,  a  layer  of  fat  globules  hke  cream  may  rise 
to  the  surface  of  the  serum.  Fat  is  found  in  a  free  state  in  this  finely  divided 
condition  in  the  blood  plasma  so  long  as  it  is  being  absorbed  in  the  intestine. 
During  starvation  it  disappears  entirely,  the  serum  becoming  perfectly  clear. 
Thus  part,  at  any  rate,  of  the  fat  which  is  absorbed  from  the  gut  is  carried 
thence  by  the  lymphatic  channels  in  the  form  of  neutral  fat  to  the  blood 
stream,  by  which  it  is  distributed  to  the  various  tissues  of  the  body,  gradually 
leaving  the  blood  stream  in  a  manner  which  at  present  has  not  been  deter- 
mined. Not  all  the  fat  which  is  absorbed  takes  this  path  by  wav  of  the 
50 


786  l'liYSIOLocY 

lymphatics  and  the  thoracic  duct.  Ligature  of  the  thoracic  duct,  if  effective, 
certainly  impedes  the  absorption  of  fat,  but  does  not  abolish  it.  If  the 
thoracic  duel  lymph  be  collected  during  the  absorption  of  a  given  quantity  of 
fat  from  the  intestine,  not  more  than  60  per  cent,  of  the  fat  which  has  disap- 
peared from  the  gut  can  be  recovered  from  the  lymph.  What  happens  to 
the  remainder  we  do  not  know.  Apparently  it  does  not  reach  the  blood 
in  a  finely  divided  condition.  If  the  thoracic  duct  be  ligatured,  the  per- 
centage of  fat  in  the  blood  rapidly  falls  to  a  minimum  which  remains 
constant,  even  during  starvation.  If  now  fat  be  administered,  although  a 
considerable  proportion  of  it  may  be  absorbed,  the  percentage  of  fat  in  the 


•»• 


••  • 


Fig.  361.  Columnar  epithelium  from  small  intestine  of  frog  stained  with  osmic 
acid  to  show  fat  absorption. 
A,  five  hours  after  a  meal  of  olive  oil;  B,  three  hours  later.  It  should  be  noticed 
that  the  fat  globules  first  formed  grow  in  size  in  the  course  of  digestion,  pointing 
to  a  gradual  deposition  of  fat  on  the  globules  from  solution  in  the  protoplasm. 
(Schafer.  ) 

blood  is  not  raised.  If  therefore  the  fat  is  absorbed  directly  into  the  blood, 
it  cannot  be  in  the  particulate  condition,  and  it  must  be  in  such  small 
quantities  at  a  time  that  it  is  at  once  removed  from  the  blood  by  the  tissues 
through  which  this  fluid  flows.  It  is  difficult  to  imagine  that  any  large 
proportion  of  this  lost  fraction  of  the  fat  is  absorbed  into  the  blood  stream 
in  the  form  of  soaps,  since,  as  Munk  has  shown,  soaps  injected  into  the 
blood  stream  act  as  poisons  and  give  rise  to  a  great  fall  of  blood  pressure, 
incoagulability  of  the  blood,  and  a  condition  of  coma.  We  must  therefore 
leave  out  of  account  for  the  present  the  mechanism  of  absorption  of  this  lost 
fraction  and  endeavour  to  trace  the  course  of  the  absorption  of  that  part  of 
the  fat  which  makes  its  way  into  the  lymphatics. 

Microscopic  examination  of  a  section  of  the  villus  during  fat  absorption 
shows  that  the  absorption  occurs  for  the  most  part  through  the  epithelial 
cells.  These  are  found  closely  packed  with  fat  granules  (Fig.  361)  which, 
small  at  the  beginning  of  the  process  of  absorption,  rapidly  enlarge  till  they 
occupy  the  greater  part  of  the  cell  lying  between  the  nucleus  and  the  basilar 
striated  border.  Most  observers  are  agreed  that  no  fat -globules  are  to  be 
seen  within  the  border  itself. 


T1IF   ABSORPTION    OF  THF    FOODSTUFFS 


787 


According  to  Alt  liianii  tlie  fat  granules  found  in  the  cells  during  absorption  are  them- 
selves produced  by  a  transformation  of  fuchsinophile  granules  which  are  present  in  the 
cell  even  during  the  fasting  condition.  At  an  early  stage  the  small  fat  granules  can  be 
stained  so  as  to  show  a  distinct  fuchsinophile  envelope.  Altmann  interprets  this  appear- 
ance as  showing  that  the  epithelial  cells  take  up  the  fat  in  a  dissolved  form,  probably 
in  a  hydrolysed  condition,  and  that  a  process  of  synthesis  then  occurs  in  the  granules 
leading  to  the  formation  and  accumulation  of  fat.  When  the  process  of  absorption  is 
proceeding  actively,  the  meshes  of  the  villus  contain  a  number  of  free  fat  granules,  and 
the  leucocytes  in  these  meshes  are  generally  found  also  full  of  these  granules.     According 


*-' 


•V-At, 


Flu.  362.  A.  Vertical  section  through  intestinal  epithelium  of  a  rat  during  fat 
absorption,  b.  Horizontal  section  through  deeper  parts  o£  the  cells,  showing 
exi  ration  of  fine  fat  globules  into  the  intercellular  clefts.    (Reutek.) 

to  Sehafer  an  important  function  in  the  transfer  of  the  granules  from  epithelial  cells 
to  central  lacteal  was  performed  by  the  leucocytes.  These  were  supposed  to  take  up 
the  fat  granules  extruded  by  the  epithelial  cells  at  the  base  of  the  villi,  to  wander  into 
the  central  lacteal  where  they  broke  down,  furnishing  in  this  way  the  molecular  basis 
of  the  chyle  as  well  as  its  protein  constituents.  This  view  was  strongly  combated  by 
Heidenhain,  who  pointed  out  that  many  of  the  granules  staining  darkly  with  osmic 
acid  were  not  necessarily  fat,  and  that  the  number  of  leucocytes  within  the  villi  were 
hardly  sufficient  to  account  for  the  amount  of  material  observed.  According  to  Beuter 
the  epithelial  cells  take  up  fat  in  a  dissolved  condition  through  the  striated  border, 
and  deposit  it  as  granules  of  neutral  fat  in  the  inner  portion  of  the  protoplasm.  From 
here  the  fat  is  passed  on  by  the  protoplasm  by  the  side  of  the  nucleus  and  extruded  in 
the  form  of  very  fine  granules  in  the  deeper  parts  of  the  inter-epithelial  clefts,  winch 
thus  function  as  true  excretory  channels  for  the  epithelial  cells  (Fig.  362). 

It  is  probable  that  the  muscular  mechanism  of  absorption  described 
many  years  ago  by  Brlicke  plays  an  important  part  in  the  absorption  of  fats, 
but  it  is  difficult  to  furnish  any  experimental  proof  of  the  manner  in  which 
this  mechanism  works.  Repeated  contractions  of  the  muscle  fibres  of  the 
villus  would  tend  to  empty  the  spaces  into  the  central  lacteal,  and  this  in  its 
turn  into  the  submucous  plexus  of  lymphatics,  so  that  the  lymph  in  the 
.•spaces  is  constantly  renewed  and  passes  laden  with  absorbed  fat  particles  into 
the  valved  lymphatics  of  the  mesentery. 


788  PHYSIOLOGY 

It  was  long  considered  that  the  fats  were  taken  up  by  the  ephithelial  cells 
from  the  intestine  as  line  particles  of  neutral  fat,  the  chief  use  of  the  pan- 
creatic juice  being  to  aid  the  formation  of  an  emulsion  of  fat  in  the  intestines. 
There  seems  to  be  little  doubt  that  this  was  an  error,  and  that  the  fats  are 
absorbed,  dissolved  in  the  bile,  either  as  soap  or  as  fatty  acid .  The  arguments 
for  this  view  can  be  shortly  .summarised  as  follows  : 

(1)  Although  the  bile  does  not  dissolve  neutral  fats,  it  has  a  strong  solvent 
action  on  fatty  acids,  on  soaps,  and  even  on  the  insoluble  calcium  soaps. 
This  solvent  power  is  greatest  in  the  case  of  oleic  acid,  of  which  bile  can  dis- 
solve 19  per  cent.  It  is  very  small  in  the  case  of  pure  stearic  acid,  but  the 
solubility  of  the  latter  acid  is  largely  increased  if  it  be  associated  as  usual  with 
oleic  acid.  Moore  has  shown  that  this  solvent  action  is  chiefly  conditioned 
by  the  bile  salts,  aided  by  the  lecithin  and  cholesterin  also  present  in  the  bile, 
a  solution  of  lecithin  and  cholesterin  in  bile  salts  having  a  greater  solvent 
power  than  the  salts  alone. 

(2)  The  presence  of  bile  in  the  intestine  is  essential  for  the  normal 
absorption  of  fat.  If  the  bile  be  cut  off  by  occlusion  of  the  bile  ducts  or  by 
the  establishment  of  a  biliary  fistula,  the  utilisation  of  fat  sinks  from  about 
98  per  cent,  to  about  40  per  cent.,  the  unabsorbed  fat  appearing  in  the 
fasces.  This  large  undigested  residue  of  fat  hinders  also  the  absorption  of 
the  other  foodstuffs  by  covering  them  with  an  insoluble  layer,  so  that 
nutrition  as  a  whole  may  suffer  considerably. 

(3)  Absorption  ma)r  also  be  interfered  with  by  ligature  of  the  pancreatic 
duct.  This  result  is  probably  due  to  the  absence  of  the  fat-splitting  ferments 
of  the  pancreatic  juice  from  the  intestine.  If  the  fseces  be  analysed  it  is  found 
that  a  very  large  proportion  of  the  fat  has  been  split  into  fatty  acids  in  the 
course  of  its  passage  through  the  alimentary  canal.  This  lipolysis  has  how- 
ever been  carried  out  by  the  agency  of  micro-organisms,  i.e.  in  the  lower 
segments  of  the  gut  where  the  greater  part  of  the  bile  has  been  already 
reabsorbed  into  the  portal  circulation.  If  fat,  in  a  finely  divided  form  such 
as  cream  or  milk,  be  given  to  animals  deprived  of  their  pancreas,  a  certain 
proportion  of  it  is  absorbed.  Under  these  conditions  a  considerable  degree 
of  lipolysis  may  occur  in  the  stomach  itself,  so  that  the  fats  would  be  already 
hvdrolysed  when  they  came  in  contact  with  the  bile  in  the  duodenum. 

(4)  It  was  shown  by  Schiff,  by  means  of  his  amphibolic  fistula,  that  the 
bile  which  is  poured  into  the  gut  undergoes  a  circulation,  being  re-absorbed 
from  the  lowrer  parts  of  the  digestive  tube,  carried  to  the  liver  by  the  portal 
vein,  and  re-secreted  in  the  bile.  The  same  quantity  of  bile  salts  may 
therefore  be  used  over  and  over  again  as  a  vehicle  for  the  transfer  of  the  fatty 
acids  and  soaps  from  the  lumen  of  the  gut  into  the  epithelial  cells. 

(5)  Substances  which  are  physically  almost  identical  with  fats,  e.g. 
petroleum  or  paraffin,  are  not  absorbed  even  when  introduced  into  the  intes- 
tine in  the  finest  possible  emulsion.  If  neutral  fat  be  melted  with  a  soft 
paraffin  and  the  resulting  mixture  made  into  a  fine  emulsion  and  administered, 
it  is  found  that  the  intestine  rejects  the  paraffin,  but  takes  up  the  neutral 
fat.    This  result  can  be  explained  only  by  assuming  that  the  fat  in  the 


THE  ABSORPTION  OF  THE   FOODSTUFFS  789 

particles  has  been  actually  dissolved  out  by  the  digestive  juices  and  has 
been  absorbed  in  a  state  of  solution. 

We  may  sum  up  the  processes  involved  in  digestion  and  absorption  of 
fat  as  follows  :  Neutral  fat  is  hydrolysed  into  fatty  acid  and  glycerin  under 
the  action  of  the  gastric  juice,  the  pancreatic  juice,  and  the  succus  entericus, 
the  effect  of  the  gastric  juice  being  however  extremely  limited  unless  the 
fat  be  presented  to  it  in  a  finely  divided  condition.  The  lipolytic  action  of 
the  pancreatic  juice  and  succus  entericus  is  largely  aided  and  increased  by  the 
simultaneous  presence  of  bile  which,  in  virtue  of  the  bile  salts  and  lecithin 
and  cholesterin  it  contains,  enables  the  pancreatic  juice  to  enter  into  close 
relation  with  the  fat,  and  dissolves  the  products  of  the  activity  of  the  ferment, 
so  that  this  can  attack  renewed  portions  of  the  neutral  fat.  As  a  result 
of  this  lipo lysis  there  are  formed  glycerin,  which  is  soluble  in  water,  and 
fatty  acids  or  soaps,  according  as  the  reaction  of  the  medium  is  acid  or 
alkaline.  The  alkaline  soaps  are  soluble  in  water,  the  soaps  of  magnesium 
and  calcium  are  soluble  in  bile,  free  fatty  acids  are  soluble  in  bile  acids.  The 
fat  is  thus  reduced  to  a  condition  in  which  it  is  soluble  in  the  intestinal 
contents  whatever  their  reaction.  In  this  state  of  solution  its  constituents 
are  taken  up  by  the  cells  of  the  intestinal  mucosa.  Within  the  cells  a 
process  of  synthesis  takes  place,  the  soaps  being  split  and  the  fatty  acids  thus 
set  free  or  absorbed,  being  combined  with  glycerin  with  the  elimination  of 
water. to  form  neutral  fat,  which  appears  as  fine  granules  in  the  cell  .proto- 
plasm. By  an  active  process  of  excretion  these  granules  are  extruded  in  a 
somewhat  more  finely  divided  form  into  the  intercellular  clefts  and  into  the 
spaces  of  the  villus,  whence  by  the  contractions  of  the  musculature  of  the. 
villus  they  are  forced  with  the  lymph  transuding  from  the  capillary  blood- 
vessels into  the  central  lacteal,  and  thence  along  the  mesenteric  lymphatics 
to  the  thoracic  duct.  This  description  would  apply  to  about  60  per  cent,  of 
the  fat  which  is  absorbed.  It  is  probable  that  all  the  fat  which  is  absorbed 
is  taken  up  in  a  dissolved  condition,  but  whether  the  remaining  40  per  cent, 
enters  the  blood  stream ,  or  is  utilised  and  broken  down  in  the  tissues  of  the 
intestinal  wall  itself,  we  have  no  means  of  judging.  Under  normal  circum- 
stances the  utilisation  of  fat  is  almost  complete.  By  the  time  the  intestinal 
contents  have  arrived  at  the  lower  end  of  the  ileum  95  per  cent,  of  the  fat 
has  been  absorbed.  Removal  of  the  whole  large  intestine  was  found  by 
Vaughan  Harley  not  to  affect  fat  absorption  in  the  dog. 

THE   ABSORPTION   OF   CARBOHYDRATES 

As  a  result  of  the  action  of  the  various  digestive  juices,  all  the  carbo- 
hydrate constituents  of  the  normal  diet  of  man  are  reduced  to  the  state  of 
monosaccharides.  The  absorption  of  these  digestive  products  may  take 
place  at  any  part  of  the  alimentary  canal,  the  greatest  part  in  the  act  of 
absorption  being  taken  by  the  small  intestine.  By  the  time  that  the  food 
has  arrived  at  the  ileocsecal  valve,  practically  the  whole  of  the  carbohydrate 
constituents  of  the  food  have  been  absorbed.  All  experimenters  are  agreed 
that  the  carbohydrates  pass  into  the  body  by  wray  of  the  vessels  of  the  portal 


790  PHYSIOLOGY 

system.  The  lymph  Erom  the  thoracic  duct  contains  no  more  sugar  than 
docs  tlic  arterial  blood  taken  'it  the  same  time,  whereas  several  observers  have 
obtained  an  increased  percentage  of  sugar  in  the  portal  blood  during  the 
absorption  of  a  big  carbohydrate  meal. 

Of  the  carbohydrates  of  the  food.  some,  like  starch,  dextrin,  glycogen,  are 
colloidal  and  indifmsible;  others,  such  as  the  disaccharides,  cane  sugar,  milk  ■ 
sugar,  and  maltose,  are  soluble  and  diffusible ;  and  the  products  of  the  action 
of  digestive  ferments  on  these  two  classes,  namely  the  monosaccharides, 
mannose,  fructose,  glucose  and  galactose,  are  also  soluble  and  diffusible.  The 
problem  as  to  the  mechanism  involved  in  the  passage  of  these  substances 
across  the  intestinal  wall  into  the  blood  vessels  has  been  already  dealt  with 
in  treating  of  the  absorption  of  water  and  salts.  The  most  striking  fact  is  the 
relative  impermeability  of  the  intestinal  wall  to  the  disaccharides  as  compared 
with  the  monosaccharides.  The  intestinal  wall  is  apparently  able  to  take 
up  in  any  quantity  only  such  sugars  as  can  be  utilised  by  the  cells  of  the 
organism.  For  this  purpose  the  disaccharides  are  useless ;  cane  sugar  or 
lactose  introduced  into  the  blood  vessels  or  subcutaneously  is  excreted  quan- 
titatively in  the  urine  and,  as  might  be  expected,  does  not  increase  in  any 
way  the  glycogen  of  the  liver.  When  maltose  is  injected  in  the  same  manner, 
a  certain  proportion  of  it  is  utilised  owing  to  the  fact  that  the  blood  and 
fluids  of  the  body  contain  a  ferment,  maltase,  capable  of  converting  the 
disaccharide  into  the  monosaccharide,  glucose.  The  absorption  of-  these 
disaccharides  occurs  therefore  much  more  slowly  from  the  intestine  than  does 
the  absorption  of  monosaccharides,  the  process  of  absorption  being  always 
preceded  by  and  waiting  for  the  process  of  hydrolysis.  Thus  huge  doses 
of  cane  sugar  may  be  taken  without  causing  the  appearance  of  cane  sugar 
in  the  blood  or  urine.  It  has  been  found  that  sugar  does  not  appear  in  the 
urine  until  as  much  as  320  grm.  of  cane  sugar  have  been  ingested,  whereas 
any  quantity  of  glucose  over  100  grm.  may  give  rise  to  glycosuria.  Lactose 
is  absorbed  still  more  slowly  and,  in  animals  whose  intestine  is  free  from  the 
ferment  lactase,  is  not  absorbed;  large  doses  of  lactose  in  such  animals 
therefore  give  rise  to  diarrhoea.  The  behaviour  of  the  intestinal  wall  to 
the  non-assimilable  sugars  of  artificial  origin  has  not  yet  been  sufficiently 
investigated.  It  would  be  interesting  to  inquire  whether  the  rate  of  absorp- 
tion of  the  different  sugars  is  in  any  way  determined  by  their  stereomeric 
configuration,  whether,  for  instance,  ^-glucose  would  be  absorbed  as  rapidly 
as  the  ordinary  rf-glucose. 

THE   ABSORPTION   OF   PROTEINS 

In  very  few  departments  of  physiology  has  there  been  so  great  a  revo- 
lution in  our  ideas  as  in  that  relating  to  protein  absorption,  especially  as  to 
the  form  in  which  it  is  absorbed  from  the  alimentary  canal,  and  its  fate  after 
absorption.  As  to  the  channel  by  which  it  obtains  entry  into  the  circulation, 
practical  agreement  reigns  that  it  is  absorbed  by  the  blood  vessels.  Almost 
every  physiologist  who  has  occupied  himself  with  the  investigation  of  the 
lymph  flow  from  the  thoracic  duct  has  been  impressed  by  the  fact  that  the 


THE  ABSORPTION  OF  THE  FOODSTUFFS  791 

variations  in  the  amount  of  lymph  to  be  obtained  in  this  way  bear  no 
relation  to  the  condition  of  the  animal  as  regards  the  state  of  digestion.  Nor 
do  we  find  any  appreciable  increase  in  the  amount  of  lymph  flow  or  in  the. 
amount  of  proteins  contained  in  this  lymph  during  digestion.  The  small 
increase  observed  by  Asher  and  Barbara  would  be  sufficiently  accounted  for 
by  the  increased  blood  supply  to  the  intestines  during  digestion,  and  is 
insufficient  to  accoimt  for  the  absorption  of  any  appreciable  quantity  of  the 
protein  which  is  being  taken  up  from  the  alimentary  canal.  Moreover  it  was 
shown  by  Schmidt  Mulheim  that  the  absorption  of  proteins  was  not  inter- 
fered with  as  the  result  of  ligature  of  the  thoracic  duct  and  that,  after  this 
duct  had  been  ligatured,  the  ingestion  of  proteins  was  followed  at  the  usual 
interval  by  the  increased  output  of  urea,  which  is  the  invariable  concomitant 
of  protein  absorption  and  assimilation.  We  must  therefore  conclude  that 
the  products  of  protein  digestion  are  taken  up  by  the  epithelial  cells  and 
passed  on  by  these  into  the  blood  vessels. 

During  the  absorption  of  a  protein  meal  changes  have  been  described  by  various 
observers  in  the  structures  of  the  villus.  In  nearly  every  case  there  is  marked  increase 
in  the  number  of  mitotic  figures  in  the  epithelium  lining  the  follicles  of  Lieberkiihn. 
According  to  Hofmeister  there  is  during  absorption  an  increase  in  the  number  of 
leucocytes  in  the  villi,  and  this  observer  ascribed  an  important  function  to  these 
cells  in  the  absorption  of  protein.  Heidenhain  showed  that  this  increase  of 
leucocytes  was  not  constant  in  all  animals,  and  bore  no  relation  to  the  amount  of 
absorption  that  was  taking  place,  and  was  quite  inadequate  to  account  for  the  total 
absorption  that  was  carried  on.  On  the  other  hand,  several  observers  have  described 
changes  in  the  epithelium  as  the  result  of  protein  digestion.  According  to  Reuter  the 
epithelial  cells  become  swollen,  their  protoplasm  stains  less  deeply,  and  at  their  basal 
ends  the  cells'  limits  disappear,  the  protoplasm  being  apparently  distended  with  hyaline 
coagulable  material  (Fig.  363).  Reuter  regards  this  appearance  as  a  direct  expression 
of  the  taking  up  of  proteins  in  a  dissolved  form  and  their  conversion  near  the  bases 
of  the  cells  into  coagulable  proteins ;  but  further  evidence  on  this  subject  is  necessary 
before  we  can  attach  much  importance  to  such  an  interpretation  of  the  appearances 
observed. 

Under  the  influence  of  the  gastric  juice  the  proteins  of  the  food  are 
resolved  during  their  stay  in  the  stomach  into  albumoses  and  peptones.  In 
the  small  intestine  the  process  of  hydration  is  carried  further,  the  trypsin  of 
the  pancreatic  juice  carrying  the  proteins  through  the  stage  of  secondary 
albumoses  and  peptones,  and  converting  them  into  a  mixture  of  amino-acids 
and  polypeptides.  The  same  end-products  result  from  the  action  of  the 
erepsin  of  the  intestinal  wall  on  the  albumoses  and  peptones  produced  by 
gastric  digestion.  The  digestive  juices  finally  reduce  the  proteins  therefore 
to  a  mixture  of  amino-acids,  with  a  certain  remainder  of  polypeptides  con- 
sisting of  two  or  three  of  the  amino-acids  associated  together,  which  do  not 
undergo  further  disintegration  under  the  action  of  the  intestinal  ferments. 
The  final  products  give  no  biuret  test.  The  first  question  we  have  to  decide 
is  to  what  extent  the  proteins  are  reduced  to  their  ultimate  hydration  pro- 
line! s  before  absorption.  We  have  evidence  that  protein  may  be  absorbed 
by  the  small  intestine  without  having  undergone  any  hydration  whatsoever. 
The  absorption  of  serum  protein  has  been  discussed  already  in  dealing  with 
the  mechanism  of  absorption  of  salt  solutions  from  the  gut.     In  a  series  of 


792 


PTIYSIOLOfJY 


experiments  made  by  Friedlander,  the  absorptions  of  various  proteins  were 
compared  after  their  introduction  into  loops  of  the  .small  intestine  which  had 
been  washed  free  from  ferment.  During  a  period  of  three  hours  this  author 
found  that  21  per  cent,  of  the  proteins  of  egg  white  or  of  blood  serum  were 
absorbed.  During  the  same  period,  of  alkali  albumin  which  had  been  intro- 
duced into  the  loops,  69  per  cent,  was  absorbed.     On  the  other  hand,  when 


Fig.  3G3.     Figures  (from  Eetjter)  showing  changes  in  intestinal  epithelium 

induced  by  absorption  of  protein. 

I,  epithelium  of  fasting  rat;    II,  initial  stage;  III,  later  stage  of  protein 

absorption. 

syntonin  and  casein  were  introduced  into  the  intestine,  no  absorption  what- 
ever was  observed.  As  to  the  condition  in  which  such  unchanged  protein 
reaches  the  blood  stream,  our  knowledge  is  still  imperfect.  Foreign  proteins, 
such  as  egg  albumin,  or  the  serum  of  other  species  introduced  into  the  blood 
stream,  may  cause  poisonous  effects  and  give  rise  to  albuminuria,  to  lowering 
of  blood  pressure,  or  to  alteration  of  the  coagulability  of  the  blood.  If 
injected  in  small  quantities  they  excite,  as  a  reaction  on  the  part  of  the 
organism,  the  production  in  the  blood  serum  of  a  precipitin,  and  the  presence 
of  the  precipitin  may  be  looked  upon  therefore  as  a  test  by  which  we  may 
decide  whether  these  proteins  have  passed  through  the  intestinal  wall 
unchanged.  In  most  cases  it  is  found  that,  however  abundant  the  amount 
of  protein  administered  in  the  soluble  form,  none  of  it  appears  in  the  urine, 


THE  ABSORPTION  OF  THE  FOODSTUFFS  793 

nor  is  any  precipitin  formation  aroused.  Ascoli  has  however  observed  such 
events  occasionally  to  follow  the  administration  of  large  doses  of  egg  white, 
and  it  has  been. shown  that  there  is  a  difference  in  the  behaviour  of  animals  to 
the  introduction  of  soluble  protein  into  their  alimentary  canal,  according  as 
they  are  new  born  or  are  more  than  a  few  days  old.  It  seems  that  during  the 
first  few  days  of  fife  the  cellular  lining  of  the  alimentary  canal  is  permeable 
to  foreign  proteins,  whereas  later  on  any  protein  which  is  taken  up  unchanged 
from  the  gut  does  not  arrive  in  the  same  unchanged  condition  in  the  blood 
stream. 

The  absorption  however  of  unchanged  proteins  can  play  but  a  small 
part  in  the  assimilation  of  protein  as  a  whole.  Animals  very  rarely  take 
coagulable  proteins  in  a  condition  in  which  they  will  arrive  at  the  small 
intestine  in  a  state  of  solution  unchanged.  Even  in  the  camivora  the  living 
tissues  taken  into  the  stomach  will  undergo  coagulation  by  the  acid,  and  will 
then  be  dissolved  by  the  gastric  juice.  In  man  practically  all  the  proteins  of 
the  food  are  either  insoluble  or  are  rendered  insoluble  by  the  process  of 
cooking.  For  absorption  to  take  place  it  is  therefore  necessary  that  this 
insoluble  or  coagulated  protein  should  be  brought  into  solution,  and  this 
process  is  accomplished,  together  wath  hydration,  by  means  of  the  ferments 
of  the  gastric  and  pancreatic  juices. 

This  process  of  solution  has  long  been  regarded  as  the  cluef  object  of  the  digestive 
ferments.  Although  both  Kuhne  and  Schmidt  Miilheim  were  aware  of  the  production 
of  aniino-acids  such  as  leucine  and  tyrosine  as  the  result  of  digestion,  they  regarded 
their  production  as  evidence  of  a  waste  of  material.  Proteoses  and  peptones  are  soluble, 
diffusible,  and  rapidly  absorbed  from  the  alimentary  canal,  and  there  is  no  doubt  that 
a  large  proportion  of  the  products  of  protein  digestion  are  taken  up  by  the  absorbing 
membrane  in  this  form.  For  many  years  physiologists  were  occupied  with  the  problem 
as  to  the  fate  of  these  peptones  and  proteoses  after  their  entrance  into  the  mucous 
membrane.  They  do  not  pass  as  such  into  the  blood.  The  injection  of  small  quantities 
of  proteose  and  peptone  into  the  blood  gives  rise  to  the  excretion  of  these  substances  by 
the  kidneys ;  injection  of  larger  quantities  has  pronounced  poisonous  effects,  which  were 
first  studied  by  Schmidt  Miilheim  and  Fano.  If  samples  of  blood  be  taken  either  from 
the  portal  vein  or  from  the  general  circulation  after  a  heavy  protein  meal,  no  trace 
either  of  proteose  or  of  peptone  is  to  be  found  in  the  blood.  The  observations  of  Hof- 
meister  and  others  to  the  contrary  depend  on  the  fact  that  these  observers  employed  a 
method  for  the  separation  of  coagulable  protein,  as  an  antecedent  to  the  testing  for 
proteoses,  which  was  in  itself  capable  of  producing  small  traces  of  these  substances. 
Hofmeister  showed  that  during  the  absorption  of  a  protein  meal  the  mucous  membrane 
either  of  the  stomach  or  of  the  intestine,  if  rapidly  killed  by  plunging  into  boiling  water 
directly  it  was  taken  from  the  animal,  always  contained  a  considerable  amount  of 
peptone,  and  similar  observations  were  made  by  Neumeister.  If  however  the  mucous 
membrane  was  kept  warm  for  half  an  hour  after  removal  from  the  body,  the  peptone 
disappeared.  Salvioli,  under  Ludwig's  guidance,  introduced  peptone  into  a  loop  of 
gut  which  was  kept  alive  by  passing  defibrinated  blood  through  its  vessels.  At  the 
end  of  some  hours  the  loop  was  found  to  contain  a  certain  amount  of  coagulable  protein, 
but  no  trace  of  peptone,  nor  was  any  trace  of  the  latter  substance  found  in  t  lie  blood 
which  had  been  passed  through  the  vessels.  These  observations  were  interpreted  as 
pointing  to  a  regeneration  in  the  intestinal  wall  of  coagulable  protein  from  the  proteose 
and  peptone  taken  up  from  the  gut,  and  opinions  were  divided  whether  the  most 
important  part  of  tins  regeneration  was  to  be  ascribed  to  the  leucocytes  of  the  villi 
(Hofmeister)  or  to  the  epithelial  cells  of  the  mucous  membrane  itself. 

It  is  evident  that  such  a  conclusion  was  not  justified  by  the  experiments.     All  that 


794  PHYSIOLOGY 

these  experiments  showed  was  thai  the  proteoses  and  peptones  disappeared,  i.  e.  were 
converted  into  something  which  did  not  give  the  biuret  test.  The  discovery  of  the 
ferment  erepsin  bj  I  lohnheim  led  I  his  observer  to  repeat  the  experiments  of  Hofmeistei 
and  Neumeister  with  a  view  to  testing  the  conclusions  drawn  by  these  physiologists. 
Cohnheim  found  that,  although  it  was  perfectly  true  thai  proteose  and  peptone  disap- 
peared when  intestinal  mucous  membrane  ;i m I  peptone  were  placed  together  in  the 
presence  of  either  blood  or  of  Binger's  fluid,  this  disappearance  was  due,  not  to  a  regener- 
ation of  coagnlablc  protein,  but  to  the  fact  that  the  erepsin  of  the  mucous  membrane 
carried  the  process  of  hydrolysis  a  step  further,  converting  the  proteoses  and  peptones 
into  t  he  ultimate  crystalline  products  of  protein  hydrolysis.  Similar  observations  were 
made  by  Kutscher  and  Seemann,  who  showed  that  at  any  time  after  a  protein  meal  these 
end-products,  especially  leucine,  tyrosine,  lysine,  and  arginine,  were  to  be  found  in  the 
contents  of  the  small  intestine.  A  repetition  of  Salvioli's  experiment  by  Cathcart  and 
I.e.  it  lies  deprived  this  also  of  much  of  its  significance.  It  was  found  that  the  artificial 
circulation,  although  sufficient  to  maintain  the  activity  of  the  muscular  wall  of  the 
intestine,  as  evidenced  by  the  peristaltic  movements,  was  insufficient  to  keep  the  mucous 
membrane  alive.  After  one  hour's  experiment  the  loop  contained  a  mass  of  epithelial 
cells  mixed  with  the  products  of  the  action  of  erepsin  on  the  introduced  peptone  solution. 
In  no  case  was  there  any  diminution  in  the  amount  of  uncoagulable  nitrogen,  i.  e.  there 
was  no  formation  of  coagulable  protein,  while  the  processes  of  absorption  had  been 
brought  by  the  desquamation  entirely  to  a  standstill. 

All  the  evidence  shows  that  protein,  however  introduced,  whether  as 
coagulated  protein  or  as  albvtmose  and  peptone,  undergoes  complete 
hydrolysis  either  in  the  gut  or  in  the  wall  of  the  gut  before  entering  the 
blood  stream.  It  should  thus  be  possible  to  feed  an  animal  on  a  diet  in 
which  the  necessary  protein  had  been  replaced  by  the  corresponding  amount 
of  ultimate  products  of  protein  hydrolysis,  i.  e.  by  a  mixture  which  would 
give  no  biuret  reaction. 

Sufh  a  possibility  w\as  formerly  negatived  on  theoretical  grounds  by  Kiihne  and  by 
Bunge.  It  was  thought  by  these  observers  either  that  the  animal  body  lacked  the 
power  of  synthesis  of  proteins  from  these  crystalline  products  (hydration  products),  or 
that  any  complete  hydration  occurring  in  the  intestine  would  involve  such  a  loss  of 
energy  to  the  body  as  to  be  unteleological.  Neither  of  these  theoretical  objections  is 
justified  in  fact.  We  know  from  the  researches  of  Fischer  and  others  that,  although  the 
different  proteins  in  our  food  present  a  marvellous  qualitative  similitude,  in  that  all  of 
them  yield  on'hydrolysis  the  same  kinds  of  amino-acids,  there  are  great  differences  in 
the  relative  amounts  of  these  amino-acids  contained  in  different  proteins.  Thus  in 
gelatin,  glycine  is  contained  in  considerable  quantities,  but  is  absent  in  many  of  the  other 
proteins.  C'aseinogen  is  distinguished  by  the  large  amount  of  leucine  that  it  yields, 
while  gliadin,  the  chief  protein  of  wheat  flour,  contains  very  large  amounts  of  glutamic 
acid.  It  is  difficult  to  imagine  how,  for  instance,  muscle  protein  could  be  formed  from 
wheat  protein,  a  process  continually  occurring  in  the  growing  animal,  unless  we  assumed 
that  the  protein  molecule  is  first  entirely  taken  to  pieces,  and  that  its  constituent  mole- 
cules are  then  selected  by  the  growing  cells  of  the  body  and  built  up  in  the  order  and 
proportions  which  are  characteristic  of  muscle  protein.  Moreover,  when  we  measure 
the  amount  of  energy  change  involved  in  the  hydrolysis  of  the  proteins,  we  find  it  is 
relatively  small.  There  is  not  a  loss  of  5  per  cent,  of  the  total  energy  available — i.  e.  the 
heat  of  combustion  of  the  products  of  pancreatic  digestion  would  differ  from  that  of 
the  original  protein  submitted  to  digestion  by  less  than  5  per  cent.  The  energy  of  the 
protein  as  evolved  in  the  body  lies,  not  in  the  coupling  of  the  amino-acids  with  one 
another,  or  indeed  in  the  coupling  of  the  nitrogen  to  the  carbon  but,  like  that  of  the 
other  foodstuffs,  in  the  carbon  itself,  and  is  derived  from  the  combustion  of  the  carbon 
of  the  molecule  under  the  influence  of  the  oxidising  processes  of  the  body  into  carbon 
dioxide. 


THE  ABSORPTION  OF  THE   FOODSTUFFS  795 

The  experimental  decision  of  this  question  was  first  attempted  by  0.  Loewi, 
who  found  that  it  was  possible  to  keep  a  dog  in  a  state  of  nitrogenous 
equilibrium  on  a  diet  containing  fat,  starch,  and  a  pancreatic  digest  of 
protein  which  contained  no  substances  giving  the  biuret  test.  These 
results  have  been  confirmed  for  carnivora  by  Henderson,  by  Liithje,  by 
Abderhalden  and  Rona,  and  by  Henri ques  and  Hansen.  According  to 
Abderhalden,  it  is  possible  to  keep  an  animal  alive  when  the  nitrogen  in  his 
food  is  represented  entirely  by  the  end-products  of  pancreatic  digestion. 
The  same  result  cannot  be  attained  by  the  administration  of  the  products 
of  acid  hydrolysis  of  protein,  but  this  may  be  due  either  to  the  racemisation  of 
the  ammo-acids  under  the  action  of  the  strong  acid,  or  to  the  fact  that  the  acid 
splits  up  certain  polypeptide  groupings  which  are  still  contained  in  the  trypsin 
digest,  and  which  possibly  cannot  be  synthetised  by  the  cells  of  the  body. 

We  are  justified  therefore  in  concluding  that  while  a  certain  small 
proportion  of  the  proteins  of  the  food  may  be  absorbed  \mchanged,  a  much 
larger  proportion  is  taken  up  as  proteoses  and  peptones  or  as  amino-acids. 
The  proteoses  and  peptones  are  however  rapidly  changed  in  the  mucous 
membrane  itself  into  amino-acids,  which  we  may  regard  as  the  form  in 
which  practically  all  the  protein  of  the  body  is  presented  to  the  absorbing 
mechanisms  of  the  alimentary  canal  for  absorption  and  for  passing  on 
into  the  circulating  fluids. 

THE  FATE  OF  THE  AMINO-ACIDS  AFTER  ABSORPTION  BY  THE 
INTESTINAL  EPITHELIUM.  During  a  condition  of  starvation  the  normal 
protein  requirements  of  the  body,  or  rather  of  the  active  tissues,  are  met 
at  the  expense  of  the  less  active  tissues.  The  protein  characteristic  of  any 
tissue  can  be  taken  down,  removed  to  another  part  of  the  body,  and  built 
up  into  the  protein  characteristic  of  some  other  active  tissue.  It  is  difficult 
to  conceive  that  such  a  transference  and  transformation  could  occur  in  any 
other  way  than  by  a  more  or  less  thorough  disintegration  of  the  protein 
molecule  at  one  place  and  its  synthesis  at  the  other,  and  we  know  from  the 
researches  of  Hedin  and  others  that  every  tissue  contains  intracellular 
ferments  which  are  capable  of  effecting  the  disintegration  of  the  protein 
molecule,  and  are  responsible  for  the  autolytic  degeneration  of  tissues  after 
death.  If  therefore  the  normal  interchange  of  protein  between  the  tissues 
is  accomplished,  as  we  know  it  to  be  in  plants,  by  the  disintegration  of  the 
proteins  into  their  constituent  amino-acids  and  their  subsequent  reintegra- 
'  tion.  there  is  no  a  priori  reason  to  believe  that  the  blood  carries  the  proteins 
from  the  alimentary  canal  to  the  tissues  in  any  other  form  than  that  of 
amino-acids.  The  experimental  proof  of  this  conclusion  was  hardly  possible 
before  the  invention  of  a  reliable  method  for  the  detection  of  small  quantities 
of  amino-acids  in  the  blood  and  tissues.  This  is  rendered  possible  by  van 
Slyke's  method  in  which,  after  the  separation  of  coagulable  proteins  by 
alcohol,  the  amino-acids  are  determined  by  measuring  the  nitrogen  evolved 
on  addition  of  nitrous  acid.  Van  Slyke  has  shown  that  the  blood  always 
contains  a  certain  amount  of  amino-acids  even  during  fasting.     After  a 


796  PHYSIOLOGY 

protein  meal  there  is  a  considerable  increase  in  the  amount  of  ammo-acids. 
Thus  Hie  blood  of  fasting  animals  coirl  ains  from  3- 1  i o  5-1  milligrams  amino- 
acid  nitrogen  per  Juo  c.c.  Blood  taken  after  food  contains  8-6  to  10-2 
milligrams  amino-acid  nitrogen  per  100  c.c.  of  blood.  The  question  of  the 
fate  of  ammo-acids  thus  absorbed  from  the  intestine  to  the  blood  is  decided 
by  an  estimation  of  the  amino-acid  content  of  the  different  tissues  after 
the  injection  of  amino-acids  into  the  blood.  Van  Slyke  Jms  found  that 
after  the  injection  of  amino-acids  only  a  certain  proportion  is  excreted 
with  the  urine,  and  that  the  rest  of  the  amino-acids  rapidly  disappears 
from  the  blood  and  is  taken  up  by  the  tissues  without  undergoing  any 
immediate  chemical  change,  though  in  the  case  of  certain  tissues,  such 
as  the  muscles,  a  definite  saturation  point  exists  which  sets  the  limit  to  the 
amount  of  amino-acids  that  can  be  absorbed.  On  the  other  hand,  the 
capacity  of  the  internal  organs,  and  especially  of  the  liver,  for  the  absorption 
of  amino-acids  is  much  greater. 

It  is  worthy  of  note  however  that  the  absorption  of  amino-acids  by  the 
tissues  from  the  blood  is  never  complete,  i.  e.  the  amino-acids  of  the  blood 
must  be  in  a  state  of  equilibrium  with  those  of  the  tissues,  although  the  con- 
centration in  the  latter  may  be  much  greater  than  in  the  former.  If  several 
hours  be  allowed  to  elapse  after  the  injection  of  amino-acids  before  the 
analysis  of  the  tissue  is  undertaken,  it  is  found  that  the  amino-acid  nitrogen 
content  of  the  liver  may  have  returned  to  normal,  although  the  concentration 
in  the  muscles  has  suffered  no  appreciable  fall.  Since  we  have  evidence 
that  the  circulation  of  amino-acids  through  the  liver  gives  rise  in  this  organ 
to  the  formation  of  urea,  we  must  conclude  that  this  organ  is  especially 
responsible  for  the  breakdown  of  the  products  of  protein  digestion  which  are 
not  directly  required  for  replacing  tissue  waste.  This  breakdown  must 
involve  a  process  of  deamination.  We  may  therefore  conclude  that  the 
amino-acids  normally  produced  by  a  protein  digestion  are  absorbed  without 
further  change  into  the  blood  stream.  They  then  circulate  throughout  the 
body,  a  certain  proportion  of  them  being  built  up  in  each  tissue  into  the 
proteins  characteristic  of  that  tissue  in  order  to  replace  the  waste  caused  by 
wear  and  tear.  The  rest,  probably  the  major  part  of  the  protein,  is  taken  up 
by  the  liver,  where  it  imdergoes  deamination,  the  nitrogen  moiety  being 
rapidly  converted  into  urea  and  excreted  by  the  kidneys,  while  the  non- 
nitrogenous  moiety  is  carried  to  the  working  tissues  to  which  it  serves  as  a 
ready  and  immediate  source  of  energy. 

The  fact  that  not  only  the  blood  but  also  the  tissues  contain  amino-acids,' 
even  after  complete  starvation  for  some  days,  shows  that  these  substances 
are  intermediate  steps  not  only  in  the  synthesis  but  in  the  breaking  down  of 
body  proteins.  Free  amino-acids  are  thus  the  protein  currency  of  the  body, 
just  as  glucose  is  the  carbohydrate  currency.  In  the  fasting  body  we  must 
regard  the  processes  of  autolysis  as  the  main  source  of  the  amino-acids  found 
in  the  tissues,  and  it  is  by  autolysis  that  the  proteins  of  the  resting  tissues  are 
made  available  in  starvation  for  those  whose  continued  working  is  essential 
for  the  maintenance  of  life.    The  fact  that  high  protein  feeding  does  not 


THE  ABSORPTION  OF  THE  FOODSTUFFS  797 

appreciably  increase  the  amiiio-acid  content  of  the  tissues,  shows  that  any 
storage  of  nitrogen  in  the  organism  must  take  place,  not  in  the  form  of 
amino-acids,  but  as  body  protein. 

It  was  formerly  thought  that  the  deaniination  of  amino-acids  occurred  on  a  large 
scale  in  the  wall  of  the  alimentary  canal,  on  the  grounds  that  a  larger  amount  of 
ammonia  was  present  in  the  portal  blood  than  in  the  arterial  blood.  It  seems  probable 
however  that  the  source  of  this  excess  of  ammonia  is  to  be  found  in  intestinal  bacterial 
changes,  and  that  the  major  portion  of  the  amino-acids  is  actually  absorbed  unchanged. 
The  view  of  Abdcrhalden  that  the  amino-acids  are  synthetised  in  the  intestinal  wall 
to  serum  proteins,  and  absorbed  in  that  form  into  the  blood  stream,  need  here  only 
be  mentioned,  since  it  lacks  experimental  support. 

THE   ACTUAL   COURSE   OF   DIGESTION 

In  a  recent  series  of  papers  London  describes  the  course  of  digestion  of  meals  of 
various  characters  in  dogs  winch  had  been  provided  with  fistula?  in  one  of  the  following 
places  :  (a)  gastric  fistula  (into  the  fundus  of  the  stomach);  (b)  pyloric  fistula  (on  the 
duodenal  side  of  the  pylorus);  (c)  duodenal  fistula  (about  one  foot  below  the  pylorus); 
(</)  jejunal  fistula  (about  the  middle  of  the  small  intestine) ;  (e)  ileum  fistula  (just  above 
the  csecum). 

We  may  take  as  an  example  the  course  of  digestion  of  a  meal  composed  of  200  grin. 
of  bread.  This  is  eaten  by  the  animal,  mixed  with  the  saliva  and  swallowed.  On 
arriving  in  the  stomach  it  gives  rise  to  the  secretion  of  gastric  juice.  In  a  series  of 
special  experiments  London  found  that  on  the  average  200  grm.  of  bread  evoked  the 
secretion  of  20  grm.  of  saliva,  about  10  grm.  of  mucus  from  the  coats  of  the  stomach, 
and  about  315  grm.  of  gastric  juice.  The  secretion  of  gastric  juice  is  continuous  during 
the  whole  time  that  the  food  remains  in  the  stomach.  Li  the  animal  with  a  pyloric 
fistula,  one  to  two  minutes  after  the  meal  had  been  taken,  a  few  drops  of  alkaline  fluid 
were  extruded  from  the  opening.  From  three  to  eight  minutes  after  the  conclusion 
of  the  meal  small  quantities  of  clear  acid  gastric  juice  were  repeatedly  extruded.  The 
first  admixture  of  the  food  with  the  outflow  from  the  fistula  occurred  at  eight  to  twelve 
minutes  after  the  completion  of  the  meal,  and  after  this  time  the  pylorus  continued 
to  open  at  regular  intervals  of  ten  to  forty  seconds,  discharging  each  time  a  small 
amount  of  fluid  composed  of  particles  of  undigested  bread  mixed  with  gastric  juice. 
One  and  a  half  hours  later  the  pylorus  began  to  open  less  regularly  and  the  fluid  became 
of  a  more  pasty  consistence,  devoid  of  lumps  of  undigested  bread.  In  the  fourth, 
fifth,  and  sixth  hours  after  the  meal  the  pylorus  opened  only  once  every  one  or  two 
minutes,  and  towards  the  end  of  this  period  the  fluid  extruded  was  clear.  The  following 
Table  shows  the  percentage  amount  of  food  taken  which  had  left  the  stomach  at 
the  end  of  each  hour  after  the  meal : 


First  hour 
Second  hour 
Third  hour 
Fourth  hour- 
Fifth  hour 
Sixth  hour 


32-6     per  cent. 

17-9 

29-5 

1-87 

6-66 

4-21 


The  large  proportion  of  the  ingested  food  leaving  the  stomach  during  the  first  two 
or  three  hours  can  hardly  be  regarded  as  normal.  Since  in  these  experiments  there  was 
a  free  outflow  from  the  pylorus  and  the  food  was  not  allowed  to  enter  the  duodenum, 
the  local  reflex,  evoked  by  the  presence  of  acid  in  the  duodenum,  was  absent.  The 
gastric  contents  obtained  in  this  way  were  analysed  in  order  to  find  what  changes 
had  been  wrought  on  the  food  by  the  gastric  juice.  It  was  found  that  32  per  cent. 
of  the  bread  had  been  brought  into  solution.  This  solution  had  affected  the  proteins 
more  than  the  carbohydrates.  Thus  07  per  cent,  of  the  nitrogen  had  been  brought 
into  soluble  form,  consisting  chiefly  of  proteoses  and  peptones.     No  amino-acids  were 


798  PHYSIOLOGY 

formed.     Only  25  per  cent,  of  the  starch  of  the  bread  had  been  rendered  soluble,  and 

of  fins,  L'l  per  cent,  was  in  the  form  of  ilex  trim;  .1111 1  I  |  »■  i  i  rut.  111  tin-  form  of  sugar. 
No  absorption  however  either  of  the  digested  proteins  or  of  the  digested  carbohydrates 
mas  ever  found  to  take  place  in  the  stomach 

DUODENAL  DIGESTION.  The  influence  exerted  liy  the  paneroatic  juice,  bile, 
and  succus  en  ten  i  -us.  poured  out  on  the  food  in  the  duodenum,  was  studied  by  analysis  of 
the  intestinal  contents  leaving  the  intestine  by  a  fistula,  either  at  the  lower  end  of 
the  duodenum,  or  in  the  jejunum,  or  in  the  ileum.  From  the  duodenal  fistula  the 
expulsion  of  food  occurs  at  repeated  intervals,  but  in  a  somewhat  irregular  fashion, 
its  movements  being  determined  partly  by  the  contractions  of  the  stomach  and  partly 
by  those  of  the  duodenal  wall.  Usually  a  large  gush  is  followed  by  a  series  of  small 
gushes.  Although  only  a  foot  intervenes  between  the  duodenal  fistula  and  the  pyloric 
fistula,  a  great  difference  is  observed  in  the  character  of  the  intestinal  contents  obtained 
in  the  two  cases.  The  outflow  from  the  duodenum,  being  mixed  with  the  pancreatic 
juice  and  the  bile,  is  yellow  in  colour  and  increased  in  amount.  With  a  meal  of  200  grm. 
t  here  is  secreted  on  the  average  130  grm.  of  bile  and  140  grm.  of  pancreatic  juice.  During 
its  passage  through  the  duodenum  the  carbohydrates  of  the  food  undergo  considerable 
changes,  so  that  even  one  foot  below  the  pylorus  we  find  that  one-half  to  three-fifths 
of  the  carbohydrates  Lave  been  converted  into  dextrine  and  sugar.  A  further  digestion 
of  the  proteins  also  takes  place  amounting  to  about  one-tenth  of  the  whole  protein 
taken  with  the  food. 

On  deducting  the  amount  of  juices  which  have  been  added  to  the  food,  it  is  found 
that  even  in  this  short  length  of  intestine  absorption  has  taken  place  of  about  one-sixth 
of  the  ingested  food,  about  one-fourth  of  the  carbohydrates  having  been  absorbed 
and  about  one-eighth  of  the  proteins. 

In  a  dog  with  a  fistula  about  the  middle  of  its  smaU  intestine,  the  outflow  began 
six  to  fifteen  minutes  after  the  meal,  and  lasted  six  or  seven  hours.  The  outflow  was 
by  small  gushes  repeated  at  intervals  of  five  to  ten  seconds,  separated  by  intervals  of 
one  to  five  minutes,  during  which  nothing  appeared  at  the  orifice  of  the  cannula.  The 
material  obtained  was  quite  different  in  character  from  that  flowing  from  the  duodenal 
fistula.  The  pasty  character  had  disappeared,  the  material  forming  a  frothy,  orange- 
yellow,  even  jelly-like  mass  with  practically  no  trace  of  undigested  bread. 

From  a  fistula  in  the  ileum  the  outflow  occurred  at  long  intervals  of  three  to  fifteen 
minutes  and  was  much  scantier  than  that  obtained  from  the  jejunal  fistula,  consist- 
ing of  a  thick  jelly-like,  orange-coloured  mass.  Both  proteins  and  carbohydrates  were 
entirely  digested,  and  in  the  case  of  the  former  the  chief  products  of  digestion  consisted 
of  amino-acids.  Thus  in  one  experiment,  after  four  large  meals  of  500  grm.  of  meat 
each  had  been  given  in  order  to  obtain  sufficient  quantity  for  analysis,  175  grm.  of 
soluble  substances  were  obtained.  Prom  this  were  isolated  tyrosine,  leucine,  alanine, 
aspartic  acid,  lysine,  and  traces  of  arginine  and  histidine. 

From  a  fistula  in  the  caecum  there  was  no  outflow  until  four  or  five  hours  after  the 
meal  had  been  taken.  The  material  from  the  gut  was  then  extruded  in  fsecal-like 
masses  at  long  intervals  of  one  half  to  one  hour.  This  regular  outflow  lasted  for  about 
six  hours.  The  reaction  of  the  contents  was  strongly  alkaline,  with  no  food  particles, 
and  the  material  contained  merely  debris  of  cells,  with  small  traces  of  sugar,  dextrine 
and  unaltered  starch.  The  absorption  of  the  foodstuffs  is  thus  practically  complete 
by  the  time  that  the  food  has  reached  the  lower  end  of  the  small  intestine. 

The  following  Table  gives  the  total  amounts  obtained  in  a  series  of  experiments 
from  the  different  fistula?  after  administration  of  200  grm.  of  bread,  and  also  the 
percentage  amount  of  foodstuffs  which  had  been  absorbed  before  the  food  had  arrived 
at  the  level  of  the  fistula  in  question  : 

Total  amounts  obtained        Absorbed 
from  200  grm.  of  bread  per  cent. 

Pyloric  fistula        ....  691  grm.  0 

Duodenal  fistula    ....  691    „  1745 

Jejunal  fistula        ....  585    „  :;7'77 

Ileum  fistula  ....  412    „  67-65 

Caecal  fistula  ....  80    „  94-34 


SECTION  XI 

THE    F^CES 

The  faeces  are  often  regarded  as  representing  the  undigested  or  indigestible 
constituents  of  the  food  which  have  escaped  solution  and  absorption  in  their 
passage  through  the  alimentary  canal.  This  view  is  hardly  correct  as  applied 
to  man  or  to  the  carnivora.  In  these  the  absorption  of  the  constituents  of 
a  meal,  whether  consisting  of  fats,  proteins,  or  carbohydrates,  is  practically 
complete  by  the  time  that  the  food  has  arrived  at  the  lower  end  of  the 
ileum.  The  faeces,  in  fact,  are  not  derived  from  the  food,  but  are  produced 
almost  entirely  in  the  alimentary  canal  itself.  This  is  shown  by  the  fact 
that  on  analysing  the  faeces  no  soluble  carbohydrates  or  proteins,  albu- 
moses,  peptones,  or  amino-acids  are  to  be  found.  After  a  meal  of  meat 
microscopic  examination  of  the  faeces  reveals  no  trace  of  striated  muscle 
fibres.  Moreover,  animals  in  a  state  of  complete  starvation  form  faeces 
which  do  not  differ  in  their  composition  from  the  faeces  which  are  found 
after  feeding  with  meat,  eggs,  sugar,  or  cooked  starch,  though  the  amount 
is  less  in  a  state  of  inanition  than  under  normal  circumstances.  In  one 
experiment  Hermann  isolated  a  loop  of  gut,  joining  its  ends  together  so 
that  a  continuous  ring  was  formed.  The  continuity  of  the  gut  was  then 
restored  by  suturing  the  two  free  ends.  After  some  weeks  the  isolated  loop 
was  found  to  contain  a  semi-solid  material  similar  to  faeces  in  appearance, 
consistence,  and  chemical  composition.  It  contained  a  large  amount  of 
phosphoric  acid,  lime,  and  iron. 

So  long  as  vegetables  or  coarsely  ground  cereals  are  excluded  from  the 
diet,  the  nature  of  the  latter  does  not  alter  the  chemical  constitution  or 
appearance  of  the  faeces.  Under  these  circumstances  the  faeces  have  the 
following  composition  : 

Water  .  .  .         .  65  to  67  per  cent. 

Nitrogen       .  .  .  .       5  to    9       „ 

Ether  extract        .  .  .  12  to  18 

Ash 11  to  22       „ 

The  ash  consists  chiefly  of  lime  and  phosphoric  acid  with  some  iron  and 
magnesia.  The  ethereal  extract  contains  fatty  acids  and  a  small  amount 
of  lecithin.  Neutral  fat  is  present  in  very  small  proportions.  The  faeces  also 
contain  small  quantities  of  cholalic  acid  and  its  products  of  decomposition, 
dyslvsin,  and  coprosterin,  a  body  allied  to  cholesterin,  and  a  certain  amount 
of  purine  bases  consisting  of  guanine,  adenine,  xanthine,  and  hypoxanthine. 
On  the  average  the  fasces  contain  about  0-11  grm.  of  purine  bases  per  diem, 

799 


Si  II I 


IMIYSIOLOCY 


about  seven  times  as  much  as  is  contained  in  the  urine  passed  in  the  same 
time.  The  material  basis  of  the  faeces  seems  to  be  largely  desquamated 
epithelial  cells  from  the  intestinal  wall,  and  bacteria,  of  which  countless 
numbers,  chiefly  dea.il ,  are  present.  It  has  been  reckoned  that  as  much  as 
50  per  cent,  of  the  Eeeces  may  consist  of  the  dead  bodies  of  bacteria. 

Very  different  is  the  composition  of  faeces  if  the  food  contains  a  large 
amount  of  cellulose.  Not  only  does  the  ingested  cellulose  pass  unchanged 
into  the  fseces,  but  large  quantities  of  other  substances  enclosed  in  the 
cellulose  walls  may  also  escape  digestion  and  absorption.  Moreover  the 
increased  bulk  of  the  undigested  residue  stimulates  peristalsis,  and  thus 
quickens  the  passage  of  the  food  through  the  gut  to  such  an  extent  that  the 
digestive  ferments  have  not  time  to  exert  their  full  action  on  the  digestible 
constituents  of  the  food.  The  influence  of  the  character  of  the  food  is  well 
illustrated  by  a  comparison  of  the  amount  and  composition  of  the  fseces  on 
different  kinds  of  bread  (Rubner) : 


Kind  of  bread 


Bread  from  line  flour 
Bread  from  coarse  flour 
Brown  bread 


132-7 

252-8 
317-8 


24-8 
40-8 
75-79 


Percentage  of 
ingested  lood 


4-03 
6-66 
12-23 


2-17 
3-24 
3-80 


The  following  Table  is  also  instructive.  In  this  Table  Rubner  calculates 
the  amount  of  faeces  which  a  man  would  pass  in  twenty  four  hours  if  he 
satisfied  his  energy  requirements  at  the  expense  of  one  only  of  the  different 
kinds  of  food  enumerated.  The  numbers  refer  to  the  amount  of  organic 
material  which  would  be  excreted  in  the  faeces  : 


Meat    .... 

.     26  grin. 

Rice   .... 

50  gnu 

Eggs    .... 

•     26    „ 

Maize 

•       51    „ 

Macaroni 

■     27    „ 

Turnips 

•     101    „ 

Wheaten  bread     . 

.     36    „ 

Potatoes 

.     133    „ 

Milk     .... 

.     42    „ 

Coarse  brown  bread 

•     146    „ 

The  indigestible  cellulose  in  the  food  is  not  without  value.  It  has  been 
shown  previously  that  the  peristaltic  contractions  of  the  intestine  are  roused 
primarily  by  the  mechanical  stimulus  of  distension.  If  the  food  is  capable 
of  entire  digestion  and  absorption,  the  amount  of  fasces  formed  is  limited 
to  that  produced  by  the  intestinal  wall  itself.  The  small  bulk  exercises 
very  little  stimulating  effect  on  the  intestine,  and  the  movements  of  the 
latter  will  therefore  tend  to  be  sluggish,  especially  in  the  absence  of  the 
mechanical  stimulus  determined  by  muscular  exercise.  The  presence  of  a 
certain  amount  of  cellulose  in  the  diet  may  therefore  be  of  considerable 
advantage  by  giving  bulk  to  the  faeces  and  ensuring  the  proper  regular  evacu- 
ation of  the  lower  gut.  It  is  probable  that  the  constipation  which  is  so 
common  a  disorder  in  civilised  communities  is  due  as  much  to  the  refinement 
in  the  preparation  of  the  food  as  to  the  prevalence  of  sedentary  occupations 
incident  on  the  working  of  such  communities. 


CHAPTER    XI 
THE    HISTORY    OF   THE    FOODSTUFFS 

SECTION    I 

PROTEIN    METABOLISM 

In  dealing  with  the  metabolism  of  the  body  as  a  whole  we  saw  reason  to 
believe  that  the  proteins  taken  in  with  the  food  might  be  regarded  as  having 
a  twofold  destiny.  One  part,  and  under  normal  circumstances  the  greater 
part,  is  applied  to  the  production  of  energy,  iu  this  respect  discharging  a 
function  which  might  equally  well  be  performed  by  the  fats  and  carbohy- 
drates of  the  food.  In  its  second  function  protein  cannot  be  replaced  by  any 
other  foodstuff,  since  it  alone  contains  the  necessary  elements  as  well  as  the 
groupings  of  these  elements  which  are  essential  for  the  building  up  of  the 
living  tissues.  We  saw  reason  to  believe  that  this  tissue  metabolism  ac- 
counted however  for  a  small  part  only  of  the  nitrogen  of  the  food.  For  this 
reason  it  is  possible  to  ensure  health  and  a  condition  of  nitrogenous  equili- 
brium with  amounts  of  protein  in  the  diet  of  man  which  might  vary  between 
40  and  200  grm.  per  diem.  The  more  protein  that  is  taken  in  with  the  food 
the  greater  is  the  relative  amount  which  is  applied  to  the  energy  needs  of 
the  body.  If  therefore  we  would  attempt  to  find  out  what  are  the  end- 
products  of  the  tissue  metabolism,  we  should  confine  the  energy  metabolism 
of  proteins  within  the  smallest  possible  limits  by  reducing  the  quota  of  pro- 
tein in  the  diet  to  its  minimum.  Folin  has  shown  that  if  we  compare  the  com- 
position of  the  urine  obtained  under  these  two  conditions,  namely,  on  a  diet 
containing  a  normal  quantity  of  protein  and  on  a  diet  containing  a  minimal 
amount,  we  find  evidence  of  a  qualitative  difference  between  the  two 
kinds  of  metabolism.  The  difference  is  well  brought  out  in  the  Tables  given 
here.  On  a  large  diet  the  greater  part  of  the  nitrogen  can  be  regarded 
as  derived  directly  from  the  food,  whereas  on  a  small  diet  a  relatively  larger 
proportion  of  it  must  come  from  protein  which  has  been  previously  built  up 
into  the  tissues.  Folin  distinguishes  these  two  sources  of  the  nitrogen 
of  the  urine  as  exogenous,  i.  e.  that  from  the  food,  and  endogenous,  i.  e.  derived 
from  the  tissues.  Two  facts  stand  out  in  comparing  these  two  urinary 
analyses.  In  the  first  place,  on  a  normal  protein  diet  the  urea  accounts  ior 
87  per  cdnt.  of  the  total  nitrogen  of  the  urine.  On  an  excessive  protein  diet 
this  percentage  may  rise  to  90  or  95.  On  the  low  protein  diet  the  percentage 
51  801 


802 


PHYSIOLOGY 


TABLES  1  and   II 
Distribution  of  Nitrogen  in  Urine  on  Various  Diets 


July  18 

July  20 

Ordinary  diet 
1170  C.C. 

Low  protein  diet 
385  c.c. 

Vol.  of  urine 

Total  nitrogen 

16-8  grm. 

3-60  grm. 

Urea     . 

14-70  grm.  =  87-5% 

2-20  grm.  =  61-7  % 

Ammonia 

0-49  grm.  =    3-0  % 

0-42  grm.  =  11-3% 

Urio  acid 

0-18  grm.  =    1-1% 

0-09  grm.  =    2-5  % 

Creatinine 

0-58  grm.  =    3-6  % 

0-60  grm.  =  17-2  % 

Undetermined 

0-85  grm.  =    4-9%   ' 

0-27  grm.  =    7-3% 

Total  S03      . 

3  64  grm. 

0-76  grin. 

Inorganic  SOa 

3-27  grm.  =  900  % 

0-46  grm.  =  00-5  % 

Ethereal  S03 

019  grm.  =    5-2% 

0-10  grm.  =  13-2  % 

Neutral  S 

0-18  grm.  =    4-8  % 

0-20  grm.  =  26-3  % 

of  nitrogen  appearing  as  urea  is  reduced  to  60.  On  the  other  hand,  practi- 
cally identical  amounts  of  creatinine  are  obtained  under  the  two  conditions, 
so  that  whereas  on  the  full  diet  it  amounts  only  to  3-6  per  cent.,  on  the  low 
protein  diet  it  forms  as  much  as  17  per  cent,  of  the  total  nitrogen  output. 


0  4  8  12  16  20  24rlours 

Fig.  3G4.  The  hourly  variation  in  the  excretion  of  nitrogen  after  a  meal. 
The  meal  was  given  at  0.  The  thick  line  represents  the  average  ab- 
sorption of  the  food  from  the  alimentary  canal.  The  thin-lined  curves 
represent  the  N.  oxcretion  (1)  after  a  meal  of  1000  grm.  meat;  (2)  after  500 
grm.  meat  and  150  grm.  fat;  (3)  after  a  meal  of  500  grm.  meat;  (4)  and 
(5)  both  represent  the  excretion  in  a  fasting  animal.  (From  Tigerstedt 
after  Feder.) 

We  are  therefore  justified  in  regarding  urea  as  to  a  large  extent  exogenous  in 
origin,  and  as  derived  directly  from  the  nitrogenous  moiety  of  the  protein 
molecule,  which  may  not  at  any  time  have  formed  part  of  the  living  tissues 
of  the  bodv. 


PROTEIN  METABOLISM  803 

On  giving  a  large  protein  meal  to  a  dog,  the  urea  in  the  urine  rapidly 
rises,  and  at  the  end  of  four  or  five  hours  50  per  cent,  of  the  total  nitrogen 
taken  in  with  the  food  has  appeared  in  the  urine  as  urea  (Eig.  364).  If  we 
take  into  account  that  the  digestion  of  a  meat  meal  in  this  animal  may  go 
on  for  eight  hours,  we  are  justified  in  the  statement  that  by  far  the  greater 
portion  of  the  protein  nitrogen  taken  with  the  food  is  excreted  almost 
directly  after  absorption  as  urea  in  the  urine.  Urea  is  therefore  to  be  re- 
garded in  the  first  place  as  an  index  to  the  amount  of  protein  absorbed.  We 
have  seen  that  the  end-products  of  protein  digestion  in  the  intestine  are 
the  amino-acids ;  and  that  these  are  the  immediate  precursors  of  the  urea 
is  shown  by  the  fact  that  the  administration  of  these  bodies  is  followed  very 
rapidly  by  the  appearance  of  the  whole  of  their  nitrogen  hi  the  urine  as 
urea. 

The  formation  of  urea  from  the  amino-acids  is  accomplished  in  a  very 
simple  fashion.  If  amino-acids  be  treated  with  the  pulp  of  various  organs, 
there  is  a  production  of  ammonia,  which  is  not  observed  when  no  amino-acids 
are  added  to  the  pulp.  Thus  leucine,  glycine,  tyrosine  and  cystine  give 
rise  to  ammonia,  while  none  of  this  substance  is  produced  from  phenylalanine. 
This  production  of  ammonia  is  due  to  the  presence  of  deaminising  ferments 
in  the  cells  of  the  various  tissues.  According  to  van  Slyke  the  liver  plays 
the  chief  part  in  the  break-down  of  amino-acids,  though  there  is  no  reason 
to  deny  the  possession  of  similar  powers  to  the  other  tissues,  e.  g.  the  muscles 
of  the  animal  body.  As  a  result  of  this  deamhiisation  ammonia  is  set  free 
in  the  body,  and  this  ammonia  is  rapidly  converted  into  urea.  Whether 
the  ammonia  enters  the  circulation  as  ammonium  carbonate  or  as  ammonium 
carbamate  is  uncertain,  but  in  either  form  it  will  be  quickly  changed  into 
urea.  This  conversion  involves  a  process  of  dehydration.  The  ammonium 
carbonate  loses  2  molecules  of  water  and  the  ammonium  carbamate  1  mole- 
cule, as  follows  : 

/ONH4  ,NHa 

Co/  —  2H20=CO;( 

^OHN,  XNH2 

or 
/ONE,  yKH2 

CO/  —  H.,0  =  CO 

XNH2  XNH, 

Although  there  is  normally  a  small  amount  of  ammonia  in  the  urine,  it  is 
not  increased  by  injection  or  administration  of  ammouium  carbonate  or 
carbamate.  Either  of  these  two  substances  administered  to  man  or  to  an 
animal  gives  rise  simply  to  a  corresponding  increase  in  the  urea  of  the  urine. 
A  large  body  of  evidence  points  to  the  liver  as  being  the  chief  seat  of 
conversion  of  ammonia  salts  into  urea.  Thus  Schroder  has  shown  that  the 
liver,  even  after  removal  from  tlie  body,  has  the  power  to  transform 
ammonium  carbonate  into  urea.  Defibrinated  blood  mixed  with  ammonium 
carbonate  was  passed  for  one  hour  through  a  surviving  liver.  It  was  then 
found  that  the  ammonium  carbonate  had  disappeared  and  that  its  place 
was  taken  by  urea,  which  could  be  extracted  in  a  crystallised  form. 


804 


PHYSIOLOGY 


Confirmatory  evidence  of  this  function  of  the  liver  was  supplied  by 
Schroder's  experiments  on  birds.     In  these  animals  the  chief  nitrogenous 

e\,  ret  ion  is  not  urea,  but  ammonium  urate,  60  per  cent,  of  the  nitrogen  of 
the  semi  solid  urine  appearing  in  the  form  of  uric  acid.  In  birds  there  is 
naturally  a  communication  between  the  portal  system  and  the  general  venous 
system  by  means  of  the  vein  of  Jacobson,  which  connects  the  lower  branches 
of  t  he  portal  vein  with  ,-as  a  rule,  the  left  renal  vein  (Fig.  365).  On  this  account 
the  liver  can  be  cut  or  t  of  the  body  or  of  the  circulation  without  entailing 
the  rapid  death  of  the  bird,  which  may  live  for  three  or  four  days,  and  pass 
urine  after  the  operation.  The  urine  is  however  fluid,  and  the  uric  acid, 
instead  of  accounting  for  GO  per  cent,  of  the  total  nitrogen,  now  forms  only 


ton    Inf.  Vena  Cava 


V.  of  Jacobson 
Inf.  mes.  v. 

Caudal   v- 


Rectum 


Fig.  365.  Diagram  to  show  the  arrangement  of  the  veins  in  the  bird, 
with  the  communication  of  the  renal  and  portal  veins.  (After 
Mokat.) 


5  per  cent.  The  place  of  the  greater  part  of  the  uric  acid  has  been  taken 
by  ammonium  lactate,  which  therefore  seems  to  be  the  chief  immediate 
precursor  of  the  uric  acid  in  the  urine  of  birds.  We  shall  have  occasion 
to  consider  the  method  of  transformation  of  ammonium  lactate  to  uric 
acid  more  fully  when  dealing  with  the  origin  of  the  latter  body. 

It  is  by  no  means  easy  to  perform  similar  experiments  in  mammals, 
since  it  is  difficult  to  cut  off  the  flow  of  blood  through  the  fiver  without 
altogether  stopping  the  circulation  through  the  abdominal  viscera.  Ligature 
of  the  portal  vein,  which  would  be  a  necessary  step  in  the  extirpation  of  the 
fiver,  causes  the  blood  to  be  dammed  up  behind  the  ligature  in  the  portal 
area.  The  intestinal  wall  gets  full  of  effused  blood,  the  blood  pressure  falls 
steadily,  and  the  animal  dies  within  a  few  hours,  being  bled  to  death,  so  to  ■ 
speak,  into  its  portal  vessels.  A  way  of  obviating  this  difficulty  was  sug- 
gested by  a  Russian  surgeon,  Eck,  and  was  successfully  carried  out  by  Pawlow. 
Before  ligature  of  the  portal  vein,  this  vessel  was  joined  to  the  vena  cava 


PROTEIN  METABOLISM  805 

ard  an  artificial  opening  made  connecting  the  himen  of  the  two  vessels, 
so  that,  after  the  ligature,  the  blood  could  flow  directly  into  tie  general 
circulation  without  passing  through  the  liver.  Some  animals  operated 
on  in  this  way  showed  no  abnormal  symptoms  whatsoever.  There  was  a 
rapid  formation  of  a  collateral  circulation  so  that  the  blood  could  get  round 
the  ligature  to  the  liver.  Under  all  circumstances  a  path  to  the  liver  was 
still  open  by  the  hepatic  artery,  but  to  arrive  here  the  blood  from  the  ali- 
mentary canal  had  first  to  pass  through  the  general  circulation.  A  certain 
number  of  animals  wore  found  to  be  particularly  susceptible  to  the  nature 
of  their  diet.  On  a  diet  largely  consisting  of  carbohydrates  they  maintained 
good  health.  After  a  large  meat  meal  however  they  became  ill,  and  in 
many  cases  suffered  from  tremors  and  convulsions  ending  in  coma.  At  the 
same  time  there  was  a  definite  increase  of  ammonia  in  the  urine,  chiefly 
in  the  form  of  ammonium  carbamate.  Pawlow  and  Nencki  therefore 
ascribed  the  symptoms  observed  in  these  dogs  after  a  heavy  meat  meal 
to  a  condition  of  '  ammonisemia,'  and  regarded  the  liver  as  an  organ  which 
is  normally  concerned  in  protecting  the  rest  of  the  body  from  ammonia, 
produced  in  the  alimentary  tract,  by  converting  this  substance  into  the 
innocuous  neutral  body,  urea. 

We  thus  see  that  the  urea,  which  appears  in  the  urine  so  rapidly  after 
an  ingestion  of  protein,  does' not  signify  a  total  disintegration  of  the  protein 
molecule,  bat  is  merely  the  result  of  the  throwing  off  of  the  nitrogenous 
part  of  the  protein  molecule  by  a  process  of  deamination.  This  deamination 
may  be  a  purely,  hydrolytic  change  or  it  may  be  associated  with  oxidation 
or  reduction.  Deamination  of  alanine,  for  instance,  by  simple  hydrolysis 
would  result  in  the  formation  of  lactic  acid  (an  oxy-fatty  acid). 

CH,  CH3 

I  I 

CH.NK,  +  H„0  =  NH3  +  CHOH 

COOH  COOH 

If  the  deamination  were  accompanied  with  oxidation,  the  corresponding 
keto-fatty  acid  would  be  formed,  thus 

CH3.CHNH2.COOH  +  0  =  NH3  +  CH3CO.COOH 

Alanine  Pyruvic  acid 

If  reduction  took  place  at  the  same  time,  the  result  would  be  the  production 
of  a  saturated  fatty  acid  such  as  propionic  acid.  Rnoop  has  shown  that 
all  three  cases  may  occur.  The  investigation  of  the  stages  in  deamination, 
and  indeed  in  the  disintegration  of  fatty  derivatives  generally,  is  rendered 
difficult  by  the  fact  that  all  the  intermediate  products  undergo  further 
change  and  leave  the  body  in  a  state  of  complete  oxidation  as  carbon  dioxide 
and  water.  If  however  an  amino-acid  group  be  administered  as  part 
1  >f  an  aromatic  compound,  i.e.  forming  a  side-chain  of  the  benzene  ring, 
!t  is  protected  from  complete  oxidation  by  the  stability  of  this  ring.  The 
oxidation  of  the  fatty  side-chain  may  proceed  to  a  certain  degree,  so  that 


SOfi  PHYSIOLOGY 

intermediate  products  of  metabolism  may  be  excreted  still  attached  to  the 
benzene  i«icleus.  In  the  a-amino-acida  the  point  where  disintegration 
first  occurs  is  the  a-group.  Deamination  Knoop  finds  most  usually  asso- 
ciated with  oxidation.     The  primary  product  is  therefore  an  a-keto-acid. 

Further  oxidation  affects  the  CO  group,  so  that  carbon  dioxide  is  eliminated 

and  the  next  lower  acid  in  the  fatty  acid  series  is  produced.  Thus  from 
alanine  the  body  would  produce  pyruvic  acid,  CH,.CO.COOH,  and  this 
on  further  oxidation  would  form  acetic  acid,  CH3.COOH,  and  carbon  dioxide. 
On  the  other  hand,  these  keto-acids  may  undergo  reduction  to  an  oxy-acid,  or 
even  a  step  further,  to  a  fatty  acid,  though  the  conditions  which  determine 
whether  oxidation  or  reduction  shall  take  place  have  not  yet  been  fully 
studied. 

This  loss  of  nitrogen  diminishes  little,  if  at  all,  the  energy  value  of  the 
amino-aeids  of  the  body.  The  following  table  shows  the  heat  equivalents 
of  some  of  the  amino-acids  and  their  corresponding  fat  and  oxy-acids  : 

_  ,    .  Calories 

Substance  per  grm.  molecule 

Leucine  .....  855 


Isobutylacetio  acid 
Alanine 
Propionic  acid 
Lactic  acid     . 
Pyruvic  acid 


837 
389 
367 
329 

not  determined 


These  heat  equivalents  represent  the  heat  evolved  on  the  total  oxidation 
of  the  substances  in  question.  In  the  case  of  the  amino-acids,  part  of  the 
molecule  is  not  oxidised,  the  nitrogen  leaving  the  body  not  as  free  nitrogen 
but  as  urea.  To  obtain  the  total  possible  heat  value  of  an  amino-aoid  to 
the  body,  we  must  subtract  from  its  heat  equivalent  half  the  heat  equivalent 
of  urea,  (an  amino-acid  contains  1  atom  of  nitrogen,  while  urea  contains 
2  atoms,  so  that  one  molecule  of  urea  is  produced  from  2  molecules  of  an 
amino-acid.)  The  heat  equivalent  of  urea  being  80,  the  physiological 
heat  equivalent  of  leucine  will  be  not  855  but  815,  while  the  physiological 
heat  equivalent  of  alanine  will  be  349,  as  against  329  for  lactic  acid.  Thus 
even  in  the  case  of  the  smallest  molecule,  the  loss  of  energy  attendant  on 
simple  deamination  and  conversion  into  the  corresponding  oxy-acid  amounts 
to  little  more  than  5  per  cent.,  and  the  proportion  will  be  much  smaller  in 
the  case  of  the  larger  molecules.  We  are  accustomed  to  regard  the  urea 
excretion  as  an  index  to  protein  metabolism.  In  truth  it  is  an  index  only 
of  the  deamination  of  the  protein  constituents,  and  it  tells  us  nothing  what- 
ever about  the  fate  of  that  part  of  the  protein,  the  non-nitrogenous  part, 
which  contains  95  per  cent,  or  more  of  the  total  energy  of  the  protein  food. 
The  rise  in  the  rate  of  excretion  of  urea  after  a  protein  meal  was  regarded 
both  by  Voit  and  Pfliiger  as  a  sign  that  the  cells  of  the  body  prefer  to  use 
protein  for  all  their  requirements,  if  this  substance  were  available.  We 
see  now  that  the  rapid  output  of  urea  after  a  protein  meal  affords  no  basis 


PROTEIN  METABOLISM  807 

for  this  view,  but  is  rather  a  sign  that  the  body,  after  satisfying  its  modest 
needs  for  the  repair  of  its  tissue  waste,  has  no  need  for  the  rest  of  the  nitro- 
genous content  in  its  food,  and  that  this  must  be  got  rid  of  before  the  really 
valuable  part,  the  energy-giving  part,  of  the  protein  molecule,  is  admitted 
into  the  metabolic  cycle  of  the  cells. 

The  important  problem  in  the  energy  metabolism  of  protein  is  thus  not 
the  origin  of  the  urea,  but  the  fate  and  nature  of  the  substances  that  are 
left  after  deamination.  We  have  seen  that  the  protein  when  taken  as  a 
food,  more  than  either  of  the  other  two  foodstuffs,  causes  a  direct  augmenta- 
tion of  the  respiratory  exchanges  of  the  body.  Thus  in  one  experiment  by 
Rubner,  an  animal  previously  starved  received  on  one  day  574  Calories 
protein,  on  another  day  54-2  Calories  fat,  and  on  the  third  day  57  Calories 
carbohydrates  per  kilo,  body  weight.  During  hunger  the  total  metabolism 
per  kilo,  body  weight  amounted  to  37-5  Calories ;  with  meat;  to  46  Calories ; 
with  fat,  to  39-4  Calories ;  with  carbohydrates,  to  39-4  Calories.  Compared 
with  the  metabolism  during  starvation  the  rise  per  cent,  with  protein  was 
24-3,  and  with  fat  and  carbohydrates  5-1.  This  surplus  output  of  energy 
resulting  from  the  administration  of  protein  cannot  be  ascribed  to  increased 
work  thrown  on  the  digestive  organs;  There  is  no  evidence  that  this  is 
greater  in  the  case  of  proteins  than  it  would  be  with  carbohydrates  or  fats ; 
and  even  if  the  capacity  of  these  organs  be  strained  to  their  utmost  by 
administration  of  large  quantities  of  bones,  the  increase  in  the  C02  output 
which  results  is  not  so  great  as  that  following  a  large  protein  meal.  It 
might  be  concluded  that  the  CHO  moiety  of  the  protein  undergoes  oxidation 
more  rapidly  than  either  glucose  or  the  ordinary  fats  of  the  diet,  and  that 
its  metabolism  is  dependent  rather  on  the  quantity  presented  to  the  organism 
than  on  the  actual  needs  of  the  cells  of  the  body.  The  work  of  Lusk  points 
however  to  the  earlier  view  of  Voit  as  being  correct,  according  to  which 
protein  food  acts  as  a  stimulant  to  all  the  metabolic  processes  of  the  body. 
Lusk  has  shown  that  this  specific  dynamic  action  of  protein  is  possessed 
also  by  certain  of  the  amino-acids  resulting  from  its  decomposition,  but  not 
by  all.  Thus  while  glycine  and  alanine  exert  a  well  marked  specific  dynamic 
action,  glutamic  acid,  leucine  and  tyrosine  exert  little  or  no  effect  upon 
heat  production.  The  question  then  arises  whether  this  increased  heat 
production  resulting  from  the  ingestion  of  glycine  is  due  to  the  rapid  dis- 
integration and  oxidation  of  the  glycine  molecule  itself,  or  is  due  to  a  direct 
stimulating  action  upon  the  body  cells.  The  question  was  decided  by  giving 
glycine  to  an  animal  which  had  been  rendered  diabetic  by  the  injection  of 
the  phlorhizine.  Under  these  circumstances  glycine  is  converted  quanti- 
tatively into  glucose,  which  is  excreted  in  the  urine,  so  that  the  CHO  moiety 
of  the  glycine  molecule  undergoes  no  oxidation  in  the  body.  Notwith- 
standing this  fact  glycine  produces  the  same  augmentation  of  metabolism  in 
the  phlorhizir.ised  animal  as  it  would  in  a  normal  animal.  The  same  results 
were  obtained  with  alanine,  so  that  it.  must  be  concluded  that  the  specific 
dynamic  action  of  protein  is  due  to  the  quality  possessed  by  certain  of  the 
amino-acids  of  stimulating  the  cells  of  the  body  and  raising  their  rate  of 


808  PHYSIOLOGY 

metabolism.  But  it  is  not  the  amiiio-acids  themselves  that  are  the  stimu- 
lants. This  is  shown  by  the  fact  that  when  amino-acids  are  built  up 
to  form  new  tissues,  as  in  the  baby  or  in  the  animal  recovering  from 
starvation,  they  exert  no  specific  dynamic  action.  This  action  only 
occurs  when  the  amino-acids  undergo  deamination,  and  must  therefore  be 
the  result  of  the  products  of  this  deaminalion.  Lusk  suggests  that  in 
the  case  of  glycine  and  alanine,  the  stimulating  substances  may  be 
glycollic  and  lactic  acids,  but  there  is  no  direct  proof  of  this  suggestion. 
We  know  in  fact  very  little  of  the  nature  of  the  substances  that  are  left 
after  deamination.  Since  they  contain  only  the  elements  carbon,  hydro- 
gen, oxygen,  one  would  expect  to  find  that  they  could  replace  either 
fat  or  carbohydrate.  So  far  as  concerns  the  production  of  energy  this 
is  true.  Moreover,  as  we  shall  see  in  dealing  with  the  metabolism  of 
carbohydrates,  we  have  definite  evidence  that  part  of  this  non-nitrogenous 
moiety  of  the  protein  molecule  may  be  converted  into  sugar  or  glycogen. 
Thus,  of  the  amino-acids  formed  by  the  digestion  of  proteins,  glycine,  alanine, 
aspartic  acid  and  glutamic  acid  can  be  converted  quantitatively  under  appro- 
priate circumstances  into  glucose.  On  the  other  hand,  leucine,  phenylala- 
nine and  tyrosine  yield  no  glucose,  even  in  the  diabetic  animal,  but  may 
in  the  liver  undergo  conversion  into  aceto-acetic  acid,  which  is  a  stage  in 
the  oxidative  disintegration  of  fats.  In  spite  of  this  latter  fact  we  have 
no  evidence  that  fat  may  be  formed  from  this  part  of  the  protein  molecule ; 
at  any  rate,  no  fat  which  can  be  stored  in  the  body  and  give  rise  to  the 
production  of  adipose  tissue.  The  reason  why  the  CHO  remainder  of  the 
protein  molecule  is  so  prone  to  oxidation  and  does  not.  like  an  excess  of 
carbohydrates,  undergo  conversion  into  fats  in  the  body,  we  shall  have  to 
consider  in  greater  detail  in  dealing  with  the  fate  of  this  latter  class  of  sub- 
stances. We  need  however  considerably  more  evidence  as  to  the  extent 
to  which  deamination  occurs  and  as  to  its  conditions  and  end-products 
before  we  can  hope  to  determine  the  cause  for  the  rapid  breakdown  of  these 
end-products  in  the  body. 

The  Synthesis  of  Amino- Acids 

Many  though  not  all  of  the  processes  in  the  body  are  reversible.  If 
the  body  can  effect  deamination  of  an  ammo-acid,  there  seems  no  reason 
why  it  should  not  carry  out  the  reverse  change  and  synthesise  an  amino-acid 
from  its  corresponding  fatty  or  oxy-acid  and  ammonia.  Knoop  has  shown 
that,  given  a  right  molecular  grouping,  the  fatty  acid  residue  may  in  the 
body  react  with  ammonia  to  form  an  amino-acid.  The  proof  of  this  fact 
was  facilitated  by  the  discovery  that  the  next  higher  homologue  of  phenyl- 
alanine, namely,  phenyl-a-amino-butyric  acid,  when  administered  to  an 
animal,  was  excreted  in  large  quantities  in  the  urine  as  an  ether-soluble 
acetyl  derivative,  which  was  easity  isolated  in  a  state  of  purity.  If  then  this 
amino-acid  were  formed  in  the  body,  one  might  expect  to  find  it  without 
difficulty  in  the  urine.  Knoop  found  that  the  administration  of  either 
phenyl-a-keto-butyric  acid  or  phenyl-a-oxybutyric  acid  led  to  the  excretion 


PROTEIN  METABOLISM  809 

of  the  corresponding  ainino-acid  in  the  urine.  Since  keto-acids  occur  as  the 
ordinary  products  of  the  breakdown  of  amino-acids  and  also  as  the  inter- 
mediate products  of  oxidation  of  oxy-acids,  e.  g.  lactic  acid,  it  is  evident  that 
the  animal  body  can  assimilate  ammonia  and  form  amino-acids,  provided 
only  that  it  is  supplied  with  the  proper  non-nitrogenous  acids.  These  latter 
need  not  be  derived  from  proteins  at  all  but,  like  lactic  acid,  be  a  result  of 
carbohydrate  metabolism.  Thus,  if  the  fitting  non-nitrogenous  food  be  given 
{e.g.  oxy-fatty  acids,  or  carbohydrates,  from  which  these  bodies  may  be 
formed),  part  of  the  nitrogen  set  free  by  protein  disintegration  might  be 
recombined  with  the  formation  of  amino-fatty  acids  without  giving  rise  to 
urea  or  appearing  in  any  way  in  the  nitrogen  balance-sheet  of  the  body. 
This  possibility  enjoins  the  necessity  of  caution  in  interpreting  the  results  of 
metabolism  experiments  where  the  nitrogen  excreted  is  taken  to  represent 
the  total  protein  metabolism  of  the  body. 

Are  the  Amino-acids  interconvertible  ? 
Although  the  animal  organism  is  apparently  capable  of  synthetising 
amino-acids  from  ammonia  and  the  corresponding  keto-  or  oxy-fatty  acid, 
it  is  unable  to  convert  one  amino-acid  into  another.  On  this  account  many 
proteins  are  inadequate  as  food  substances  since  they  do  not  contain  the 
necessary  amino-acid  groups.  Life  cannot  be  supported  on  such  bodies  as 
zein  or  gelatin,  which  are  lacking  in  the  tryptophane  and  tyrosine  groups. 
The  failure  in  these  cases  is  not,  as  has  been  generally  supposed,  owing  to 
an  inability  to  assimilate,  i.  e.  synthetise,  nitrogen  as  ammonia,  but  to  the 
fact  that  in  the  animal  the  apparatus  is  wanting  for  the  manufacture  of  some 
of  the  oxy-fatty  acids  and  other  radicals  which  form  the  non-nitrogenous 
part  of  the  amino-acids.  This  view  receives  confirmation  from  the  fact  that 
the  simplest  of  the  amino-fatty  acids,  namely,  glycine,  can  be  easily  manu- 
factured in  the  body,  acetic  acid  being  one  of  the  latest  stages  in  the  oxidation 
of  most  carbohydrates  and  fats.  It  has  been  shown  that  alanine  too  can 
be  easily  manufactured  by  the  body,  by  the  animation  of  the  three  carbon 
acids  or  oxy-acids  derived  from  the  breakdown  of  glucose  or  glycogen. 

The  Excretion  of  Ammonia 

A  large  proportion  of  the  urea  appearing  in  the  urine  after  a  protein 
meal  is  exogenous  and  is  derived  by  a  rapid  separation  of  ammonia  from  the 
proteins  or  their  disintegration  products  almost  immediately  after  their 
absorption.  The  greater  part  of  the  ammonia  is  converted  in  the  liver  into 
urea,  which  is  excreted  by  the  kidney.  A  certain  small  proportion  of  the 
nitrogen  in  the  urine  is  generally  turned  out  in  the  form  of  ammonia.  This 
proportion  is  not  increased  by  the  administration  of  ammonium  carbonate. 
If  ammonium  chloride  be  given  to  a  starving  rabbit,  it  appears  in  the  urine 
unchanged,  and  so  increases  the  proportion  of  ammonia  hi  this  fluid.  If 
however  the  ammonium  chloride  be  administered  at  the  same  time  as  the 
animal  is  receiving  its  ordinary  vegetable  diet,  there  is  no  increase  in  the 
ammonia  in  the  urine,  the  whole  of  the  ammonium  chloride  being  converted 


810  PHYSIOLOGY 

into  urea.  The  factor,  which  determines  the  proportion  of  ammonia  in  the. 
urine, is  the  relative  proportion  of  acids  and  bases  which  have  to  he  eliminated 
from  t  he  body.  The  normal  reaction  of  urine,  though  acid  as  regards  certain 
indicators,  can  be  regarded  as  neutral  since  it  contains  no  free  acids,  the 
'  acidity  '  being  due  to  the  presence  in  solution  of  such  substances  as  acid 
sodium  phosphate.  If  the  fixed  alkalies  in  the  food  are  sufficient  to  combine 
with  the  whole  of  the  acids  excreted  from  the. body,  then  the  ammonia  will  be 
completely  converted  into  urea  and  eliminated  as  such.  If  however  a  dose 
of  mineral  acid  be  administered  to  an  animal,  this  must  be  excreted  in  com- 
bination with  a  base.  If  the  fixed  alkalies  available  do  not  suffice  for  this 
purpose,  the  neutralisation  of  the  acid  is  effected  by  coupling  with  ammonia. 
The  ammonia  of  the  urine  is  therefore  an  index  to  the  amount  of  acids  which 
are  excreted.  These  acids  may  be  introduced  directly  with  the  food,  as  when 
mineral  acids  are  administered  by  the  mouth,  or  may  be  the  product  of 
abnormal  metabolic  processes  occurring  in  the  body.  Thus  under  certain 
circumstances,  e.  g.  in  complete  carbohydrate  starvation,  there  is  a  failure 
in  the  last  stages  of  the  oxidation  of  fats,  and  oxy-fatty  acids,  viz.  oxybutyric 
acid  and  aceto-acetic  acid,  are  produced  in  the  body  in  large  quantities, 
but  cannot  undergo  further  disintegration.  The  alkalescence  (electrical 
neutrality)  of  the  fluid  media  of  the  body  is  a  necessary  condition  for  the 
continuance  of  the  life  of  the  cells  and  especially  of  the  normal  processes 
of  oxidation.  It  is  therefore  essential  for -the  preservation  of  life  that  the 
acids  thus  formed  and  accumulating  as  a  result  of  the  impaired  oxidative 
processes  should  be  neutralised,  carried  to  the  kidneys,  and  excreted  by  them 
in  combination  with  some  base.  When  these  acids  are  produced  in  large 
quantities,  the  alkalies  of  the  food  and  of  the  tissues  do  not  suffice  for  their 
neutralisation.  Ammonia,  which  is  a  constant  intermediate  stage  in  the 
production  of  urea,  is  then  utilised  for  this  purpose  and  the  acids  appear  in  the 
urine  in  combination  with  ammonia.  The  ammonia  of  the  urine  therefore 
gives  valuable  information,  not  as  to  the  total  nitrogenous  exchanges  of  the 
body,  but  as  to  the  formation  of  acids  in  abnormal  quantities  during  the 
processes  of  metabolism. 

The  Fate  of  Arginine. 

There  is  one  other  method  in  which  urea  may  be  formed  by  a  rapid 
alteration  of  the  proteins  taken  in  with  the  food.  Nearly  all  the  ordinary 
proteins  contain  arginine  as  an  integral  part  of  their  molecule.  This  sub- 
stance can  be  regarded  as  formed  by  a  coupling  of  guanidine  with  amino- 
valerianic  acid  and  as  analogous  to  the  most  prominent  extractive  of  muscle, 
namely,  creatine,  which  is  methyl  guanidine  acetic  acid.  On  heating  either 
of  these  substances  with  baryta  water,  it  undergoes  hydrolysis  and  is  decom- 
posed with  the  formation  of  urea  and,  in  the  case  of  arginine,  a-<5-diamino- 
valerianic  acid ;  in  the  case  of  creatine,  methyl  amino-acetic  acid  or  sarco- 
sine.  It  has  been  shown  by  Dakin  and  Kossel  that  the  same  change  may  be 
effected  under  the  agency  of  a  ferment,  arginase,  which  is  contained  in 
extracts  of  the  intestinal  wall  or  of  the  liver.    We  have  every  reason  to 


PROTEIN  METABOLISM  811 

believe  therefore  that  a  certain  small  proportion  of  the  urea,  which  appears 
in  the  urine  after  the  ingestion  of  protein,  is  due  to  this  hydrolytic  splitting 
of  the  arginine  contained  in  the  protein  molecule.  The  other  moiety  of  the 
arginine,  namely,  the  diamino-valerianic  acid,  probably  undergoes  the  same 
changes  as  the  other  amino-acids,  such  proportion  of  it  as  is  not  required  for 
the  building  up  of  the  tissues  of  the  body  being  deaminised  and  giving  rise  to 
urea  and  some  CHO  group  in  the  manner  already  discussed. 

THE   ENDOGENOUS   OR   TISSUE   METABOLISM   OF   PROTEINS 

On  comparing  the  output  of  the  various  nitrogenous  excreta  given  in 
Folin's  Tables  quoted  above  (p.  802),  we  see  that  on  a  low  protein  diet,  when 
the  exogenous  or  energy  metabolism  of  this  foodstuff  is  reduced  to  a  mini- 
mum, the  only  substance  which  does  not  undergo  simultaneous  diminution 
is  the  creatinine.  Whereas  on  an  ordinary  diet  free  from  meat,  it  accounts 
only  for  about  3  per  cent,  of  the  total  nitrogen  output,  on  the  low  diet 
it  forms  as  much  as  17  per  cent.  The  conclusion  at  once  suggests  itself  that 
creatinine,  more  than  all  the  other  constituents  of  the  urine,  must  be  regarded 
as  an  index  of  the  tissue  metabolism  of  protein.  Let  us  see  what  facts  can 
be  adduced  in  favour  of  this  view. 

Creatinine  has  the  formula  : 

NH  =  C.N(CH3).CH, 

I  I    " 

NH CO 

and  may  be  regarded  as  derived  by  a  process  of  dehydration  from  creatine 
(methyl  guanidine  acetic  acid). 

NH  =  C.N(CH3).CH2COOH 

NH2 

It  may  be  formed  from  tliis  latter  substance  by  boiling  for  three  hours  with 
strong  hydrochloric  acid.  Creatine  has  long  been  known  as  the  most 
abundant  nitrogenous  extractive  in  the  body.  It  exists  in  relatively  large 
quantities  in  muscle;  and  in  meat  extracts,  such  as  Liebig's,  it  occurs  to  the 
extent  of  10  or  12  per  cent.  It  has  been  calculated  that  the  body  of  a  man 
at  any  time  contains  about  90  grm.  of  this  substance.  On  boiling  creatine 
with  baryta  water,  it  undergoes  hydrolysis  with  the  formation  of  urea  and 
sarcosinc  or  methyl  glycine. 


CH3 

CH3 

*C.N.CH,COOH  +  H20  = 
NH./ 

NH2\ 

>co- 

NH/ 

1 

|-  HN.CH2COOH 

Creatine 

Urea 

Methyl  slycuie  • 

Owing  to  the  ease  with  which  this  formation  of  urea  from  creatine  may  be 
brought  about  outside  the  body,  it  was  natural  that  this  substance  should 
be  regarded  as  an  important  precursor  of  the  urea  in  the  urine.    The  view 


812  PHYSIOLOGY 

was  held  till  recently  however,  on  the  ground  of  experiments  by  Voit,  that 
creatine  administered  in  the  food  appeared  in  its  entirety  as  creatinine  in  the 
urine,  so  that  if  creatine  were  liberated  from  the  muscles  in  their  normal 
processes  of  metabolism,  it  would  pass  to  the  kidneys  and  be  excreted  as 
creatinine  without  undergoing  further  decomposition.  On  this  account  too, 
the  creatinine  in  the  urine  was  regarded  as  derived  almost  exclusively  from 
the  creatinine  taken  in  with  the  food.  The  analyses  given  in  Folin's  Tables 
show  that  in  one  respect  at  any  rate  this  view  was  incorrect.  Creatinine  is 
excreted  in  considerable  quantities  even  when  the  man  is  on  a  creatine-free 
diet,  or  even  when  his  food  is  almost  free  from  protein.  It  has  been  found 
moreover  by  Folin  that  creatine  administered  by  the  mouth  may  disappear 
in  the  body.  This  is  especially  the  case  if  the  animal  or  man  is  on  an 
insufficient  protein  diet,  but  there  is  no  evidence  of  a  corresponding  increase 
in  urea  formation.  If  a  larger  amount  be  given,  creatine  appears  as  such  in 
the  urine.  In  most  cases  a  certain  minute  proportion  escapes  and  causes  an 
increase  in  the  quantity  of  creatinine.  Under  abnormal  circumstances,  e.g. 
during  illness,  when  the  physiological  activities  of  the  body  are  lowered,  a 
portion  of  the  creatine  may  be  found  in  the  urine  in  an  unchanged  con- 
dition. If  creatinine  is  to  be  regarded  in  any  way  as  the  index  of  tissue 
metabolism,  its  amount  ought  to  vary  with  the  extent  of  this  metabolism. 
Thus  it  should  be  increased  when  there  is  an  exaggeration  of  the  disintegrative 
processes  in  the  tissues,  and  should  be  diminished  when  the  nutritive  changes 
in  these  tissues,  especially  in  the  muscles,  are  reduced  to  a  minimum.  The 
end-products  of  tissue  metabolism  therefore  should  be  increased  under  the 
following  conditions  : 

(1)  Increased  motor  activity  involving  increased  wear  and  tear  of  the 
muscular  tissues. 

(2)  In  fevers,  especially  in  those  where  there  is  severe  toxaemia  and  rapid 
wasting  of  the  muscles  of  the  body. 

On  the  other  hand,  it  should  be  diminished  where  the  activity  of  the 
muscular  tissue  is  reduced  to  a  minimum,  as  under  the  influence  of  sleep  or 
soporifics,  or  where  the  bulk  of  the  muscular  tissue  is  reduced  as  well  as  its 
activity,  as  in  cases  of  widespread  muscular  atrophy  and  paralysis.  The 
excretion  of  creatinine  has  been  investigated  under  these  various  conditions 
by  van  Hoogenhuyze  and  Verploegb,  and  their  results  bear  out  the  view 
expressed  above  as  to  the  intimate  relation  of  creatinine  with  the  tissue 
metabolism  of  protein. 

During  protein  starvation  the  uric  acid  output,  though  diminished,  does 
not  show  a  change  which  is  at  all  proportional  to  that  shown  by  the  urea. 
This  substance  also  might  therefore  represent  an  end-product  of  tissue 
metabolism.  Since  however  uric  acid  is  an  outcome  of  the  metabolism  of 
a  special  group  of  bodies,  the  nucleins  and  purine  bases,  we  shall  have  to 
devote  a  complete  section  to  its  consideration. 

Although  the  urea  is  diminished  in  protein  starvation,  it  still  remains  the 
most  abundant  nitrogenous  constituent  of  the  urine.  We  are  therefore  not 
justified  in  excluding  this  substance  from  the  products  of  tissue  metabolism. 


PROTEIN  METABOLISM  813 

If  any  creatine  undergoes  complete  oxidation  in  the  body  during  protein 
starvation,  a  certain  proportion  of  the  urea  might  be  derived  in  this  way. 
We  shall  see  later  that  uric  acid  may  possibly  also  undergo  further  oxidation 
with  the  formation  of  urea.  Even  during  complete  protein  starvation,  some 
of  the  urea  which  is  turned  out  may  be  the  expression  of  a  utilisation  of  pro- 
tein through  deamination  for  the  energy  needs  of  the  body.  The  active  cells 
are  bathed  everywhere  with  a  tissue  fluid  in  which  proteins  form  a  prepon- 
derating constituent,  and  it  is  possible  that,  even  in  the  times  of  greatest 
protein  need,  these  cells  utilise  the  proteins  of  their  surrounding  medium, 
though  in  a  reduced  degree,  for  the  production  of  energy.  In  this  case  the 
active  cell  would  initiate  the  utilisation  by  throwing  off  that  part  of  the 
protein  molecule,  namely,  NH2,  which  is  useless  to  the  cell  as  a  source  of 
energy,  so  that  deamination  would  be  carried  out  in  the  working  tissues,  and 
not,  as  in  the  rapid  formation  of  urea  after  a  heavy  meal,  in  the  liver. 

SULPHUR 

Sulphur  occurs  in  the  urine  in  three  forms,  namely,  as  ordinary  inorganic 
sulphates,  as  ethereal  sulphates  (indoxyl-  and  skatoxyl-sulphates),  and  in  an 
unoxidised  condition  often  termed  neutral  sulphur.     There  is  no  doubt  that 
part  of  the  latter  consists  of  cystine,  part  of  sulphocyanates,  and  in  some 
animals  mercaptan  compounds.     The  excretion  of  the  inorganic  sulphates 
rises  pari  passu  with  that  of  the  urea,  so  that  very  soon  after  the  throwing 
off  of  the  NH2  group,  there  must  be  also  a  removal  and  oxidation  of  the  greater 
part  of  the  sulphur  contained  in  the  cystine  group  of  the  protein  molecule. 
So  far  as  regards  the  metabolism  of  the  body  as  a  whole,  the  ethereal  sul- 
phates may  be  classed  with  the  inorganic  sulphates.    They  are  excreted  in 
varying  quantity  according  to  the  extent  of  the  decomposition  processes  which 
are  occurring  in  the  intestine.     Under  the  influence  of  these  processes  the 
tryptophane,  produced  in  the  pancreatic  digestion  of  proteins,  is  converted 
into  indol  and  skatol.    These  two  substances,  after  absorption,  are  deprived  of 
their  poisonous  qualities  by  oxidation  and  conjugation  with  sulphuric  acid 
to  form  the  indoxyl-  and  skatoxyl-sulphates  of  the  urine,  both  of  which  are 
innocuous.    If  the  processes  of  putrefaction  are  increased,  as  in  intestinal 
obstruction,  the  relative  amount  of  sulphate  appearing  in  the  conjugated 
form  is  also  increased.     On  administration  of  phenol  a  large  proportion  of 
the  sulphate  appears  in  the  urine  conjugated  with  phenol  or  with  products  of 
its  oxidation.     If  the  normal  putrefactive  processes,  which  go  on  in  the 
intestine,  are  abolished  by  the  administration  of  intestinal  antiseptics  such 
as  naphthalene  or  calomel,  the  ethereal  sulphates  practically  disappear 
from  the  urine.    We  cannot  therefore  regard  the  absence  or  diminution  of 
the  ethereal  sulphates  during  protein  starvation  as  throwing  any  light  on  the 
endogenous  protein  metabolism.     On  the  other  hand,  the  fact  that  the 
neutral  sulphur  undergoes  no  decrease  suggests  that  this  part  of  the  sulphur 
nut  put  of  the  organism  may  be  connected  with  tissue  metabohsm.    Further 
observations  on  the  output  of  neutral  sulphur  during  fever  or  wasting  diseases 
are  necessary  before  a  definite  conclusion  can  be  arrived  at  on  this  point. 


814  PHYSIOLOGY 

THE   FATE   OF   THE   AROMATIC   AND   OTHER   CYCLIC 
GROUPS   IN   THE   PROTEIN   MOLECULE 

A  typical  protein  such  as  can  be  utilised  as  a  complete  foodstuff  con- 
tains, in  addition  to  the  aniino-acids  of  the  fatty  series,  a  number  of  other 
nitrogenous  derivatives  of  cyclic  compounds,  including  benzene,  indol,  pyrrol, 
and  iminazol.  Substances  such  as  gelatin,  from  which  some  of  these 
groupings  are  absent,  cannot,  as  we  have  seen,  entirely  replace  protein  in  the 
food.  So  far  we  are  acquainted  with  three  compounds  of  the  aromatic 
series  among  the  products  of  disintegration  of  the  protein  molecule.  These 
are  tyrosine,  phenylalanine,  and  tryptophane.  Since  these  substances  are 
also  contained  in  the  protein  constituents  of  the  tissues,  we  may  assume 
that,  after  they  have  been  set  free  by  the  digestive  hydrolysis  of  proteins,  they 
are  absorbed  and  built  up  again  with  the  other  aniino-acids  in  appropriate 
groupings.  Like  these  they  are  susceptible  of  complete  oxidation  in  the 
body,  so  that  they  can  contribute  to  the  supply  of  energy.  Any  one  of  these 
substances,  administered  with  the  food  or  subcutaneously,  is  entirely 
destroyed,  with  the  production  of  urea,  carbon  dioxide,  and  water.  In  this 
respect  they  present  a  marked  contrast  to  almost  all  other  compounds  of 
the  aromatic  series.  In  these  we  find  that  the  benzene  ring  is  extremely 
stable,  so  that,  although  changes  may  occur  in  its  side-chains,  the  benzene 
ring  itself  appears  intact  in  the  urine,  and  is  not  broken  up  in  the  body. 
Thus  benzoic  acid,  benzylalcohol,  and  phenyl  propionic  acid,  when 
administered,  are  passed  in  the  urine  as  hippuric  acid  (benzoyl  glycine). 
Indol  and  skatol,  which  are  closely  allied  to  tryptophane,  undergo  oxida- 
tion in  the  body  without  further  modification  and  appear  in  the  urine  as' 
conjugated  aromatic  sulphates. 

Some  fight  is  thrown  on  the  conditions  of  breakdown  of  these  aromatic 
bodies  by  the  study  of  a  rare  disorder  in  metabolism,  which  may  occur  in 
certain  families  and  is  known  as  alcaptonuria.  In  this  condition,  which  is 
congenital  and  lasts  throughout  life,  the  urine  darkens  considerably  when 
made  alkaline  and  exposed  to  tfie  air.  It  has  the  power  of  reducing  Fehling's 
solution,  so  that  the  presence  of  sugar  might  be  suspected.  On  analysis 
the  peculiarities  of  the  urine  are  found  to  be  due  to  the  presence  in  it  of  a 
substance  known  as  homogentisic  acid.     Tins  is  dioxyphenyl  acetic  acid. 


CH2COOH 

The  amount  of  this  substance  in  the  urine  bears  a  constant  ratio  to  the 
nitrogen  excreted.  It  does  not  disappear  during  starvation,  and  is  much 
increased  on  a  large  protein  diet.  It  must  therefore  be  derived  from  the 
disintegration  of  proteins  both  exogenous  and  endogenous.  If  tyrosine  or 
phenylalanine  be  administered  to  patients  affected  with  this  disorder,  both 
substances  are  quantitatively  converted  into  homogentisic  acid.    The  ratio 


PROTEIN  METABOLISM  815 

of  this  acid  to  the  total  nitrogen  indicates  that  the  whole  of  the  tyrosine  and 
phenylalanine  of  the  protein  molecule,  whether  set  free  in  the  alimentary 
canal  or  hi  the  tissue  metabolism,  is  converted  into  homogentisic  acid.  It 
is  not  possible  to  conceive  of  the  direct  conversion  of 


OH 


HO 
/  \ 
tyrosine  I    into  homogentisic  acid 


CHjCOOH 
CHo.CHNHj.COOH 

The  tyrosine  must  first  be  reduced  to  phenylalanine 


OKj.CHNHj.COOH 

and  then  tins  substance  must  undergo  oxidation  into  homogentisic  acid. 
Since  phenyl  lactic  acid  and  phenyl  pyruvic  acid,  but  not  phenyl  acetic 
acid,  are  also  converted  hi  alcaptonuric  patients  to  homogentisic  acid,  it 
has  been  suggested  that  these  two  substances  form  stages  in  the  conversion  of 
phenylalanine  into  homogentisic  acid.    Thus 


./\  /\ 


HO 


OH 


\/  \/ 

CH20HOH.COOH         CHgCO.COOH  CH2COOH 

Plieuyl  lactic  Phenyl  pyruvic  Homogentisic 

It  is  further  thought  that  under  normal  circumstances  the  phenyl  deriva- 
tives, tyrosiue  and  phenylalanine,  are  oxidised  to  homogentisic  acid  as  in  the 
alcaptonuric  patient.  In  the  normal  individual  however,  the  introduction  of 
two  hydroxyl  groups  into  the  benzene  ring  leads  to  some  process,  perhaps 
of  a  ferment  character,  which  breaks  up  the  ring.  This  ferment  is  absent 
in  the  alcaptonuric,  so  that  the  transformation  of  the  phenyl  derivatives 
stops  short  at  the  stage  of  homogentisic  acid  (Garrod).  The  eminently 
specific  character  of  this  process  is  shown  by  the  fact  that,  although  these 
various  substances  undergo  complete  oxidation  in  the  body,  a  slight  modifi- 
cation in  the  chain  of  the  processes  renders  the  change  impossible.  Thus 
if  the  side  group  in  phenyl  lactic  or  phenyl  pyruvic  acid  be  converted  to 
acetic  acid  before  the  introduction  of  the  two  OH  groups  into  the  phenyl 
ring,  the  phenyl  acetic  acid  thus  produced  is  incapable  of  undergoing  further 
oxidation.  Tyrosine  in  the  intestine  undergoes  deamination  to  form 
oxyphenyl  propionic  acid  and  oxyphenyl  acetic  acid.  These  cannot  be 
further  oxidised,  but  appear  in  the  urine  as  such  or,  after  conversion  into 
kresol  or  phenol,  as  sulphuric  acid  esters. 

Somewhat  similar  conditions  apply  to  the  oxidation  of  tryptophane. 


816  PHYSIOLOGY 

This  body  is  an  indol  derivative  and  consists  of  a  benzene  ring  and  a  pyrrol 
ring  having  two  of  their  carbon  atoms  in  common.     Its  formula 

/CH\ 
HC  C C.CH,CHNH2.COUH 

I  II  II 

HC  C  CH 

i.  e.  it  is  indol  amino-propionic  acid.  It  undergoes,  like  tyrosine,  complete 
oxidation  in  the  body.  On  the  other  hand,  a  very  slight  alteration  in  the 
molecule  renders  it  incapable  of  this  change.  Thus  the  tryptophane,  set 
free  by  the  tryptic  digestion  of  proteins  under  the  influence  of  the  putre- 
factive bacteria  of  the  intestine,  may  undergo  deamination  and  reduction 
with  the  production  of  indol  propionic  acid,  and  this  by  oxidation  may  be 
converted  to  indol  acetic  acid.  The  latter  substance  by  decarboxylation  may 
be  converted  into  skatol  or,  by  oxidation  nearer  the  chain  and  further  loss 
of  carbon  dioxide,  into  indol.  Of  these  products  of  bacterial  change,  indol 
acetic  acid  may  be  found  in  the  urine,  and  indol  and  skatol  are  oxidised  to 
the  corresponding  phenols  and  pass  into  the  urine  conjugated  either  with 
sulphuric  acid  or  with  glycuronic  acid. 

Apart  from  these  putrefactive  changes  due  to  bacteria,  no  indol  derivatives 
pass  into  the  urine.  The  amount  of  the  indol  and  skatol  esters  serves 
therefore  as  an  index  of  bacterial  decomposition  in  the  alimentary  canal, 
but  gives  no  clue  to  the  total  tryptophane  metabolism  of  the  body.  If 
putrefaction  be  prevented  by  the  administration  of  calomel  or  other  intestinal 
antiseptic,  these  esters  may  entirely  disappear  from  the  urine.  On  the  other 
hand,  the  partial  obstruction  to  the  onward  passage  of  food,  caused  by 
dividing  the  small  intestine  in  two  places  a  few  inches  apart  and  replacing 
the  intervening  length  of  intestine  the  wrong  way  round,  causes  the  indican 
excretion  to  be  increased  twenty  or  thirty  fold.  Subcutaneous  injection 
of  tryptophane  in  rabbits  does  not  increase  the  indoxyl  and  skatoxyl 
sulphates  (urinary  indican)  in  the  urine,  whereas  a  considerable  increase  is 
brought  about  by  subcutaneous  injection  of  indol. 

The  pyrrol  ring  which  occurs  in  proteins  as  proline  and  oxyproline  (i.  e. 
pyrrolidine  carboxylic  acid  and  oxypyrrolidine  carboxylic  acid)  appears  to 
undergo  complete  disintegration  in  the  body.  The  steps  in  this  conversion 
are  unknown,  though  it  is  possible  that  the  ring  may  be  unlinked  so  as  to 
produce  from  the  pyrrol  ring  amino-valerianic  acid,  which  would  then  under- 
go the  process  of  deamination  with  which  we  are  already  familiar.  This  ring 
is  of  interest  since  it  appears  to  take  an  important  part  in  the  building  up 
oi  the  molecule  of  hsematin,  the  essential  prosthetic  group  of  the  haemoglobin 
molecule. 

Another  ring  grouping,  iminazol,  occurs  in  histidine,  which  is  iminazol 
a -amino-propionic  acid.  This  too  undergoes  complete  oxidation  in  the 
body.  It  is  important  to  bear  in  mind  that  this  ring  may  be  produced 
synthetically  by  very  simple  means,  i.  e.  by  the  action  of  zinc  oxide  and 


PROTEIN  METABOLISM  817 

ammonia  on  glucose,  which  results  in  a  rich  yield  of  methyl  iminazol  (v. 
p.  115).  The  same  grouping  is  found  in  creatinine,  as  is  seen  by  comparing 
the  formula; : 

,CH3  /CH3 

H,C— N(  HC— Nf 

o'c-NH  XC-^ 

Creatinine  Methyl-iniinazol 

and  it  is  possible  that  this  may  furnish  a  clue  to  the  mode  of  formation  of 
creatinine  in  muscle.  Creatine  has  generally  been  regarded  as  the  primary 
product  of  muscular  metabolism,  but  it  is  possible  that  the  ring-grouping  is 
the  original  one  and  that  creatine  is  produced  by  hydrolysis  occurring  in  this 
ring. 

The  iminazol  group  is  at  present  chiefly  interesting  in  that  it  contributes 
to  the  formation  of  the  complex  ring  compounds  known  as  the  purines.  Since 
the  purine  metabolism  is  closely  connected  with  the  question  of  the  origin 
of  uric  acid,  we  may  consider  these  questions  together. 


SECTION  II 

NUCLEIN    OR   PURINE   METABOLISM 

In  an  undifferentiated  cell  the  proteins,  as  such,  form  but  a  small  part,  the 
mass  of  the  cell  being  composed  of  conjugated  proteins.  The  nucleo-proteins 
are  especially  abundant  constituents  of  nuclei,  and  therefore  occur  to  a 
greater  or  less  extent  in  all  the  ordinary  animal  foods,  eggs  and  milk  excepted. 
Just  as  the  metabolism  of  proteins  is  the  metabolism  of  the  ammo-acids,  so 
the  metabolism  of  the  nucleo-proteins  and  nucleins  is  essentially  comprised 
in  the  history  of  its  main  constituents,  i.  e.  the  purines. 

The  nucleo-proteins  themselves  are  bodies  of  very  varying  composition. 
If  any  cellular  tissue  such  as  thymus  or  liver  be  extracted  with  water  or  salt 
solution,  a  fluid  is  obtained  from  which  a  precipitate  can  be  thrown  down 
by  the  addition  of  acid.  This  precipitate  as  a  rule  is  soluble  in  excess  of 
acid  or  in  alkalies.  If  subjected  to  gastric  digestion  it  undergoes  solution, 
leaving  behind  a  residue  of  nuclein  which  is  rich  in  phosphorus.  The  amount 
of  this  residue  varies  with  the  strength  of  the  artificial  gastric  juice  employed, 
so  that  the  method  cannot  be  looked  upon  as  in  any  way  quantitative, 
and  the  question  arises  whether  the  original  nucleo-protein  is  to  be  regarded 
as  an  association  or  a  combination  of  nuclein  with  ordinary  protein.  The 
most  convenient  source  for  the  preparation  of  nucleins  is  from  the  heads  of 
fish  spermatozoa.  All  nucleins  are  associations  or  compounds  of  nucleic  acids 
with  proteins  belonging  to  the  class  of  protamines  or  histones.  The  nucleins 
of  fish  spermatozoa  contain  protamine  as  one  of  their  constituents.  On 
separating  off  the  protamine,  nucleic  acids  can  be  isolated.  These  acids 
have  been  named  either  according  to  their  source  or  according  to  the  purine 
base  which  is  their  most  prominent  constituent.  Only  from  inosinic  acid,  the 
nucleic  acid  of  muscle,  has  it  been  found  possible  to  prepare  crystalline  deriva- 
tives, so  that  in  all  other  cases  it  is  difficult  to  decide  whether  we  are  dealing 
with  chemical  individuals  or  with  mixtures. 

On  hydrolysing  any  of  the  nucleic  acids  by  heating  with  strong  mineral 
acid,  they  are  broken  down  into  a  series  of  bodies  belonging  to  the  following 
four  groups :  (1)  phosphoric  acid,  (2)  purine  bases,  (3)  pyrimidine  bases, 
(1)  a  carbohydrate.  The  chief  purine  bases  obtained  from  the  hydrolysis 
of  nucleic  acid  are  guanine  and  adenine. 

Hypoxanthine  and  xanthine  are  often  obtained  as  products  of  decom- 
position of  nucleic  acid,  but  are  generally  formed  by  the  deamination  and 
oxidation  of  guanine  and  adenine.    Fischer  has  shown  that  all  these  bodies 

818 


NUCLEIN   OR  PURINE  METABOLISM  819 

are  derivatives  of  a  base  purine.  They  contain  a  central  chain  of  three 
carbon  atoms  to  which  is  attached  on  each  side  a  urea  group,  so  that  they 
may  be  regarded  as  diureides.     Purine  itself  has  the  formula 

N=CH 

I       I 
HC     C— NH 

N— 0— N^ 

Purino 

The  relation  of  the  purine  bases  obtained  from  disintegration  of  nucleic  acid 
to  purine  itself  has  been  given  on  p.  100.  From  these  formulae  we  see  that 
adenine  and  hypoxanthine  are  related  to  one  another,  adenine  being 
6-aminopurine,  while  hypoxanthine  is  6-oxypurine.  In  the  same  way 
guanine  and  xanthine  are  related,  guanine  being  2-amino-6-oxypurine, 
while  xanthine  is  2-6-dioxypurine.  The  investigation  of  the  relationships 
of  these  bases  was  of  interest  to  physiologists  since  it  brought  to  light  the 
close  relation  which  they  have  to  uric  acid,  a  substance  which  has  been 
known  as  a  constituent  of  urine  and  urinary  calculi  for  a  long  time,  having 
been  discovered  in  1776  by  Scheele.  Uric  acid  is  2-6-8-trioxypurine  and 
has  the  formula 

HN— CO 


i  io  C— NHV  . 

!    |     ||         >co 

HN— C— NH/ 

Uric  acid  =  2-6-S-trioxypurino 


The  pyrimidine  bases,  which  are  also  obtained  from  the  hydrolysis  of 
nucleic  acid,  are  derived  from  a  pyrimidine  nucleus  which  is,  so  to  speak, 

/N 

half  a  purine  nucleus,  consisting  of  a  G(      chain  joined  to  a  3-carbon  chain. 

Three  pyrimidine  bases  have  been  isolated  from  the  decomposition  products 
of  nuclein,  namely,  thymine,  cytosine,  and  uracil. 

After  separation  of  the  purine  and  pyrimidine  bases  and  phosphoric  acid, 
a  substance  is  left  over  which  gives  the  reactions  of  a  carbohydrate. 

This  carbohydrate  differs  in  different  nucleic  acids.  In  plant  nucleic  acid,  as  well 
;is  in  guanylic  acid  from  the  pancreas  and  inosinic  acid  from  muscle,  the  carbohydrate 
is  a  pentose,  d-ribose.  Most  nucleic  acids  of  animal  origin  yield  Iscvulinic  acid  on 
hydrolysis  and  must  therefore  contain  a  hexose. 


FORMATION   OF   NUCLEINS   IN   THE   BODY 

In  the  case  of  the  proteins  we  saw  reason  to  believe  that  in  the  higher 
animals  at  any  rate,  there  was  no  power  of  converting  one  amino-acid  into 
another  (with  the  exception  of  the  lowest  members  of  the  series,  namely, 
glycine  and  alanine),  and  that  on  this  account  the  food  had  to  contain 
representatives  of  every  amino-acid  (or  perhaps  of  the  corresponding  oxy- 


820  PHYSIOLOGY 

fatty  acid)  necessary  to  the  building  up  of  the  tissue  proteins.  The  nucleins, 
on  the  other  hand,  can  certainly  be  synthetised  by  the  animal.  This  is 
shown  by  the  fact  that  the  hens'  egg  before  incubation  contains  practically 
no  nuclein  or  purine  bases.  During  incubation  tissues  are  formed,  and 
there  is  a  rapid  increase  in  the  number  of  nuclei,  so  that  the  chick  just 
before  it  is  hatched  contains  a  considerable  amount  of  nuclein  from  which 
purine  bases  can  be  extracted.  This  nuclein  must  have  been  formed  by  a 
synthesis  from  the  phospho-proteins  and  phosphatides  (phosphorised  fats) 
which  form  so  important  a  constituent  of  the  egg-yolk,  and  in  the  same  way 
the  purines  must  have  been  formed  by  a  process  of  synthesis.  This  syn- 
thesis may  occur  by  a  conjugation  of  two  urea  molecules  with  the  3-carbon 
chain  which  is  so  prominent  a  feature  in  the  proximate  principles  of  the 
body  {e.g.  in  lactic  acid,  alanine,  and  all  the  compound  amino-acids  of 
which  alanine  is  a  constituent).  Methyliminazol,  representing  one-half  of 
the  purine  ring,  can  be  formed  simply  by  allowing  ammonia  and  glucose  to 
stand  in  contact  with  zinc  hydroxide.  The  power  of  synthesis  of  purines 
possessed  by  the  body  must  complicate  the  question  of  their  fate  after 
ingestion,  since  it  is  evident  either  that  they  can  be  destroyed  and  excreted 
in  some  other  form  or  that  the  products  of  their  destruction  may  be  built 
up  into  fresh  purine  or  nuclein  molecules.  In  the  same  way,  in  the  growing 
child  there  is  a  rapid  increase  in  the  nuclein  of  the  body,  although  the  only 
food  ingested  is  milk,  which  contains  but  an  insignificant  amount  of  nuclein. 

» 
FATE   OF   NUCLEINS   IN    THE   BODY 

Nucleins  and  nucleic  acids  are  dissolved  by  the  pancreatic  juice,  but  no 
digestion  of  the  nucleic  acid  occurs  in  the  alimentary  tract  other  than  by 
the  action  of  micro-organisms.  We  must  assume  therefore  that  the  nucleic 
acid  is  taken  up  by  the  cells  of  the  intestinal  wall  unchanged. 

Ingestion  of  nucleic  acid  is,  in  man,  followed  by  an  increased  excretion  of 
uric  acid  in  the  urine,  so  that  we  regard  this  substance  as  the  end-product 
of  nuclein  metabolism  in  the  body.  It  is  evident  that  the  uric  acid  of  the 
'  urine  may  be  derived  either  from  the  nucleins  of  the  food  or  from  the 
nucleins  of  the  tissues  of  the  body,  the  uric  acid  in  these  two  cases  being 
spoken  of  as  exogenous  and  endogenous  respectively.  By  digestion  of 
nucleic  acids  with  animal  tissues  or  extracts  of  animal  tissues  under  varying 
conditions,  it  is  possible  to  bring  about  all  the  changes  involved  in  the 
conversion  of  the  purine  bases  contamed  in  them  into  uric  acid.  In  the 
intestinal  wall,  or  after  absorption  into  other  tissues  of  the  body,  the  nucleic 
acid  is  subjected  to  hydrolytic  changes  by  the  agency  of  ferments  which 
may  be  classed  as  nucleases.  These  are  however  of  different  kinds,  the 
phosphonuclease  splitting  off  the  phosphoric  acid  and  leaving  the  nucleo- 
sides, wThile  the  purine  nucleases,  which  are  more  effective  in  a  slightly 
alkaline  medium,  split  off  the  purines,  leaving  the  phosphoric  acid  com- 
bined with  the  carbohydrate.  The  purines  set  free  in  this  way  undergo 
further  changes.  The  hypoxanthin  derived  from  inosinic  acid  is  converted 
under  the  action  of  an  oxidase  first  into  xanthine  and  then  into  uric  acid. 


NUCLEIN  OR  PURINE   METABOLISM 


821 


This  was  one  of  the  earliest  facts  discovered  in  the  metabolism  of  purines. 
Horbaczewski  showed  that,  if  spleen  pulp  be  digested  with  blood  for  some  time,  it  is 
possible  to  extract  a  considerable  amount  of  xanthine  from  the  mixture.  If  however 
oxygen  be  bubbled  through  the  fluid,  the  xanthine  disappears,  its  place  being  taken 
by  uric  acid. 

From  the  more  complex  nucleic  acids  the  amino-purines,  adenine  and 
guanine,  are  set  free.  These  first  undergo  deamination  under  the  action 
of  special  ferments,  adenase  and  guanase,  and  are  thus  converted  into 
hypoxanthine  and  xanthine  respectively.  These  bodies  subsequently, 
under  the  action  of  oxidases,  may  be  converted  into  uric  acid. 

All  these  changes  occur  in  the  living  body,  though  not  necessarily  in  the  order  just 
set  out.  Thus  when  the  pyrimidine  derivatives  are  administered  to  dogs,  they  pass 
out  unchanged.  If  however  free  nucleic  acid  be  administered  to  the  animal,  no  trace 
of  these  derivatives  can  be  found  in  the  urine,  so  that  they  must  have  undergone  com- 
plete  oxidation.  In  the  same  way  the  dog's  liver  is  able  to  deaminise  completely 
the  adenine  group  of  nucleic  acid,  converting  it  into  hypoxanthine,  but  is  without 
effect  on  free  adenine.  It  is  evident  therefore  that  the  various  ferments  which  have 
been  described  act  partly  on  the  whole  nucleoside  molecule,  partly  on  the  products 
of  its  decomposition,  and  that  the  results  of  the  action  of  the  body  ferments  are  not 
the  same  in  the  two  cases. 

If  we  make  this  reservation,  namely,  that  the  constituent  parts  of  the  nucleic,  acid 
molecule  may  undergo  changes  while  still  bound  to  the  other  parts,  we  may  represent 
diagrammatically  the  formation  of  uric  acid  from  nucleic  acid  as  follows  : 


Ferments 
Nuclease 

Deaminase 

Hydrolysis 

Oxidase 

Oxidase 

Oxidase 
(Uricase) 

or 
Nuclease 


Nucleio  acid 


Phosphoric  acid         Guanosine         Adenosine         Uridine        Cytidine 

Xanthosine  Inosine  Fate  unknown 

I  I 

Xanthine     Hypoxanthine 

'     ,     I 
Xanthine 


I 
Uric  acid 

Allantoin  (in  dogs) 

Nucleic  acid 

I 
4  Mononucleotides 


Purine  nuclease 

Pentose-phosphoric  acid    Guanine  Adenine       Pyrimidine  bases 

Deaminase 
(Guanase  and  adenase) 


<  taddase 


Oxidase 


Xanthine   Hypoxanthine 

r     I 
Xanthine 

_J 
Uric  acid 


822  PHYSIOLOGY 

The  question  arises  whether  the  uric  acid  excreted  by  a  man  represents 
the  whole  of  the  nucleins  which  have  been  destroyed  in  the  body.  Although 
complete  equivalence  has  been  found  between  the  amount  of  hypoxanthine 
ingested  and  the  amount  of  uric  acid  excreted,  the  same  equivalence  has 
not  been  established  in  the  case  of  nucleic  acid,  and  the  important  question 
arises  whether  uric  acid  once  formed  is  stable  or  whether  it  may  undergo 
further  changes  before  being  excreted.  In  many  animals,  such  as  the  dog, 
the  amount  of  uric  acid  in  the  urine  is  only  minute,  the  chief  purine 
derivative  in  this  fluid  being  allantoin.  Allantoin  is  formed  when  uric 
acid  is  oxidised  with  potassium  permanganate,  the  following  changes 
taking  place  : 

NH— CO  NH— CO 

II.  II 

CO     C— NH  +  O  +  H20  =  CO  NH2     +  C02 

|       ||  >C0  >co 

NH— C— NH'  NH— CH— NH 

The  same  transformation  can  be  effected  by  extracts  made  from  the 
liver  of  the  dog  and  probably  of  other  animals.  The  ferment  carrying  out 
this  change  is  known  as  uricase.  No  such  ferment  is  found  in  human  liver 
or  any  human  organs,  and,  according  to  Jones  and  others,  uric  acid  once 
formed  in  the  human  organism  is  not  further  oxidised.  The  small  trace 
of  allantoin  which  may  occur  in  human  urine  is  directly  derived  from  the 
food.  Modern  research  does  not  confirm  the  idea  which  was  formerly 
held  that  a  portion  of  the  uric  acid  formed  might  undergo  further  oxidation 
in  man  with  the  production  of  urea. 

On  the  other  hand  it  is  important  to  bear  in  mind  the  possibility  that 
some  of  the  uric  acid  which  occurs  in  human  urine  may  be  formed  by  a 
process  of  synthesis.  We  have  seen  already  that  in  the  bird  the  greater 
part  of  the  uric  acid  is  formed  not  from  purines  at  all  but  by  a  process  of 
synthesis  from  lactic  acid  and  ammonia,  and  though  we  have  no  evidence 
of  a  similar  change  occurring  in  the  mammal,  we  are  not  able  definitely  to 
exclude  its  possibility. 

EXCRETION   OF   URIC   ACID 

The  complexity  of  these  various  processes  in  man  renders  it  a  difficult 
task  to  form  a  clear  idea  of  the  origin  of  the  urinary  uric  acid  and  of  the 
conditions  which  determine  the  variations  in  the  amount  excreted  at 
different  times.  Under  ordinary  circumstances  a  man  excretes  about  half 
a  gramme  of  uric  acid  per  day.  In  addition  the  urine  contains  a  small 
amount  of  purine  bases,  the  ratio  of  these  bases  to  the  uric  acid  being 
generally  about  1  :  6.  From  10,000  litres  of  human  urine  Kriiger  and 
Salomon  succeeded  in  isolating  the  following  purine  bases  : 

Xanthine    ....     10-1  grin. 
Hypoxanthine  .  .       8-5    „ 

Adenine      .  .  .       -  .       3-5    „ 


NUCLEIN  OR  PURINE  METABOLISM 


823 


The  same  urine  would  probably  have  contained  about  500  grm.  of  uric 
acid.  As  we  should  expect,  the  amount  of  uric  acid  in  the  urine  varies  with 
the  diet.  The  following  Tables  from  Bunge  give  the  composition  of  the 
urine  secreted  (1)  on  a  mixed  diet,  (2)  on  a  diet  mainly  composed  of  meat, 
(3)  on  a  diet  mainly  composed  of  bread  : 


Twenty-four  hours                                     Mixed 

Meat 

Bread 

Quantity  c.c.        . 

1500 

1672 

1920 

Urea 
Uric  acid 

grm. 

33 

•55 

67 
1-3 

20 
•25 

Ammonia 

•9 

21 

•9 

Creatinine 

•77 

•9 

•4 

Hippuric  acid  . 
Sulphates 
Sodium  chloride 

•4 
2 
16-5 

4-6 
7-5 

1-2 
•   8-2 

Phosphates 
Potassium 

316 
2-5 

3-4 
3-3 

1-6 
1-3 

Calcium,  m 

ignesi 

um,  i 

non,  colo 

iring  matter, 

jases,  ferments. 

An  attempt  has  been  made  to  arrive  at  the  amount  of  uric  acid  produced 
endogenously,  i.  e.  from  the  breakdown  of  the  tissues,  from  a  study  of  the 
quantity  of  uric  acid  in  the  urine  under  varying  conditions  of  food.  During 
starvation,  when  the  man  is  living  on  his  own  tissues,  one  might  expect  the 
uric  acid  to  be  increased  in  consequence  of  disintegration  of  the  tissues. 
It  has  been  suggested  that  the  amount  of  the  endogenous  uric  acid  in  the 
urine  would  be  obtained  by  an  analysis  of  the  urine  from  patients  taking 
a  diet  free  from  purine  bases,  but  containing  sufficient  nitrogen  to  maintain 
nitrogenous  equilibrium.  It  is  impossible  however  to  arrive  at  any 
constant  figure  for  the  endogenous  uric  acid.  Even  in  the  entire  absence 
of  purine  derivatives  from  the  diet,  the  amount  of  uric  acid  increases  with 
the  total  nitrogenous  metabolism.  This  fact  is  well  shown  in  the  Tables 
by  Folin  (already  quoted)  of  the  composition  of  the  urine  on  a  low  and  a 
high  protein  diet  respectively.  Although  in  each  case  care  was  taken  to 
exclude  purine-containing  bodies  from  the  food,  the  output  of  uric  acid 
on  the  high  nitrogenous  diet  was  double  as  much  as  on  the  low  diet.  All 
we  can  say  is  that  uric  acid  is  constantly  being  derived  from  the  tissue 
disintegration,  but  that  it  varies  under  different  conditions  of  nutrition  as 
well  as  under  different  conditions  of  activity  of  the  body. 

There  are  two  maiii  conditions  which  give  rise  to  a  marked  increase  in 
the  output  of  endogenous  uric  acid.  These  are  (1)  severe  muscular  activity, 
(2)  febrile  states  accompanied  by  increased  nitrogenous  metabolism.  Since 
both  these  conditions  are  associated  with  an  increased  breakdown  of  muscle 
substance,  we  may  regard  the  uric  acid  as  derived  especially  from  the 
hypoxanthine  or  its  precursors,  such  as  inosinic  acid,  contained  in  the 
muscle. 


824 


1MIVSI0L0GY 


The  foods  which  are  especially  effective  in  causing  increase  in  the 
exogenous  uric  acid  are  those  rich  in  nuclein,  such  as  sweetbreads  or  liver 
and  those  rich  in  hypoxanthine  <>r  its  precursors,  such  as  meat  or  meat 
extract. 

When  these  foods  are  taken,  or  when  nucleic  acid  itself  is  administered,  a  con- 
dition of  leucocytosis  is  generally  produced,  the  number  of  leucocytes  in  the  blood 
being  increased  as  much  as  three  times.  It  has  been  suggested  that  the  uric  acid  is 
actually  formed  by  a  disintegration  of  the  newly  formed  leucocytes  and  not  by  a  direct 


x 

_        L 

/      5  ys  "V         ^ 

5             "17-                 \             "-• 

-   N         i       **•■                     \ 

-—'^h?*—-             — te~s-- 

i"        -                                  % 

'                                                                                                              \ 

-                                                                                                                  V 

''                  i                          I         I         T       + 

Fig.  366.  Curves  showing  the  hourly  excretion  of  uric  acid  and  urea  after  a  singlo 
meal.  (Hopkins.)  The  continuous  line  =  uric  acid  output;  the  dotted 
line  =  urea  output. 

conversion  of  the  purines  of  the  food.  It  is  quite  possible,  as  suggested  by  Schittenhelm, 
that  the  leucocytes  play  a  part  in  the  transference  of  the  nucleins  from  the  intestine 
to  the  circulation.  But  the  absence  of  any  absolute  proportionality  between  the  degree 
of  leucocytosis  and  the  amount  of  uric  acid  excreted  points  to  the  probability  of  a  direct 
conversion  of  the  purines  of  the  food  into  uric  acid. 


URIC   ACID   IN   GOUT 

Gout  is  a  condition  in  which  deposits  of  urate  of  soda  occur  in  the  cartilages  of  the 
joints,  the  great  toe  joint  being  the  seat  of  predilection  for  this  disorder.  The  deposit 
is  generally  associated  with  an  acute  inflammation  of  the  joint.  In  normal  individuals 
the  amount  of  uric  acid  in  the  blood  is  too  small  to  be  detected.  Uric  acid  is  readily 
excreted  by  the  healthy  kidneys.  If  the  production  of  uric  aeid  be  largely  increased 
by  the  administration  in  large  quantities  of  foodstuffs  rich  in  purines,  it  becomes 
possible  to  demonstrate  the  actual  presence  of  uric  acid  in  the  blood.  In  gout  there 
is  constantly  an  increased  amount  of  uric  acid  in  the  blood,  probably  in  the  form  of 
sodium  urate,  even  when  the  patient  is  on  a  purine-free  diet,  so  that  gout  may  be  re- 
garded, from  one  point  of  view  at  any  rate,  as  a  uricaemia  of  endogenous  origin.  On 
the  other  hand,  the  output  of  uric  acid  in  the  urine  is  not  increased,  and  may  in  fact 
be  somewhat  smaller  than  normal.  It  might  be  thought  that  the  presence  of  uric 
acid  in  the  blood  must  therefore  be  due  to  diminished  power  of  excretion  of  this  sub- 
stance by  the  kidneys.  This  view  is  difficult  to  reconcile  with  the  fact  that,  if  uric 
acid  be  injected  subcutaneously  into  gouty  subjects,  it  is  stated  to  be  excreted  in  the 
urine  exactly  in  the  same  way  and  as  rapidly  as  in  normal  persons.  It  has  been 
suggested  that  gout  consists  essentially  in  a  disturbance  in  the  various  fermentative 
mechanisms  which  are  responsible  for  the  changes  undergone  by  the  purines,  so  that 


NUCLEIN  OR  PURINE  METABOLISM  825 

there  is  an  increased  amount  not  only  of  uric  acid  itself  but  of  various  intermediate 
products  in  its  formation  from  the  purine  bases  of  the  food  and  of  the  tissues.  The 
deposit  of  the  uric  acid  in  the  joint  cartilages,  characteristic  of  acute  gout,  appears  to  be 
simply  a  crystallisation  of  urate  of  soda  from  a  supersaturated  solution  of  this  substance 
in  the  blood.  The  whole  question  of  the  pathology  of  gout  and  of  the  disordered 
metabolism,  which  may  precede  or  intervene  between  actual  acute  attacks  of  the  disease, 
is  in  need  of  further  investigation.  Especially  is  it  important  to  determine  the  influence 
on  this  condition  not  only  of  the  nucleins  and  proteins  of  the  food,  but  of  the  other 
constituents  such  as  carbohydrates  and  fats.  Speaking  broadly,  gout  is  a  disease 
of  the  well-to-do,  of  the  person  who,  while  pursuing  a  sedentary  or  no  occupation,  is 
not  limited  in  his  food-supply.  It  is  almost  unknown  in  the  labouring  class,  where 
hard  manual  work  is  combined  with  a  bare  sufficiency  of  food.  It  seems  therefore 
that  it  is  not  so  much  the  supply  of  purines  in  the  diet  which  must  be  controlled  as  the 
general  conditions  of  nutrition,  which  determine  the  fermentative  changes  in  the  purines 
either  of  the  food  or  tissues  under  normal  conditions  of  metabolism. 


SECTION  III 

THE    HISTORY   OF   FAT   IN    THE    BODY 

Fat  is  found  in  the  body  in  various  situations.  In  a  fat  animal  the  largest 
amount  occurs  in  the  panniculus  adiposus  in  the  subcutaneous  tissues. 
Large  quantities  are  also  found  surrounding  the  abdominal  organs  and 
between  the  layers  of  the  mesentery  and  great  omentum.  In  this  adipose 
tissue  the  fat  is  enclosed  within  and  distends  connective-tissue  cells,  the 
protoplasm  of  which  is  reduced  to  a  thin  pellicle  round  the  fat  globule. 
Fat  is  also  found  in  the  form  of  granules  in  more  highly  specialised  cells, 
such  as  the  secreting  cells  of  the  liver  or  the  muscle  cells.  The  condition 
of  these  cells  is  often  spoken  of  as  fatty  infiltration,  or  fatty  degeneration, 
according  to  the  circumstances  which  are  responsible  for  bringing  about 
the  deposition  of  fat.  We  shall  have  to  discuss  later  on  how  far  we  are 
justified  in  assuming  any  real  distinction  between  these  two  processes. 
From  the  physiological  standpoint  the  most  important  intracellular  depot 
of  fat  is  in  the  liver.  If  this  organ  be  deprived  of  glycogen  and  fat  by 
starvation,  a  fatty  meal  gives  rise  to  a  great  deposition  of  fat  in  its  cells. 
There  is  apparently  an  antagonism  between  the  processes  which  lead  on 
the  one  hand  to  the  deposition  of  glycogen  and  on  the  other  to  the  deposition 
of  fat.  Thus  an  excessive  carbohydrate  diet,  which  induces  great  deposition 
of  fat  in  the  subcutaneous  tissues,  causes  only  the  formation  of  glycogen 
in  the  liver.  The  glycogen  must  be  got  rid  of  before  it  is  possible  to  cause 
the  deposition  of  fat.  On  this  account,  the  normal  content  in  fat  of  the 
livers  of  different  animals  varies  with  their  ordinary  diet.  Fishes,  e.  g.  the 
cod,  which  take  but  little  carbohydrate  in  their  food,  have  generally  a  very 
large  quantity  of  fat  in  their  livers.  Herbivorous  animals,  as  a  rule,  have 
practically  no  fat  in  the  liver. 

Fat  also  occurs  in  certain  secretions,  e.g.  the  milk  and  the  sebum,  its 
function  in  the  latter  case  being  mainly  protective. 

Besides  the  visible  deposit  of  fat  found  in  adipose  tissue  and  in  other 
situations,  a  large  amount  of  fat  is  always  present  built  up  into  the  proto- 
plasm of  the  cells  in  such  a  condition  that  its  presence  cannot  be  detected 
by  histological  means.  The  presence  or  absence  of  visible  fatty  globules 
affords  very  little  clue  to  the  total  quantity  of  fat  in  the  cells.  Thus  in  one 
case  the  heart  nmscle,  which  had  undergone  extreme  fatty  degeneration 
and  was  loaded  with  fat  globules,  contained  19  per  cent,  of  its  dried  weight 
of  fat.  A  heart  muscle  taken  from  a  normal  animal  at  the  same  time, 
presenting  no  visible  fat  globules,  contained  17  per  cent,  of  fat. 

826 


THE  HISTORY  OF  FAT  IN  THE  BODY  827 

COMPOSITION   OF   FAT 

The  fats  occur  generally  in  the  form  of  triglycerides  of  various  fatty 
acids.  In  adipose  tissue  the  acids  are  chiefly  stearic,  palmitic,  and  oleic, 
the  consistency  of  the  fat  depending  on  the  relative  amount  present  of 
triolein,  with  its  low  melting-point.  In  certain  animals  the  glycerides  of 
more  unsaturated  fatty  acids  occur.  Thus  lard  contains  about  10  per 
cent,  of  fats  belonging  to  the  linoleic  series.  The  fats  of  cows'  milk,  though 
consisting  chiefly  of  the  three  above-mentioned,  include  also  the  esters  of 
butyric  and  caproic  acids  in  fair  amounts,  and  traces  of  the  intermediate 
acids,  caprylic,  capric,  lauric,  and  myristic  acids. 

The  '  fat '  extracted  from  the  tissues  (e.  g.  heart   muscle)   includes   a  % 
considerable  amount  of  '  phosphatides  '  (lecithins,  etc.).      It  also  contains 
a  much  larger  proportion  of  unsaturated  fatty  acids  of  the  linoleic  and  even 
lower  series,  so  that  its  '  iodine  value '  is  generally  found  relatively  high 
(120  as  compared  with  40  to  60  in  adipose  tissue). 

FUNCTIONS   OF  FAT 

First  and  foremost  must  be  mentioned  the  significance  of  fat  as  a  reserve 
food  store.  The  power  of  the  organism  to  store  up  reserve  carbohydrate  is 
strictly  limited.  The  liver  of  man  can  probably  not  accommodate  more 
than  150  grm.  of  glycogen,  and  assuming  that  the  muscles  of  the  body  may 
contain  an  equal  amount,  300  grm.  represents  the  extreme  limit  of  storage 
of  carbohydrates  in  the  body.  On  the  other  hand,  in  most  animals  there 
is  practically  no  limit  to  the  amount  of  fat  which  can  be  laid  down,  and 
over-feeding,  whether  with  carbohydrates  or  fats,  leads  to  the  deposition 
of  fat.  This  fat  does  not  enter  into  the  normal  metabolism  of  the  body, 
but  is  available  for  use  whenever  the  needs  of  the  body  are  increased  above 
its  income. 

As  to  the  part  taken  by  fat,  especially  the  hidden  fat  of  the  working 
cells,  in  the  chemical  processes  'which  deternune  the  life  of  the  cell,  our 
knowledge  is  still  very  scanty.  Fats  enter  into  the  constitution  of  the 
complex  bodies,  lecithin  and  myelin,  which  form  important  constituents  of 
the  limiting  membrane  of  every  living  cell.  As  constituents  of  the  mem- 
brane itself,  fatty  substances  therefore  have  a  protective  action,  and  also 
regulate  the  passage  of  substances  into  the  cell  across  the  membranes. 

The  presence  of  lecithin  as  an  integral  constituent  of  all  protoplasm, 
and  of  the  first  products  of  disintegration  of  protoplasm,  suggests  that 
this  substance  may  play  a  part  in  the  normal  transformations  which  occur 
within  the  cell,  and  may  represent,  so  to  speak,  the  currency  into  which 
fat  is  transformed  in  order  to  participate  in  the  vital  processes,  and  that 
it  is  in  this  form  that  the  energy  of  fat  is  utilised  for  the  needs  of  the  cell. 

ORIGIN   OF   FAT   IN   THE   BODY 

Fat  formation  is  the  result  of  an  excess  of  iilcome  over  expenditure. 
As  soon  as  the  latter  exceeds  the  former  the  fat  store  is  drawn  upon,  so  that 


828  PHYSIOLOGY 

adipose  tissue  is  the  one  which  presents  the  greatest  loss  during  starvation. 
As  much  as  97  per  cent,  of  the  total  fat  of  the  body  may  disappear  during 
this  process.  We  have  therefore  to  consider  what  part  is  played  by  each 
class  of  foodstuffs  in  the  formation  of  fat.  Can  this  substance  be  formed 
from  all  three  classes  of  foodstuffs  \ 

FORMATION  FROM  THE  FAT  OF  THE  FOOD.  Experiment  has 
shown  that  the  composition  of  the  fat  of  any  animal  is  by  no  means  constant 
and  can  be  varied  within  wide  limits  by  alterations  in  the  nature  of  the 
fat  presented  in  the  food.  This  dependence  of  the  composition  of  the  fat 
on  the  fats  of  the  food  is  shown  strikingly  in  an  experiment  performed  by 
Lebedeff.  Two  dogs,  after  a  preliminary  period  of  starvation,  were  fed, 
one  on  a  diet  containing  a  large  proportion  of  linseed  oil,  and  the  other  on 
a  diet  containing  much  mutton  suet.  After  some  weeks,  when  the  animals 
had  put  on  a  large  amount  of  fat,  they  were  killed,  and  it  was  found  that 
whereas  the  fat  of  the  dog  which  had  been  fed  on  mutton  suet  was  solid 
at  50°  O,  that  of  the  dog  fed  on  oil  was  still  fluid  at  0°  C.  It  has  been 
shown  moreover  that,  by  feeding  animals  with  fatty  acids  not  usually  found 
in  the  body,  these  are  laid  down  in  the  adipose  tissue.  Thus  colza  oil 
contains  a  glyceride  of  erucic  acid,  and  an  animal,  as  Muuk  has  shown, 
fed  on  colza  oil  lays  on  fat  in  which  erucic  acid  is  present.  The  same 
physiologist  has  observed  that,  after  the  administration  of  various  fatty 
acids  to  a  man  with  a  chylous  fistula,  the  glycerides  of  the  corresponding 
fatty  acids  made  their  appearance  in  the  chyle,  whether  these  fatty  acids 
were  those  normal  to  man  or  consisted  of  substances,  such  as  erucic  acid, 
not  generally  found  in  human  fat.  One  must  conclude  therefore  that  the 
fats  taken  with  the  food,  if  not  immediately  required  for  the  energy  needs 
of  the  body,  are  laid  down  without  change  in  the  adipose  tissues,  as  well 
as  in  the  cells  of  the  body.  The  mechanisms  involved  in  the  translation  of 
fat  from  the  alimentary  canal  to  the  tissues  are  of  the  simplest  possible 
description  and  involve  only  changes  of  hydrolysis  and  dehydrolysis.  The 
fats  are  hydrolysed  in  the  gut  and  are  resynthetised  to  a  certain  extent 
in  their  passage  into  the  epithelium.  In  the  chyle  and  blood  they  probably 
wander  chiefly  as  neutral  fats,  to  be  rehydrolysed  for  their  passage  into 
the  cells  of  the  body,  which  they  may  enter  either  in  the  form  of  soaps  or 
possibly  as  fatty  acids  dissolved  in  some  of  the  constituents  of  protoplasm. 
FORMATION  OF  FAT  FROM  CARBOHYDRATES.  It  has  long  been 
the  experience  of  farmers  that  animals  might  be  fattened  on  a  diet  in  which 
carbohydrates  predominate.  The  chemical  difficulty  involved  in  the  trans- 
formation of  carbohydrates  into  fats  has  often  led  to  a  doubting  attitude 
on  the  part  of  chemists  towards  this  transformation.  Voit  put  forward 
the  view  that,  when  fats  are  formed  in  the  body  as  a  result  of  an  excessive 
carbohydrate  diet,  they  are  formed,  not  directly  by  a  transformation  of 
carbohydrate,  but  from  the  proteins  of  the  food,  the  role  of  the  carbohydrates 
of  the  food  being  simply  to  protect  the  proteins  from  disintegration  and 
oxidation,  so  that  thej  whole  of  their  carbon  can  be  utilised  for  the 
formation  of  fat. 


THE   HISTORY  OF  FAT  IN  THE  BODY  829 

Definite  evidence  has  however  been  brought  forward,  especially  by 
Lawes  and  Gilbert,  for  the  transformation  of  carbohydrates  into  fats.  In 
these  experiments  two  young  pigs  ten  weeks  old  of  the  same  litter,  with 
approximately  equal  weights,  were  taken.  One  was  killed  and  the  fat 
and  total  nitrogen  in  the  body  estimated.  From  the  amount  of  nitrogen 
the  maximum  possible  quantity  of  proteins  present  was  calculated.  The 
second  was  fed  on  barley  for  four  months.  The  barley  was  measured  and 
analysed,  as  well  as  the  amount  of  undigested  fat  and  protein  that  passed 
through  the  animal.  At  the  end  of  the  four  months  the  second  animal 
was  killed  and  analysed.  It  was  found  that  the  animal  contained  1-56 
kilos,  more  protein  and  8-6  kilos,  more  fat.  It  had  taken  up  with  the  food 
7-49  kilos,  more  protein  and  0-66  kilo.  fat.  If  we  subtract  the  protein  added 
to  the  body  (1-56)  from  that  taken  up  with  the  food  (7-49),  there  is  a 
remainder  of  5-93  kilos,  which  might  possibly  have  given  rise  to  fat.  But 
7-9  kilos,  of  fat  had  been  added  in  the  body — a  far  larger  amount  than 
could  possibly  have  arisen  from  the  maximum  amount  of  protein  left  over 
for  the  purpose.  At  least  5  kilos,  of  fat  in  this  experiment  must  have  been 
derived  from  the  direct  conversion  of  the  carbohydrates  of  the  food.  We 
must  conclude  that  fat  can  be  formed  directly  from  carbohydrates,  although 
how  and  where  this  conversion  takes  place  is  at  present  quite  unknown. 
The  fats  formed  on  a  carbohydrate  diet  are  deposited  chiefly  in  the  sub- 
cutaneous tissue.  For  the  reasons  already  given  the  liver  is  found  free  from 
fat  under  these  conditions.  In  the  fat  formed  from  carbohydrate  the  two 
saturated  acids,  palmitic  and  stearic  acid,  predominate.  On  this  account 
tii<-  fat  has  a  firm  consistencv  and  a  high  melting-point.  The  fats  of  low 
melting-point,  such  as  olein,  are  absorbed  more  readily  from  the  intestine 
than  those  of  high'  melting-point.  Where  the  fat  of  the  body  is  chiefly 
derived  from  the  fat  of  the  food,  it  tends  to  be  of  the  more  fluid  acids  and 
contains  a  larger  percentage  of  olein. 

Although  it  is  impossible  to  trace  out  all  the  steps  in  the  process  of 
conversion  of  sugar  into  fatty  acid,  we  are  acquainted  with  certain  reactions 
which  may  throw  some  light  on  the  nature  of  the  changes  involved.  If 
we  compare  the  formula  of  dextrose  with  that  of  the  corresponding  fatty 
acid,  caproic  acid, 

(H.j  CH,OH 

I  I 

CH.,  CHOH 

I  "  I 

OH,  CHOH 

I  "  I 

CH2  CHOH 

I  "  I 

CH„  OHOH 

COOH  CHO 

we  see  that  the  conversion  involves  a  considerable  loss  of  oxygen.     In 
order  to  convert  three  molecules  of  glucose,  C6H1206,  into  one  molecule 


830  PHYSIOLOGY 

of  stearic  acid,  C18H3802,  it  is  necessary  to  split  off  1G  atoms  of  oxygen. 
That  this  setting  free  of  oxygen  actually  occurs  in  the  transformation  of 
carbohydrate  into  fat  is  shown  by  the  study  of  the  respiratory  exchanges  of 
animals  which  are  rapidly  laying  on  a  store  of  fat  at  the  expense  of  a  carbo- 
hydrate food.  Thus  the  marmot,  towards  the  end  of  summer,  eats  large 
quantities  of  carbohydrate  food  and  very  rapidly  lays  on  a  thick  layer  of 
subcutaneous  fat  to  last  it  during  the  winter.  If  glucose  were  entirely 
oxidised  in  the  bud}',  the  amount  of  oxygen  absorbed  would  be  exactly 
equal  to  the  amount  of  carbon  dioxide  evolved.     Thus 

r2H12°6  +  602  =  CC02  +  6H2°- 

In  this  case  the  respiratory  quotient  would  be 

6C02  =  2 
602 

If  however  oxygen  is  being  set  free  by  the  conversion  of  part  of  the 
carbohydrate  into  fat,  this  oxygen  will  be  available  for  the  oxidation  of 
other  portions  of  the  carbohydrate.  The  animal  will  not  need  to  take  in 
so  much  oxygen  from  outside  for  the  production  of  the  same  amount  of 
carbon  dioxide,  and  the  carbon  dioxide  output  of  the  animal  will  therefore 
be  greater  than  its  oxygen  intake.  Pembrey  has  shown  that  under  these 
conditions  the  respiratory  quotient  may  be  as  high  as  1>5.  We  cannot 
assume  however  that  the  process  of  conversion  of  glucose  into  fatty  acids 
takes  place  by  this  simple  process  of  deoxidation.  The  change  is  probably 
a  more  complex  one,  and  occurs  in  separate  stages.  Glucose  easily  breaks 
up  under  the  action  of  ferments  into  two  molecules  of  lactic  acid,  and 
lactic  acid  can  be  equally  easily  converted  into  aldehyde  and  formic  acid, 
thus  : 

C6Hj,Oe  =  2C'3H603  lactic  acid,  and 

CH3" 

I  CH3        H 

CHOH=    |        +    | 

|  CHO       COOH 

COOH 

Now  aldehydes  possess  a  marked  tendency  to  combine  with  other 
molecules  of  itself  or  other  substances,  i.  e.  to  undergo  polymerisation. 
Thus  from  two  molecules  of  aldehyde  we  get  one  molecule  of  aldol, 

CH3 

I 
CH3  CHOH 

2  |  =  | 

CHO  CH, 

I 
CHO 

which  by  a  simple  transposition  of  oxygen  would  give  butyric  acid,  or  by 
oxidation  would  give  /3-oxybutyric  acid,  a  substance  which  occurs  during 
various  abnormal  conditions  of  metabolism. 

The  fats  occurring  in  the  body,  e.  g.  in  milk,  include  only  the  fatty  acids 


THE  HISTORY  OF  FAT  IN  THE  BODY  831 

wit  b  an  even  number  of  carbon  atoms  (v.  p.  117).'  We  may  probably  assume 
from  this  fact  that  the  building  up,  as  well  as  the  breaking  down,  of  fatty 
acids  occurs  by  two  carbon  atoms  at  a  time.  Although  heating  aldehyde 
or  aldol  with  potash  or  any  other  polymerising  agent  gives  rise  to  a  mixture 
of  many  substances,  it  is  probable  that  under  the  catalytic  agencies  at  the 
disposal  of  the  living  cell  these  synthetic  changes  are  directed  entirely  in 
one  direction,  so  that  from  butyric  acid  we  shall  have  hexoic,  caprylic, 
capric  acid,  and  so  on.  The  process  would  seem  to  take  place  more  easily 
through  pyruvic  acid,  as  described  on  p.  119.  Why  the  process  comes  to 
ai  i  end  with  the  formation  of  the  16  and  18  carbon  atoms  it  is  difficult  to 
see.1  Possibly  with  the  formation  of  acids  whose  rnelting-point  is  higher 
than  that  of  the  body  temperature,  a  certain  stability  is  imparted  to  them 
which  prevents  their  further  circulation  and  ready  synthesis  to  the  still 
higher  acids. 

With  regard  to  the  glycerine  which  is  a  necessary  constituent  of  the 
neutral  fats  laid  down  in  the  body,  there  is  no  difficulty  in  accounting  for 
its  formation  from  the  carbohydrates.  By  a  simple  splitting  of  glucose, 
we  may  obtain  two  molecules  of  glyceraldehyde, 

CH,OH 

CHOH 

I 
CHOH 

I 
CHOH 

I 
CHOH 

I 
CHO 

which  by  reduction  is  readily  converted  into  the  corresponding  alcohol 
glycerine,  CH2OH.CHOH.CH2OH. 

We  may  conclude  then  that  fats  are  formed  by  the  body  with  ease 
from  carbohydrates,  and  that  in  all  probability  this  change  involves  a 
building  up  of  the  fatty  acid  from  the  lower  members  by  the  successive 
addition  of  a  group  containing  two  atoms  of  carbon.  The  whole  change, 
as  Leathes  has  shown  (v.  p.  118),  is  an  exothermic  one.  For  the  formation 
of  one  molecule  of  palmitic  acid,  four  molecules  of  glucose  would  be  required, 
and  12-5  per  cent,  of  the  total  energy  of  the  glucose  would  be  set  free  as 
heat. 

THE  FORMATION  OF  FAT  FROM  PROTEINS.  Among  the  decom- 
position products  of  proteins,  the  amino-derivatives  of  the  fatty  acids  take 
a  prominent  part.  Of  these  some  may  be  converted  into  carbohydrate  in 
the  body,  while  others  such  as  leucine  and  tyrosine  may  give  rise  to  aceto- 
acetic  acid.  It  seems  therefore  that  these  latter  might  in  their  turn  be 
built  up  by  the  process  we  have  just  discussed  into  the  higher  members 

1  From  the  fats  extracted  from  the  kidney  Dunham  has  isolated  carnaubic  acid, 

CvfH.aOo. 


CH2OH 

I 
=  2  CHOH 

I 
CHO 


832  PHYSIOLOGY 

of  the  series.  For  many  years,  as  a  result  of  the  investigations  of  Voit, 
the  proteins  were  indeed  regarded  as  the  chief,  if  not  the  sole,  source  of 
the  fats  of  the  body,  and  it  needed  the  energetic  assaults  of  Pfliiger  on  this 
doctrine  in  1891,  before  it  could  be  clearly  examined  by  physiologists. 

Let  us  see  what  are  the  grounds  for  assuming  a  formation  of  fat  from 
protein.  In  the  first  place,  there  is  a  well-known  experiment  by  Voit. 
A  dog  was  fed  with  large  quantities  of.  lean  meat  for  a  considerable  time. 
Voit  found  that  the  whole  of  the  nitrogen  of  the  intake  was  excreted,  but 
that  a  certain  percentage  of  carbon  was  retained  in  the  body,  and  that 
the  percentage  of  this  carbon  was  greater  than  could  be  accounted  for  by 
the  deposition  of  glycogen  in  the  liver  and  muscles.  He  therefore  assumed 
that  it  must  have  been  laid  down  as  fat.  Pfliiger  showed  that  these  con- 
clusions were  not  justified  by  Voit's  results,  and  were  really  based  on  the 
fact  that  too  high  a  figure  had  been  assumed  for  the  carbon  of  the  meat. 
Whereas  Voit  found  that  the  animal  had  laid  on  56  grm.  of  fat  during 
one  day  of  the  experiment,  a  recalculation  of  the  same  results  by  Pfliiger 
shows  that  the  animal  could  not  have  put  on  more  than  3-9  grm.  of  fat, 
an  amount  which  might  quite  well  be  accounted  for  by  the  fat  and  glycogen 
present  in  the  meat.  Pfliiger  has  shown  moreover  that  an  animal  may 
be  fed  in  any  quantities  for  weeks  on  the  leanest  meat  that  it  is  possible 
to  procure,  without  putting  on  any  fat  at  all ;  and,  as  we  have  seen,  increasing 
the  ration  of  protein  increases  simply  the  nitrogenous  and  general 
metabolism  of  the  body. 

Although  therefore  we  must  assume  that  the  healthy  body  does  not 
normally  form  fat  from  protein,  there  are'  certain  pathological  conditions 
which  seem  at  first  to  tell  in  favour  of  such  a  conversion.  Thus  during 
certain  diseases,  such  as  diphtheria,  pernicious  anaemia,  and  as  the  result 
of  poisoning  by  phosphorus,  the  majority  of  the  organs  of  the  body  undergo 
acute  fatty  degeneration.  The  fiver  may  be  enlarged.  All  its  cells  are 
studded  with  fat  granules  which  are  apparently  formed  by  a  change  in 
the  protoplasm  of  the  cells.  This  change  was  long  interpreted  as  due  to 
a  direct  conversion  of  protein  into  fat.  More  exact  analyses  have  shown 
that  during  fatty  degeneration  the  total  fat  in  the  body  is  not  increased. 
Thus  one  observer  took  124  pairs  of  frogs  and  poisoned  one  of  each  pair 
with  phosphorus.  The  animals  were  then  killed,  and  the  whole  of  them 
analysed.  The  difference  in  the  content  of  fat  between  the'  poisoned  and 
unpoisoned  animals  fell  within  the  limits  of  experimental  error,  so  that 
there  had  been  no  increase  in  the  fat  of  the  body  as  the  result  of  the  poison- 
ing. In  some  of  these  cases  the  liver  is  actually  enlarged,  but  this 
deposition  of  fat  in  the  cells  is  due  to  the  immigration  of  the  fat  from  other 
parts  of  the  body  and  not  to  conversion  of  the  protein  of  the  cells.  This 
is  shown  by  the  facts  that  the  composition  of  the  fat  in  the  degenerated 
liver  varies  according  to  the  composition  of  the  fat  in  the  rest  of  the  body, 
and  that,  if  abnormal  fats  are  given  with  the  food,  such  as  erucic  acid  or 
iodine  fats,  these  are  found  in  the  fat  extracted  from  the  fiver.  In  fatty 
degeneration  two  processes  are  at  work  :  one  is  the  immigration  of  fats 


THE  HISTORY  OF  FAT  IN  THE   BODY  833 

from  other  parts  of  the  body ;  the  second,  and  probably  the  more  important 
one,  is  a  change  in  the  relation  of  the  fat  to  the  protoplasm  of  the  cell. 

It  was  long  stated  that  the  fat  of  milk  was  not  increased  by  feeding  with 
fats,  but  only  by  feeding  with  proteins.  More  recent  researches  have  given 
contrary  results.  The  dependence  of  the  composition  of  milk  fat  on  the 
composition  of  the  fat  present  in  the  body  or  administered  in  the  food  is 
shown  by  the  fact  that  cows  fed  on  oilcake  may  produce  a  butter  which 
is  useless  for  commercial  purposes  owing  to  its  low  melting-point.  In  one 
experiment,  when  a  cow  was  fed  on  linseed  oil,  the  iodine  number  of  the 
milk  fat  rose  from  30,  its  normal  figure,  to  704.  After  the  introduction 
of  iodine  fat  subcutaneously,  iodine  fats  are  found  in  the  milk.  In  another 
experiment  a  bitch,  which  had  been  fed  with  mutton  suet  and  had  deposited 
in  its  tissues  a  fat  of  liigh  melting-point,  produced  a  milk  the  iodine  number 
of  which  was  the  same  as  that  of  the  mutton  suet.  In  this  case  the  fat 
of  the  milk  had  evidently  been  derived  from  the  tissues,  since  during  the 
lactation  the  animal  was  being  fed  on  meat  which  was  poor  in  fat.  The 
same  dependence  of  fatty  secretion  on  diet  has  been  found  in  geese,  where 
the  composition  of  the  oil  secretion  of  the  feather  glands  has  been  altered 
by  giving  unusual  fats,  such  as  sesame  oil,  with  the  food. 

We  must  conclude  that  the  protein  of  the  food  does  not  give  rise  to 
fat  in  the  body.  A  nearer  consideration  of  the  composition  of  the  proteins, 
taken  in  connection  with  our  discussion  as  to  the  mechanism  by  means  of 
which  the  fat  is  built  up  in  the  body,  might  help  to  account  for  this  fact. 
The  fatty  acids  formed  by  the  disintegration  of  proteins  are  chiefly  the 
lower  acids  of  the  series,  such  as  acetic  and  propionic,  which  would  undergo 
rapid  oxidation  in  the  body.  Butyric  acid  has  not  yet  been  found  among 
the  products  of  disintegration  of  the  proteins,  and  the  6-carbon  acid, 
derived  from  leucine,  is  not  the  normal  acid,  but  is  a  branched  chain,  viz. 
isobutyl-acetic  acid. 

THE   UTILISATION   OF   FATS   IN   THE   BODY 

The  constant  presence  of  fat,  and  bodies  allied  to  fat,  in  protoplasm, 
from  whatever  source  obtained,  suggests  that  these  substances  can  enter 
directly  into  the  chemical  changes  on  which  the  life  of  the  cell  depends 
and  that  they  play  an  essential  part  in  vital  phenomena.  The  direct 
utilisation  of  fat  for  the  needs  of  the  body  is  also  indicated  by  the  results 
of  experiments  on  man  and  the  lower  animals.  After  a  few  days'  starva- 
tion the  body  may  be  regarded  as  practically  free  from  stored  carbohydrate. 
The  sole  source  of  the  energy  which  is  evolved  under  these  circumstances 
must  be  fats  and  proteins,  and  it  is  possible  to  determine  by  an  estimation 
of  the  nitrogen  output  the  exact  fraction  of  the  total  energy  evolved  which 
is  to  be  ascribed  to  protein  metabolism.  Thus  in  the  case  of  Cetti,  the 
professional  faster,  it  was  found  that  the  nitrogenous  metabolism  per  unit 
of  body  weight  remained  fairly  constant  between  the  fifth  and  tenth  days 
of  starvation,  and  corresponded  to  an  average  of  1  gnn.  of  protein  per 
kilo  body  weight  daily.  In  order  to  convert  this  amount  of  protein  into 
53 


834 


PHYSIOLOGY 


urea,  carbonic  acid,  sulphuric  acid,  and  water,  nearly  2  gnu.  of  oxygen 
would  be  required  in  the  twenty-four  hours,  i.  e.  about  1  c.c.  per  minute. 
Cetti's  total  oxygen  consumption  was  at  the  rate  of  5  c.c.  per  kilo  per 
minute,  so  that  four-fifths  of  the  oxygen  absorbed  was  required  for  the 
oxidation  of  non-nitrogenous  substances,  and  these,  as  we  have  seen, 
could  only  have  been  fats.  Li  animals  with  a  large  store  of  fat  the  pro- 
portion of  the  energy  obtained  at  the  cost  of  the  fats  may  be  still  greater. 
In  dogs  Rubner  and  Voit  reckoned  that  only  10  to  16  per  cent,  of  the  total 
energy  was  derived  from  proteins,  the  rest,  i.  e.  84  to  90  per  cent.,  being 
obtained  from  the  oxidation  of  fats. 

The  oxidation  of  fats  supplies  energy  not  only  for  the  production  of 
heat  but  also  for  the  performance  of  mechanical  work,  and  it  seems  probable 
that  the  utilisation  of  the  fat  occurs  in  the  muscular  tissues  themselves. 
Fat  is  found  as  a  normal  constituent  of  all  muscle  fibres,  and  the  amount 
of  this  substance  is  greater  in  proportion  to  the  activity  of  the  muscles 
concerned.  Thus  the  ever-active  heart  muscle,  and  the  red  muscles  of 
the  diaphragm,  contain  larger  amounts  of  fat  than  the  pale  voluntary 
muscles  which  have  to  undertake  only  short  periods  of  activity.  In  the 
human  heart  muscle  15  per  cent,  of  the  solids  are  soluble  in  ether,  and 
more  than  one-half  of  the  ether  extract  is  composed  of  fat,  and  is  suffi- 
cient to  supply  the  energy  of  the  contracting  heart  for  six  or  seven  hours' 
work. 

The  degree  to  which  the  muscles  during  contraction  call  upon  each 
class  of  foodstuffs  may  be  judged  from  the  respiratory  quotient.  If  the 
body  has  previously  supplied  the  greater  part  of  its  needs  at  the  expense 
of  fats,  it  will  continue  to  do  so  during  muscular  work.  This  is  well  shown 
in  the  following  Table,  in  which  the  oxygen  consumption  and  respiratory 
quotient  are  compared  in  a  man  resting  and  working  on  three  different 
diets,  one  principally  fat,  one  principally  carbohydrate,  and  the  other 
principally  protein  : 


Resting 

Working 

kg.  m. 
of  work 
done 

Per  kg.  m.  of  work 

Diet 

principally                c.c.  oxy- 
gen used 
per  min. 

Eesp. 
quo- 
tient 

c.c.  oxygen 
used  per 

Eesp. 
quo- 
tient 

c.c. 

oxygen 

used 

Cal. 

Tat    .          .         .          319 
Carbohydrate      .          277 
Protein       .          .306 

0-72 
0-90 
0-80 

1029 
1029 
1127 

0-72 
0-90 
0-80 

354 
346 
345 

201 
217 
2-38 

9-39 

10-41 

11-35 

__, 

We  may  conclude  then  that  the  tissues  of  the  body  are  able  to  obtain 
their  energy  by  the  direct  utilisation  of  the  fats  which  they  contain.  The 
changes  in  the  fat  molecules,  which  are  involved  in  the  utilisation  of  their 
energy,  are  still  to  be  determined.  The  energy  of  fat  is  available  only  on 
its  oxidation.  The  transformation  of  fats  into  fatty  acids  or  glycerine, 
or  the  synthesis  of  fats  from  aldehydes  or  from  carbohydrates,  which  we 


THE  HISTORY  OF  FAT  IN   THE  BODY  835 

have  discussed  in  the  previous  section,  do  not  involve  any  large  changes 
of  energy.  Weight  for  weight,  butyric  acid  with  its  4  carbon  atoms  has 
practically  the  same  heat  value  as  stearic  acid  with  its  18  carbon  atoms, 
or  stearine  with  its  57  carbon  atoms.  We  have  therefore  to  determine 
what  changes  the  great  fat  molecule  undergoes  before  it  is  brought  into  a 
condition  in  which  it  may  undergo  oxidation  and  set  free  the  energy  required 
for  the  purposes  of  the  body.  The  general  tendency  of  metabolic  research 
of  recent  years  is  to  show  that  the  living  cell  is  in  a  position  to  effect  all 
changes  which  do  not  involve  a'  large  evolution  or  absorption  of  energy  in 
either  direction.  In  the  plant  cell,  at  any  rate,  the  fatty  acids  may  be 
converted  into  ammo-acids,  or  the  latter  may  be  deaminised,  as  occurs 
in  the  liver,  into  fatty  or  oxyacids.  Dextrose  may  pass  into  maltose  and 
starch,  or  starch  may  be  converted  into  maltose  or  dextrose.  If  therefore 
fats  are  constantly  being  made  from  carbohydrates,  or  from  the  lower 
molecules  such  as  aldehyde,  by  a  process  of  repeated  addition  of  a  group 
containing  two  carbon  atoms,  it  seems  possible  that  the  same  change  might 
go  on  in  a  reverse  direction  when  fats  are  broken  down  previous  to 
oxidation. 

In  the  germination  of  oily  seeds  the  utilisation  of  the  fat  is  preceded 
by  the  splitting  of  the  higher  fatty  acids  into  acids  of  lower  molecular 
weight.  Although  we  cannot  trace  out  in  the  animal  body  the  stages  in 
the  breakdown  of  a  large  fatty  acid,  such  as  stearic  acid,  we  can,  by  a  certain 
artifice  much  used  in  metabolic  experimentation,  bring  forward  evidence 
in  favour  of  the  view  that  the  breakdown,  like  the  building  up  of  fats, 
occurs  by  two  carbon  atoms  at  a  time.  When,  in  the  process  of  breaking 
down,  a  fat  finally  arrives  at  the  four-  or  two-carbon  stage,  it  is  quickly 
oxidised  and  is  therefore  not  traceable  in  the  excretions  or  in  the  fluids  of 
the  body.  This  end  stage  may  however  be  preserved  from  oxidation 
by  hanging  it,  so  to  speak,  on  to  an  aromatic  ring.  If  acetic  acid  or  ethyl 
alcohol  be  administered  in  small  quantities,  it  is  entirely  oxidised.  If 
however  these  bodies  be  attached  to  a  benzene  ring  and  be  administered 
as  a  phenacetic  acid  or  phenylethyl  alcohol,  they  are  excreted  in  the  oxidised 
form  of  phenaceturic  acid,  which  is  simply  a  combination  of  phenacetic 
acid  with  glycine.  In  the  same  way  benzoic  acid  and  benzyl  alcohol  are 
excreted  in  the  form  of  hippuric  acid,  thus  : 

C6HB.COOH  +  NH2.CH2.COOH  =  C6H5.CO.NH.CH2.COOH  +  H20 

Benzoic  acid  Glycine  Hippuric  acid 

Phenacetic  acid,  C6H5.CH2COOH,  is  excreted  as  C6H5.CH2.- 
CO.NH.CHoCOOH.  In  each  case  the  fatty  side-chain  is  protected  from 
further  oxidation  by  its  attachment  to  the  benzene  ring  and  by  the  tacking 
on  of  the  glycine  molecule. 

With  phenylpropionic  acid  two  carbon  atoms  of  the  side-chain  are 
oxidised,  and  the  remaining  benzoic  acid  excreted  as  hippuric  acid.  Phenyl- 
butyric  acid  undergoes  a  similar  change :  two  carbon  atoms  are  oxidised 
away,  leaving  phenylacetic  acid,  which  is  excreted  as  phenylaceturic  acid. 


836  PHYSIOLOGY 

If  phenyl  valerianic  acid  be  given,  four  carbon  atoms  are  oxidised  away 
and  benzoic  acid  is  left,  and  appears  in  the  urine  as  hippuric  acid.  In 
each  case  the  oxidation  of  the  side-chain  occurs  by  two  carbon  atoms  at 
a  time,  and  it  seems  probable  that  a  similar  change  will  occur  in  the  ordinary 
fatty  acid,  the  last  stages,  in  the  absence  of  any  protective  ring  compound, 
being  oxidised  like  the  earlier  groups  and  therefore  not  detectable  in  the 
excretions. 

Evidence  in  the  same  direction  is  afforded  by  certain  cases  in  which 
the  oxidative  power  of  the  body  for  fats  is  inadequate,  either  by  reason  of 
morbid  changes  in  the  oxidative  powers  of  the  body,  or  as  the  result  of 
what  we  may  call  an  overstrain  of  the  fat -oxidising  powers.  Such  a  con- 
dition is  found  in  the  acetonuria  of  acute  acidosis,  such  as  occurs  in  the 
end  stages  of  diabetes.  The  oxybutyric  and  diacetic  acids  occurring  in 
the  urine  in  this  condition  were  formerly  thought  to  be  derived  from  the 
carbohydrates  of  the  food,  or  from  sugar  abnormally  produced  in  the 
bod)7.  The  condition  of  acidosis  however  is  often  brought  on  directly 
as  the  result  of  putting  the  patient  on  a  strict  anti-diabetic  diet,  i.  e.  one 
consisting  chiefly  or  exclusively  of  fats  and  proteins,  and  may  be  produced 
in  a  healthy  man  by  simple  starvation,  when  the  body  has  only  at  its  dis- 
posal its  stored-up  fats  and  proteins.  It  occurs  in  a  marked  degree  on 
the  administration  of  a  diet  consisting  almost  entirely  of  fats.  Thus  in 
one  experiment  a  healthy  man  took  as  his  sole  diet  for  five  days  a  daily 
ration  of  250  grm.  of  butter,  200  grm.  of  oil,  and  a  little  wine.  The  result 
was  an  intense  acidosis,  such  as  is  only  found  in  the  severest  cases  of 
diabetes,  diacetic  acid,  oxybutyric  acid,  and  acetone  being  found  in  the 
urine  in  large  quantities.  On  the  last  day  of  the  experiment  these  acids 
caused  so  much  of  the  nitrogen  in  the  urine  to  appear  as  ammonia  that  of 
the  5-8  grm.  total  nitrogen  excreted  only  2-7  grm.  were  in  the  form  of  urea, 
while  as  much  as  2-1  grm.  were  present  as  ammonia. 

If,  during  a  period  of  starvation  in  man,  a  day  is  interpolated  on  which 
100  grm.  of  protein  are  taken,  the  amount  of  acetone  excreted  falls  below 
that  obtained  on  the  other  days  when  the  individual  is  living  chiefly  at 
the  cost  of  his  own  fat.  These  facts  indicate  that  the  chief  source  of  the 
/5-oxybutyric  acid  and  the  diacetic  acid  is  the  fat  of  the  food  or  of  the 
body.  The  condition  of  acidosis  is  more  easily  brought  about  by  ingestion 
of  butyric  acid  than  of  the  higher  acids,  such  as  palmitic  or  stearic,  sug- 
gesting that  whatever  fatty  acid  is  given  it  is  finally  reduced  to  butyric 
acid  before  its  oxidation,  and  that  in  the  condition  of  acidosis  it  is  merely 
the  last  stages  of  this  oxidation  which  are  at  fault.  We  are  thus  justified 
in  concluding  that  the  oxidative  breakdown  of  fats  occurs  always  by  an 
oxidation  in  the  fi  position. 

We  take,  for  instance,  the  6-carbon  stage  : 

CH3.CH2.CH2.CH2.CH2.COOH 

the  first  change  which  probably  occurs  is  the  oxidation  : 

CH„.CH,.CH.,.CHOH.CH,.COOH 


THE  HISTORY  OF  FAT  IN  THE   BODY  837 

A  further  change  is  the  complete  oxidation  of  the  last  two  groups  and  the 
production  of  Butyric  acid  : 

CH3.CH2.CH2.C'OOH 

This  then  undergoes  again  oxidation  hi  the  yS  position,  with  the  production 
of  /?-oxybutyric  acid  : 

CH3.CHOH.CH2.COOH 

and  then  again  is  converted  to  diacetic  acid, 

CH3.CO.CH2.COOH 

In  the  normal  individual  this  last  stage  undergoes  complete  oxidation, 
both  oxybutyric  acid  and  diacetic  acid  given  to  a  healthy  person  being 
completely  destroyed  in  the  body.  It  is  only  under  the  abnormal  conditions 
which  we  have  mentioned  above  that  these  last  stages  fail  of  complete 
oxidation,  and  are  excreted  unchanged  in  the  urine. 

THE   QUESTION   OF   THE   FORMATION   OF   SUGAR   FROM   FAT 

The  ease  with  which  the  anirnal  body  performs  the  difficult  chemical 
operation  of  transforming  carbohydrate  into  fat  suggests  that  under 
appropriate  conditions  it  might  effect  the  reverse  change.  Is  there  any 
evidence  that  in  the  animal  body  sugar  may  be  derived  from  fat  ?  Such 
a  conversion  is  of  normal  occurrence  during  the  germination  of  fatty  seeds, 
starch  sugar  and  cellulose  being  formed  at  the  expense  of  the  stored-up 
fats  of  the  seeds.  If  such  seeds  be  allowed  to  germinate  over  mercury  in 
a  confined  volume  of  oxygen,  they  are  found,  like  seeds  containing  chiefly 
carbohydrate  reserves,  to  absorb  oxygen  and  to  give  off  carbon  dioxide. 
Whereas  however  in  the  latter  case  the  amount  of  carbon  dioxide  evolved 
is  almost  equal  to  the  oxygen  absorbed,  in  the  case  of  the  fatty  seeds  much 
less  carbon  dioxide  is  given  out  than  would  correspond  to  the  volume  of 
oxygen  absorbed,  so  that  the  total  volume  of  gas  above  the  seeds  diminishes. 

The  same  change  in  the  relation  of  oxygen  intake  to  carbon  dioxide 
output  is  found  under  certain  conditions  in  animals.  During  hibernation, 
as  Pembrey  has  shown,  the  marmot  has  a  very  low  respiratory  quotient, 
which  may  not  be  greater  than  0-3  or  04.  This  means  that  the  animai 
takes  in  more  oxygen  than  the  carbon  dioxide  which  it  gives  out,  and  this 
intake  of  oxygen  can  be  so  marked  as  to  cause  an  appreciable  increase  in 
the  weight  of  the  animal,  which  imder  such  circumstances  is  literally  living 
on  air.  This  retention  of  oxygen  can  only  be  explained  by  assuming' that 
there  is  a  conversion  of  substances  containing  a  small  amount  of  oxygen 
into  substances  containing  a  larger  amount  of  oxygen  going  on  in  the  body, 
such  a  conversion  as  that  of  fats  into  carbohydrates.  Just  as  the  high 
respiratory  quotient  obtained  from  a  marmot  during  the  period  of  putting 
on  fat  was  shown  to  be  associated  with  a  conversion  of  carbohydrate  into 
fat,  so  does  the  abnormally  low  quotient  obtained  during  hibernation 
indicate  the  reverse  change  of  fat  into  carbohydrate. 

The  same  conversion  has  been  alleged  to  take  place  in  certain  cases  of 


838  PHYSIOLOGY 

diabetes.  In  many  cases  when  the  diabetic  animal  is  living  on  a  purely 
protein  diet,  a  uniform  ratio  lias  boon  found  to  exist  between  the  glucose 
or  dextrose  and  the  nitrogen  excreted. 

-    equals  generally  2-8. 

In  certain  other  cases  se  constant  D  :  N  ratio  of  3-65  has  been  found.  The 
former  represents  a  conversion  of  45  per  cent.,  the  latter  of  58  per  cent., 
of  protein  into  sugar.  In  a  few  cases  however,  even  during  complete 
starvation,  the  ratio  D  :  N  has  been  found  to  be  much  greater  than  that 
given  above  and  to  amount  to  as  much  as  10  or  12.  These  animals  are 
stated  to  be  practically  free  from  carbohydrates,  so  that  the  sugar  excreted 
in  the  urine  can  come  only  from  the  breakdown  of  proteins  or  fats.  ,It  is 
impossible  by  any  means  whatever  to  break  up  a  protein  molecule  so  as  to 
get  from  it  ten  times  as  much  dextrose  as  corresponds  to  the  nitrogen,  and 
Pfliiger  concludes  that  in  cases  where  such  a  high  D  :  N  ratio  exists  the 
dextrose  must  have  been  derived  by  a  conversion  of  the  fats  of  the  body. 
This  conclusion  is  by  no  means  generally  accepted  (cp.  p.  852).  If  correct,  it 
would  bear  out  the  general  statement  made  above,  namely,  that  in  the  living 
body  practically  all  the  chemical  changes  are  reversible,  and  that  the  living 
cell  can  so  regulate  the  conditions  of  the  reaction  that  the  reversible  reaction 
becomes  practically  complete  in  either  direction,  the  direction  being  deter- 
mined by  the  needs  of  the  body  at  the  time. 

Accepting  this  generalisation,  the  chemical  mechanism  by  which  fats 
are  converted  into  carbohydrates  must  be  the  reverse  of  that  by  which 
carbohydrates  are  changed  into  fats.  The  2-carbon  group  split  off  from 
the  large  fatty  molecules  would  be  utilised  for  the  building  up  of  the  sugar 
molecule.  We  know  that  such  a  synthesis  can  take  place  from  such  simple 
groups  as  formic,  glycollic,  or  glyceric  aldehyde.  Though  it  is  impossible 
to  deny  to  any  cell  of  the  body  the  power  of  effecting  the  conversion  of 
fats  into  carbohydrates,  or  carbohydrates  into  fats,  the  chief  centre  for 
such  conversions  is  probably  the  chemical  factory  of  the  body,  namely, 
the  liver.  It  is  significant  that  in  the  course  of  fatal  diabetes,  in  which 
the  fat  disappears  entirely  from  the  body,  and  there  is  wasting  of  prac- 
tically all  the  tissues,  the  liver  is  the  only  organ  which  retains  its  weight 
imchanged.  During  this  disease  there  has  been  an  enormous  amount 
of  work  done  in  the  conversion  of  proteins  and  possibly  of  fats  into  carbo- 
hydrates which  could  not  be  utilised  by  the  body,  and  the  large  size  of 
the  liver  at  death  suggests  that  the  work  of  transformation  has  been  performed 
by  this  organ. 


SECTION  IV 

THE   METABOLISM    OF    CARBOHYDRATES 

All  the  carbohydrates  which  are  taken  in  with  the  food  are  ultimately 
transformed  in  the  alimentary  tract,  or  in  its  walls,  into  the  three  mono- 
saccharides, glucose,  fructose,  and  galactose.  These  three,  together  with 
mannose,  are  the  only  sugars  which  are  directly  fermentable  and  directly 
assimilable  by  higher  animals.  A  consideration  of  their  structural  formulae 
shows  that  they  are  fairly  easily  interconvertible,  galactose  presenting  the 
greatest  divergence  from  the  general  type.  This  conversion  actually  takes 
place  in  watery  solution.  If  a  solution  of  any  one  be  left  for  some  months, 
it  will  be  found  to  contain  all  four  at  the  end. 

Since  these  monosaccharides,  for  the  greater  part  glucose,  must  enter 
the  blood  in  large  quantities  during  the  absorption  of  a  heavy  carbohydrate 
meal,  one  would  expect  to  find  a  greater  proportion  in  the  blood  during 
such  a  meal  than  during  a  pericd  of  starvation.  The  amount  of  reducing 
sugar  in  the  blood  however  is  practically  constant,  and  varies  between 
0-1  and  0-15  per  cent. 

Searching  for  the  origin  of  this  constant  proportion  of  reducing  sugar, 
Claude  Bernard  found  that  the  blood  of  the  hepatic  vein  in  a  fasting  animal 
contained  more  sugar  than  the  blood  taken  at  the  same  time  from  the  portal 
vein.  Although  the  reliability  of  this  experimental  result  has  been  put  in 
doubt  by  more  recent  investigators,  it  was  important  in  that  it  attracted 
Bernard's  attention  to  the  liver.  If  the  liver  be  taken  from  an  animal  which 
has  been  dead  for  some  time,  and  extracted  with  water,  the  extract  is  found 
to  contain  a  large  quantity  of  reducing  sugar  (glucose).  If  however  it  be 
removed  immediately  the  animal  is  dead,  its  vessels  washed  out  with  ice-cold 
saline  fluid,  and  it  be  then  cut  up  and  thrown  into  boiling  water,  ground  and 
extracted,  the  extract,  after  separation  of  the  coagulable  proteins,  contains 
hardly  a  trace  of  sugar,  and  no  more  than  is  present  in  the  blood.  The 
fluid  is  however  opalescent ;  and  Bernard  found  that  this  opalescence  was 
due  to  the  presence  of  a  substance  at  that  time  new  to  science,  belonging  to 
the  class  of  polysaccharides.  This  substance  he  called  glycogen,  i.  e.  the 
sugar-former. 

After  a  carbohydrate  meal,  glycogen  may  be  present  in  very  large 
amounts  in  the  liver,  up  to  12  per  cent,  of  the  weight  of  the  fresh  liver. 
Prom  its  solution  in  water  it  can  be  thrown  down  by  the  addition  of  alcohol 
to  60  per  cent.     When  collected  and  dried,  it  forms  a  snow-white  powder, 

839 


840  PHYSIOLOGY 

tasteless  and  odourless,  with  a  formula  identical  with  that  of  starch,  viz. 
CcH1005.  Like  starch,  it  is  hydrolysed  by  the  action  of  acids  and  super- 
heated water,  or  of  amylolytic  ferments,  into  dextrine,  maltose,  and  finally 
glucose.  It  gives  with  iodine  a  mahogany-red  colour,  which  disappears  on 
boiling,  but  returns  again  on  cooling. 

It  is  not  possible  to  extract  the  whole  of  the  glycogen  from  a  tissue  by  merely 
boiling  it  with  water.  Kiilz  introduced  on  this  account  the  method  of  dissolving 
the  tissues  in  caustic  alkali,  then  throwing  down  the  protein  with  phosphotungstic 
acid,  and  in  the  filtrate  precipitating  the  glycogen  with  alcohol.  This  method  has 
been  modified  by  Pfliiger  as  follows  :  100  grm.  of  the  tissue  (fiver  or  muscle)  are  heated 
with  100  c.c.  caustic  potash  containing  00  to  70  per  cent.  KHO  for  twenty-four  hours 
in  the  water  bath.  The  solution  is  then  cooled,  diluted  with  200  c.c.  of  water,  and 
treated  with  800  c.c.  alcohol  of  96  per  cent.  The  precipitate  of  glycogen  is  filtered  off 
and  washed  several  times  with  66  per  cent,  alcohol.  The  precipitate  of  glycogen  is 
now  washed  with  a  little  water  into  a  small  beaker,  neutralised  carefully  with  acetic 
acid,  and  then  introduced  into  a  100  c.c.  flask.  To  the  solution  5  c.c.  of  hydrochloric 
acid  of  1-19  sp.  gr.  are  added,  and  the  mixture  is  made  up  to  85  c.c.  The  flask  is  then 
heated  in  the  water  bath  for  three  hours.  By  this  means  the  whole  of  the  glycogen 
is  converted  into  glucose,  which  can  be  estimated  by  Fehling's  method  or  by  Allihn's 
method.  In  practice  it  is  more  accurate  to  estimate  the  glycogen  in  the  form  of  sugar 
than  to  weigh  it  directly.  If  large  quantities  of  glycogen  are  expected  in  the  tissue, 
the  inversion  of  the  glycogen  must  be  carried  out  in  a  larger  beaker,  and  only  an  aliquot 
portion  taken  for  titration. 

The  large  amount  of  sugar  found  in  the  liver  which  has  been  left  in  the 
body  is  due  to  the  conversion  of  glycogen  into  glucose.  This  conversion  has 
been  variously  ascribed  to  the  activity  of  the  surviving  liver-cells,  or  to  the 
action  of  an  amylase  ferment  present  in  the  liver-cells.  That  it  is  really  a 
ferment  action  is  proved  by  the  fact  that  the  liver  may  be  dehydrated  with 
alcohol,  dried  and  powdered,  and  kept  for  months  in  this  condition  without 
any  alteration  occurring  in  the  glycogen.  If  however  the  coagulated  liver 
be  mixed  with  water  and  allowed  to  remain  at  the  temperature  of  the  body 
for  some  hours,  the  glycogen  is  found  to  disappear  and  give  place  to  glucose. 


FORMATION    OF   GLYCOGEN 

Glycogen  is  most  readily  formed  from  the  carbohydrates  of  the  food. 
In  order  to  obtain  a  large  amount  from  the  liver,  the  animal  is  fed  twelve  to 
twenty-four  hours  previously  on  a  meal  which  is  rich  in  carbohydrates. 
Not  all  carbohydrates  will  give  rise  to  the  formation  of  glycogen.  Only 
those  which  we  have  mentioned  as  directly  assimilable,  i.  e.  which  will  give 
rise  in  the  alimentary  tract  to  mannose,  glucose,  fructose,  or  galactose,  will 
cause  an  increased  formation  of  glycogen.  The  conversion  involves  a  direct 
polymerisation  of  the  glucose,  produced  either  directly  from  the  foods  or  by 
a  molecular  rearrangement  taking  place  in  one  of  the  other  three  of  these 
monosaccharides . 

Glycogen  can  also  be  formed  from  the  proteins  of  the  food,  or  from  the 
products  of  their  disintegration,  the  ammo-acids.    By  means  which  we 


THE  METABOLISM  OF  CARBOHYDRATES  841 

shall  consider  shortly,  it  is  possible  to  free  the  liver  of  animals  entirely 
from  glycogen  :  if  such  animals  be  fed  on  a  diet  of  washed  fibrin  or  of  pure 
caseinogen,  or  even  on  the  ultimate  products  of  pancreatic  digestion  of 
proteins  (containing  therefore  only  amino-acids),  and  be  killed  shortly  after- 
wards, the  liver  is  found  to  contain  glycogen.  It  does  not  seem  to  be  possible 
for  the  liver  to  manufacture  glycogen  out  of  fats.  At  any  rate,  that  is  the 
interpretation  which  is  generally  placed  on  experiments  on  feeding  with 
fats.  In  these  experiments  it  is  found  that  if  fats  be  administered  to  an 
animal  after  the  liver  has  been  freed  from  glycogen,  although  the  liver  may 
store  up  fats  it  does  not  store  up  any  glycogen. 

If  an  animal  be  starved,  the  glycogen  gradually  disappears  from  the 
liver,  although  even  at  the  end  of  ten  or  twelve  days'  complete  deprivation 
of  food  small  traces  of  glycogen  may  still  be  found  in  this  organ.  If  starva- 
tion be  combined  with  hard  work;  if,  for  instance,  a  dog  be  made  to  drag 
about  a  milk-cart  on  the  second  day  of  the  starvation  period,  its  liver 
becomes  quite  free  from  glycogen.  The  same  disappearance  of  glycogen 
may  be  produced  by  any  means  which  evoke  an  increased  muscular 
activity,  e.  g.  poisoning  with  strychnine.  Of  the  various  reserve  materials 
which  are  available,  the  carbohydrate  is  the  first  to  be  called  upon  to 
meet  the  increased  needs  of  the  tissues  during  functional  activity,  such  as 
muscular  work  or  increased  heat  production.  Thus  the  glycogen  rapidly 
disappears  from  the  liver  of  a  rabbit  which  has  been  immersed  in  a 
cold  bath. 

The  glycogen  of  the  liver  represents  a  reserve  material  analogous  to  the 
reserve  carbohydrates  stored  up  as  starch  in  different  parts  of  plants. 
When  the  blood  is  loaded  with  carbohydrates,  a  considerable  proportion  is 
laid  down  as  the  inert  polysaccharide  glycogen.  As  soon  as  the  supply  of 
sugar  to  the  blood  is  withdrawn,  the  tissues  continue  to  use  the  sugar  of  the 
blood,  which  is  made  up  at  the  expense  of  the  glycogen  in  the  liver.  In  every 
liver-cell  therefore,  a  twofold  process  is  always  going  on,  namely,  a  building 
up  of  glycogen  by  the  activity  of  the  liver-cells,  and  a  breaking-down  of 
glycogen  under  the  action  of  the  ferment  formed  in  the  liver-cells.  Which  of 
these  two  processes  preponderates  depends,  in  the  normal  animal,  on  the 
percentage  amount  of  sugar  in  the  blood  which  is  circulating  through  the 
organ. 

On  account  of  the  importance  of  glycogen  as  a  reserve  material  it  is 
produced  and  stored  up  in  almost  all  growing  tissues,  to  be  utilised  in  their 
subsequent  development.  Thus  it  is  foruid  in  large  quantities  in  the  placenta 
during  a  certain  period,  in  foetal  muscles,  and  in  various  other  situations.  It 
is  found  in  yeast,  in  oysters,  and  in  the  muscles  of  the  body  generally.  In 
fcetal  muscles  it  may  amount  to  as  much  as  40  per  cent,  of  the  total  dried 
solids.  The  glycogen  of  the  adult  muscle  is  apparently  utilised  during 
muscular  work,  and  diminishes  in  amount  with  activity  of  the  muscle.  In 
adult  muscles  it  never  reaches  anything  like  the  percentage  which  is  found  in 
the  liver.  The  average  ameunts  found  by  Schondorf  in  the  different  tissues 
were  as  follows : 


842 


PHYSIOLOGY 


Maximum  ncr  cent. 
of  fresh  tissue. 

.Minimum  percent.   1 
(if  fresh  tissue. 

Liver     ..... 

18-69 

7 -.300 

Muscle  . 

3-72 

0-720 

Heart    . 

1-32 

0-104 

Bone 

1-90 

0-197 

Intestines 

1-84 

0-026 

Skin      . 

1  -68 

0-090 

Blood    . 

0-0066 

00016 

THE   UTILISATION   OF   SUGAR   IN   THE   BODY 

Arterial  blood  is  always  found  to  contain  between  0-12  and  0-15  per 
cent,  of  sugar  in  the  form  of  glucose.  The  same  amount  is  found  whether 
the  blood  be  taken  from  an  animal  after  a  heavy  carbohydrate  meal  or 
from  one  in  a  condition  of  complete  starvation.  The  constancy  of  the  sugar 
content  of  the  blood  suggests  that  this  substance  is  a  necessary  constituent 
of  the  circulating  fluid,  necessary,  that  is  to  say,  for  the  nutrition  of  the 
tissues.  That  it  is  being  used  up  in  all  the  processes  of  the  body  is  shown 
by  the  immediate  alteration  in  the  respiratory  quotient  which  occurs 
when  the  food  is  changed  from  a  mixed  diet  to  one  consisting  mainly  of 
carbohydrate.  An  important  factor  in  the  maintenance  of  a  constant  sugar 
content  in  the  blood  is  the  reconversion  of  the  stored-up  glycogen  of  the 
liver  into  sugar.  The  glycogen  is  not  however  the  sole  source  of  the  sugar, 
since  in  complete  starvation  the  sugar  content  of  the  blood  remains  constant 
even  after  the  last  traces  of  glycogen  have  disappeared  from  the  liver.  If  the 
liver  be  cut  out  of  the  body  or  removed  from  the  circulation,  during  the 
few  hours  that  the  animal  survives  there  is  a  steady  diminution  hi  the  blood 
sugar,  pointing  to  the  liver  being  the  chief,  if  not  the  sole,  source  of  the  blood 
sugar.  In  some  animals,  e.g.  the  carnivora,  it  would  seem  that  the  liver 
can  continue  to  supply  sugar  to  the  blood  on  a  diet  which  includes  only 
proteins  and  fats,  and  we  have  already  seen  that  in  such  animals  glycogen 
itself  can  be  stored  up  at  the  expense  of  protein.  It  is  doubtful  whether  a 
perfectly  normal  existence  is  possible  in  man  in  the  total  absence  of  carbo- 
hydrates from  the  food,  though  there  is  no  doubt  that  in  the  northern  nations, 
e.g.  the  Eskimos,  the  amount  of  carbohydrate  consumed  is  very  small  in 
comparison  with  the  fats  and  proteins.  During  muscular  exercise  the 
increased  output  of  energy  is  associated  with  a  corresponding  increase  in  the 
absorption  of  oxygen  and  in  the  output  of  carbon  dioxide,  pointing  to  a 
consumption  of  carbohydrate  and  fat  in  the  contracting  muscles.  We  might 
therefore  assume  that  sugar  is  being  normally  released  by  the  liver  into  the 
blood-stream  so  as  to  maintain  the  proportion  of  this  substance  in  the  blood 
at  a  certain  level,  and  that  the  sugar  is  as  constantly  being  taken  up  and  oxi- 
dised in  the  muscles,  where  it  serves  as  a  source  of  energy.  According  to 
Chauveau  and  Kaufmann  the  venous  blood  flowing  from  a  contracting 
muscle  contains  less  sugar  than  the  arterial   blood  flowing  to  the  muscle. 


THE  METABOLISM  OF  CARBOHYDRATES  843 

A  similar  consumption  of  glucose  occurs  in  the  isolated  contracting 
mammalian  heart  when  fed  with  Ringer's  fluid  containing  a  small  trace  of 
glucose.  A  heart,  fed  with  blood  and  performing  a  normal  amount  of  work, 
may  use  about  4  mg.  sugar  per  gramme  of  heart  muscle  per  hour.  That  the 
question  of  utilisation  of  sugar  by  the  tissues  is  highly  complex  is  shown  by 
a  study  of  the  conditions  under  which  sugar  may  appear  in  the  urine.  We 
learn  thereby  to  appreciate  to  some  extent  the  significance  of  carbohydrates 
both  as  sources  of  energy  and  as  foods  for  the  tissues,  though  we  are  still  a 
long  way  from  unravelling  all  the  changes  which  the  sugar  must  undergo 
in  the  cell  before  it  appears  once  again  in  the  oxidised  products,  carbon 
dioxide  and  water. 

GLYCOSURIA 

Normal  urine  always  contains  a  small  proportion  of  sugar,  about  1  part 
per  1000,  i.  e.  about  the  same  as  the  blood  itself.  For  the  detection  of  these 
small  traces  of  sugar  in  the  urine  special  methods  are  necessary.  The  term 
glycosuria  is  not  employed  unless  sugar  appears  in  quantities  large  enough 
to  give  a  reaction  with  Fehling's  solution  or  with  the  phenylhydrazine  test. 
Such  a  condition  may  easily  be  brought  about  by  the  injection  of  sugar 
subcutaneously  or  intravenously.  It  is  then  found  that  any  trace  of  the  di- 
saccharides,  cane  sugar  or  lactose,  introduced  in  the  circulation,  is  excreted 
in  the  urine.  A  rather  larger  quantity  of  maltose  may  be  injected  slowly 
without  appearing  in  the  urine,  since  the  blood  serum  contains  a  ferment, 
maltase,  which  converts  the  maltose  into  glucose.  Glucose,  fructose,  man- 
nose,  or  galactose,  if  introduced  slowly  into  the  circulation,  are  stored  up 
as  glycogen  in  the  liver.  If  however  the  percentage  of  sugar  in  the  blood 
rises  above  2  parts  per  1000,  the  sugar  (generally  glucose)  appears  in  the 
urine.  When  this  condition  of  hyperglycsemia  (excess  of  sugar  in  the  blood) 
is  set  up,  the  concentration  of  the  sugar  in  the  urine  no  longer  corresponds 
to  that  in  the  blood.  If  the  blood  contains,  e.  g.  4  parts  per  1000,  the  urine 
may  contain  from  2  to  7  per  cent,  of  sugar.  Up  to  a  certain  point  then, 
blood-sugar  is  kept  back  by  the  kidneys  as  a  necessary  food  material  for  the 
tissues.  Any  excess  above  the  normal  apparently  acts  as  a  foreign  substance 
and  is  excreted  by  the  kidneys  in  a  concentration  much  greater  than  that 
in  which  it  exists  in  the  blood  serum. 

(1)  ALIMENTARY  GLYCOSURIA.  A  state  of  hyperglycaemia  may  be 
induced  by  the  administration  of  abnormally  large  quantities  of  glucose 
by  the  mouth.  The  amount  has  to  exceed  in  a  healthy  individual 
100  grm.  in  order  that  it  shall  appear  in  the  urine.  In  certain  individuals 
the  power  of  assimilating  glucose  may  be  deficient  so  that  an  alimentary 
glycosuria  may  be  caused  by  any  over-indulgence  in  carbohydrate  food. 
In  the  healthy  person  it  is  hardly  possible  to  produce  glycosuria  by  the 
administration  of  starchy  foods,  since  the  liver  can  store  up  the  excess  of 
glucose  as  fast  as  it  is  produced  from  the  starch  by  digestion  and  absorbed 
into  the  blood  stream. 

(2)  DIABETIC  PUNCTURE.  It  was  shown  by  Claude  Bernard  that 
puncture  of  the  floor  of  the  fourth  ventricle  in  rabbits  is  often  followed 


844  PHYSIOLOGY 

immediately  by  an  excessive  secretion  of  urine  and  the  appearance  of  sugar 
in  this  fluid.  The  glycosuria  may  last  from  twenty-four  to  thirty  hours. 
If  at  the  end  of  this  time  the  animal  be  killed,  the  liver  is  found  to  be  free 
from  glycogen .  A  sample  of  blood  taken  during  the  height  of  glycosuria  may 
contain  from  3  to  4  parts  of  sugar  per  1000.  In  order  that  the  experiment 
may  succeed  it  is  important  that  the  animal  be 'previously  well  fed.  If  the 
puncture  or  '  piqfire  '  be  carried  out  on  an  animal  that  has  been  starved  or 
whose  liver  has  been  freed  by  any  means  from  glycogen,  no  glycosuria 
is  produced.  It  is  evident  that  the  effect  of  the  pvmcture  has  been  to  cause 
a  rapid  conversion  of  the  glycogen  previously  stored  up  in  the  liver  into 
glucose.  The  glucose  so  formed  escapes  into  the  blood,  raising  the  sugar 
content  of  this  fluid  above  the  normal,  and  the  excess  is  immediately  excreted 
by  the  kidneys  together  with  an  increased  amount  of  water.  A  similar 
temporary  hyperglycaemia  and  glycosuria  may  be  brought  about  by  fright, 
struggling  or  the  administration  of  anaesthetics;  but  the  effect  is  absent, 
if  both  splanchnic  nerves  have  been  previously  divided  above  the  supra- 
renals.  It  has  been  shown  (Elliott,  Cannon)  that  all  these  conditions  are 
associated  with  an  increased  discharge  of  adrenaline  from  the  medulla  of 
the  suprarenals  into  the  circulation.  Since  the  injection  of  adrenaline  itself 
causes  a  condition  of  diabetes  similar  in  all  its  limitations  and  aspects  to 
'  puncture  diabetes,'  it  is  now  generally  believed  that  the  two  conditions  are 
identical,  and  that  the  diabetic  puncture  acts  through  the  splanchnic  nerves 
on  the  suprarenals,  setting  free  adrenaline,  which  passing  to  the  liver  causes 
a  rapid  '  mobilisation  '  of  the  stored-up  glycogen,  and  a  consequent  hyper- 
glycsemia  and  glycosuria,  lasting  as  long  as  the  glycogen  store  holds  out. 

(3)  PHLORIDZIN  DIABETES.  Phloridzin  is  a  glucoside  extracted  from 
the  root  cortex  of  the  apple-tree.  It  may  be  decomposed  into  a  sugar 
and  phloretin.  When  phloridzin  or  phloretin  is  administered  by  the  mouth 
or  subcutaneously,  it  gives  rise  to  glycosuria,  unaccompanied,  at  first  at  any 
rate,  by  any  other  symptom.  The  urine  may  contain  from  5  to  15  per  cent, 
of  glucose.  The  glycosuria  induced  in  this  way  differs  from  the  forms 
already  described  in  the  fact  that  it  is  not  due  to  hyperglycsemia.  Analysis 
of  the  blood  shows  that  the  sugar  is  slightly  diminished  rather  than  increased. 
The  excretion  of  glucose  seems  to  be  due  to  a  specific  effect  of  the  drug 
upon  the  kidneys.  If  cannulas  be  placed  in  the  two  ureters  so  as  to  collect 
the  urine  from  each  kidney  separately,  and  a  small  dose  of  phloridzin  be 
then  injected  by  a  hypodermic  syringe  into  the  left  renal  artery,  the  urine 
flowing  from  the  left  ureter  will  in  two  minutes  be  found  to  contain  sugar, 
while  the  urine  from  the  right  kidney  will  not  contain  any  sugar  for  another 
five-  or  ten  minutes.  The  effect  therefore  is  rapidly  to  drain  off  sugar  from 
the  blood.  In  order  to  maintain  the  sugar  content  of  the  blood  at  its  normal 
height,  the  liver  must  manufacture  fresh  sugar  to  take  the  place  of 
that  lost  by  the  kidneys.  In  the  first  instance  the  liver  will  utilise  its 
stored-up  glycogen  for  this  purpose.  If  a  dose  of  phloridzin  be  given  to 
each  of  two  animals  and  one  animal  killed  as  soon  as  the  excretion  of  sugar 
is  coming  to_an  end,  the  liver  will  be  found  free  from  glycogen.    If  now  a 


THE  METABOLISM  OF  CARBOHYDRATES 


845 


second  dose  of  pliloridzin  be  given  to  the  other,  which  may  be  regarded  as 
free  from  glycogen,  glycosuria  is  produced  as  before,  and  the  excretion  of 
sugar  can  be  continued  indefinitely  by  repeated  administration  of  the  drug. 
So  long  as  sufficient  food  is  given,  including  carbohydrates,  the  loss  of  sugar 
does  not  entail  any  increase  in  the  destruction  of  the  tissues ;  but  if  the  drug 
be  administered  to  starving  animals  the  waste  of  sugar  has  to  be  made  good 
at  the  expense  of  material  other  than  carbohydrate.  The  source  of  the 
sugar  excreted  under  these  circumstances  is  the  protein  of  the  tissues.  The 
nitrogen  excreted  in  the  urine  rises  in  amount  in  proportion  to  the  quantity 
of  sugar  excreted,  and  there  is  a  constant  ratio  between  the  amount  of 
nitrogen  and  the  amount  of  sugar  excreted  in  the  urine.  In  different  experi- 
ments this  ratio  D  :  N  varies  from  2-8  : 1  to  3-6  :  1.  If  meat  be  administered 
to  such  starving  animals  with  glycosuria,  the  D  :  N  ratio  does  not  alter ;  the 
amount  of  nitrogen  in  the  urine  increases,  but  the  sugar  increases  in  the 
same  proportion.  The  sugar  production  is  therefore  proportional  to  the 
protein  metabolism  and  must  be  derived  from  protein.  The  source  of  the 
sugar  is  the  amino-acids  of  which  the  protein  is  composed.  It  has  been 
shown  by  Lusk,  Embden,  and  Dakin  that  the  following  amino-acids  yield 
large  amoimts  of  glucose  when  administered  to  a  phloridzinised  animal : 
glycine,  alanine,  serine,  cystine,  aspartic  acid,  glutamic  acid,  ornithine, 
proline  and  arginine.  We  must  assume  that  these  amino-acids  produced 
in  digestion  or  by  the  autolysis  of  the  tissues  undergo  deamination  and  that 
the  sugar  is  formed  by  a  process  of  synthesis  from  the  oxyacids  thereby 
produced.  On  the  other  hand  leucine,  tyrosine  and  phenylalanine  give  no 
increase  in  the  output  of  sugar.  It  is  however  just  these  amino-acids  which 
seem  to  follow  the  fine  of  fat  metabolism,  since  they  are  converted  into 
aceto-acetic  acid  when  perfused  through  a  dog's  hver;  and  the  adminis- 
tration of  fats  to  phloridzinised  dogs  is  also  without  effect  on  the  sugar 
excretion.  The  drain  of  sugar  from  the  organism  determined  by  the  action 
of  phloridzin  on  the  kidneys  thus  necessitates  a  continued  breakdown  of  the 
nitrogenous  tissues  of  the  body  in  the  effort  to  maintain  a  normal  supply  of 
sugar  to  the  tissues,  and  unless  excessive  feeding  be  employed  the  animal 
must  waste.  The  great  increase  in  the  nitrogenous  output  resulting  from  the 
condition  of  phloridzin  diabetes  is  shown  in  the  following  table  (Lusk) : 


Goat 

Uoa 

D 

N 

D:N 

n 

63-55 
65-30 
65-84 
64-60 

N        i     D  :  N 

Fasting 

Fasting 

Fasting  and  diabetic 

Fasting  and  diabetic 

Fasting  and  diabetic 

Fasting  and  diabetic 

20-33 
26-08 
23-39 
19-01 

3-72 
3-71 
4-90 
8-83 
8-06 
6-84 

4-15 
2-95 
2-90 

2-78 

4-04    ,       — 
4-17    ;      — 
12-66        .vui;  i 
18-76        3-38 
18-57        3-54 
17-29        3-71 

1  The  high   D:N  ratio  on  the  first  day  is  evidently  due  to  the  conversion  of 
the  glycogen  still  present  in  the  body. 


846  PHYSIOLOGY 

The  constant  drain  of  sugai  will  in  time  involve  a  relative  carbohydrate 
starvation  of  the  tissues,  which  will  make  good  their  energy  requirements  as 
much  as  possible  at  the  expense  of  protein  and  fat.  The  administration  of 
meat  will  diminish  the  fat  metabolism  to  a  certain  extent,  but  since  it  does 
not  alter  the  D  :  N  ratio,  it  would  appear  that  the  latter  does  not  depend  in 
any  way  on  the  quantity  of  fat  undergoing  oxidation.  This  is  shown  in  the 
following  respiration  experiment  (Mandel  and  Lusk)  on  a  dog  with  phloridzin 
glycosuria,  in  which  the  metabolism  during  starvation  and  after  ingestion  of 
meat  was  determined : 


jj  .  N            1     Calories  from 
protein 

Calories  from     1         Calories 
fat                         total 

Fasting    .         .          .               3-69                    80-2                  274H                  354-6 
300  grm.  meat           .     !          3-55                  161-9                  261-7                   123-6 

The  enormous  waste  of  energy  involved  in  such  a  constant  loss  of  sugar 
will  be  apparent  if  we  consider  that  a  D  :  N  ration  of  3-65  means  that  52-5 
per  cent,  of  the  energy  in  the  protein  taken  as  food  or  set  free  from  the  tissues 
is  lost  to  the  organism  in  the  form  of  glucose.  According  to  Rubner  28-5  of 
the  energy  of  meat  protein  is  not  utilised  in  the  body,  but  is  liberated  simply 
as  heat  (specific  dynamic  action).  If  we  accept  this  view  and  add  this 
28-5  per  cent,  lost  as  heat  to  the  52-5  per  cent,  lost  as  sugar,  there  would 
remain  a  balance  of  only  19  per  cent,  actually  available  for  the  vital  activities 
of  the  tissues.  It  is  not  to  be  wondered  at  that  the  nitrogenous  metabolism 
may  be  increased  three-  to  five-fold  as  a  result  of  the  artificial  induction  of 
the  diabetic  condition. 

The  carbohydrate  starvation  has  other  deleterious  effects,  since  we  have 
evidence  that  a  certain  amount  of  carbohydrate  food  is  a  necessary  con- 
dition for  both  fat  and  protein  metabolism.  The  necessity  of  carbohydrate 
for  the  assimilation  of  protein  is  brought  out  in  an  experiment  by  Cathcart. 
It  has  long  been  known  that  carbohydrate  administration  has  a  sparing 
effect  on  protein  metabolism.  If  an  animal  or  man  be  starved,  the  nitro- 
genous output  sinks  to  a  certain  level  and  there  remains  practically  stationary. 
If  now  pure  carbohydrate  food  be  administered  sufficient  to  meet  the  energy 
requirements  of  the  animal  or  man  (about  35  Calories  per  kilo),  there  is  at 
once  a  rapid  drop  in  the  output  of  nitrogen  and  therefore  in  the  protein 
waste  of  the  tissues.  Fat  has  a  much  slighter  or  no  sparing  effect  on  the 
nitrogenous  metabolism.  Indeed  in  certain  experiments  by  Cathcart  the 
administration  of  fat  caused  an  actual  rise  in  the  nitrogenous  output. 

The  importance  of  carbohydrates  is  borne  out  by  the  results  of  feeding  animals 
with  proteins  which  have  been  digested  with  pancreatic  juice  until  the  biuret  reaction 
has  disappeared.  After  Loewi  had  shown  that  it  was  possible  to  maintain  nitrogenous 
equilrbriuru  in  dogs  witli  such  a  digest,  Lesser  was  unable  to  confirm  his  results. 
But  it  has  been  pointed  out  that  the  essential  difference  between  the  two  observers 
«;is  that  Loewi  gave  an  abundant  supply  of  carbohydrates  with  the  digest,  while  Lesser 
omitted  carbohydrates  altogether  and  administered  fats  and  protein  digest  alone. 


THE  METABOLISM  OF  CARBOHYDRATES  817 

The  evidence  that  the  carbohydrates  play  a  necessary  part  in  the  meta- 
bolic history  of  fats  has  already  been  mentioned  (v.  p.  836).  We  have  seen 
that  in  the  absence  of  carbohydrates  the  last  stages  in  the  oxidation  of  fats 
make  default,  so  that  the  partially  oxidised  fatty  acids,  oxybutyric  acid  and 
aceto-acetic  acid,  accumulate  in  large  quantities  and  are  excreted  as  such  or 
as  acetone  in  the  urine.  Not  only  does  this  involve  a  loss  of  energy  to  the 
body,  but  these  organic  acids  require  other  bases  for  their  neutralisation. 
Up  to  a  certain  point  they  will  be  excreted  in  the  urine  in  combination  with 
the  fixed  alkalies.  When  these  are  no  longer  present  in  sufficient  quantity, 
the  acids  will  be  excreted  in  combination  with  ammonia,  so  that  the  ammonia 
of  the  urine  is  largely  increased.  If  the  condition  of  carbohydrate  starvation 
be  continued,  this  mechanism  of  neutralisation  is  insufficient  and  the  pheno- 
mena of  acidosis  dyspnoea  and  coma  ensue,  resulting  in  the  death  of  the 
animal. 

Another  effect  of  continued  administration  of  phloridzin  is  fat  infiltration 
of  the  liver.  This  is  merely  a  result  of  the  carbohydrate  starvation.  A 
similar  condition  of  fat  infiltration  can  be  brought  about  by  feeding  with 
pure  protein  plies  fat.  The  liver  seems  to  be  able  to  act  as  a  storehouse 
either  of  fat  or  of  carbohydrate,  so  that  there  is  an  inverse  ratio  between 
the  amount  of  glycogen  and  the  amount  of  fat  stored  up  in  the  liver  at 
any  given  time.  It  has  been  shown  that  the  fat  in  the  liver  under  these 
circumstances  is  simply  fat  which  has  been  transferred  to  this  organ  from 
the  ordinary  fat  depots,  subcutaneous  tissues,  etc.,  of  the  body. 

(4)  PANCREATIC  DIABETES.  Von  Mering  and  Minkowski  found  that 
total  excision  of  the  pancreas  gives  rise  to  a  severe  and  rapidly  fatal  diabetes, 
which  presents  many  similarities  to  the  severer  cases  of  diabetes  in  man. 
Owing  to  the  fact  that  the  tissues  of  a  diabetic  are  extremely  prone  to  in- 
fection, it  is  often  difficult  after  total  excision  of  the  pancreas,  when  diabetes 
has  been  set  up,  to  procure  healing  of  the  wounds  without  suppuration. 
The  operation  is  therefore  usually  carried  out  in  two  stages.  In  the  first 
stage  one  small  portion  of  the  tail  of  the  pancreas  is  transplanted  under  the 
skin  of  the  abdomen,  while  the  rest  of  the  gland  is  excised.  Such  animals 
do  not  get  diabetes  and  therefore  recover  quickly  from  the  operation.  When 
the  wounds  are  quite  healed  the  transplanted  portion  is  removed  through  a 
simple  skin  incision.  The  second  operation  is  followed  in  a  few  hours  by  the 
appearance  of  a  large  amount  of  sugar,  5  to  10  per  cent.,  in  the  urine.  The 
glycosuria  persists,  the  animal  rapidly  wastes,  and  finally  dies  at  the  end 
of  two  or  three  weeks  from  diabetic  coma.  From  the  nature  of  the  operation 
it  is  evident  that  the  condition  of  diabetes  observed  under  these  circumstances 
has  nothing  to  do  with  the  presence  or  absence  of  the  pancreatic  secretion 
from  the  intestine,  since  this  secretion  is  cut  off  at  the  first  operation,  and 
diabetes  does  not  make  its  appearance  until  the  second  small  portion  of  the 
gland  is  removed.  Moreover  ligature  of  the  ducts  of  the  pancreas  or  obstruc- 
tion of  the  ducts  by  the  injection  of  melted  paraffin  does  not  give  rise  to 
diabetes.  The  excretion  of  sugar  by  the  kidneys  is  due  to  an  increase  in  the 
BUgar  content  of  the  blood.     The  blood-sugar  may  amount  to  between  4  and 


848  lMIYSIOLOGY 

5  parts  per  1000.  This  state  of  hyperglycemia  and  the  excretion  of  sugar 
in  the  urine  persist  even  when  the  animal  is  completely  starved  oris  fed  on  a 
pure  protein  or  protein  plus  fat  diet.  Moreover,  as  in  phloridzin  glycosuria, 
we  find  a  constant  ratio  between  the  sugar  and  the  urinary  nitrogen,  the  D  :  N 
ratio  being  usually  about  2-8.  The  administration  of  protein  food  to  an 
animal  previously  starved  increases  the  output  of  nitrogen,  but  increases 
at  the  same  time  the  output  of  glucose.  No  similar  increase  in  the  glucose 
excretion  is  observed  as  a  result  of  the  administration  of  fat.  We  must 
conclude  therefore  that,  in  the  absence  of  carbohydrate  from  the  diet,  the 
excess  of  sugar  in  the  blood  as  well  as  that  escaping  by  the  urine  is  derived 
from  the  breakdown  of  the  proteins  of  the  tissues.  On  the  other  hand,  the 
power  of  the  animal  to  assimilate  or  utilise  carbohydrate  is  diminished  and 
sometimes  entirely  abolished,  so  that  glucose  administered  to  a  starving 
animal  with  pancreatic  diabetes  may  appear  quantitatively  in  the  urine. 
The  amount  absorbed  by  the  alimentary  canal  is  simply  added  to  the  amount 
which  would  have  been  excreted  if  no  food  had  been  given.  In  most  cases, 
at  any  rate  during  the  first  week  after  total  extirpation,  there  is  apparently 
still  some  power  of  carbohydrate  assimilation,  since  administration  of 
glucose  causes  a  transitory  rise  in  the  respiratory  quotient  (Moorhouse). 
Glycogen  disappears  entirely  from  the  liver;  but  the  muscles,  especially 
the  heart,  may  contain  a  normal  or  an  increased  amount  of  glycogen.  There 
is  a  rapid  wasting  of  all  the  tissues  of  the  body,  including  the  fats  and  pro- 
teins, and  finally  the  animal  is  destroyed  by  the  accumulation  of  the  products 
of  imperfect  oxidation  of  the  fatty  acids. 

It  is  still  very  difficult  to  say  definitely  why  removal  of  the  pancreas 
brings  about  this  condition  or  what  disturbance  of  metabolism  is  primarily 
responsible  for  it.  Two  views  have  been  put  forward.  According  to  one, 
the  primary  disturbance  is  the  diminished  or  absent  power  of  utilisation 
of  sugar  by  the  tissues;  according  to  the  second,  an  increased  production 
of  sugar  by  the  liver.  There  is  no  doubt  that  in  the  diabetic  animal  the 
power  of  utilising  carbohydrates  is  deficient.-  This  is  shown  by  the  low 
respiratory  quotient  and  by  the  fact  that  administration  of  glucose  to 
the  animal  causes  an  almost  corresponding  increase  in  the  amount  of 
glucose  excreted  in  the  urine.  But  the  loss  of  power  of  utilisation  is  not 
absolute,  at  any  rate  in  the  first  week  of  the  disorder.  Administration  of 
glucose  causes  a  slight  and  temporary  rise  in  the  respiratory  quotient, 
and  if  20  gins,  of  glucose  be  administered,  it  is  often  possible  to  recover 
only  about  15  to  18  grns.  from  the  urine.  Moreover  the  increased  amount 
of  glycogen  in  the  heart  muscle  of  diabetic  dogs  points  to  a  persistent  power 
of  assimilation  of  sugar  by  this  organ.  The  heart  from  a  diabetic  animal, 
if  fed  with  its  own  blood,  can  be  shown  to  use  up  not  only  the  sugar  circu- 
lating in  the  blood  but  also  its  store  of  glycogen,  and  this  utilisation  is 
especially  marked  if  the  heart  be  made  to  work  excessively  by  raising  the 
arterial  resistance  and  administering  adrenaline;  but  taken  as  a  whole  the 
power  of  utilising  glucose  is  very  inferior  to  that  possessed  by  normal 
animals.     One  of  the  most  striking  features  of  the  condition  caused  by  total 


THE  METABOLISM  OF  CARBOHYDRATES  819 

extirpation  of  the  pancreas  is  the  rapid  diminution  of  the  fat  depots  of  the 
body,  attended  by  a  marked  condition  of  lipaemia  and  accumulation  of  fat 
in  the  liver.  The  blood  is  so  full  of  fat  globules  that  it  ha3  been  compared 
in  appearance  to  strawberries  and  cream.  One  of  the  first  effects  of  extir- 
pation of  the  pancreas  is  therefore  a  rapid  fat  mobilisation,  and  the  respiratory 
quotient  agrees  with  that  obtained  when  the  metabolic  needs  of  the  body 
are  being  mainly  satisfied  at  the  expense  of  the  fat.  The  sugar  of  the  urine, 
after  the  depletion  of  the  glycogen  store  of  the  liver,  is  derived  from  the 
protein,  and  the  protein  tissues  of  the  body  therefore  diminish  as  rapidly 
as  the  fat  stores.  On  the  theory  of  deficient  utilisation,  it  is  thought  that 
th.'-.'  tissues  suffer  from  carbohydrate  starvation,  even  though  they  are 
bathed  in  a  medium  containing  an  increased  amount  of  sugar,  and  that 
the  liver  hi  response  to  some  call  from  the  tissues  turns  first  its  glycogen 
and  later  on  the  proteins  of  the  body  into  sugar  to  supply  this  lack — all 
to  no  purpose  however  since  the  tissues  are  unable  to  avail  themselves  of 
the  sugar  or  ferment. 

According  to  the  second  view,  the  primary  disorder  affects  only  the 
liver.  This  organ  is  freed  from  some  restraining  influence  on  its  power  of 
manufacturing  sugar  from  glycogen  and  from  protein,  so  that  the  blood  is 
flooded  with  sugar,  which  is  therefore  excreted  in  the  urine.  Any  deficient 
utilisation  of  the  sugar  would  be  regarded  as  secondary  to  a  poisoning  of 
the  tissues  by  this  overloading  of  their  nutrient  fluids  with  sugar.  It  is 
certain  that  the  sugar  production  in  diabetes  is  excessive,  as  is  shown  by 
the  rapid  wasting  of  the  protein  tissues  to  give  rise  to  the  sugar;  and  that 
this  over-production  takes  place  in  the  liver  is  proved  by  the  fact  that 
extirpation  of  this  organ  in  the  diabetic  animal  causes  a  rapid  disappear- 
ance of  the  sugar  from  the  blood. 

According  to  the  Vienna  school  (Rudinger,  Falta,  and  others),  a  close 
interaction  exists  between  the  thyroid,  the  suprarenals,  the  pancreas,  and 
the  liver;  the  thyroid  to  a  slight  extent,  the  pancreas  still  more,  inhibiting 
the  glycogenic  tunctions  of  the  liver,  while  the  suprarenals  through  their 
tion  of  adrenalin  stimulate  this  function.  Glycaemia  and  glycosuria 
d  by  extirpation  of  the  pancreas  would  therefore  be  ascribed  to  an 
unchecked  activity  of  the  suprarenals.  An  important  difference  however 
to  exist  between  the  two  conditions.  Adrenalin  glycosuria  comes 
to  an  end  when  the  glycogen  store  of  the  liver  is  exhausted,  whereas  pan- 
creatic diabetes  continues  until  the  death  of  the  animal,  long  after  all  traces 
of  glycogen  have  disappeared  from  the  liver.  We  do  not  yet  know  how  the 
pancreas  affects  sugar  production  or  utilisation  in  the  normal  animal.  It 
is  generally  assumed  that  it  secretes  into  the  blood  stream  a  hormone  which 
may,  according  to  the  view  of  the  nature  of  diabetes  which  we  adopt,  pass 
to  the  tissues  and  enable  them  to  utilise  sugar,  or  pass  to  the  liver  and  inhibit 
the  sugar  production  in  this  organ.  A  very  small  portion  of  the  pancreas 
is  sufficient  for  this  purpose,  but  we  have  been  unable  to  imitate  the  action 
of  t  he  pancreas  still  in  vascular  connection  with  the  body  by  injection  or 
administration  of  extracts  cf  this  organ.  Even  connection  of  a  healthy 
54 


850  PHYSIOLOGY 

animal  with  a  diabetic  animal  by  means  of  its  blood  vessels,  so  as  to  allow 
the  healthy  blood,  presumably  provided  with  the  products  of  .secretion  of 
the  pancreas,  to  circulate  through  the  diabetic  animal,  does  not  abolish 
the  condition  of  hyperglyceemia  in  the  latter,  though  connection  of  the 
portal  vein  of  the  healthy  animal  with  that  of  the  diabetic  animal  has, 
according  to  Hedon,  had  the  effect  of  stopping  the  condition  of  glycosuria. 
Further  work  is  required  on  this  point. 

We  thus  see  that  the  pancreas  has  a  two-fold  function,  namely,  the 
secretion  of  a  digestive  juice  into  the  intestine  and  the  exercise  by  some 


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®      §■ 
.-•'/.'' 


Fig.  367.  (A)  and  (B)  show  an  islet  with  the  surrounding  tissue  in  a  resting  gland  (A) 
and  after  exhaustion  with  .secretin  (B).  In  (A)  the  secreting  acini  are  charged  with 
zymogen  granules.  In  (B)  these  have  entirely  disappeared.  On  the  other  hand  no 
change  is  noticeable  in  the  cells  of  the  islet.  In  the  latter  the  granular  cells  are 
the  b  cells,  and  the  clear  hyaline  cells  are  the  a  cells,  (m)  showing  what  aro  called 
Minkowski  granules.  Tho  granulation  of  this  cell  is  regarded  by  Bensley  as  due  to 
postmortem  changes. 

means  or  other  of  an  influence  on  general  metabolism,  the  absence  of  which 
is  followed  by  the  supervention  of  diabetes.  Corresponding  with  this 
two-fold  function,  two  kinds  of  structures  are  present  in  the  gland,  the 
secreting  acini  and  the  islets  of  Langerhans.  These  latter,  though  arising 
in  connection  with  the  ducts,  are  solid  masses  of  cells  and  have  no  com- 
munication with  the  lumen  of  the  ducts.  According  to  Bensley  and  Lane 
the  islet  cells  may  be  divided  into  two  varieties  which  have  been  given  the 
name  of  A  and  B  cells,  according  as  their  granules  are  fixed  respectively 
by  alcoholic  or  watery  solutions.  It  has  been  shown  both  by  Bensley  and 
by  Homans  that  these  cells  undergo  no  alterations  when  the  gland  is  excited 
to  secrete  by  the  injection  of  secretin.  On  the  other  hand,  if  four-fifths 
of  the  pancreas  be  removed,  the  remaining  part  may  gradually  become 
inadequate  to  prevent  diabetes,  and  Homans  has  shown  that  when  under 
these  circumstances  diabetes  supervenes,  the  granules  disappear  from  the 


THE  METABOLISM  OF  CARBOHYDRATES  851 

B  cells.  Changes  have  also  been  found  in  the  islets  of  Langerhans  in  fatal 
cases  of  diabetes  in  man.  It  seems  therefore  probable  that  what  we  may 
term,  for  lack  of  a  better  word,  the  antidiabetic  functions  of  the  pancreas, 
are  associated  with  and  dependent  on  the  integrity  of  the  islets  of  Langerhans. 
(5)  DIABETES  IN  MAN.  In  its  severer  forms  the  diabetes  of  man 
resembles  very  closely  that  produced  in  the  dog  by  total  extirpation  of 
the  pancreas.  The  output  of  urine  is  largely  increased  and  the  frequency 
of  micturition  is  often  the  first  symptom  noticed.  On  examination  the 
urine,  though  light  in  colour,  is  of  a  high  specific  gravity,  1030  to  1035, 
and  may  contain  from  5  to  10  per  cent,  of  sugar.  The  appetite  is  largely 
increased,  but  in  spite  of  the  large  amount  of  food  taken  the  body  wastes. 
The  excessive  quantity  of  fluid  lost  by  the  body  gives  rise  to  a  constant 
thirst.  The  patient  may  die  after  some  months  or  years  in  a  condition 
of  diabetic  coma.  Warning  of  the  onset  of  this  condition  is  given  by  the 
rise  of  ammonia  in  the  urine  and  by  the  appearance  of  oxybutyric  and 
diacetic  acids.  The  breath  may  smell  of  acetone,  and  this  substance  may 
also  be  present  in  the  urine.  On  the  other  hand,  the  diabetic  state  is 
attended  by  diminished  resistance  of  the  tissues  to  infection.  A  pimple 
nun-  become  a  carbuncle ;  a  slight  sore  on  the  foot  may  give  rise  to  a  rapidly 
spreading  gangrene  of  the  lower  extremity;  tubercular  infection  of  the 
lungs  spreads  rapidly  to  the  whole  organ  so  as  to  stimulate  pneumonia. 
The  patient  may  thus  die  of  some  such  intercurrent  infection  before  the 
onset  of  coma.  In  a  few  cases  the  pancreas  is  found  to  be  atrophied  or 
diseased,  but  in  the  large  majority  no  marked  pathological  change  is  to  be 
observed  in  this  organ.  Yet  the  condition  is  essentially  similar  to  that 
which  occurs  in  pancreatic  diabetes.  The  radical  defect  is  the  inability, 
relative  or  complete,  of  the  organism  to  assimilate  carbohydrate.  We 
may  find  all  grades  between  such  cases  and  those  in  which  there  is  still  a 
considerable  power  of  assimilation.  In  order  to  determine  the  grade  of  the 
disorder,  it  is  usual  to  give  a  test  diet  with  a  certain  proportion  of  carbo- 
hydrate, e.g.  100  grro.  of  bread  with  meat,  bacon,  eggs,  butter,  green 
vegetables,  cheese,  lettuce,  coffee  and  wine.  If  the  urine  remains  free 
from  sugar  on  this  diet,  the  diabetes  is  mild  in  character.  More  bread 
may  then  be  added  to  the  diet  from  time  to  time  until  sugar  appears  in 
the  urine  and  the  limit  of  tolerance  for  carbohydrate  has  been  reached. 
In  many  cases  the  sugar  will  disappear  from  the  urine  on  the  administration 
of,  a  diet  consisting  entirely  of  proteins  and  fats.  When  this  has  been 
effected,  carbohydrates  may  be  added  in  small  proportions  to  the  diet  until 
the  limit  is  found  at  which  the  assimilatory  powers  of  the  patient  are  reached. 
It  seems  that  administration  of  any  carbohydrate  in  excess  of  this  limit  is 
of  disadvantage  to  the  patient  and  hastens  the  progress  of  his  disorder. 
When  the  power  of  assimilating  carbohydrates  is  entirely  abolished,  the 
prognosis  is  almost  absolutely  fatal.  This  point  may  be  determined  in 
two  ways.  In  the  first  place,  a  patient  with  no  power  of  carbohydrate 
assimilation  will  continue  to  excrete  sugar  in  the  urine  on  a  pure  protein- 
fat  diet,  and  the  D  :  N  ratio  will  be  2-8  or  higher.     Information  may  also 


/ 


852  PHYSIOLOGY 

I btained  from  a  study  of  his  respiratory  quotient.    The  production  oi 

dextrose  from  protein  involves  the  absorption  of  oxygen.  Oxygen  will 
therefore  be  taken  in  which  will  not  reappear  as  carbon  dioxide  in  the 
expired  air.  In  severe  cases  of  diabetes  bherefore,  tin",  respiratory  quotient 
will  fall  below  that  representing  fat  metabolism,  i.  e.  below  0-7.  In  most 
cases  of  diabetes,  where  there  is  still  some  power  of  assimilating  carbo- 
hydrate and  of  storing  up  glycogen,  the  respiratory  quotient  will  be  found 
approximately  normal.  A  very  low  respiratory  quotient  is  a  sign  of  the 
severity  of  the  disorder. 

This  study  of  the  conditions  of  carbohydrate  metabolism  shows  how  all 
three  classes  of  foodstuffs  co-operate  in  the  maintenance  of  the  chemical 
processes  which  he  at  the  root  of  the  existence  and  the  activities  of  living 
organisms.  We  see  how  fallacious  were  the  ideas  that  the  proteins  alum: 
were  necessary  for  life  and  that  protoplasm  was  simply  living  protein. 
Protoplasm,  i.  e.  the  material  substrate  of  life,  must  be  regarded  as  a  complex 
in  which  proteins,  fats,  carbohydrates,  nucleins,  salts,  and  water  all  play 
a  part  and  of  which  each  is  an  essential  constituent.  In  the  higher  animals 
proteins  are  necessary  to  furnish  the  proteins  of  the  tissues,  and  the  food 
must  contain  just  those  ammo-acids  which  are  requisite  for  the  building 
up  of  the  proteins  characteristic  of  each  separate  tissue.  Moreover  certain 
groups  of  the  protein  molecule  appear  to  be  destined  to  serve  as  mother- 
substances  of  hormones  and  other  chemical  compounds  which  play  a 
dynamic  rather  than  a  static  part  in  the  phenomena  of  life,  and  supply  con- 
ditions of  activity  rather  than  material  for  the  production  of  energy.  The 
carbohydrates  not  only  act  as  sources  of  energy,  but  are  necessary  to  the 
building  up  of  the  proteins  into  the  protoplasmic  complex.  Without 
them  moreover,  this  complex  caimot  properly  utilise  the  fat  contained  in 
itself  or  supphed  in  its  food.  On  the  other  hand,  the  carbohydrates  by 
themselves  are  not  available  as  food,  but  require  some  connecting  link, 
which  may  be  protein  or  nitrogenous  in  character,  to  enable  their  associa- 
tion with  the  active  part  of  the  protoplasm  and  their  utilisation  by  oxidation. 
At  the  same  time  there  is  a  certain  possibility  of  interconversion  between 
these  different  substances;  sugar  may  be  formed  from  proteins,  fats  from 
carbohydrates.  On  the  other  hand,  the  formation  of  fats  from  proteins  is 
apparently  impossible  in  the  cells  of  the  higher  animals,  and  the  evidence 
for  the  formation  of  sugar  from  fat  is  limited  to  the  study  of  the  respiratory 
quotient  in  hibernating  animals.  With  the  exception  of  a  few  cases  quoted 
by  Pfluger  and  von  Noorden,  no  support  for  such  a  conversion  is  obtained 
from  the  conditions  observed  in  the  glycosuria  caused  by  the  administration 
of  phloridzin  or  by  extirpation  of  the  pancreas. 


CHAPTER  XII 

THE    BLOOD 

In  the  unicellular  animals  and  in  the  lowest  metazoa,  the  cells  are  bathed 
by  the  medium  in  which  the  organisms  live,  and  are  therefore  exposed  to 
all  the  changes  in  the  composition  of  this  fluid  which  may  be  brought  about 
by  cosmic  events.  With  the  evolution  of  a  body  cavity  filled  with  fluid, 
the  tissue  cells  are  set  free  from  the  necessity  of  adapting  their  metabolism 
to  wide  ranges  of  chemical  composition,  being  bathed  by  an  internal  medium 
which  is  maintained  practically  constant  in  its  characters  for  any  given 
type.  With  increasing  differentiation  the  fluid  of  the  ccelorn,  which  may 
he  called  blood,  becomes  enclosed  in  branching  systems  of  tubes,  and  its 
circulation  is  provided  for  by  the  development  of  contractile  chambers  at 
some  point  or  points  of  the  tubes.  In  all  the  higher  animals,  the  blood, 
the  common  medium  and  means  of  exchange  for  all  parts  of  the  body, 
circulates  through  a  closed  system  of  tubes,  a  constant  flow  being  kept  up 
by  the  action  of  the  heart.  It  is  separated  from  the  tissue  elements  them- 
selves by  the  walls  of  the  blood  vessels.  The  free  interchange  of  material 
between  blood  and  tissues  is  facilitated  by  the  tenuity  of  the  vascular  wall. 
Tim-  interstices  of  the  tissues  contain  a  fluid,  the  'tissue  fluid,'  any  excess 
di'  which  is  drained  off  by  special  channels  known  as  lymphatics  and  carried 
hack  to  the  blood.  Interchange  between  the  blood  and  the  tissue  cells 
can  be  effected  partly  by  diffusion,  partly  by  a  direct  exudation  or  filtration 
of  the  fluid  parts  of  the  blood  with  certain  of  its  constituents  through  the 
capillary  walls.  Since  the  function  of  the  blood  is  to  act  as  the  common 
nutritive  medium  of  all  parts  of  the  body,  it  has  to  convey  food  materials 
In. in  (he  digestive  organs  and  oxygen  from  the  lungs  to  the  tissues.  From 
these  it  receives  in  exchange  their  waste  products,  namely,  carbon  dioxide 
and  the  results  of  nitrogenous  metabolism,  and  carries  them  away  to  the 
excretory  organs,  such  as  the  lungs  and  kidneys,  by  which  they  are  elimin- 
ated. It  is  evident  that  the  composition  of  the  blood  must  vary  from  time 
to  time  and  place  to  place  according  to  the  condition  of  activity  and  the. 
In i h.i ion  of  the  organ  which  it  is  traversing.  The  organs  of  the  body  arc 
adjusted  to  respond  to  very  minute  changes  in  the  composition  of  the  cir- 
culating fluid,  and  add  to  or  subtract  from  its  constituents  according  as 
these  arc  present  in  deficiency  or  excess.  The  changes  are  therefore  kepi, 
within   infinitesimal  limits;  in  most  cases  they  are  within  the  limits  of 

853 


854  PHYSIOLOGY 

errors  of  analysis,  and  we  may  therefore  treat  the  blood  as  a  fluid  of  approxi- 
mately constant  composition  and  qualities. 

Blood  obtained  from  a  mammal  is  an  opaque  fluid  varying  in  tint 
according  to  the  vessel  from  which  it  is  derived,  being  scarlet  when  taken 
from  an  arterj  purplish  in  colour  when  taken  from  a  vein,  the  difference 
1„  in-  determined  by  the  degree  of  oxygenation  of  the  blood.  On  shaking 
venous  blood  with  air,  it  takes  up  oxygen  and  acquires  the  scarlet  colour 
characteristic  of  arterial  blood.  If  examined  in  a  thin  layer  under  the 
microscope,  its  opacity  is  seen  to  be  due  to  the  fact  that  it  is  not  homo- 
geneous, but  consists  of  a  number  of 
corpuscles  of  different  kinds  sus- 
pended in  a  light  yellow  transparent 
fluid.  In  order  to  make  out  the 
characters  of  these  corpuscles  the 
blood  should  be  diluted  with  some 
fjjjSp         (<!!!)  '  normal '  fluid,  such  as  0-9  per  cent. 

^ga^  sodium  chloride.     It  is  then  seen  to 

tc|P  contain    two    classes    of    corpuscles. 

Fig.  368.    Non-nucleated  red  blood  discs     Much   the   most   numerous    are  the 
of  human  blood.    On  the  right  of  the     '  red    corpuscles.'      These    differ    in 

figure  the  corpuscles  are  seen  en  edge.  j.  ,,        11       i 

(Swale  Vincent.)  appearance    according   as   the    blood 

is  derived  from  a  mammal  or  from 
one  of  the  lower  orders  of  vertebrates.  In  all  the  latter  it  is  a  nucleated 
cell.  In  the  frog,  for  instance,  it  is  an  oval  bi-convex  disc  containing  an 
oval  nucleus  in  the  centre.  In  man  and  other  mammals  the  red  corpuscle 
is  a  bi-concave  circular  disc  (Fig.  368),  varying  in  size  in  different  species. 
The  average  sizes  of  the  corpuscles  in  man  are  given  in  the  following  Table  : 

Diameter 7-1  to  7-8  /t 

Thickness  (at  periphery)        .  .  .     2-5  fi 

Thickness  (at  centre)   .  .  .  .     1-0  to  2-0  ju. 

In  the  blood  of  man  there  is  an  average  of  five  million  red  blood  discs 
in  every  cubic  millimetre  of  blood. 

The  other  kind  of  formed  element,  the  white  corpuscle  or  leucocyte, 
is  present  in  much  smaller  numbers  than  the  red  corpuscle,  there  being  in 
human  blood  an  average  of  one  leucocyte  to  every  500  red  corpuscles.  These 
leucocytes  are  colourless  cells,  somewhat  larger  than  the  red  blood  discs  of 
man,  presenting  one  or  more  nuclei  and  a  granular  or  hyaline  protoplasm. 
When  examined  on  the  warm  stage  they  are  seen  to  be  amoeboid,  and  many 
of  them,  like  the  amoeba,  have  the  power  of  ingesting  granules  of  carmine, 
food,  or  dead  bacteria  with  which  they  may  come  in  contact. 

-  In  addition  to  these  two  classes,  a  third  body  is  generally  described 
unde?  the  name  of  '  blood  platelets  '  or  hsematoblasts.  These  are  especially 
well  seen  when  the  blood  has  been  received  directly  into  an  excess  of  osmic 
acid.  It  is  still  doubtful  whether  they  are  pre-existent  in  the  circulating 
blood  or  are  formed  in  the  plasma  by  a  process  of  precipitation. 


THE   BLOOD  855 

Unless  special  precautions  are  taken,  the  examination  of  blood  obtained 
from  a  blood  vessel  is  interfered  with  by  the  process  of  clotting,  which 
ensues  shortly  after  the  blood  has  left  the  vessels.  If  blood  be  received 
into  a  beaker  it  is  at  first  perfectly  fluid,  so  that  it  can  be  poured  from 
one  beaker  to  another.  After  a  space  of  time  varying  from  three  to  eight 
minutes  it  begins  to  be  viscous,  and  if  poured  out  of  the  beaker  leaves 
an  adherent  layer  on  the  sides  of  the  vessel.  A  minute  later  the  whole 
mass  of  the  blood  becomes  solid  and  the  beaker  can  be  inverted  without 
spilling  its  contents.  If  a  section  be  made  of  this  blood  clot,  it  is  found 
to  owe  its  solidity  to  a  network  of  fine  threads  of  a  protein  substance  named 


Fig.  3G9.  Network  of  fibrin,  after  washing  away  the  corpuscles  from  a  film  of 
blood  that  has  been  allowed  to  clot;  many  of  the  filaments  radiate  from  little 
clumps  of  blood  platelets.     (Schafer.) 

fibrin,  which  have  formed  throughout  the  plasma  and  enclosed  the  corpuscles 
in  their  meshes  (Fig.  369).  On  leaving  the  clot  for  some  hours,  drops  of 
yellow  fluid  appear  on  its  surface  and  run  together.  The  whole  clot  con- 
tracts, and  finally  there  is  a  reduced  clot  floating  or  suspended  in  a  yellowish 
fluid  known  as  serum.  If  after  the  blood  has  left  the  vessels  it  be  whipped 
with  a  bunch  of  twigs,  or  stirred  with  a  glass  rod,  the  filaments  of  fibrin  as 
they  are  formed  are  deposited  on  the  twigs.  After  three  or  four  minutes 
the  twigs  can  be  withdrawn  and  the  spongy  fibrin  collected.  The  blood 
which  is  left  consists  only  of  the  corpuscles  plus  serum,  and  will  not  clot, 
since  its  fibrin  has  been  removed.  It  is  known  as  defibrinated  blood.  Since 
the  corpuscles  are  apparently  unchanged  in  the  meshes  of  the  clot  and 
clotting  can  be  produced  in  blood  plasma  entirely  separated  from  corpuscles, 
we  must  look  upon  the  process  of  coagulation  as  determined  in  the  main 
by  changes  in  the  blood  plasma.  We  can  regard  the  blood  therefore  as  a 
tissue  consisting  of  a  fluid  matrix,  which  is  extremely  unstable  and  under- 
goes change  when  it  leaves  the  vessels,  and  as  having  embedded  in  its  matrix 
formed  elements  or  cells  of  various  kinds. 


SECTION  I 

THE   WHITE   BLOOD   CORPUSCLES 

Amckboid  cells  are  a  constant  constituent  of  the  ccelomic  fluid  in  all 
classes  of  animals.  Even  in  the  lower  metazoa,  where  there  is  not  yet  a 
body  cavity;  wandering  mesoderm  cells  are  present  which  apparently 
discharge  fractions  analogous  in  all  respects  to  those  of  the  white  blood- 
corpuscles  of  mammals.  On  carefully  examining  a  specimen  of  human 
blood,  either  fresh  or  in  the  form  of  a  thin  stained  film,  several  varieties 
of  these  cells  are  seen  to  be  present.  In  a  fresh  specimen  we  can  distinguish 
the  following  varieties  : 

(a)  A  cell  with  a  lobed  nucleus  and  finely  granular  protoplasm ; 


Fig.  370.     Various  forms  of  leucocytes. 

a,  eosinophils  corpuscle;  h,  ordinary  polynuclear  leucocyte  (' neutrophile ')  j 

c,  hyaline  corpuscle;  d,  lymphocyte. 

(b)  A  small  cell  consisting  almost  entirely  of  a  nucleus  surrounded  by 
:i  lli in  layer  of  protoplasm; 

(c)  A  cell  with  a  single  nucleus  and  clear  hyaline  protoplasm ; 

(d)  A  cell  with  a  lobed  or  reniform  nucleus,  the  cytoplasm  being  beset 
with  large  coarsely  refracting  granules. 

'rinse  four  types  are  known  as  the  finely  granular  or  polymorphonuclear 
cell,  the  lymphocyte,  the  hyaline  corpuscle,  and  the  coarsely  granular 
corpuscle. 

The  differentiation  of  the  various  types  of  leucocytes  is  more  easily 
made  if  recourse  be  had  to  staining  with  mixtures  of  aniline  dyes.  This 
method  was  introduced  by  Ehrlich,  who  classified  leucocytes  according  to 
1  fie  staining  characters  of  their  granules,  dividing  the  latter  into  : 

(a)  Those  staining  with  acid  dyes,  such  as  eosin — acidophile  or  eosino- 
phil granulation; 

(h)  Those  staining  with  basic  dyes — basophile; 
856 


THE  WHITE  BLOOD  CORPUSCLES       '  857 

(c)  Those  staining  only  with  a  mixture  of  the  acid  and  basic  dyes  and 
therefore  spoken  of  as  neutrophile. 

An  acid  dye  is  generally  a  salt  in  which  the  colouring  matter  plays  the  part  of  an 
acid  radical.  Thus  eosin  is  the  sodium  salt  of  the  coloured  acid  tetrabrom-fluorescein. 
Basic  dyes  possess  basic  colour  radicals.  An  example  of  this  class,  methylene  blue, 
is  the  chloride  of  the  coloured  base  tetramethyldiphenthiazine.  Neutral  dyes,  accord- 
ing to  Ehriich,  are  those  in  which  a  colour  base  is  combined  with  a  colour  acid,  such  as 
the  eosinate  of  methylene  blue,  or  the  pi  crate  of  rosaniline. 

In  preparations  stained  with  mixtures  of  these  dyes  we  may  distinguish 
the  following  types : 

(1)  The  polymorphonuclear  cells.  These  present  a  lobed  nucleus,  and 
their  protoplasm  contains  abundant  fine  neutrophile  granules.  They  form 
about  70  per  cent,  of  the  total  leucocytes.  If  the  specimen  be  overstained 
with  eosin,  the  granules  may  take  on  a  red  stain. 

(la)  A  few  cells  are  sometimes  seen  with  a  horseshoe  or  hour-glass 
nucleus  and  presenting  a  few  neutrophile  granules.  These  are  spoken  of 
as  transitional  cells,  and  have  been  supposed  to  represent  an  intermediate 
stage  between  large  mononuclear  or  hyaline  cells  and  the  polymorphonuclear 
leucocyte.    They  do  not  form  more  than  1  per  cent,  of  the  leucocytes. 

(2)  The  lymphocytes  are  small  cells  with  a  round  nucleus  surrounded 
by  a  thin  layer  of  hyaline  protoplasm  which  is  free  from  granules.  These 
form  23  per  cent,  of  the  leucocytes. 

(3)  Large  mononuclear  or  hyaline  corpuscles.  These  cells  are  two  or 
three,  times  the  size  of  a  red  corpuscle,  and  possess  a  large  oval  nucleus 
which  stains  feebly  with  basic  dyes.  In  normal  blood  not  more  than  2  per 
cent,  of  the  leucocytes  are  of  this  type. 

(4)  In  every  well-stained  blood  film  the  eosinophile  corpuscle  is  very 
evident,  although  forming  not  more  than  3  per  cent,  of  the  white  corpuscles. 
The  nucleus  is  generally  single,  but  is  often  crescent-shaped  or  reniform. 
The  protoplasm  is  crammed  with  large  discrete  highly  refractive  granules 
which  stain  deeply  with  eosin  and  give  micro-chemical  reactions  for  iron 
as  well  as  phosphorus.  The  granules,  which  in  man,  dog,  and  rabbit  are 
spherical,  are  cuboidal  in  the  horse,  and  in  birds  have  the  shape  of  short 
rods. 

(5)  A  cell  which  is  found  with  difficult}7,  but  is  apparently  a  normal 
constituent  of  human  blood,  is  the  basophile  leucocyte.  This,  which  is 
somewhat  smaller  than  the  polymorphonuclear  cell,  has  a  lobed  or  tri-lobed 
nucleus  and  presents  a  number  of  granules  in  its  protoplasm  which  stain 
deeply  with  basic  dyes.  It  is  sometimes  spoken  of  as  a  '  Mast '  cell,  the 
German  term  for  the  cell  being  used  without  translation.  It  does  not 
form  more  than  0-5  per  cent,  of  the  total  leucocytes  of  the  blood.  The 
granules  are  practically  invisible  in  fresh  specimens,  in  this  respect  pre- 
senting a  contrast  with  the  eosinophile  granules.  The  leucocytes  as  a 
whole  undergo  variations  in  number  according  to  the  physiological  state 
of  the  animal  and  are  increased  during  digestion,  specially  of  a  protein 


858  PHYSIOLOGY 

meal.     They  vary  from  one  in  300  to  one  in  600  red  corpuscles   or,  taken 
as  a  whole,  from  18,000  to  9000  per  cubic  millimetre  of  blood. 

FORMATION   OF   THE   LEUCOCYTES 

In  classifying  the  white  corpuscles  of  the  blood,  it  is  essential  to  know 
whether  the  different  varieties  we  have  described  represent  phases  in  one 
and  the  same  corpuscle  or  a  number  of  different  cells  of  separate  origin. 
The  question  as  to  the  specificity  of  each  kind  of  leucocyte  cannot  be 
regarded  as  settled.  According  to  some  observers,  Gulland  and  others,  all 
the  leucocytes  are  derived  from  one  kind  of  cell,  namely,  the  lymphocyte. 
Ehrlich  and  his  school,  on  the  other  hand,  regard  each  type  as  forming  a 
tissue  sui  generis,  originating  in  separate  localities  and  from  distinct  kinds  of 
cells.  Since  division  of  the  leucocytes  in  the  blood  itself  appears  to  be  an 
occurrence  of  the  utmost  rarity,  we  must  locate  the  original  seat  of  forma- 
tion of  these  cells  in  two  tissues.  Lymphocytes  are  derived  from  the  adenoid 
tissue  forming  the  lymphatic  glands  and  the  lymph  nodules  surrounding 
so  many  of  the  mucous  cavities.  These  lymphatic  nodules  present  towards 
their  centre  a  clearer  zone,  consisting  of  cells  rather  larger  than  those  of 
the  periphery  and  known  as  the  '  germ  centre.'  The  nuclei  in  these  cells 
present  a  well-marked  reticular  arrangement,  and  nuclear  figures  are  often 
to  be  seen.  By  the  division  of  these  cells  lymphocytes  are  formed,  pushing 
towards  the  periphery  of  the  nodule,  where  they  make  their  way  into  the 
lymph  sinus  and  are  carried  slowly  by  the  lymph  into  the  blood.  Some 
of  these  lymphocytes  may  possibly  pass  directly  through  the  capillary 
wall  into  the  blood  stream. 

The  other  tissue  concerned  in  the  formation  of  leucocytes  is  the  bone 
marrow.  This  is  the  chief  blood-forming  tissue  of  the  body,  since  it  is 
responsible  also  for  the  production  of  all  red  blood  corpuscles  which  are 
formed  during  adult  life.  Iu  the  red  marrow  are  seen  a  number  of  cells 
known  as  myelocytes.  These  contain  a  single  rounded  nucleus  and  a  well- 
marked  protoplasm  which  may  be  non-granular  or  may  contain  granules, 
generally  eosinophile  in  character  but  sometimes  basophile.  It  is  stated 
that  all  intermediate  stages  are  to  be  fouud  in  the  bone  marrow  between 
these  '  myelocytes '  and  the  polymorphonuclear  leucocyte  as  well  as  the 
eosinophile  leucocyte.  It  is  certain  that  in  the  disease  leukaemia,  which 
is  associated  with  an  increased  number  of  leucocytes  in  the  blood,  there 
may  be  an  increase  either  of  eosinophile  cells  or  of  neutrophile  cells,  and 
either  condition  is  associated  with  changes  in  the  red  bone  marrow.  We 
may  therefore  provisionally  arrange  the  leucocytes  of  the  blood  according 
to  their  origin  as  follows  : 

(1)  Small  lymphocyte  derived  from  lymphoid  tissue. 

(2)  Large  mononuclear  or  hyaline  corpuscle  :  doubtful  whether  derived 
by  a  growth  of  (1)  or  from  a  myelocyte. 

(3)  Polymorphonuclear  leucocyte  formed  in  bone  marrow. 

(4)  Eosinophile  cell  derived  from  similar  cells  in  the  bone  marrow. 
This  origin  of  the  eosinophile  corpuscle  is  rendered  more  probable  by  the 


THE  WHITE  BLOOD   CORPUSCLES  859 

fact  that  the  shape  of  the  granule,  which  differs  from  one  species  to  another, 
is  the  same  whether  the  cell  be  derived  from  the  blood  or  the  bone  marrow. 
The  intermediate  or  transitional  cell  may  be  derived  either  from  the 
lymphocyte  or  from  a  myelocyte.  Li  many  cases  of  leukaemia  the  myelocyte 
passes  into  the  blood  in  large  numbers  without  undergoing  the  changes 
necessary  to  convert  it  into  the  typical  blood  cell.  We  find  then  mono- 
nuclear cells  which  are  either  free  from  granules  or  contain  eosinophil  or 
basophile  granules. 

FUNCTIONS   OF  THE   LEUCOCYTES 

PHAGOCYTOSIS.  We  have  seen  that  the  leucocytes  from  whatever 
animal  they  be  taken  present  two  phenomena,  viz.  that  of  amoeboid  move-* 
ment  and  that  of  ingesting  foreign  particles  which  may  be  presented  to 
them.  On  account  of  this  power  of  eating  up  foreign  particles  they  are 
frequently  spoken  of  as  '  phagocytes,'  in  this  respect  resembling  unicellular 
organisms  and  the  undifferentiated  cells  of  many  kinds  of  tissue.  All  the 
phenomena  connected  with  the  process  of  inflammation  in  higher  animals 
are  directed  to  the  assemblage  of  leucocytes  at  the  spot  which  is  the  seat 
of  injury  or  of  infection,  so  that  they  may  devour  and  remove  either  the 
injured  tissue  or  the  invading  micro-organisms.  This  process  plays  therefore 
an  important  part  in  determining  the  immunity  of  any  animal  against 
infection ;  though  in  the  higher  animals  it  is  assisted  by  a  number  of  other 
mechanisms  directed  towards  the  same  end,  which  we  shall  have  to  discuss 
in  a  subsequent  chapter.  The  use  of  phagocytosis  is  not  however  confined 
to  the  protection  of  the  organism  against  infection.  Wherever  any  effete 
O]  dead  tissue  has  to  be  cleared  away,  whether  as  the  result  of  injury  or 
in  the  course  of  metamorphosis  of  organs,  the  leucocytes  play  an  important 
part.  Thus  in  the  great  rearrangement  of  tissues  which  occurs  in  the 
larval  state  of  insects,  the  removal  of  the  muscle  fibres  which  are  no  longer 
required  is  effected  by  the  accumulation  of  phagocytes  around  them.  The 
phagocytes  may  send  processes  into  the  muscle  substance,  which  dissolve 
this  tissue  and  then  eat  it  up.  The  absorption  of  the  tail  of  the  tadpole 
is  effected  in  the  same  way  by  means  of  phagocytes.  In  mammals,  including 
man.  the  moulding  of  the  long  bone  which  occurs  in  the  process  of  growth 
is  effected  by  continual  and  coincident  processes  of  absorption  and  new 
formation  of  bone.  The  absorption  is  carried  out  by  means  of  special 
phagocytes  formed  by  the  aggregation  of  a  number  of  leucocytes,  the 
well-known  'giant  cells'  or  niyeloplaxes  which  form  so  prominent  a 
constituent  of  bone  marrow. 

The  blood  corpuscles  represent  the  wandering  phagocytes  of  the  bod  v. 
There  axe  fixed  phagocytes,  of  which  the  niyeloplaxes  just  mentioned  nun- 
be  regarded  as  a  type.  Other  members  of  this  class  are  the  endothelial 
cells  (Kupfer's  '  Sternzellen  ')  which  line  the  capillaries  of  the  liver.  If  a 
suspension  of  carmine  or  of  micro-organisms  be  injected  into  the  blood 
stream,  these  endothelial  cells  are  found  a  little  later  to  have  taken  up 
large  numbers  of  the  foreign  bodies.     Under  normal  circumstances  these 


8G0  PHYSIOLOGY 

cells,  as  well  as  some  similar  cells  in  the  spleen,  take  up  effete  red  blood 
corpuscles  and  destroy  them.  During  the  process  of  degeneration  of  a 
peripheral  nerve  brought  about  by  its  separation  from  the  ganglion  cells 
of  which  its  fibres  are  the  processes,  a  marked  proliferation  of  the  nerve 
nuclei  occurs.  These  become  surrounded  with  protoplasm  and  act 
the  part  of  phagocytes,  loading  themselves  with  the  fat  globules  set  Iree 
by  the  degeneration  of  the  myelin  sheath.  To  the  same  class  of  fixed 
phagocytes  may  possibly  be  ascribed  certain  of  the  plasma  cells  of  the 
connective  tissues. 

That  the  polymorphonuclear  leucocytes  are  endowed  with  these 
phagocytic  properties  is  universally  acknowledged,  but  some  doubt  still 
exists  as  to  how  far  the  other  types  of  leucocytes,  which  we  have  described, 
can  function  as  phagocytes.  It  is  probable  that  the  lymphocytes,  and 
certainly  the  large  mononuclear  or  hyaline  corpuscles,  are  endowed  with 
these  properties.  The  granular  corpuscles,  namely,  eosinophile  and  baso- 
phil, are  thought  by  some  to  function  as  unicellular  glands  and  to  react 
to  infection,  not  by  englobing  the  micro-organisms,  but  by  discharging 
substances  stored  up  in  their  granules  which  have  a  poisonous  effect  on 
the  micro-organisms,  and  so  prepare  them  for  subsequent  ingestion  by  the 
polymorphonuclear  leucocytes. 

The  other  functions,  which  have  been  ascribed  to  leucocytes,  are  un- 
important as  compared  with  their  role  as  phagocytes,  and  are  all  of  them 
questionable.  Thus  some  authors  ascribe  to  leucocytes  a  significant 
part  in  the  taking  up  of  fat  from  the  intestine  and  its  carriage  into  the 
lymphatic  system.  In  the  coagulation  of  the  blood  the  leucocytes  have 
been  supposed  to  act  by  the  discharge  of  substances  which  may  be 
precursors  of  the  fibrin  ferment.  In  the  invertebrate  the  wandering 
mesoderm  cells  not  only  remove  the  injured  tissue  but  apparently  give 
rise  to  new  connective  tissues.  The  same  function  was  formerly  assigned 
to  the  leucocytes  of  mammals  by  Ziegler;  and  Metchnikoff  believed 
that,  after  the  removal  of  any  injured  tissue,  the  emigrated  leucocytes 
undergo  elongation  to  form  so-called  fibroblasts,  by  the  further  division 
of  which  are  produced  the  white  fibres  of  the  connective  tissues  as  well  as 
the  branched  connective-tissue  cells.  Most  authors  at  the  present  time 
have  come  to  the  conclusion  that  the  work  of  the  leucocytes  is  complete 
with  the  removal  of  dead  or  injured  tissue,  and  that  the  process  of  regenera- 
tion is  carried  out  by  the  plasma  cells  of  the  connective  tissue,  which  enlarge, 
undergo  division,  and  form  the  fibroblasts  of  the  developing  tissue.  These 
plasma  cells  can  change  their  position  and  act  as  phagocytes,  eating  up 
and  digesting  the  polymorphonuclear  leucocytes  which  have  prepared 
the  way  for  their  regenerative  activity.  Their  amoeboid  power  is  shown 
by  the  fact  that  if  two  sterile  cover  glasses  be  introduced  under  the  skin, 
new  connective  tissue  is  formed  between  the  cover  glasses ;  and  this  method 
has  been  adopted  by  Ziegler  for  the  study  of  the  cellular  changes  involved 
in  the  regeneration  of  this  tissue. 


SECTION  II 

THE    RED    BLOOD   CORPUSCLES 

The  red  blood  corpuscles,  or  erythrocytes,  in  man  and  other  mammals  arc 
nucleated  bi-concave  discs,  about  7  to  8^  (;^Vu  hi.)  hi  diameter  and  about 
one-third  of  this  in  thickness.  The  colour  of  a  single  corpuscle  when  viewed 
under  the  microscope  is  yellow,  the  red  colour  being  apparent  only  when 
larger  numbers  are  seen  together.  The  red  corpuscles  form  about  50  per 
cent,  of  the  total  mass  of  the  blood,  there  being  about  5,000,000  red  corpuscles 
in  even'  cubic  millimetre  of  blood.  They  are  soft,  flexible,  and  elastic,  so  that 
they  can  readily  squeeze  through  apertures  and  canals  narrower  than 
themselves  without  undergoing  permanent  distortion.  Each  red  corpuscle 
consists  of  a  framework  or  stroma,  composed  chiefly  of  protein  material, 
containing  in  its  meshes  or  in  a  state  of  loose  chemical  combination  a  red 
colouring  matter,  haemoglobin,  to  which  is  due  the  colour  of  the  corpuscles 
and  of  the  blood  itself. 

It  is  only  in  mammalia  that  the  red  corpuscles  are  of  the  character 
described.  In  the  camel  they  are  oval  in  shape,  but  otherwise  resemble  the 
corpuscles  of  other  mammals.  In  all  other  classes  of  vertebrata  the  red 
corpuscles  are  oval,  nucleated  cells.  The  haemoglobin  is  diffused  through  the 
protoplasm  of  the  cell  body  and  does  not  extend  to  the  nucleus.  During 
the  early  part  of  foetal  life  the  corpuscles  of  mammals  are  also  nucleated,  but 
in  the  adult  condition  the  erythrocytes,  except  under  abnormal  conditions, 
lose  all  traces  of  the  nucleus  before  entering  the  blood  stream.  The  small 
size  and  great  number  of  the  red  corpuscles  determine  that  a  very  large  area 
of  surface  of  red  corpuscles  is  exposed  to  the  plasma.  The  volume  of  each 
corpuscle  has  been  estimated  as  -0000000722  mm.3,  and  its  surface  as 
•000128  mm.2,  so  that  the  total  surface  of  red  corpuscles  in  the  blood  of  a 
man  weighing  about  70  kilos,  (assuming  his  total  blood  as  ^:i  of  the  body 
weight)  would  be  about  3000  sq.  metres,  or  1500  times  the  surface  of  the 
body  itself.  This  great  extent  of  surface  is  of  importance  in  facilitating 
the  exchange  of  material,  especially  oxygen,  between  the  corpuscle  itself 
and  the  surrounding  plasma. 

OSMOTIC  RELATIONSHIPS  OF  THE  RED  CORPUSCLE.  If  the  blood 
plasma  be  concentrated  by  evaporation  or  by  the  addition  of  neutral 
salts,  its  osmotic  pressure  rises  and  water  diffuses  from  the  corpuscles  into 
the  plasma  in  order  to  equalise  the  osmotic  pressure  within  and  without  the 
corpuscle.     The  latter  therefore  becomes  wrinkled  or  crenated.     On  the 

801 


862  1'IIYSIOLOGY 

other  hand,  dilution  of  the  plasma  diminishes  its  osmotic  pressure  below 
that  of  the  corpuscles,  and  water  therefore  passes  into  the  latter,  which  swell 
up  and  become  spherical;  and,  if  the  plasma  be  made  sufficiently  dilute,  the 
corpuscles  burst  with  the  liberation  of  the  haemoglobin  they  contain.  The 
corpuscles  of  mammalian  blood  neither  gain  nor  lose  volume  in  a  solution 
containing  0*9  per  cent,  sodium  chloride.  The  osmotic  pressure  as  deter- 
mined by  the  freezing-point  of  such  a  solution  is  identical  with  that  of  the 
blood.  For  frogs'  blood  such  a  solution  would  be  too  concentrated  and 
bring  about  crenation.  The  salt  solution  which  is  normal  for  frogs'  blood 
contains  only  0-65  per  cent,  sodium  chloride. 

Although  the  average  molecular  concentration  of  blood  plasma  in  mammals  is 
equivalent  to  that  of  a  0-9  per  cent,  sodium  chloride  solution,  it  may  vary  even  in  one 
animal  within  fairly  wide  limits,  as  is  shown  by  (lie  following  determinations  of  the 
freezing-point  of  blood  serum  taken  from  animals  under  various  circumstances  : 

Man  (healthy) —0-56  to  -0-600 

Dog -0-55  „  —0-645 

<  )x -0-55  „  -0-662 

Rabbit -0-55  „   -0-620 

The  behaviour  of  the  red  corpuscles,  when  immersed  in  solutions  of 
sodium  chloride  of  different  concentrations,  shows  that  its  limiting  mem- 
brane or  most  external  layer  is  impermeable  to  sodium  chloride.  If  this 
salt  be  added  to  defibrinated  blood  and  the  crenated  corpuscles  separated 
by  the  centrifuge,  practically  the  whole  of  the  added  sodium  chloride 
remains  in  the  plasma  or  serum.  The  red  corpuscle  is  impermeable  to  most 
neutral  salts  as  well  as  to  cane  sugar  and  glucose.  We  may  therefore  make 
'  normal '  solutions  with  sodium  chloride,  sodium  sulphate,  potassium 
nitrate,  or  cane  sugar,  taking  care  that  each  of  the  solutions  shall  be  isotonic 
with  a  0-9  per  cent,  solution  of  sodium  chloride.  On  the  other  hand,  a 
solution  of  urea  behaves  towards  the  corpuscles  like  distilled  water.  If 
some  red  corpuscles  be  added  to  a  1  per  cent,  solution  of  urea  in  normal 
salt  solution,  they  neither  shrink  nor  swell ;  and  if  the  mixture  be  centrifuged, 
and  the  corpuscles  and  supernatant  fluid  examined  separately,  the  percen- 
tage of  urea  in  the  two  cases  will  be  found  identical,  though  there  would  be 
a  great  preponderance  of  sodium  chloride  in  the  supernatant  fluid.  If  a 
1  or  2  per  cent,  solution  of  urea  in  water  be  added  to  defibrinated  blood,  the 
corpuscles  will  swell  up  and  burst  just  as  if  distilled  water  had  been  added. 
There  are  a  large  number  of  substances  to  which  the  corpuscles  are  per- 
meable, e.g.  alcohol,  chloroform,  ether,  etc.  In  their  permeability  the 
corpuscles  resemble  most  other  vegetable  and  animal  cells  in  permitting  the 
passage  of  all  those  substances  that  are  soluble  in  fats  and  the  allied  sub- 
stances, cholesterin,  lecithin,  and  protagon,  which  are  invariable  constituents 
of  all  living  cells.  According  to  Overton  the  external  limiting  pellicle  of 
the  red  corpuscles,  as  in  most  living  cells,  is  formed  by  a  lecithin-cholesterin 
compound,  whose  solvent  power  determines  the  permeabihty  of  the  cell  by 
foreign  substances.     If  therefore  we  wish  to  stain  the  living  cell,  we  must 


THE  RED  BLOOD   CORPUSCLES  863 

choose  some  dyestufi,  such  as  methylene  blue  or  neutral  red,  which  is  soluble 

in  such  lipoid  bodies. 


CHEMISTRY   OF    THE    RED    BLOOD   CORPUSCLES 

The  red  corpuscles  consist  of  two  parts,  haemoglobin  and  stroma,  probably 
in  a  state  of  loose  chemical  combination.  By  various  means  it  is  possible  to 
destroy  this  combination  and  to  dissolve  out  the  haemoglobin,  leaving  the 
colourless  swollen-up  stroma  floating  in  the  plasma.  At  the  same  time  the 
blood  becomes  darker  but  more  transparent,  and  is  spoken  of  as  '  laked ' 
blood. 

It  has  been  thought  by  Schwann,  Schafer,  and  others  that  the  red  corpuscle  con- 
sists of  a  solution  of  haemoglobin  included  within  an  envelope  which  contains  lecithin 
and  cholesterin  and  forms  the  stroma.  Though  the  haemoglobin  can  be  separated  from 
the  stroma  by  very  simple  means,  it  is  difficult  to  believe  that  it  is  in  watery  solution. 
Thus  the  blood  corpuscles  contain  a  greater  percentage  of  solids  than  any  soft  tissue 
of  the  body.  The  blood  corpuscles  have  36-7  per  cent,  solids,  as  against  muscular 
tissue  with  25  per  cent,  or  nervous  with  22  per  cent,  solids.  Of  these  solids,  95  per 
cent,  consist  of  haemoglobin,  so  that  the  solution  would  have  to  contain  at  least  30  per 
cent,  haemoglobin.  No  solution  of  haemoglobin  of  this  strength  can  be  prepared.  In 
many  animals,  such  as  the  rat  and  guinea-pig,  it  is  sufficient  merely  to  'lake'  the 
blood,  i.  e.  to  bring  the  haemoglobin  into  solution  in  the  surrounding  plasma  or  serum, 
in  order  to  make  the  haemoglobin  crystallise  out.  Some  form  of  combination  is  there- 
fore necessary  in  the  corpuscles  if  merely  to  keep  the  ha-moglobin  from  separating  out 
in  a  crystalline  form. 

Blood  may  be  "laked'  by  any  of  the  following  means: 

(a)  Addition  of  a  small  amount  of  ether. 

(b)  Free  dilution  with  water. 

(c)  Alternate  freezing  and  thawing  of  the  blood. 
(<I)  Addition  of  bile  salts. 

(e)  The  action  of  foreign  blood  serum  or  of  various  haemolysins  whose 
nature  we  shall  have  to  discuss  later. 

From  such  laked  blood  we  may  prepare  either  haemoglobin  or  stroma. 

In  order  to  separate  the  stroma  from  the  haemoglobin,  blood,  which  has  been  de- 
fibrinated  or  prevented  from  clotting  by  the  addition  of  a  little  sodium  oxalate,  is 
centrifuged  until  all  the  formed  elements  are  thrown  down  as  a  solid  cake  at  the  bottom 
of  the  tube.  The  tube  is  then  tilled  up  with  normal  saline  fluid  and  again  centrifuged, 
and  this  process  repeated  twice  in  order  to  wash  away  adherent  plasma  or  serum.  After 
the  final  washing  two  volumes  of  distilled  water  saturated  with  ether  are  added  to  one 
volume  of  caked  corpuscles.  The  corpuscles  swell  up  and  their  haemoglobin  passes 
into  solution  into  the  surrounding  fluid.  The  blood  is  laked.  The  fluid  is  once  more 
centrifuged  in  order  to  throw  down  white  blood  corpuscles.  A  1  per  cent,  solution 
of  acid  sodium  sulphate  is  now  added  drop  by  drop  until  the  solution  acquires  the 
opaque  appearance  presented  by  ordinary  blood.  The  action  of  tins  salt,  as  of  dilute 
is  to  precipitate  the  swollen-up  stromata,  which  reacquire  the  power  of  reflecting 
fight  from  their  surfaces  and  restore  the  opacity  to  the  blood.  On  centrifuging,  the 
stromata  are  thrown  down,  and  can  be  collected  and  washed  with  distilled  water  several 
tune.-,  on  the  centrifuge. 


864  PHYSIOLOGY 

The  stroma  protein  forms  only  aboirl    1  per  eent.  of  the  total  solids  of 

the  corpuscle.  It  is  insoluble -in  dilute  acids,  but  easily  soluble  in  dilute 
alkalies.  On  gastric  digestion  the  greater  part  dissolves,  leaving  a  residue 
which  is  rich  in  phosphorus,  and  has  been  called  nuclein.  Stroma  protein  is 
bherefore  spoken  of  as  a  nucleo-protein.  Wooldridge,  who  devised  the 
method  given  above  for  the  preparation  of  pure  stromata,  regarded  the 
protein  as  a  compound  of  protein  and  lecithin.  The  substance  certainly 
contains  a  large  quantity  of  lecithin,  the  greater  part  of  which  is  present  in 
the  precipitate  obtained  on  gastric  digestion.  According  to  Wright  the 
nuclein  residue  yields  purine  bases  on  hydrolysis,  and  is  therefore  rightly 
classed  with  the  other  nucleins  from  tissue  cells  and  contained  in  nuclei. 

From  tliclaked  solution  of  corpuscles,  oxyhemoglobin  can  be  obtained  in  a  crystalline 
form  with  varying  readiness  according  to  the  animal  from  which  the  blood  is  derived. 
Thus  in  the  case  of  the  rat,  the  guinea-pig,  the  dog,  and  the  horse  it  is  sufficient  merely 
to  cool  the  laked  blood,  preferably  in  a  freezing  mixture  to  about  —  10°  C.  in  order  to 
obtain  a  large  crop  of  haemoglobin  crystals.  Crystallisation  is  facilitated  by  the  addi- 
tion of  25  per  cent,  of  absolute  alcohol  to  the  mixture,  though  the  use  of  alcohol  certainly 
tends  to  interfere. with  the  subsequent  purification  and  solubility  of  the  hemoglobin. 
Oxyhemoglobin  can  be  recrystallised  by  dissolving  it  in  weak  alkali  at  35°  C,  cooling 
the  solution  to  0°  C,  and  then  adding  cold  alcohol  to  25  per  cent,  and  allowing  the 
mixture  to  stand  for  some  days  at  a  temperature  of  —  5°  to  —  10°  C.  In  the  case  of 
those  bloods  which  yield  oxyhemoglobin  crystals  with  greater  difficulty,  it  is  better  to 
add  to  the  laked  blood  an  equal  volume  of  a  saturated  solution  of  ammonium  sulphate. 
The  precipitate  of  globulins  is  filtered  off  and  the  filtrate  allowed  to  stand  in  a  cool 
place.     Crystals  of  haemoglobin  then  come  down  in  quantity. 


PROPERTIES   OF   HAEMOGLOBIN 

The  crystals  thus  obtained  are  as  a  rule  microscopic  in  size.    Most 
animals  yield  an  oxyhemoglobin  which  crystallises  in  rhombic  prisms  or 

needles  belonging  to  the  rhombic  system. 
In  the  guinea-pig  the  crystals  are  tetrahe- 
dral  in  form,  while  the  oxyhemoglobin  of 
the  squirrel  crystallises  normally  in  the 
form  of  six-sided  plates.  On  recrystalh- 
sation  however,  a  squirrel's  haemoglobin 
can  be  obtained  as  a  mixture  of  rhombic 
prisms  with  rhombic  tetrahedra.  The 
water  of  crystallisation  of  oxyhsemoglobin 
Fig.  371.  Crystals  of  oxyhemoglobin.  varies  in  different  animals  between  3  and 
1.  Fromrat.^2.  From  guinea-pig.  Q  per  ^^     The  solubility  of  the  crystals 

differs  according  to  the  animal  from  which 
they  have  been  derived,  and  is  in  direct  proportion  to  the  difficulty  with 
which  the  crystals  are  obtained.  They  are  more  soluble  in  highly  diluted 
solutions  of  ammonia  and  the  caustic  alkalies  and  their  carbonates  than  in 
water.  A  solution  of  haemoglobin  will  not  diffuse  through  parchment  paper; 
the  elementary  analysis  of  oxyhemoglobin  crystals  gives  somewhat  varying 


THE  RED  BLOOD  CORPUSCLES 


865 


results  according  to  the  animal  employed.    In  the  case  of  the  oxyhaemo- 
globin  of  the  dog,  Jaquet  obtained  the  following  figures : 


C 

a 

N 
Ie 
S 
O 


In  100  parts 

.     53-91 

.       54-97 

.       6-62      . 

7-22 

.     15-98      . 

16-3S 

.       0-333    . 

0-336 

.       0-54      . 

0-568 

.     22-62      . 

.       20-93 

The  chief  differences  between  different  animals  appear  to  have  relation 
to  the  sulphur.  Haemoglobin  from  the  hen  contains  0-857  per  cent,  sulphur. 
All  specimens  are  alike  in  containing  a  constant  proportion  of  iron,  as  is 
shown  in  the  following  Table  : 


Oxyhemoglobin  of 

Dog 
Horse 
Ox 
Hen 


Fo  per  cent. 

.  0-336  .. 

.  0-335  .. 

.  0-336  .. 

.  0-336  .. 


Authority 

Jaquet. 
Zinofisky. 
Hiifner. 
Jaquet. 


On  the  assumption  that  each  molecule  of  oxyhsemoglobin  contains  one 
atom  of  iron,  its  molecular  weight  would  be  16,660,  and  this  result  is  borne 
out  by  the  volume  of  oxygen  or  carbonic  oxide  which  can  enter  into  combina- 
tion with  haemoglobin.  It  has  been  suggested  by  Bunge  that  the  enormous 
size  of  the  hasmoglobin  molecule  finds  a  teleological  explanation;  if  we 
consider  that  iron  is  eight  times  as  heavy  as  water,  a  compoimd,  which  would 
float  easily  along  with  the  blood  current  through  the  vessels,  could  be  secured 
only  by  the  iron  being  taken  up  by  so  large  an  organic  molecule.  Oxy- 
haenioglobin  is  a  compound  in  definite  proportions  of  oxygen  and  haemo- 
globin or  reduced  haemoglobin.  It  can  be  easily  dissociated  and  is  split  up  by 
such  simple  means  as  exposure  to  a  vacuum.  If,  for  instance,  some  arterial 
blood  or  solution  of  oxyhemoglobin  be  introduced  into  a  Torricellian 
vacuum,  the  fluid  is  seen  to  give  off  bubbles  of  gas,  and  the  colour  changes 
from  a  brilliant  scarlet  to  a  dull  bluish  red.  In  this  process  each  gramme  of 
oxyhaemoglobin  gives  off  1-34  c.c.  of  oxygen.  The  same  change  can  be 
effected  by  treating  a  solution  of  oxyhaernoglobin  with  reducing  agents  such 
as  an  alkaline  solution  of  ferrous  tartrate  (Stokes's  fluid)  or  ammonium 
sulphide ;  in  the  latter  case  reduction  is  aided  by  gently  warming  the  solu- 
tion. Another  reagent  of  value  for  effecting  the  reduction  of  oxyhaemoglobin 
is  a  solution  of  hydrazine.  The  oxygen  in  oxyhaemoglobin  can  be  replaced 
by  equivalent  quantities  of  other  gases.  Thus  if  carbon  monoxide  gas 
be  led  through  a  solution  of  oxyhaemoglobin,  oxygen  is  given  off  and  its 
place  is  taken  by  an  equal  volume  of  carbon  monoxide  with  the  formation  of 
a  more  stable  compound,  carbon  monoxide  haemoglobin.  This  body  is  dis- 
sociated only  with  extreme  slowness  and  is  unaffected  by  the  addition  of 
reducing  agents.  By  using  special  precautions  to  prevent  oxidation  of  the 
gas,  the  carbon  monoxide  can  be  replaced  in  this  compound  by  nitric  oxide, 
55 


866 


PHYSIOLOGY 


NO.  We  have  therefore  a  series  of  three  compounds  which  can  be  arranged 
in  order  of  stability,  thus  : 

NO-koemoglobin. 

CO-hsemoglobin. 

02-hsemoglobin. 

The  poisonous  properties  of  carbon  monoxide  are  due  to  its  power  of  turning 
out  the  oxygen  from  the  oxyhemoglobin,  thus  depriving  the  tissues  of  the 
oxygen  which  is  normally  carried  to  them  by  the  red  corpuscles. 

Hemoglobin  and  its  derivatives  give  well-marked  absorption  spectra. 
Thus  dilute  solutions  of  oxyhemoglobin  placed  in  front  of  the  slit  of  a 
spectroscope  show  two  well-marked  absorption  bands  between  Fraunkofer's 


A    a 

Tf  7  "   ' 

tajniilin  Inn 

B  C            I 

111  l  1  1 1  l  l  1 

ii  i Tj  i 

,  .  T  , 

,   i    ,   T    , 

of 

,    ,    i 

H 

I 

1 

J 

i  I 

' 

VI 

H 

■ 

9H 

m 

91  wej 

*    i  ■ 

■        I 

JsI'Ii.'iQJIiWmw 
*    A'  o|  i 

I  llll  1 1  /6U 
$  or       m 

'"+'i 

i'+i 

II      1     J.      ™ 
G 

1      1     ,1^ 

Fio.  372.  The  spectra  of  oxyhemoglobin  in  different  grades  of  concentration, 
of  (reduced)  haemoglobin,  and  of  carbon  monoxide  haemoglobin.  {After 
Preyer  and  Gamoee.) 

1  to  4.  Solution  of  oxyha:moglobin  containing  (1)  loss  than  '01  per  cent., 
(2)  -09  per  cent.,  (3)  "37  per  cent.,  (4)  -8  per  cent.  (5)  Solution  of  (reduced) 
haemoglobin  containing  about  -2  per  cent.  (6)  Solution  of  carbon  monoxide 
haemoglobin.  In  each  of  the  six  cases  the  layer  brought  before  the  spectroscope 
was  1  cm.  in  thickness.  The  letters  (A,  a,  etc.)  indicate  Fraunhofer's  lines  and 
the  figures  wave-lengths  expressed  in  ,  crtrVirir  millimetre. 

lines  D  and  E.  The  centre  of  the  band  nearest  to  D  corresponds  to  2  579, 
and  is  often  spoken  of  as  the  band  a,  while  the  second  band,  the  one  next 
to  E,  which  can  be  called  the  band  jj,  is  broader,  has  less  sharply  defined 
edges,  and  its  centre  corresponds  approximately  to  I  544.  On  concentrating 
the  solution  or  using  thicker  layers,  a  rjoint  is  reached  at  which  the  two  bands 
fuse  into  one,  and  with  a  still  stronger  solution  it  will  be  found  that  the  whole 
of  the  spectrum  is  absorbed  with  the  exception  of  the  red  end. 

The  above  figure  shows  the  spectrum  of  oxyhaernoglobin  in  varying 
concentrations,  a  stratum  one  centimetre  thick  being  examined.  If  a 
reducing  agent  be  added  to  the  solution  of  oxyhemoglobin,  the  two  bands 
disappear  and  their  place  is  taken  by  a  more  diffuse  band  lying  midway 
between  the  two  (Fig.  372,  5),  its  centre  corresponding  to  I  555.     This  is  the 


THE  RED  BLOOD   CORPUSCLES  867 

absorption  spectrum  of  haemoglobin  or  reduced  haemoglobin.  The  spectrum 
of  carboxyhaemoglobin  is  very  similar  to  that  of  oxyhemoglobin,  the  bands 
however  being  shifted  slightly  towards  the  red  end.  This  solution  is  of 
a  brighter  red  than  oxyhemoglobin.  Its  tint  is  best  observed  on  diluting 
the  blood  to  a  large  extent,  when  oxyhaemoglobin  acquires  a  yellowish  tint, 
while  the  pink  colour  of  CO-haemoglobin  is  retained  so  long  as  any  colour  is 
visible.  The  fact  that  CO-hsemoglobin  is  not  altered  by  reducing  agents 
can  be  shown  In  adding  ammonium  sulphide  to  CO-haenioglobin  and  examin- 
ing with  the  spectroscope,  when  no  change  is  observed. 

All  these  derivatives  of  haemoglobin,  besides  their  absorption  bands  in  the  visible 
spectrum,  have  characteristic  absorption  of  light  in  the  ultra-violet  spectrum,  as  has 
lucii  shown  by  Gamgee.  In  the  case  of  oxyhemoglobin  this  absorption  causes  a  band 
(Soret's  band)  which  occupies  the  greater  part  of  the  spectral  region  between  Fraun- 
hofer's  lines  G  and  H.  In  reduced  haemoglobin  this  band  is  displaced  towards  the 
visible  part  of  the  spectrum. 

Another  compound  of  haemoglobin  with  oxygen  is  >nethcemoglobin.  This 
substance,  although  not  of  normal  occurrence  in  the  body,  is  foimd  in  urine 
and  in  blood  whenever  there  is  a  sudden  breaking  down  of  red  blood 
corpuscles  with  the  setting  free  of  haemoglobin  m  the  blood  plasma.  It  may 
be  prepared  by  the  addition  of  a  ferricyanide,  permanganate,  or  nitrite,  or 
other  oxidising  or  reducing  agents  to  the  laked  blood  or  to  solutions  of  oxy- 
haemoglobin.  It  is  a  chocolate-brown  substance,  crystallisable,  and  gives  a 
distinct  absorption  band  in  the  red  between  Fraunhofer's  lines  C  and  D.  It 
is  unaltered  by  exposure  to  a  vacuum.  On  treatment  with  reducing  agents 
however,  such  as  Stokes's  fluid,  the  methsemoglobin  is  converted  into 
haemoglobin,  from  which  by  shaking  with  air  oxyhaemoglobin  can  be 
reformed.  The  fact  that  met  haemoglobin  cannot  be  reduced  by  exposure 
to  a  vacuum  indicates  that  it  is  a  compound  of  oxygen  with  haemoglobin,  in 
which  the  oxygen  is  in  a  different  state  of  combination.  According  to 
Buckmaster  methsemoglobin  contains  only  half  as  much  oxygen  as  oxy- 
haemoglobin, so  that  the  composition  of  the  two  bodies  might  be  represented. 

A 

Hli  (oxyhaemoglobin)  and  Hb  =  O  (methsemoglobin). 
\d 
The  change  from  oxyhaemoglobin  to  methsemoglobin  is  not  effected  however 
by  a  simple  shifting  of  the  oxygen  groups,  but  must  be  assumed  to  involve 
two  distinct  events.  The  whole  of  the  oxygen  in  loose  combination  with 
haemoglobin  is  given  off,  and  the  oxygen  in  the  methaemoglobin  molecule  is 
derived  from  the  oxidising  agent  added,  so  that  ferricyanide  of  potash,  for 
instance,  is  converted  into  ferrocyanide.1  Since  the  whole  of  the  oxygen 
in  the  oxyhaemoglobin  is  given  off  on  the  addition  of  potassium  ferricyanide, 
we  may  use  this  fact  in  order  to  determine  the  total  amount  of  oxygen  in 
combination  in  the  blood. 

1  Whin  the  change  is  effected  by  reducing  agents,  we  must  assume  that  the  oxygen 
of  the  water  or  air  is  the  source  of  that  required  for  the  oxidation  of  the  reduced  haemo- 
globin to  methsemoglobin. 


868  PHYSIOLOGY 

^DERIVATIVES  OF  HEMOGLOBIN.  Hemoglobin  is  a  compound  of 
an  iron-containing  coloured  group  (the  prosthetic  group)  with  a  protein, 
which  probably  varies  somewhat  in  different  animals.  The  prosthetic  group 
is  identical  in  every  case  where  it  has  been  examined.  A  separation  of  the 
prosthetic  group  from  the  protein  moiety  can  be  effected  with  extreme  ease, 
and  occurs  whenever  the  hsemoglobin  is  treated  with  weak  acids,  with 
alkalies,  or  is  heated  above  70°  C.     The  protein  group  is  known  as  globin. 

In  order  to  separate  globin,  oxyhemoglobin  crystals  are  dissolved  in  water  and 
treated  with  small  quantities  of  very  dilute  hydrochloric  acid.  A  precipitate  of  pig- 
ment forms  which,  if  the  hsemoglobin  used  be  free  from  inorganic  salt,  rapidly  dissolves 
in  excess  of  the  acid.  Alcohol  and  ether  are  then  added  in  such  relative  quantities 
that  the  ether  separates  rapidly  from  the  aqueous  solution.  The  colouring  matter 
(hamiatin)  dissolves  in  the  ether,  whilst  the  protein  (globin)  remains  in  solution 
in  the  water.  The  solutions  are  separated  by  a 
»*  ""'i-^x.-r-t  separating  funnel  and  ammonia  added  carefully  to 

■  '  \   -Jjy    %  "vJr  '  the  aqueous  solution.     This  throws  down  a  pre- 

"^~U  «  *%     "r-  v  cipitate  of  the  protein,  which  is  soluble  in  acids 

vfe  f  I  ^_   "^   'i  ^  ^        4         and  alkalies  and  coagulable  on  heating ;  the  coagu- 
,  ^v     \  *      V"   ^    4        lum  however  is  soluble  in  acids.     It  is  precipitated 
1  /      V     ^        W\-\'N        by  ammonia  in  the  presence  of  ammonium  chloride. 

r^t    K    '  j  ^    ^.  _  _        n  contains  as  much  as  16-89  per  cent,  nitrogen, 

y*  s  i      7  antl   yields    a   considerable    amount  of   the   basic 

'     ,,        -£■       ^'      .,    "'    1 1        derivatives  on  hydrolysis.      It  is  therefore  classified 
*>•'•?  rh     .  ^^       *K'\-     ^'        with  the  histones. 

^A.        »  _  +  Hsemoglobin  yields  about  94  per  cent,  of 

t  >-\  globin  and  about  4-5  per  cent,  of  the  chromo- 

Fm.373.    Haemiu  crystals.  genie  group,  hsematin.    In  order  to  obtain 

hcematin  in  a  pure  condition,  it  is  usual  to 
start  with  the  crystalline  derivative  of  hsemoglobin  known  as  hwmin. 
When  some  dried  blood  is  heated  with  a  crystal  of  common  salt  and 
placed  in  acetic  acid  on  a  slide,  a  residue  is  obtained  in  which  a  number 
of  reddish-brown  needles  are  embedded  known  as  Teichmann's  crystals  or 
hsernin  crystals  (Fig.  373).  The  preparation  of  these  crystals  is  often  used 
as  a  convenient  test  for  the  identification  of  blood. 

In  order  to  obtain  them  in  large  quantities  the  following  method,  devised  by 
Chalfejew,  is  employed.  One  volume  of  defibrinated  blood  is  added  to  four  volumes  of 
glacial  acetic  acid  previously  heated  to  80°  C.  As  soon  as  the  temperature  has  fallen  to 
00°  C.  the  liquid  is  again  warmed,  and  then  allowed  to  cool.  Crystals  are  formed 
which  are  allowed  to  stand  for  twelve  hours  and  are  then  separated  and  washed  by 
decantation,  first  with  distilled  water  and  then  with  graduated  strengths  of  alcohol. 
In  order  to  purify  these  crystals,  the  crude  material  is  shaken  for  fifteen  minutes  with  a 
mixture  of  chloroform  and  pyridine.  The  solution  is  filtered  and  then  thrown  into 
glacial  acetic  acid  previously  saturated  with  sodium  chloride  and  heated  to  105°  C. 
A  few  drops  of  concentrated  hydrochloric  acid  are  then  added  and  the  mixture  allowed 
to  stand  for  twenty-four  hours.  The  crystals  which  separate  out  are  filtered  off, 
washed  with  dilute  acetic  acid,  and  then  dried. 

Hsernin  crystals  have  been  regarded  as  hydrochloride  of  hsematin. 
Elementary  analysis  shows  that  they  have  the  following  formula  (Will- 
statter) :  (C33H3  OiN4Cl  Fe.     By  dissolving  hsernin  in  alkalies  and  throwing 


THE  RED  BLOOD  CORPUSCLES 


869 


the  solution  into  an  excess  of  acid,  a  precipitate  is  obtained  which  is  haematin. 
Haematin  forms  a  powder  of  bluish-black  colour,  and  metallic  lustre.  It  is 
insoluble  in  water,  alcohol,  or  ether,  but  is  slightly  soluble  in  glacial  acetic 
acid  and  in  absolute  alcohol.  It  is  easily  soluble  in  concentrated  sulphuric 
acid,  but  undergoes  decomposition,  losing  its  atom  of  iron  and  being  trans- 
formed into  hcematoporphyrin,  which  forms  a  deep  purple  solution.  The 
formula  of  haematin  has  not  yet  been  ascertained  with  certainty.     It  is 


J?ig.  374.     Absorption  spectra  of  haemoglobin  and  its  derivatives. 

1.  Oxyhemoglobin.  2.  Reduced  haemoglobin.  3.  Methaemoglobin. 
4.  Alkaline  methaemoglobin.  5.  Acid  haematin  in  other.  6.  Alkaline 
haematin  in  rectified  spirit.  7.  Reduced  haematin.  8.  Acid  haematopor- 
phyrin.     9.  Alkaline  haematoporphyrin.  •  (From  MacMunn.) 

probably  C33H32O4N.jFe.OH.  Its  compounds  with  acids  and  alkalies  are 
spoken  of  as  acid  and  alkaline  haematin,  and  each  gives  a  characteristic 
absorption  spectrum  (Fig.  374).  The  alkaline  solutions  exhibit  one  indis- 
tinct absorption  band  between  C  and  D,  the  acid  solutions  an  absorption 
band  also  between  C  and  D  but  nearer  to  C,  and  resembling  somewhat  the 
band  presented  by  methaemoglobin.  According  to  Hoppe-Seyler  and 
Gamgee,  perfectly  pure  solutions  of  haematin  in  alkalies  are  quite  unaffected 
by  reducing  agents;  in  the  presence  of  certain  foreign  matters  however, 
alkaline  haematin,  when  treated  with  reducing  agents,  exhibits  a  spectrum 
known  as  that  of  reduced  alkaline  haematin,  which  is  identical  with  that  of 


870  PHYSIOLOGY 

haemochromogen.  The  same  change  is  further  observed  when  alkaline 
haematin,  made  by  the  action  of  alkalies  on  ordinary  blood,  is  treated  with 
reducing  agents  such  as  ammonium  sulphide.  Since  this  substance,  hsemo- 
chromogen,  is  responsible  for  the  respiratory  functions  of  the  haemoglobin, 
i.  e.  the  power  of  its  molecule  to  form  unstable  compounds  with  oxygen,  its 
preparation  merits  fuller  consideration. 

Hcemochromogen  is  prepared  by  the  action  of  caustic  alkalies  on 
haemoglobin  in  the  absence  of  oxygen.  For  this  purpose  a  test-tube  con- 
taining a  solution  of  sodium  or  potassium  hydrate  is  placed  in  a  bottle  with 
two  necks  containing  a  solution  of  haemoglobin,  care  being  taken  not  to 
spill  any  of  the  alkaline  solution.  Hydrogen  is  then  passed  through  the 
larger  bottle  until  the  haemoglobin  is  entirely  reduced  and  all  the  air  is 
replaced  by  hydrogen.  The  bottle  is  then  inverted  so  as  to  mix  its  contents 
with  the  caustic  alkali,  when  haemochromogen  is  formed  and  can  be  recog- 
nised by  its  characteristic  colour  and  spectrum.  The  haemochromogen  in 
solution  has  a  cherry-red  colour,  and  when  sufficiently  diluted  shows  two 
well-marked  absorption  bands  identical  with  those  given  by  reduced  alkaline 
haematin  (Fig.  374,  7).  Of  the  two  absorption  bands  which  are  situated 
between  D  and  E,  that  nearest  to  D  has  very  sharply  denned  borders ;  the 
position  of  the  two  absorption  bands  may  be  given  in  terms  of  their  wave- 
lengths as  follows  :  /.  567  to  547  and  /.  532  to  518.  The  band  nearest  D  is 
given  by  haemochromogen  solutions  diluted  until  there  is  only  one  part 
of  the  pigment  in  25,000  parts  of  water,  so  that  the  formation  of  reduced 
alkaline  haematin  is  an  even  more  delicate  test  for  blood  than  the  spectrum 
of  oxyhemoglobin  itself.  When  CO-haemoglobin  is  treated  in  the  same  way 
with  alkali  in  the  absence  of  oxygen,  a  body  CO-hsernochrornogen  is  formed 
which  contains  exactly  the  same  volume  of  CO  in  combination  as  the  original 
CO-haemoglobin.  This  fact,  combined  with  the  possibility  of  reducing 
ordinary  alkaline  haematin  by  the  action  of  ammonium  sulphide  or  Stokes's 
fluid,  indicates  that  the  group  of  atoms  which  in  haemoglobin  is  responsible 
for  taking  up  oxygen  or  carbon  monoxide  gas  passes  unchanged  into  the 
haemochromogen  molecule.  Haemochromogen  therefore  represents  an  iron- 
containing  coloured  radical  which  can  combine  with  protein  bodies  to 
form  haemoglobin,  and  is  responsible  for  the  oxygen-combining  powers  of  the 
latter.  We  may  assume  therefore  that  oxyhemoglobin  and  CO-haemoglobin 
contain  oxyhaemochromogen  and  CO-haemochromogen  respectively. 

Hamatoporphyrin.  If  haemoglobin,  haematin,  or  haemin  be  mixed  with 
concentrated  sulphuric  acid,  it  dissolves  forming  a  purple-red  solution. 
On  pouring  this  solution  into  a  large  quantity  of  water,  haematoporphyrin 
is  thrown  down  in  the  form  of  a  brown  precipitate.  In  order  to  prepare 
haematoporphyrin,  pure  crystallised  haemin  is  added  to  a  saturated  solution 
of  hydrobromic  acid  in  glacial  acetic  acid.  The  whole  is  allowed  to  stand 
for  three  or  four  days  and  then  thrown  into  distilled  water.  The  resulting 
mixture  is  filtered  and  the  haematoporphyrin  thrown  dowrn  by  careful 
neutralisation  of  the  hydrobromic  acid  with  caustic  soda.  Haemato- 
porphyrin is  easily  soluble  in  alkalies  and  somewhat  less  readily  so  in  acids, 


THE  RED  BLOOD   CORPUSCLES  871 

forming  alkaline  and  acid  haematoporphyrin  respectively.  The  formula  of 
haematoporphyrin  has  been  given  by  Nencki  and  Sieber  as  CJ6H18N.,03, 
and  is  according  to  them  isomeric  with  the  chief  bile  pigment,  bilirubin. 
According  to  Willstatter  its  formula  is  C33H3gN406.  An  alcohohc  solution 
of  kamiatoporphyrm  acidulated  with  hydrochloric  acid  shows  two  absorption 
bands  :  one,  the  fainter,  between  C  and  D ;  and  the  other,  broader  and 
more  denned,  midway  between  D  and  E.  Solutions  of  alkaline  haemato- 
porphyrin  show  four  absorption  bands  :  a  weak  band  between  C  and  D ; 
another  between  D  and  E ;  a  more  strongly  marked  band  nearer  to  E ;  and 
a  fourth  band,  darkest  of  all,  between  b  and  F.  It  will  be  observed  that, 
in  the  formation  of  hamiatoporphyrin  from  haematin,  the  iron  of  the  latter 
has  been  split  off  by  the  action  of  the  strong  acid.  Laidlaw  has  found 
that  the  splitting  off  of  iron  occurs  much  more  readily  in  the  absence  of 
oxygen.  If  reduced  hemoglobin  be  taken,  or  defibrinated  blood  which 
has  been  allowed  to  stand  until  it  is  thoroughly  reduced,  it  is  sufficient  to 
add  15  per  cent,  hydrochloric  acid  in  order  not  only  to  convert  the  greater 
part  of  the  haemoglobin  to  haematin  but  to  split  off  the  iron  of  the  latter 
and  form  haematoporphyrin.  Haematoporphyrin  occurs  in  minute  quantities 
in  normal  urine  and  in  larger  quantities  in  certain  toxic  conditions,  especially 
in  poisoning  by  sul phonal,  when  the  urine  may  have  a  bright  purple  colour. 
Ir  is  important  to  remember  that,  although  urine  is  acid  from  the  presence 
of  acid  sodium  phosphate,  urinary  haematoporphyrin  is  always  alkaline 
haematoporphyrin  and  gives  the  spectrum  of  this  body. 

CHEMICAL  RELATIONSHIPS  OF  HAEMATIN.  Haematin,  or  haemochromogen, 
is  widely  diffused  through  the  animal  kingdom,  occurring  in  the  form  of  haemoglobin 
in  a  large  number  of  the  inveitebrata,  as  well  as  in  all  the  vertebrata  except  perhaps 
Amphioxus.  Since  the  respiratory  function  of  haemoglobin  depends  on  the  power  of 
its  iron-containing  radical  to  combine  with  a  molecule  of  oxygen,  forming  an  easily 
dissociable  compound,  it  becomes  of  interest  to  try  whether  by  a  study  of  its  disin- 
tegration products  we  can  throw  any  light  on  its  chemical  relationships  and  on  the  con- 
ditions of  its  formation  in  the  living  organism.  When  haematin  is  oxidised  with  sodium 
bichromate  and  acetic-  acid,  two  new  acids  are  formed,  called  the  haematinic  acids. 
One  of  these  has  the  formula  CgH904N,  and  the  other  C8H805.  The  first  acid  is  con- 
verted into  the  second  by  the  action  of  alkalies.  The  relationship  of  the  two  haematinic 
acids  can  be  represented  by  the  following  formulae : 

/CO  /C0\ 

C5H,(        >0  C5H,       NH 

COOH  COOH 

If,  on  the  other  hand,  haemin  or  hosmatoporphyrin  be  reduced  by  the  action  of  hydriodic 
acid  dissolved  in  acetic  acid  with  the  addition  of  phosphonium  iodide,  and  the  product 
be  distilled  with  steam,  the  distillate  contains  a  mixture  of  substituted  pyrroles  formerly 
known  as  haemopyrroes.  The  mixture  readily  oxidises  to  a  red  substance  on  exposure 
to  the  air.  If  ammonia  be  added  to  the  coloured  solution,  the  colour  changes  to  yellow 
which,  on  the  addition  of  an  ammoniacal  solution  of  zinc  chloride,  changes  to  pink 
with  .1  green  fluorescence.  These  reactions  are  also  given  by  urobilin,  one  of  the 
urinary  pigments  ami  the  chief  pigment  of  the  faeces,  as  well  as  by  hydrobilirubin,  a 
substance  obtained  by  the  action  of  tin  and  sulphuric  acid  on  an  alcoholic  solution  of 
haematin. 


872 


PHYSIOLOGY 


The  hsemopyrroles,  according  to  Willstatter,  are  three  in  number  and  have  the 
following  formula : 


CH3 


Cryptopyrrolc 

(  'JF; 


2"5 

CH3 


NH 


CHS         jC2H5 

CH3;      xCH3 
NH 


Isohaimopyrrolo 
CHj  C2H5 


CH 


NH 


The  same  substances  can  be  obtained  from  the  chlorophyll  of  plants.  On  treatment 
with  acid,  chlorophyll  loses  magnesium  and  is  converted  into  phacophytin.  From 
this  three  COOH  groups  can  be  split  off,  leaving  a  substance,  setioporphyrin. 

It  is  interesting  that  hsematoporphyrin  also  can  be  readily  converted  into  setio- 
porphyrin. On  treatment  with  pyridine  and  alcoholic  potash,  it  is  converted  into 
hasmoporphyrin  and  this  heated  with  soda  lime  gives  setioporph3Tin  (C31H36N4). 
Thus  the  same  group  forms  the  basis  both  of  the  substance  which  is  responsible  in  the 
plant  for  the  assimilation  of  carbon  from  carbon  dioxide,  and  of  the  pigment  which 
in  the  animal  is  the  carrier  of  oxygen  between  the  tissues  and  the  surrounding  medium. 
According  to  Willstatter,  setioporphyrin  and  hsematoporphyrin  are  both  built  up  of 
four  substituted  pyrrol  rings. 

Thus  hsemato porphyrin  has  the  following  structural  formula : 


C.CH=CH.OH 


COOH.GVH.C 


/ 
CH,.C=^C.CH. 


C=C.C2H4.COOH 
CH,.C=C.CH, 


and  the  same  worker  suggests  the  following  formula  for  hsemin  : 


CH3C 


C.CH, 


C.CH, 


THE  SYNTHESIS  OF  THE  BLOOD  PIGMENTS.  Chemists  have  not 
yet  succeeded  in  the  artificial  formation  of  ha?matoporphyrin.  Given 
hsernatoporphyrin  however,  evidence  has  been  brought  forward  both  by 
Menzies  and  Laidlaw  of  the  possibility  of  forming  artificially  both  hsematin 
and  haemoglobin,  or  some  substance  indistinguishable  from  the  latter. 


THE  RED  BLOOD   CORPUSCLES  873 

Reduced  haemoglobin  is  a  compound  of  haeniochromogen  and  a  protein, 
globin.  The  splitting  off  of  the  prosthetic  chromatogenic  group — haemo- 
chromogen — can  be  effected  either  by  acid  or  alkali.  When  the  latter  is 
employed,  we  obtain  a  red  solution  which  is  fairly  stable  and  can  be  con- 
verted by  shaking  up  with  air  into  ordinary  alkaline  hsematin.  With  acids 
the  decomposition  is  easily  carried  further.  Even  with  2  per  cent,  hydro- 
chloric acid  a  certain  amount  of  haematoporphyrin  is  formed,  and  if  the 
strength  of  the  acid  be  increased  to  15  per  cent,  the  whole  of  the  iron  is 
split  off  and  the  haemochromogen  is  converted  entirely  into  haematoporphyrin. 

If  oxyhemoglobin  be  treated  in  the  same  way,  it  yields  acid  or  alkaline 
haematin  directly,  so  that  hsematin  must  be  regarded  as  an  oxyhaemo- 
chromogen.  The  distinction  drawn  by  Hoppe-Seyler  between  hsemo- 
chromogen and  reduced  alkaline  hsematin  had  its  chief  ground  in  the  fact 
that  pure  haematin  is  not  reduced  to  hsemochromogen  by  the  action  of 
such  reducing  agents  as  ammonium  sulphide.  The  conversion  can  how- 
ever be  easily  effected  by  using  a  strong  reducing  agent,  such  as  hydrazine 
hydrate.  Whether  the  haematin  contains  the  whole  of  the  oxygen  of  the 
oxyhsemoglobin  is  doubtful.  According  to  Ham  and  Balean,  when 
oxyhaemoglobin  is  converted  by  means  of  acids  into  acid  haematin,  exactly 
half  the  oxygen  of  the  oxyhsemoglobin  is  given  off,  so  that  haematin 
would  contain  only  one-half  of  the  oxygen  of  the  oxyhaemoglobin.  There 
is  a  marked  difference  between  the  stability  of  haematin  and  haemochromogen. 
Li  the  oxidised  form  of  hsematin  the  iron  is  firmly  bound  and  can  be  split 
off  only  by  using  strong  sulphuric  acid,  concentrated  hydrochloric  acid 
being  insufficient  for  the  purpose. 

It  has  been  shown  by  Laidlaw  that  the  change  in  the  reverse  direction, 
i.  e.  the  combination  of  iron  with  haematoporphyrin  to  form  haemochromogen, 
may  be  effected  with  equal  ease.  One  grrn.  haematoporphyrin  prepared 
by  Nencki's  method  is  dissolved  in  dilute  ammonia  and  warmed  in  a  flask 
on  the  water-bath.  Some  Stokes's  fluid,  prepared  from  about  2  grm. 
ferrous  sulphate,  and  a  few  drops  of  a  50  per  cent,  hydrazine  hydrate 
solution  are  added.  At  the  end  of  one  or  two  hours  the  solution  is  seen 
to  be  of  a  bright  red  colour  when  examined  in  thin  layers,  and  on  dilution 
shows  the  typical  absorption  spectrum  of  haemochromogen,  which  changes 
to  that  of  alkaline  hsematin  on  shaking  with  air.  Strong  potash  is  added, 
and  the  ammonia  is  boiled  off  in  an  evaporating  dish  with  free  exposure 
to  the  air.  The  hydrazine  is  decomposed,  and  a  solution  of  hsematin 
remains  which  can  be  precipitated  by  acidification  with  hydrochloric  acid. 
The  pigment  obtained  in  this  way  agrees  in  every  respect  with  that  prepared 
from  oxyhaemoglobin.  Analysis  of  the  product  gave  9*58  per  cent,  of  iron, 
which  agrees  with  Nencki's  formula  for  hsematin,  C32H30N4O3Fe. 

A  pigment  called  turacin,  occurring  in  the  wing  feathers  of  certain  birds,  was  shown 
by  Church  to  contain  copper  and  to  yield,  on  treatment  with  strong  sulphuric  acid, 
a  substance  indistinguishable  from  haematoporphyrin.  Laidlaw  has  succeeded  in 
syn  the  rising  this  pigment  by  treating  ordinary  haematoporphyrin  obtained  from  blood 
with  ammoniacal  copper  solution,  showing  that  it  is  a  compound  corresponding  to 
hseniarin,  in  which  the  place  of  iron  is  taken  by  copper. 


874  PHYSIOLOGY 

It  was  stated  some  years  ago  by  Menzies  that  a  solution  of  impure 
haemochromogen ,  prepared  by  the  action  of  ammonium  sulphide  on  alkaline 
hsematin  obtained  in  the  ordinary  way  from  blood,  on  standing  for  some 
days  was  reconverted  into  reduced  haemoglobin.  Hani  and  Jialean  have 
confirmed  this  observation,  and  have  shown  in  addition  that  haemo- 
chromogen.  prepared  by  the  action  of  ammonium  sulphide  on  an  alkaline 
solution  of  pure  haemin,  though  perfectly  stable  by  itself,  was  rapidly 
reconverted  into  haemoglobin  if  a  solution  of  globin  were  added  to  the 
mixture.  The  same  change  took  place  if  egg-white  were  used  instead  of 
globin.  The  haemoglobin  thus  formed  was  changed  into  oxyhemoglobin 
on  shaking  with  air.  Although  in  these  experiments  the  oxyhaemoglobin 
was  not  separated  in  the  crystalline  form,  its  colour  and  spectral  characters 
are  so  very  distinctive  that  we  are  justified  in  concluding,  not  only  that  it 
is  possible  to  effect  a  recombination  of  the  haemochromogen  and  globin, 
but  also  that  other  proteins  can  take  the  place  of  globin  in  the  haemoglobin 
molecule. 

THE   LIFE-HISTORY   OF   THE   RED   BLOOD    CORPUSCLES 

The  growth  of  the  embryo  as  well  as  of  the  young  animal  must  be 
attended  with  a  continual  increase  in  the  number  of  red  blood  corpuscles 
present  in  the  body.  In  the  developing  embryo  the  first  formation  of  red 
corpuscles  occurs  in  the  vascular  area.  In  the  chick,  about  the  twentieth 
hour  of  incubation,  the  area  opaca,  which  surrounds  the  blastoderm  and 
will  later  become  the  area  vasculosa,  presents  on  examination  imder  the 
low  power  a  network  of  anastomising  strands  more  opaque  than  the  rest 
of  the  area.  On  section  these  strands  are  seen  to  be  made  up  of  cellular 
masses,  the  ordinary  mesenchyma,  with  branched  cells  and  amoeboid 
corpuscles  lying  between.  The  cells  in  these  cords  are  continually  multi- 
plying by  indirect  division.  Those  on  the  outer  side  of  the  cord  become 
the  endothelium  of  dilated  blood  vessels,  while  those  in  the  interior  acquire 
a  yellowish  colour  from  the  laying  down  of  haemoglobin  in  their  cytoplasm. 
The  cords  become  canalised  and,  as  soon  as  a  connection  is  established 
with  the  vascular  system  of  the  embryo,  the  newly  formed  blood  corpuscles 
move  slowly  on  into  the  general  circulation.  The  red  corpuscles  in  the 
bird  are  true  erythrocytes,  i.  e.  are  nucleated  cells.  The  leucocytes  seem 
to  arise  by  the  immigration  of  wandering  cells  from  the  surrounding 
mesenchyma.  Other  places  in  the  foetus  where  a  similar  growth  of  corpuscles 
proceeds  throughout  foetal  life  are  the  liver  and  the  spleen,  and  later  on 
the  bone  marrow. 

In  the  mammal  the  nucleated  erythrocytes,  though  forming  the  majority 
of  the  red  corpuscles  in  early  foetal  life,  become  fewer  and  fewer  in  number 
as  gestation  advances,  so  that  at  birth  practically  the  whole  of  the  cor- 
puscles are  of  the  non-nucleated  type.  These  however  can  be  shown  to 
be  derived  from  nucleated  red  corpuscles  by  a  process  either  of  extrusion 
or  of  degeneration  and  solution  of  the  nucleus  (Fig.  375).  The  formation 
of  red  corpuscles  does  not  cease  with  the  end  of  foetal  life  or  even  with  the 


THE  RED  BLOOD   CORPUSCLES 


875 


attainment  of  full  stature  by  the  animal.  We  have  definite  proof  that  a 
continual  formation  of  red  corpuscles  can  proceed  and  is  proceeding 
throughout  the  whole  of  adult  life.  In  an  adult  the  total  volume  of  blood 
and  the  total  number  of  corpuscles  remain  approximately  constant.  By 
bleeding  an  animal  we  can  diminish  the  total  aniotuit  of  corpuscles.  The 
first  effect  of  such  a  bleeding  is  that  the  fluid  parts  of  the  blood  are  made 
up,  so  that  the  volume  of  the  blood  is  restored  to  normal  and  the  blood 


Fig.  375.  Part  of  a  blood  vessel  from  the  yolk  sac  of  the  rabbit  embryo,  showing 
the  changes  which  occur  in  the  formation  of  erythrocytes.  (From  Schaper 
after  Maximo w.) 

a,  megaloblasts ;  b,  normoblasts  changing  into  erythroblasts ;  c,  erythroblasts, 
in  which  the  nuclei  are  disappearing;  d,  an  erythrocyte  fully  formed,  but  not  yet  disc - 
shaped:  en,  phagocytic  endothelial  cells;  /,  lymphocytes;  k,  a  divided  lymphocyte; 
n.  erythroblasts,  shrunken  with  atrophic  nucleus. 

therefore  becomes  relatively  poor  in  corpuscles.  In  a  few  weeks  however, 
the  corpuscular  content  of  the  blood  is  found  to  be  once  more  normal, 
showing  that  the  loss  of  corpuscles  has  been  followed  by  a  compensatory 
regeneration.  The  fact  that  the  pigments  constantly  leaving  the  body 
with  the  urine  and  faeces,  namely,  urochrome  and  urobilin  or  stercobilin, 
are  derived  by  means  of  the  liver  from  haemoglobin,  shows  that  a  constant 
destruction  of  red  corpuscles  must  be  proceeding.  Since  the  number  of 
corpuscles  remains  vuialtered,  this  loss  of  haemoglobin  must  be  made 
good  by  a  continual  regeneration  of  fresh  haemoglobin  and  new  red  corpuscles. 
The  seat  of  the  formation  of  red  corpuscles  in  the  higher  vertebrates  is  the 


870 


PHYSIOLOGY 


bone  marrow.  Here  we  have  a  structure  protected  from  pressure  where 
the  capillaries  and  veins  are  dilated  and  thin-walled,  and  allow  a  slow  passage 
of  blood  and  the  entry  of  newly  formed  corpuscles  through  the  imperfect 
walls  into  the  blood  stream  (Fig.  376).  That  the  marrow  is  involved 
in  the  process  is  shown  by  the  fact  that  it  is  the  only  tissue  of  the 
body  which  undergoes  an  alteration  in  appearance  when  blood  formation 
is  stimulated  by  such  means  as  repeated  bleeding  or  destruction  of  cor- 
puscles by  the  injection  of  toxic  agents.  Under  such  conditions  the  red 
marrow,  which  in  adult  mammals  is  present  only  in  the  epiphyses,  is  found 
to  have  increased  in  extent  and  in  many  cases  to  occupy  the  greater  part 


■fi     _ »d 


Fig.  376.     Section  of  red  marrow  of  mammal.     (Bohm  and  Davidoff.) 

a,  e,  erythroblasts;  6,  recticulum;  c,  myeloplax;  d,  g,  marro%v  cells; 

/,  a  marrow  cell  dividing ;  h,  a  space  which  was  occupied  by  fat. 

of  the  shaft  of  the  bone,  having  taken  the  place  of  the  yellow  marrow.  It 
is  in  the  red  marrow  therefore  that  we  must  seek  the  precursors  of  the  red 
blood  corpuscles.  In  the  bird  the  erythroblasts,  i.  e.  the  precursors  of  the 
nucleated  red  blood  corpuscles,  form  a  sort  of  inner  lining  to  the  dilated 
capillaries  of  the  marrow  (Fig.  377).  Here  we  can  see  all  grades  between 
the  colourless  nucleated  corpuscle  which  lies  nearest  the  periphery  and 
the  adult  red  oval  corpuscle  containing  haemoglobin,  lying  next  the 
lumen  and  ready  to  be  carried  away  in  the  blood  stream.  If  blood  forma- 
tion has  been  stimulated  by  repeated  bleeding,  this  blood-forming  tissue  is 
found  to  occupy  the  greater  part  of  the  lumen  of  the  marrow  capillaries. 
If  however  blood  formation  has  been  reduced  to  its  lowest  extent  by  a 
process  of  chronic  starvation,  the  erythroblasts  form  a  single  layer  of  cells 
just  inside  the  dilated  capillaries,  and  intermediate  stages  between  the  ery- 
throblasts and  the  fully  developed  erythrocytes  are  almost  entirely  wanting. 
In  the  frog  this  process  of  blood-corpuscle  formation  occurs  only  at  one 
period  of  the  year,  namely,  in  the  early  summer,  and  it  is  only  at  this  time 
that  the  bones  are  found  to  contain  red  marrow.    In  mammals  the  process 


THE  RED  BLOOD   CORPUSCLES 


877 


is  very  similar.  Li  the  red  marrow  are  a  number  of  nucleated  cells  con- 
taining haemoglobin,  which  are  thought  by  Lowit  to  be  themselves  derived 
from  colourless  nucleated  cells.  In  the  confused  medley  of  colourless  cells 
which  are  found  in  the  bone  marrow  and  are  precursors  of  all  the  varied 
corpuscles  found  in  the  blood,  it  is  difficult  to  be  certain  of  the  identity 
of  the  colourless  erythroblasts  and  to  distinguish  them  from  the  smaller 
colourless  cells  engaged  in  bone  formation  or  in  the  production  of  leuco- 
cytes. The  haemoglobin-containing  cells  are  often  to  be  seen  in  process 
of  division,  and  the  nucleated  daughter-cells  appear  to  undergo  a  process 
of  nucleolysis,  the  nucleus  being  extruded  or  dissolved.  When  blood  forma- 
tion is  quickened  as  the  result  of  previous  destruction  or  loss,  some  of  these 


Fig.  377.     Section  of  red  marrow  of  pigeon.     (Denys.) 
Ic,  eosinophile  leucocytes ;  eg,  fat  cells ;  e,  nucleus  of  endothelial  cell  of 
blood  vessel;    ca,    blood  capillary;    cr,   erythroblasts   lying   within   vascular 
endothelium  ;  glr,  fully  formed  red  corpuscles. 


immature  nucleated  blood  discs  may  make  their  way  into  the  circulation 
and  be  found  in  the  blood,  where  they  are  spoken  of  as  normoblasts. 

How  long  a  corpuscle  continues  to  exist  in  the  circulating  blood  is  not 
known.  The  experiments,  made  to  determine  the  length  of  time  during 
which  foreign  corpuscles  such  as  those  of  birds  can  be  recognised  after 
injection  into  the  circulation  of  a  mammal,  are  evidently  beside  the  mark, 
since  these  foreign  cells  will  be  destroyed  by  the  serum  and  rapidly  taken 
up  by  the  phagocytes  of  the  body.  Sooner  or  later  however,  every  cor- 
puscle undergoes  disintegration,  a  process  which  is  generally  ushered  in 
by  the  ingestion  of  the  corpuscle  by  some  phagocyte  cells.  Thus  in  the 
haemolyniph  glands  and  in  the  spleen,  we  find  large  cells  which  have  englobed 
red  corpuscles  and  in  which  we  can  recognise  pigment  granules  derived 
from  their  destruction.  The  chief  place  of  disintegration  of  the  haemoglobin 
is  certainly  the  liver,  i.  c.  the  organ  where  the  haematin  is  converted  into  bile 
pigment.  Injection  of  haemoglobin  into  the  circulation  causes  increased 
secretion  of  bile  pigment.     A  section  of  normal  liver  immersed  in  potassium 


878  PHYSIOLOGY 

ferrocyanide  and  then  in  acid  alcohol  shows  the  presence  of  iron  by  the 
assumption  of  a  blue  colour.  The  amount  of  iron  which  can  be  dernorj 
strated  in  the  liver  in  this  way  is  enormously  increased  by  any  condition 
which  augments  the  rate  of  blood  destruction.  In  the  pathological  condition 
known  as  pernicious  anaemia,  as  well  as  after  poisoning  by  the  injection  of 
pyrogallic  acid  or  tohrylene  diamine,  both  of  which  agents  cause  a  great 
destruction  of  red  blood  corpuscles,  the  liver  on  treatment  in  this  way 
assumes  a  deep  blue  colour.  In  some  cases  crystals  of  haemoglobin  have 
been  seen  within  the  nucleus  of  the  liver  cell.  In  the  destruction  of  the 
corpuscles  the  haemoglobin  is  dissociated  first  into  its  protein  and  chromo- 
genic  moieties;  the  haemochromogen  then  loses  its  iron  and  is  converted 
into  bile  pigment.  Tire  iron  remains  in  the  liver  and  is  probably  retained 
in  the  body  and  utilised  for  the  formation  of  the  fresh  haemoglobin  necessary 
for  the  newly  forming  red  blood  corpuscles  in  the  bone  marrow. 


SECTION   III 

THE    BLOOD    PLATELETS 

The  very  existence  of  these,  the  third  class  of    formed  elements  of  the 

blood,  is  still  a  matter  of  dispute.     If  a  drop  of  osmic  acid  be  placed  on  the 

finger,    which     is    then     pricked     through 

the    drop    so    that    the    shed    blood    may 

mix    with    the    fixing     fluid     directly    it 

leaves  the  vessels,  a  drop  of  the  mixture 

when    examined     under     high     powers    is 

seen    to    present    a    number    of    granular 

bodies    from    one-third    to    one-half     the 

diameter  of  a  red  blood  corpuscle.      Their 

number    has   been    variously   stated   from 

180,000   to    800,000    per   cubic   millimetre, 

so    that    they    rank    second    in    point    of 

,  i    i      ■     i  Fio.  378.  Blood  platelets,  highly  mag  - 

number    among    the    morphological     con-       nified,  showing  the  amoeboid  forms 

StituentS      of      the       blood.        Their      shape         which  they  assume  when  examined 

*  under  suitable  conditions,  and  also 

varies  considerably,      home  are    bi-convex       exhibiting  the  chromatic  particle 
structures ;  others  are  flatter  with  numerous       *hj<A  e*ch  platelet  contains,  and 

which    has    been    regarded    as    a 

processes.       They    may    be    isolated    or      nucleus.    (After  Kopscn.) 
agglutinated    into    clumps.      Their    shape, 

size,  and  number   vary  according   to   the  fluid   with   which   the  blood    is 
mixed  or  the  method  adopted  for  their  demonstration. 

When  blood  is  examined  in  Hayem's  fluid  1  nearly  all  the  blood  platelets  appear 
as  bi-convex  discs.  The  best  method  for  the  display  of  platelets  is  apparently  that 
given  by  Deetjen.  The  drop  of  blood  is  received  directly  from  the  vessels  on  to  a  sheet 
of  solid  agar  jelly  which  is  made  with  0-6  per  cent,  sodium  chloride  solution  with  the 
*  addition  pf  sodium  metaphosphate  and  bipotassium  phosphate.  When  examined  on 
this  medium  large  numbers  of  platelets  are  seen,  each  of  them  provided  with  numerous 
processes  (Fig.  378).  Their  central  part  is  more  strongly  refracting  than  the  periphery 
and  stains  with  basic  dyes,  so  that  it  has  been  regarded  as  a  nucleus. 

Similar  platelets  are  observed  when  the  blood  is  received  into  normal 
salt  solution ;    as  the   mixture  clots,  the  filaments  of  fibrin   can   be  seen 

1  Hayem's  fluid  is  made  up  as  follows  : 

Distilled  water 200  c.c. 

Sodium  chloride            .....  1  grm. 

Sodium  sulphate            .....  5  grm. 

Iodine  in  iodide  of  potassium          .          .          .  3-5  c.c. 

879 


880  PHYSIOLOGY 

often  to  radiate  from  a  disintegrated  blood  platelet  as  f  toiti  a  centre.  That 
the  blood  platelets  are  concerned  in  the  production  of  clots  is  shown  by 
the  fact  that  in  the  living  vessels  blood  platelets  aggregate  round  any 
injured  spot  in  the  vessel  wall,  and  later  fuse  together  so  as  to  form  an 
adherent  thrombus  or  clot  which  covers  the  seat  of  injury  and  helps  to 
repair  the  damage  and  to  prevent  the  escape  of  the  contents  of  the  blood 
vessel.  Blood  platelets  have  been  found  only  in  mammalian  blood  and 
are  certainly  absent  from  frogs'  blood  as  well  as  from  the  blood  of  fishes 
and  birds,  nor  can  they  be  demonstrated  in  any  of  the  serous  fluids  even  in 


Fig.  379.     Blood  corpuscles  and  blood  platelets,  within  a  small  vein. 

(SCHAFER  after  OsLER.) 

mammals.  Certain  nucleated  spindle-shaped  cells  have  been  described 
in  frogs'  blood  as  blood  platelets,  but  these  are  probably  immature 
red  blood  corpuscles  and  not  homologous  with  the  blood  platelets  of 
mammals.  (Blood  platelets  themselves  were  regarded  by  Hayem  as  stages 
in  the  formation  of  red  blood  corpuscles.)  If  the  blood  of  an  animal  be 
defibrinated  by  repeated  bleeding,  whipping  and  returning  to  the 
veins  of  the  animal,  it  will  be  found  for  the  next  few  days  to  be  quite 
free  from  blood  platelets.  There  is  no  doubt  therefore  that  it  is  possible 
by  the  most  varied  means  to  demonstrate  the  existence  of  blood  platelets 
in  shed  blood.  According  to  the  method  adopted,  so  do  the  number  and 
form  of  these  platelets  vary.  Moreover  they  can  be  seen  to  be  deposited 
from  the  circulating  blood  in  the  living  animal  on  any  injured  portion  of 
the  vessel  wall  or  on  any  foreign  body  introduced  into  the  blood  current 
(Fig.  379).  On  the  other  hand,  it  is  possible  to  obtain  blood  in  an  un- 
coagulated  state  from  the  vessels  in  which  no  trace  of  platelets  is  to  be 
observed.  As  Buckmaster  has  shown,  a  film  of  blood  examined  in  a 
platinum  loop  and  kept  carefully  at  the  temperature  of  the  body  presents 
no  platelets  on  microscopic  examination ;  and  the  same  absence  of  platelets 
is  to  be  noted  when  blood  is  received  into  sterile  blood  serum  of  the  same, 
species  of  animal  and  kept  at  the  body  temperature.  On  allowing  these 
specimens  of  blood  to  cool,  blood  platelets  make  their  appearance.  Many 
specimens  of  non-coagulable  plasma,  such  as  peptone  plasma  or  oxalate 
plasma,  can  be  separated  by  means  of  the  centrifuge  from  all  formed  ele- 
ments. If  the  plasma  be  cooled  to  0°  C.  for  twenty-four  hours,  a  precipitate 
indistinguishable  from  blood  platelets  is  found  to  have  been  produced 
under  the  action  of  cold.  We  are  therefore  probably  justified  in  con- 
cluding that  the  blood  platelets  do  not  form  a  constituent  of  normal  living 
blood,  but  are  produced  in  the  plasma  either  on  contact  with  foreign  bodies 
or  lowering  of  its  temperature  from  37°  C.  to  18°  or  20°  C.    All  the  various 


THE  BLOOD   PLATELETS  881 

fixing  fluids,  which  have  been  recommended  for  the  display  of  blood  platelets, 
may  owe  their  virtues,  not  to  the  fact  that  they  preserve,  but  to  the  fact 
that  they  'produce  platelets.  These  may  therefore  be  regarded  as  pre- 
cipitates produced  in  the  plasma  directly  it  undergoes  alterations,  their 
appearance  being  the  first  sign  of  changes  in  this  fluid.  They  consist  of 
some  substance  probably  belonging  to  the  class  of  nucleo-proteins,  and 
like  these  yield  a  precipitate  on  gastric  digestion,  and  have  a  specific  affinity 
for  basic  dyes.  Even  after  their  first  appearance  they  are  unstable,  tending 
to  undergo  further  alteration  and  to  give  oil  to  trie  surrounding  plasma 
substances  which  play  an  important  part  in  the  formation  of  fibrin  ferment 
and  in  the  coagulation  of  the  blood. 


56 


SECTION  IV 

THE   COAGULATION    OF   THE    BLOOD 

In  the  process  of  coagulation,  while  the  corpuscles  remain  to  a  large  extent 
intact,  the  plasma  becomes  solid  from  the  production  in  it  of  a  network  of 
fibrin,  being  converted  into  fibrin  plus  serum.  The  question  of  coagulation 
involves  the  consideration  of  the  precursors  of  fibrin  and  of  the  conditions 
which  determine  the  conversion  of  these  precursors  into  fibrin.  It  is  evi- 
dently impossible  to  arrive  at  any  conclusions  on  these  points  during  the  few 
minutes  which  elapse  between  the  time  at  which  the  blood  leaves  the  vessels 
and  the  appearance  of  the  clot.  We  must  therefore  find  some  means  of 
retarding  coagulation  so  that  we  may  obtain  the  plasma  free  from  corpuscles 
and  be  able  to  initiate  coagulation  in  this  cell-free  fluid  at  will.  Having 
succeeded  in  staying  the  process  of  coagulation,  it  is  always  possible  to 
obtain  a  cell-free  plasma  either  by  allowing  the  blood  to  settle  or,  better  still, 
by  the  employment  of  a  centrifugal  machine.  Under  the  influence  of 
centrifugal  force  the  corpuscles  are  thrown  rapidly  down  to  the  bottom  of 
the  tube  and  the  clear  supernatant  plasma  can  be  syphoned  off. 

METHODS  OF  PREVENTING  COAGULATION 

(1)  So  long  as  the  blood  is  in  contact  with  the  uninjured  vessel  it  remains  fluid. 
If  the  jugular  vein  of  a  large  animal  such  as  the  horse  be  tied  in  two  places,  the  blood 
contained  between  the  ligatures  will  remain  fluid,  sometimes  for  days.  If  the  tube  of 
vein  be  hung  up,  the  corpuscles  sink  to  the  bottom  and  the  plasma  in  the  upper  part 
of  the  tube  can  be  poured  from  one  vein  to  another  without  undergoing  coagulation. 
On  pouring  it  into  a  glass  vessel  or  bringing  it  into  contact  with  foreign  substances,  it 
undergoes  coagulation. 

(2)  When  an  incision  is  made  in  the  ordinary  way  into  a  blood  vessel  of  a  bird,  the 
issuing  blood  clots  very  rapidly.  The  clotting  is  initiated  by  a  substance  contained  in 
the  tissues  surrounding  the  vessels.  If  therefore  the  vessel  be  isolated  and  a  perfectly 
clean  glass  cannula  be  inserted  into  it,  care  being  taken  not  to  bring  the  cannula  in 
contact  with  any  of  the  surrounding  tissues,  blood  can  be  drawn  off  into  a  sterilised 
beaker  perfectly  free  from  dust  and  will  remain  unclotted  for  days.  Such  blood  can 
be  centrifuged  and  the  cell-free  plasma  used  for  experiment.  The  same  procedure 
does  not  apply  to  the  mammal,  where  even  the  most  scrupulous  care  to  prevent  con- 
tamination by  the  tissue  juices  will  not  prevent  the  blood  from  clotting  on  leaving  the 


(3)  Clotting  can  be  excited  even  in  the  living  vein  by  introducing  into  the  blood  any 
solid  substance  which  is  wetted  by  the  blood.  If  the  contact  of  the  blood  with  such 
substances  be  prevented  by  receiving  it  into  vessels  previously  coated  with  oil  or  with 
paraffin  and  scrupulously  free  from  dust,  clotting  may  often  be  delayed  for  many  hours. 

(4)  Cooled  plasma.     Horses'  blood  is  received  directly  into  a  narrow  vessel  immersed 

882 


THE  COAGULATION  OF  THE   BLOOD  883 

iu  ice,  so  as  to  cool  it  rapidly  to  between  0°  C.  and  1°  C.  At  this  temperature  it  remains 
fluid  for  an  indefinite  time.  The  corpuscles  sink,  and  the  supernatant  plasma  can 
be  decanted  and  filtered. 

(5)  Methods  involving  Mixture  with  Neutral  Salts,  (a)  Magnesium  sulphate.  Blood 
from  any  animal  is  received  into  one-quarter  its  bulk  of  a  25  per  cent,  solution  of 
magnesium  sulphate. 

(6)  Sodium  sulphate.  Blood  is  mixed  on  leaving  the  vessels  with  an  equal  volume 
of  half-saturated  sodium  sulphate  solution.  The  plasma  obtained  in  either  of  these 
ways  is  known  as  salt  plasma.  Clotting  is  indefinitely  delayed  in  either  case,  but  it 
can  be  induced  by  suitable  treatment  of  the  separated  plasma. 

(6)  Mellwds  depending  on  Decalcification  of  the  Blood.  Oxalate  plasma  is  obtained 
by  receiving  blood  into  a  solution  of  sodium  oxalate  so  that  the  total  blood  contains 
1  per  1000  of  the  oxalate.  Instead  of  oxalate  we  may  use  sodium  fluoride,  the 
proportion  in  this  case  being  3  parts  of  NaF  per  1000  blood. 

(7)  Melliods  depending  on  the  use  of  certain  Substances  of  Animal  Origin,  (a)  Peptone 
plasma  i3  obtained  by  injecting  rapidly  into  the  veins  of  a  dog  or  cat  in  a  fasting  con- 
dition a  solution  of  commercial  peptone  in  the  proportion  of  0-3  grm.  peptone  per  kilo, 
of  the  animal.  The  effect  of  this  injection  is  to  cause  a  rapid  fall  of  blood  pressure 
and  hurried  respiration,  and  the  animal  then  passes  into  a  state  of  coma  which  may 
last  an  hour  or  two.  On  drawing  off  the  blood  immediately  after  the  fall  of  pressure 
has  taken  place,  it  is  found  to  be  uncoagulable,  and  cell-free  plasma  can  be  obtained 
from  it  by  the  use  of  the  centrifuge.  A  number  of  animal  extracts  act  in  a  somewhat 
similar  fashion,  such  as  extract  of  crayfish,  of  mussels,  etc. 

(6)  Leech  extract  or  hirudin  plasma.  Peptone  is  efficacious  in  retarding  clotting  only 
when  it  is  injected  into  the  animal's  veins  directly,  and  has  no  influence  in  this  direction 
if  it  be  mixed  with  the  blood  as  it  flows  out  of  the  vessels.  It  has  long  been  faniiliar  to 
physicians  that  the  bites  made  by  leeches  continue  to  bleed  for  a  considerable  time, 
and  it  was  shown  by  Haycraft  that  this  is  due  to  the  presence  of  an  anticoagulating 
substance  in  the  buccal  glands  of  the  leech.  This  substance,  which  has  the  properties 
of  an  albumose,  can  be  extracted  by  boiling  from  the  anterior  half  of  the  leech.  It 
will  destroy  the  coagulability  of  the  blood  either  when  injected  into  the  blood  stream 
or  when  blood  is  received  into  a  solution  of  hirudin. 

By  any  of  these  methods  it  is  possible  to  obtain  blood  plasma  free  from 
formed  elements.  The  conditions  which  will  bring  about  coagulation  in  such 
plasmata  are  strikingly  diverse.  Thus  in  cooled  plasma  a  simple  rise  of 
temperature  is  often  sufficient  to  bring  about  coagulation.  If  however 
the  cooled  plasma  be  filtered  several  times  through  two  thicknesses  of 
filter-paper,  being  kept  at  a  temperature  of  about  1°  C.  during  the  whole 
time,  it  loses  this  spontaneous  coagulability  on  warming.  It  can  still  be 
made  to  clot  by  the  addition  of  certain  substances  such  as  blood  serum  or  the 
washings  of  a  blood  clot,  and  in  some  cases  by  the  addition  of  tissue  extracts. 

Oxalate  plasma  clots  on  simple  addition  of  lime  salts.  Sodium  sulphate 
plasma  clots  on  dilution.  Magnesium  sulphate  plasma  will  not  clot  on 
dilution,  but  needs  in  addition  the  presence  of  some  blood  serum  or  some 
substance  derived  from  blood  serum.  In  both  these  cases  tissue  extracts 
have  no  influence.  By  a  careful  study  of  one  or  two  forms  of  plasma  we  can 
arrive  at  a  conception  of  the  processes  of  coagulation,  which  enables  us  to 
understand  the  behaviour  of  all  these  various  types.  We  may  take  as 
our  type  oxalate  plasma.  Oxalate  plasma,  as  procured  by  centrifuging  a 
specimen  of  horse's  blood  containing  0-1  per  cent,  sodium  oxalate,  is  a  clear 
yellow  fluid,  perfectly  free  from  formed  elements,  which  evinces  no  tendency 


884  PHYSIOLOGY 

to  clot.  On  adding  a  drop  of  calcium  chloride  to  such  plasma,  we  see  t  hat  it 
contains  an  excess  of  oxalate  from  the  production  of  a  precipitate  of  calcium 
oxalate.  If  calcium  chloride  be  added  drop  by  drop  so  as  to  be  present  in 
slight  excess,  and  the  plasma  be  then  kept  warm,  it  will  clot  within  a  time 
varying  from  a  few  minutes  to  an  hour.  The  clot  thus  formed  is  perfectly 
firm  and  the  vessel  can  be  inverted  without  any  of  its  contents  flowing  out. 
Very  often  no  retraction  of  the  clot  takes  place,  but  if  it  be  pressed  with  a 
glass  rod  or  with  the  ringers  a  clear  serum  is  squeezed  out  and  a  mass  of  pure 
fibrin  remains.  The  place  of  hme  can  be  taken  by  strontium,  but  barium 
and  magnesium  are  powerless  to  initiate  clotting.  We  must  therefore 
conclude  that  the  presence  of  a  soluble  calcium  salt  is  one  factor  of  those 
necessary  for  coagulation.  This  is  borne  out  by  the  fact  that  a  similar 
uncoagulable  blood  is  produced  by  the  action  of  sodium  fluoride.  Some 
difficulty  however  was  felt  when  it  was  found  that  sodium  citrate  might  be 
used  instead  of  sodium  oxalate  or  fluoride,  since  sodium  citrate  does  not 
produce  in  the  blood  any  precipitate  of  insoluble  hme  salts.  Here  then 
we  have  a  blood  containing  hme  in  solution  and  yet  uncoagulable.  The 
difficulty  has  been  cleared  up  by  the  work  of  Sabbatani  and  C.  J.  Martin. 
When  sodium  citrate  is  added  to  a  hme  salt,  a  double  salt  of  sodium  calcium 
citrate  is  formed,  in  which  the  calcium  is  in  the  anion  and  forms  part  of  the 
acidic  radical.  The  mere  presence  of  dissolved  calcium  is  not  sufficient 
for  clotting  to  take  place.  It  is  necessary  that  the  calcium  should  be  in  the 
form  of  a  salt  and  in  an  iomsed  condition,  such  as  calcium  chloride  or  calcium 
sulphate. 

Though  calcium  is  a  necessary  condition  for  the  occurrence  of  coagulation, 
it  cannot  be  regarded  as  a  precursor  of  the  protein,  fibrin.  If  the  composition 
of  the  plasma,  before  coagulation  has  been  set  up,  be  compared  with  that  of 
the  serum  which  has  separated  from  the  clot,  it  is  foimd  that  plasma  con- 
tains a  protein,  fibrinogen,  not  represented  in  the  serum,  which  must  there- 
fore be  the  precursor  of  fibrin.  Fibrinogen  belongs  to  the  class  of  globulins. 
It  can  be  separated  from  oxalate  plasma  by  half-saturation  with  common 
salt.  An  equal  volume  of  a  saturated  solution  of  sodium  chloride  is 
added  to  plasma  so  that  the  whole  mixture  contains  16  per  cent,  sodium 
chloride.  The  fluid  gradually  becomes  turbid  from  the  production  of  a 
precipitate  which,  at  first  granular,  rapidly  aggregates  to  form  a  stringy, 
sliniy  solid,  which  adheres  to  the  glass  rod  used  for  stirrmg.  This  mass 
can  be  taken  out  of  the  fluid,  washed  by  kneading  with  half-saturated 
sodium  chloride  solution,  and  then  redissolved  by  the  addition  of  distilled 
water.  With  the  salt  adhering  to  the  precipitate  a  dilute  saline  fluid  is 
formed  in  which  the  fibrinogen  is  soluble.  The  fibrinogen  can  be  purified  by 
repeating  the  precipitation  and  solution,  though  it  tends  to  lose  its  solubility 
in  the  process,  so  that  purification  is  always  attended  with  some  loss.  The 
solution  of  fibrinogen  thus  obtained  is  perfectly  clear  and  colourless.  On 
warming,  practically  the  whole  of  its  protein  is  thrown  down  between  56° 
and  60°  C.  The  same  precipitate  is  produced  on  heating  the  original  plasma, 
whereas  serum  obtained  by  the  expression  of  the  clot  does  not  give  any 


THE  COAGULATION  OF  THE  BLOOD  885 

precipitate  on  heating  until  a  temperature  of  68°  to  70°  C.  is  reached.  If  a 
solution  of  fibrinogen,  obtained  by  precipitating  with  sodium  chloride  and 
dissolving  in  distilled  water,  be  treated  with  a  drop  or  two  of  calcium  chloride, 
it  rapidly  clots  with  the  formation  of  typical  fibrin.  We  might  conclude 
from  this  experiment  that  fibrin  was  a  compound  produced  by  the  union 
of  calcium  salts  with  fibrinogen.  Further  experiments  show  however  the 
untenabihty  of  this  hvpothesis.  If  the  fibrinogen  has  been  thoroughly 
purified  by  repeated  precipitation  and  re-solution,  calcium  salts  are  found 
to  have  entirely  lost  their  power  of  causing  coagulation.  Such  a  purified 
fibrinogen  can  still  be  made  to  clot  by  the  addition  either  of  serum  or  of  the 
washings  of  a  blood  clot,  or  of  the  watery  extract  of  alcohol-coagulated 
serum.  This  power  of  serum  to  convert  fibrinogen  into  fibrin  is  due  to  the 
presence  in  it  of  minute  quantities  of  a  substance  which  has  been  designated 
as  '  fibrin  ferment  '  or  thrombin.  It  has  been  regarded  as  a  ferment  because 
it  is  active  in  minimal  quantities  and  is  stated  not  to  be  appreciably  used  up 
in  the  process  of  clotting.  Thus  if  we  add  some  serum  to  a  fibrinogen 
solution  we  can  cause  clotting,  and  then  on  squeezing  the  clot  obtain  a  serum 
which  will  bring  about  coagulation  when  added  to  a  fresh  portion  of  fibrino- 
gen. Considerable  doubt  however  has  been  thrown  on  the  ferment  nature 
of  thrombin  by  the  recent  work  of  Eettger  in  Howell's  laboratory.  Eettger 
shows,  in  the  first  place,  that  the  statement  of  the  preceding  sentence  is  true 
only  if  a  large  excess  of  thrombin  solution  be  made  use  of  in  the  first  instance . 
If  small  quantities  of  thrombin  solution  be  added  to  large  quantities  of 
plasma  or  of  pure  solutions  of  fibrinogen,  the  amount  of  fibrin  obtained 
is  proportional  to  the  amount  of  thrombin  added.  This  is  shown  in  the 
following  experiment : 

5  drops  of  thrombin  gave  0-2046  grm.  fibrin. 
10      „  „  0-3573     „      „ 

20      „  „  0-6089     „      „ 

40      „  ..  1-5872     ,.       .. 

Moreover  the  action  of  thrombin  on  fibrinogen  solutions  is  almost 
independent  of  temperature,  occurring  practically  as  rapidly  at  17°  C.  as 
at  40°  C.  It  has  been  found  that  there  is  only  a  slight  increase  in  the  rate 
of  action  of  snake  venom  on  fibrinogen  solutions  when  warmed  from  20°  to 
40°  C.  Eettger  therefore  regards  fibrin  as  formed  by  the  union  of  thrombin 
and  fibrinogen.  This  union  is  apparently  very  unstable.  If  fibrin  be 
extracted  with  a  3  per  cent,  salt  solution  for  some  time,  part  of  it  goes  into 
solul  ion,  and  the  solution  is  found  to  contain  thrombin.  In  the  same  way  the 
thrombin  may  be  re-extracted  from  the  fibrin  if  the  latter  be  allowed  to 
putrefy. 

From  all  the  different  kinds  of  plasma  which  have  been  enumerated  above, 
the  purified  fibrinogen  can  be  obtained  by  the  use  of  sodium  chloride,  and 
in  every  case  can  be  made  to  clot  by  the  addition  of  serum  or  of  a  solution  of 
thrombin.  The  last  change  in  the  act  of  cl<  itting  is  therefore  the  change  from 
fibrinogen  to  fibrin,  and  this  event  is  brought  about  by  the  intervention  of 


886  PHYSIOLOGY 

thrombin.  It  cannot  be  at  this  stage  of  the  process  that  the  calcium  salts 
exercise  their  influence,  since  '  fibrin  ferment '  or  thrombin  will  cause  the 
coagulation  of  fibrinogen  in  the  total  absence  of  soluble  calcium  salts  and 
even  in  the  presence  of  a  slight  amount  of  ammonium  oxalate.  Moreover 
Hammarsten  has  shown  that  the  calcium  content  of  fibrin  is  no  greater  than 
that  of  the  fibrinogen  from  which  it  is  formed. 

The  fact  that  a  solution  of  pure  fibrinogen  is  made  to  clot  by  thrombin 
and  by  this  alone  renders  such  a  solution  an  excellent  reagent  for  the  presence 
of  the  '  ferment.'  By  this  means  we  can  show  that  thrombin  is  absent  in 
circulating  blood.  If  blood  be  received  direct  from  the  vessels  into  absolute 
alcohol  and  the  precipitate,  after  coagulation  by  alcohol,  be  extracted  by 
water,  the  extract  is  foimd  to  contain  no  trace  of  ferment.'  The  same  state- 
ment applies  to  fresh  oxalate  plasma.  If  however  oxalate  plasma  be  made 
to  clot  by  the  addition  of  calcium  salts,  the  serum  squeezed  from  the  clot 
is  found  to  contain  thrombin.  In  the  process  of  coagulation  therefore,  not 
only  is  there  a  conversion  of  fibrinogen  to  fibrin,  but  there  is  an  actual 
formation  of  the  agent  which  is  responsible  for  this  change,  namely,  thrombin 
or  fibrin  ferment.  Our  next  step  therefore  must  be  to  inquire  into  the 
precursors  of  the  thrombin  and  the  conditions  of  its  formation. 

If  oxalate  plasma  be  cooled  to  0°  C.  for  two  or  three  days,  a  scanty 
granular  precipitate  is  produced.  This  can  be  centrifuged  off  or  separated 
by  filtration  through  several  thicknesses  of  paper.  It  is  then  found  that  the 
remaining  plasma  can  no  longer  be  made  to  coagulate  by  the  addition  of 
lime  salts,  although  it  still  contains  fibrinogen,  which  is  converted  into  fibrin 
on  the  addition  of  thrombin.  If  the  precipitate  be  collected  and  treated 
with  calcium  chloride  and  the  mixture  added  to  the  oxalate  plasma,  the 
latter  clots.  The  same  effect  is  produced  if  the  precipitate  plus  calcium 
be  added  to  a  pure  solution  of  fibrinogen.  We  must  conclude  that  the  pre- 
cipitate, though  itself  not  fibrin  ferment,  will  give  rise  to  fibrin  ferment  on 
treatment  with  lime  salts.  It  was  therefore  designated  by  Hammarsten 
'  prothrombin,'  and  regarded  as  the  precursor  of  thrombin. 

Thus  far  practically  all  workers  on  the  subject  are  agreed.  Coagulation 
of  the  blood  is  due  finally  to  the  interaction  of  thrombin  and  fibrinogen. 
The  fibrinogen  is  present  as  such  in  the  circulating  plasma.  Thrombin  is 
not  contained  in  the  circulating  blood,  but  is  produced  from  some  precursor 
or  precursors  after  the  blood  has  been  shed.  For  the  production  of  thrombin 
the  presence  of  calcium  salts  is  necessary.  Further  research  on  the  nature 
of  the  precursor  '  prothrombin  '  has  shown  that  the  matter  is  not  quite  so 
simple  as  imagined  by  Hammarsten.  In  the  following  account  we  shall 
adhere  chiefly  to  that  given  by  Morawitz,  reserving  most  of  the  criticisms 
and  limitations  to  be  made  to  this  theory  for  the  historical  sketch  of  the 
theories  of  clotting  at  the  end  of  this  section. 

Oxalate  plasma,  which  has  been  separated  from  the  precipitate  of  pro- 
thrombin, can  be  made  to  coagulate  by  the  addition  of  extracts  of  almost  any 
animal  tissues  together  with  linie  salts,  and  these  therefore  were  supposed 
to  contain  prothrombin  similar  to  that  obtained  by  cooling  oxalate  plasma. 


THE  COAGULATION  OF  THE  BLOOD  887 

These  extracts  even  on  mixture  with  calcium  are  however  without  effect  on 
pure  solutions  of  fibrinogen,  and  moreover  the  precipitate  produced  by  cold, 
if  thoroughly  washed  before  treatment  with  lime  salts,  loses  its  power  of 
evoking  coagulation  in  fibrinogen  solutions.  Prothrombin  is  therefore 
unable  by  itself,  even  on  addition  of  lime  salts,  to  produce  fibrin  ferment, 
but  needs  the  co-operation  of  some  other  substance,  which  is  contained  in 
oxalate  plasma  and  which  generally  adheres  in  sufficient  quantities  to  the 
precipitate  produced  by  cooling.  Three  factors  are  therefore  necessary 
for  the  production  of  fibrin  ferment :  first,  lime  salts ;  secondly,  a  substance 
present  in  the  precipitate  of  prothrombin  as  well  as  in  most  animal 
tissues;  and  thirdly,  a  substance  present  in  solution  in  oxalate  plasma. 
These  two  latter  substances  have  been  designated  by  Morawitz  thrombo- 
kinase  and  thrombogen.  Thrombokinase  is  contained  in  tissues  and  also 
in  the  blood  platelets.  It  can  be  obtained  by  extraction  of  the  stroma 
of  the  red  blood  corpuscles  or  of  the  bodies  of  lymph  cells  or  leucocytes. 
Separation  of  the  blood  platelets  by  cooling  and  filtration  abolishes 
the  spontaneous  coagulability  of  any  form  of  plasma.  The  thrombogen 
is  contained  in  solution  in  oxalate  plasma.  It  is  therefore  concluded  that 
when  blood  leaves  the  vessels  there  is  a  disintegration  of  the  blood  platelets 
with  the  liberation  of  thrombokinase.  This  acts  upon  thrombogen  in  the 
presence  of  lime  salts  and  produces  thrombin.  By  the  intermediation  of 
the  thrombin  the  fibrinogen  also  present  in  solution  in  the  plasma  is  con- 
verted into  fibrin .  The  changes  occurring  in  shed  blood  and  resulting  in  the 
production  of  a  clot  are  therefore  mainly  concerned  with  the  production  of 
the  fibrin  ferment.  This  view  of  the  essential  characters  of  coagula- 
tion is  borne  out  by  observations  on  other  forms  of  plasma,  especially  of 
plasma  of  birds'  blood.  This  when  obtained  with  scrupulous  cleanliness 
so  as  to  avoid  any  contamination  with  dust  or  with  the  tissues  remains 
permanently  uncoagulable.  In  the  plasma  got  by  centrifuging  the  blood 
no  blood  platelets  are  to  be  seen,  and  no  precipitate  is  produced  by 
exposure  to  a  temperature  of  0°  C.  We  may  say  therefore  that  blood 
platelets  with  their  contained  thrombokinase  are  absent  from  birds'  blood, 
and  with  them  the  property  of  spontaneous  coagulability.  It  is  also 
free  from  fibrin  ferment,  but  contains  thrombogen  as  well  as  soluble  lime 
salts.  It  is  only  necessary  therefore  to  add  thrombokinase  in  the  shape 
of  a  watery  extract  of  any  tissue  in  order  to  cause  the  appearance  of  fibrin 
ferment  and  the  conversion  of  the  fibrinogen  already  present  in  the  plasma 
into  fibrin. 

In  every  case  the  initiation  of  the  act  of  clotting  would  seem  to  depend 
on  the  setting  free  of  thrombokinase  in  the  plasma.  In  mammalian  blood, 
although  thrombokinase  can  be  derived  from  red  or  white  corpuscles^  we 
have  no  reason  to  believe  that  there  is  any  appreciable  disintegration  of  these 
formed  elements  when  the  blood  leaves  the  vessels.  In  oxalate  blood 
leucocytes  can  be  seen  alive  and  exercising  amoeboid  movements  two  or  three 
days  after  the  blood  has  left  the  vessels,  and  although  certain  observers  have 
assumed  the  presence  of  explosive  corpuscles  which  break  up  directly  the 


888  PHYSIOLOGY 

lilood  loaves  the  vessels,  the  presence  of  such  corpuscles  in  the  higher  animals 
has  not  been  demonstrated,  though  in  some  invertebrata  they  are  certainly 
present.  The  sole  source  therefore  of  the  thrombokinase  is  the  very  perish- 
able formed  elements  of  which  we  have  spoken  as  the  blood  platelets.  The 
very  existence  of  this  element  is  doubtful  in  normal  blood.  What  is  certain 
is  that  any  slight  change  in  the  plasma,  whether  due  to  contact  with  a  foreign 
object  or  to  cooling  of  the  blood,  causes  the  appearance  of  these  elements. 
The  first  act  therefore'  in  coagulation  is  the  appearance  of  the  blood  platelet 
and  its  disintegration  with  the  setting  free  of  thrombokinase.  The  part 
played  by  the  platelets  in  coagulation  is  of  great  importance  in  maintaining 
the  integrity  of  the  vascular  system.  If  a  fine  needle  be  thrust  through  the 
wall  of  a  venous  capillary  which  is  kept  under  observation  by  the  microscope, 
it  will  be  seen  that  the  blood,  as  it  flows  past  the  injured  spot,  deposits  blood 
platelets  on  the  side  of  the  puncture.  These  aggregate  to  form  a  plug  closely 
adherent  to  the  wall  of  the  vessel,  which  effectively  prevents  any  escape  of 
the  contents  of  the  capillary.  The  blood  platelets  fuse  so  as  to  form  a  mass 
of  fibrin,  and  later  on  by  the  growth  of  the  adjacent  endothelial  cells  the 
thrombus  is  organised,  converted  into  connective  tissue,  and  covered  with 
a  layer  of  endothelium  continuous  with  the  rest  of  the  vessel.  The  same 
process  occurs  when  any  part  of  the  lining  membrane  of  a  large  vessel  is 
injured.  Thus  destruction  of  a  patch  of  endothelium  in  a  vein  leads  to 
the  deposition  of  blood  platelets  over  the  patch  and  the  formation  of  a 
'  thrombus  '  adherent  to  the  wall.  From  this  thrombus  coagulation  may 
spread  through  the  rest  of  the  contents  of  the  vessel  and  produce  thrombosis 
of  the  whole  vein.  Under  healthy  conditions  the  thrombus  serves  simply 
to  cover  the  bare  area  in  the  wall  of  the  vein  and  is  grown  over  later  by 
endothelium,  so  restoring  the  integrity  of  the  vessel  wall.  If  we  believe 
in  the  pie-existence  of  blood  platelets  in  the  circulating  blood,  we  must 
assume  the  first  act  in  coagulation  to  be  the  disintegration  of  these  elements 
and  the  setting  free  of  thrombokinase.  If  we  disbelieve  in  their  pre-existence, 
the  first  act  in  coagulation  must  be  a  change  in  the  plasma  itself  (which 
perhaps  can  be  regarded  as  a  dropsical  protoplasm),  leading  to  the  separa- 
tion of  an  unstable  substance,  thrombokinase,  in  the  form  of  a  disc-like 
precipitate  which  rapidly  undergoes  further  changes,  reacting  with  the 
thrombogen  remaining  in  solution  in  the  plasma  with  the  production  of  fibrin 
ferment. 

Why  does  the  blood  not  clot  in  the  vessel  ?  No  theory  of  coagulation 
can  be  satisfactory  which  does  not  account  at  the  same  time  for  the  preserva- 
tion of  the  fluidity  of  the  circulating  blood.  One  factor  at  any  rate  in  the 
prevention  of  intravascular  clotting  must  be  the  nature  of  the  surfaces  with 
which  the  blood  comes  in  contact.  The  blood,  even  of  mammals,  can  be 
prevented  for  a  time  from  clotting  if  it  be  kept  carefully  from  contact  with 
any  foreign  substance  which  is  wetted  by  it,  as  for  instance  when  it  is 
received  into  vessels  free  from  dust  and  coated  with  a  layer  of  oil  or  paraffin. 
On  the  other  hand,  free  contact  with  such  substances,  as  occurs  when  the 
blood  is  whipped,  materially  hastens  the  process  of  coagulation.     One  must 


THE  COAGULATION  OF  THE  BLOOD  88£ 

therefore  conclude  that  mere  contact  with  a  foreign  body  has  a  direct 
destructive  action  either  on  the  plasma  leading  to  the  formation  of  blood 
platelets,  or  on  the  latter,  leading  to  their  disintegration  and  the  discharge 
of  thfombokdnase.  Birds'  blood  for  instance  can  be  made  to  clot  without 
the  addition  of  tissue  juice  if,  by  increasing  the  mechanical  insult  as  by 
violent  whipping,  nitration  through  a  clay  cell,  or  addition  of  water,  we 
destroy  the  leucocytes  and  red  blood  corpuscles  so  leading  to  the  liberation 
of  their  contained  thrombokinase.  Another  factor  is  probably  the  presence 
of  what  we  may  call  antithrombins  in  circulating  blood.  Although  evidence 
of  the  existence  of  these  bodies  is  still  somewhat  uncertain,  the  fact  that 
blood  serum  often  has  an  inhibitory  effect  on  the  action  of  a  solution  of  fibrin 
ferment  points  to  the  presence  in  the  serum  of  some  antibody  to  the  ferment. 
One  must  assume  too  that  processes  of  disintegration  are  continually  occur- 
ring in  the  blood  and  involving  the  plasma,  blood  platelets,  and  leucocytes, 
just  as  we  know  them  to  affect  the  red  blood  corpuscles.  In  the  healthy 
animal  the  liberation  of  thrombokinase,  which  must  take  place  vmder  these 
circumstances,  has  no  influence  in  producing  clotting.  The  organism  therefore 
must  possess  means  of  neutralising  the  presence  of  small  quantities  either  of 
kinase  or  of  fibrin  ferment.  When  small  quantities  of  either  of  these  sub- 
stances are  injected  into  the  blood  stream,  no  coagulation  takes  place,  but  the 
blood  obtained  after  the  injection  clots  with  less  readiness  than  before,  a 
change  which  can  be  ascribed  only  to  the  production  in  the  body  of  anti- 
kinase  or  of  antithrombin.  This  production  of  anticoagulins  must  be 
continually  taking  place  and  must  co-operate  in  the  preservation  of  the  fluid 
state  of  the  blood  while  in  the  vessels. 

INTRAVASCULAR  CLOTTING.  On  account  of  the  protective  mechan- 
isms with  which  the  animal  organism  is  endowed,  the  production  of  clotting 
in  the  vessels  of  the  living  animal  is  not  readily  effected  by  the  injection 
of  thrombin.  Solutions  obtained  by  Schmidt's  method  from  alcohol- 
coagulated  serum  are  generally  without  effect,  and  we  have  to  inject  a 
very  strong  solution  of  thrombin  or  the  strong  fibrin  ferment  contained  in  the 
venom  of  certain  snakes  in  order  to  bring  about  coagulation  of  the  blood  in 
the  vessels.  Intravascular  clotting  is  more  easily  effected  by  the  injection  of 
thrombokinase.  It  was  shown  by  Wooldridge  that  normal  saline  extracts 
of  tissues  rich  in  cells,  such  as  the  thymus,  lymph  glands,  or  testis,  causes 
invariably  extensive  thrombosis.  If  such  extracts  be  acidified  with  acetic 
acid,  a  precipitate  is  produced  which  is  soluble  in  dilute  alkalies,  and  on 
gastric  digestion  yields  a  precipitate  rich  in  phosphorus.  Alkaline  solutions 
of  the  acid  precipitate  bring  about  intravascular  clotting  when  injected  into 
the  blood  stream.  According  to  Wooldridge  the  injected  substance  takes 
part  in  the  formation  of  the  clot,  and  he  therefore  gave  it  the  name  of  '  tissue 
fibrinogen.'  It  is  usual  to  regard  these  tissue  fibrinogens  as  nucleo-proteins. 
They  are  certainly  rich  in  lecithin,  and  the  precipitate  obtained  from  them  on 
gastric  digestion  may  contain  as  much  as  25' per  cent,  of  this  substance. 
They  must  be  derived  either  from  the  cytoplasm  or  from  the  interstitial 
fluid  of  the  tissues,  and  it  is  still  doubtful  whether  we  are  justified  in  giving 


890  PHYSIOLOGY 

them  the  name  of  micleo-proteins  or  whether  we  should  not  rather  classify 
them  with  the  phospho-protcins  which  play  so  great  a  part  in  the  building  up 
of  the  cytoplasmic  part  of  the  cell.  We  may  explain  the  action  of  these 
tissue  extracts  as  due  to  their  containing  thrombokinase.1  Their  injection 
would  resemble  therefore  the  liberation  of  thrombokinase  which  normally 
occurs  when  blood  leaves  the  vessels.  More  difficult  to  understand  is  the 
result  of  injecting  small  amounts  of  these  tissue  extracts  or  large  amounts 
in  small  doses.  A  minute  quantity  of  tissue  extract  injected  into  the  blood 
stream  produces,  not  intravascular  clotting,  but  a  delay  of  the  coagulation 
time.  Repeated  injections  of  small  doses  may  absolutely  annul  the  coagula- 
bility of  the  blood,  which  can  be  collected  by  opening  the  blood  vessels  and 
will  remain  unclotted  for  many  days.  The  same  double  effect  may  be 
observed  even  with  a  larger  dose.  In  rabbits  and  in  dogs  after  a  full  meal 
the  intravascular  coagulation  which  occurs  is  complete,  extending  through 
the  whole  vascular  system.  If  however  the  injection  be  made  into  a  fasting 
dog  the  thrombosis  produced  is  limited  to  the  portal  vein.  There  is  a  sudden 
fall  of  blood  pressure,  from  which  the  animal  gradually  recovers.  If  a  vessel 
be  opened  during  the  period  of  low  pressure,  the  blood  which  flows  out  is 
totally  uncoagulable,  and  if  the  animal  be  killed  at  this  time  a  clot  will  be 
found  filling  up  the  whole  portal  vein.  Wooldridge  described  these  two 
effects  of  injection  of  tissue  extracts,  namely  the  coagulation  and  the  loss  of 
coagulability,  as  the  positive  and  negative  phases  respectively.  Since  the 
negative  phase  has  not  been  observed  in  any  form  of  extravascular  plasma, 
we  must  ascribe  it  to  a  reaction  on  the  part  of  the  living  cells  and  probably, 
since  it  is  so  rapid  in  its  establishment,  to  the  action  of  the  cells  lining  the 
blood  vessels.  The  interest  of  these  observations  lies  in  the  relation  which 
they  bear  to  the  production  of  immunity.  If  a  toxin  such  as  that  of  diph- 
theria or  tetanus  be  injected  into  an  animal,  an  antitoxin  is  produced  in 
the  course  of  two  or  three  days.  If  now  further  doses  of  toxin  be  injected, 
its  first  effect  is  to  destroy  the  whole  of  the  antitoxin  present  in  the  circu- 
lating blood.  In  the  course  of  a  day  or  two  the  antitoxin  gradually  returns, 
and  at  the  end  of  three  days  is  found  in  larger  quantities  in  the  blood  than 
were  present  before  the  second  injection.  Every  toxin  has  therefore  a 
positive  as  well  as  a  negative  phase  of  action.  Tissue  extracts  in  their 
effect  on  coagulation  have  a  similar  positive  and  negative  phase,  but  these 
phases  are  established  within  a  few  seconds  instead  of  taking  two  or  three 
days  for  their  development.  One  cannot  but  believe  that  a  renewed  study 
of  the  conditions  of  intravascular  clotting  might  shed  important  light  on^the 
chemical  mechanism  of  production  of  immunity. 

FATE  OF  THE  FIBRIN  FERMENT.  The  substances  which  interact  for 
the  production  of  thrombin  in  shed  blood  as  well  as  thrombin  itself  are  not 
entirely  vised  up  in  the  process  of  clotting.  Blood  serum,  though  free  from 
fibrinogen,  contains  traces  of  thrombokinase  (which  can  be  precipitated  by 

1  According  to  Howell,  these  tissue  fibrinogens  consist  of  phosphatides  in  associa- 
tion with  protein.  When  separated  from  the  protein  they  are  thermostable,  and  their 
thromboplastic  effect  is  due  to  their  power  of  neutralising  antithrombin. 


THE  COAGULATION  OF  THE  BLOOD  891 

the  addition  of  dilute  acetic  acid)  and  thrombogen,  as  well  as  a  fairly  strong 
solution  of  thrombin.  Thrombin  however  rapidly  disappears  from  serum, 
so  that  a  blood  serum  which  has  been  kept  for  two  or  three  days  may  be 
almost  free  from  fibrin  ferment.  Such  a  serum  can  be  reactivated  by  the 
addition  of  small  traces  either  of  acid  or  alkali.  It  has  been  suggested  that 
the  thrombin  undergoes  a  modification  into  an  inactive  form  which  is  called 
nieta thrombin.  This  substance  has  no  relation  to  the  precursors  of  fibrin 
ferment  which  we  have  already  considered.  It  is  unaltered  by  lime  salts  or 
by  the  addition  of  thrombokinase,  but  can  be  reconverted  into  thrombin  by 
means  of  acids  or  alkalies.  According  to  Rettger  the  disappearance  of  throm- 
bin from  serum  is  due  to  its  combination  with  some  of  the  proteins  of  the 
serum.  This  combination,  like  that  of  thrombin  with  fibrinogen  to  form 
fibrin,  is  vmstable  and  can  be  broken  up  by  the  action  of  alkalies,  acids,  or  even 
of  putrefaction.  Thrombin  itself  seems  to  be  extremely  stable  and  will 
withstand  even  the  temperature  of  boiling  water  for  a  short  time.  If 
solutions  containing  thrombin  be  evaporated  to  dryness,  the  dry  residue  can 
be  heated  to  135°  C  without  destruction  of  the  thrombin. 

AVe  are  now  in  a  position  to  see  bow  far  the  theory  of  coagulation  evolved  from  a 
study  of  two  forms  of  plasma  will  serve  to  explain  the  behaviour  of  the  many  other 
kinds  of  plasma  which  have  been  the  subject  of  investigation. 

Cooled  plasma  contains  the  thrombokinase  in  the  form  of  blood  platelets  or  a 
disc-like  precipitate.  This  precipitate  can  be  separated  by  centrifuging  at  a  low 
temperature  or  by  filtration.  The  remaining  plasma  contains  only  thrombogen,  lime 
salts,  and  fibrinogen,  and  can  be  made  to  clot  by  the  addition  of  tissue  extracts  or  of 
fibrin  ferment,  but  will  not  clot  on  warming. 

In  sodium  sulphate  plasma  the  interaction  of  the  fibrin  factors  is  merely  impeded 
by  the  excess  of  salt.  All  are  still  present,  and  it  is  therefore  sufficient  merely  to  dilute 
the  plasma  in  order  to  produce  clotting. 

Magnesium  sulphate  plasma  behaves  somewhat  differently.  If  the  blood  be 
received  directly  into  magnesium  sulphate  solution,  and  the  mixture  centrifuged  while 
still  warm,  a  clear  magnesium  sulphate  plasma  is  obtained  which  will  clot  on  simple 
dilution.  If  the  blood  be  left  for  twenty-four  hours  before  centrifuging,  the  plasma 
will  not  clot  on  dilution  nor  on  addition  of  tissue  extracts.  It  contains  fibrinogen  only 
and  is  therefore  an  excellent  reagent  for  the  presence  of  fibrin  ferment.  Magnesium 
sulphate  not  only  hinders  the  interaction  of  the  fibrin  factors  but  actually  slowly 
precipitates  the  thrombokinase,  so  that  if  time  be  allowed  for  this  precipitation  to  be 
complete  the  remaining  plasma  contains  only  fibrinogen. 

Sodium  fluoride  plasma  might  be  expected  to  act  like  oxalate  plasma  since  sodium 
fluoride  is  a  precipitant  of  lime  salts.  This  salt  has  however  the  additional  property 
of  causing  a  certain  amount  of  fixation  of  the  formed  elements  of  the  blood  as  well  as 
of  the  blood  platelets.  If  it  be  thoroughly  centrifuged  so  that  the  plasma  is  obtained 
free  from  these  constituents,  it  will  no  longer  clot  with  lime  salts  l  nor  even  with  lime 
salts  plus  tissue  extracts,  but  will  clot  readily  on  addition  of  thrombin.  Although  it 
still  contains  a  certain  amount  of  thrombogen,  this  is  entangled  and  carried  down  in 
the  precipitate  of  calcium  fluoride  which  is  produced  by  the  addition  of  lime  salts,  so 
that  the  thrombokinase  has  nothing  on  which  to  exercise  its  effect.  Sodium  fluoride 
plasma  is  therefore  useful,  like  magnesium  sulphate  plasma,  as  a  test  for  the  presence 
of  thrombin.  If  water  be  added  to  the  sodium  fluoride  blood,  so  as  to  destroy  some  of 
the  formed  elements  and  liberate  their  constituents  into  the  plasma,  it  is  possible  to 
produce  clotting  by  the  simple  addition  of  lime  salts. 

1  According  to  Rettger  this  statement  is  incorrect.  ' 


892  PHYSIOLOGY 

Hirudin  plasma.  The  action  of  hirudin  is  that  of  an  antithrombin.  It  apparently 
combines  with  and  neutralises  fibrin  ferment.  Hirudin  plasma  ean  tlierefore  be  made 
to  clot  by  the  addil  ion  of  fibrin  ferment  in  sufficiently  large  quantities  to  combine  with 
all  the  hirudin  present  and  lea\e  an  evess  o\er  in  the  fluid. 

Peptone  plasma  presents  many  difficulties  in  the  explanation  of  its  behaviour. 
Peptone  itself  has  apparently  no  influence  on  t lie  coagulation  of  the  blood.  Blood 
received  into  peptone  solution  clots  as  rapidly  as  when  received  into  salt  solution.  On 
the  other  hand,  if  blood  be  received  into  peptone  blood  obtained  by  the  injection  of 
large  doses  of  peptone  into  the  veins  of  another  animal,  the  mixture  does  not  clot, 
showing  that  peptone  blood  contains  some  substance  which  inhibits  the  processes  of 
coagulation.  This  '  anticoagulin  '  must  be  produced  by  the  organism  itself  as  a  result 
of  the  injection  of  peptone,  and  evidence  has  been  brought  forward  by  Delezenne  and 
others  that  the  seat  of  formation  of  the  anticoagulin  is  in  the  liver.  Whether  the  anti- 
substance  partakes  of  the  characters  of  an  antithrombin  or  of  an  antikinase  has  not 
yet  been  definitely  ascertained.  Peptone  plasma  can  be  made  to  clot  by  the  addition 
of  (issue  extracts  even  in  small  quantities.  It  still  contains  all  the  fibrin  factors,  since 
it  will  clot  on  simple  dilution  or  on  the  passage  of  a  current  of  carbon  dioxide.  It  needs 
however  the  addition  of  large  quantities  of  fibrin  ferment  to  bring  about  coagulation. 

THE   TRANSUDATIONS 

The  earlier  work  on  the  mechanism  of  coagulation  was  largely  carried  out 
on  the  fluids  obtained  from  the  pericardial  or  pleural  cavities  or  on  hydrocele 
fluid  from  the  tunica  vaginalis.  These  as  a  rule  can  be  kept  indefinitely 
without  clotting,  but  will  clot  readily  on  addition  of  a  few  drops  of  blood 
or  the  washings  of  a  blood  clot  or  fibrin  ferment.  They  will  not  clot  on  the 
addition  of  tissue  extracts  containing  thrombokinase.  Though  they  con- 
tain leucocytes  and  even  some  red  corpuscles,  they  are  free  from  blood 
platelets.  Their  behaviour  is  readily  explained  by  the  assumption  that  they 
contain  fibrinogen,  but  are  free  from  thrombokinase  or  thrombogen.  In 
order  to  produce  coagulation  it  is  therefore  necessary  to  add  two  fibrin 
factors,  thrombokinase  and  thrombogen,  as  happens  when  we  add  blood,  or 
to  treat  them  with  fully  formed  thrombin  or  fibrin  ferment. 

HISTORY  OF  THE  COAGULATION  QUESTION.  It  is  not  surprising  that  the 
coagulation  of  the  blood,  with  the  antecedent  changes  which  lead  to  the  appearance 
of  thrombin  and  probably  represent  the  successive  stages  in  the  disintegration  of  a  fluid 
labile  protoplasmic  molecule,  i.  e.  the  change  from  life  to  death  of  the  plasma,  should 
have  been  the  subject  of  a  very  large  number  of  investigations,  and  that  even  at  the 
present  time  the  interpretation  of  the  salient  facts  presents  many  difficulties.  Some 
help  may  be  given  to  the  future  clearing  up  of  these  difficulties  by  a  study  of  the  steps 
by  which  our  present  standpoint  has  been  arrived  at.  The  universal  practice  of  bleeding 
as  a  therapeutic  measure  naturally  afforded  many  opportunities  to  physicians  for  ob- 
serving the  processes  of  coagulation  under  diseased  as  well  as  healthy  conditions.  The 
general  result  was  however  in  most  cases  a  crop  of  ill-founded  and  uncritical  theories ; 
and  it  is  not  till  the  time  of  Hewson  (1772)  that  we  meet  with  investigations  of  the 
question  carried  out  on  modern  fines  with  reference  to  observation  and  experiment 
at  each  stage.  We  owe  to  Hewson  the  discovery  that  coagulation  can  be  inhibited 
indefinitely  by  the  addition  of  neutral  salts,  such  as  sodium  sulphate,  and  it  was  by  a 
study  of  such  bloods  that  Hewson  arrived  at  the  conclusion  that  the  formed  elements 
of  the  blood  take  no  part  in  the  production  of  the  clot.  Johannes  Miiller  in  1832  came 
to  the  same  conclusion  from  a  study  of  frog's  blood.  This  he  diluted  with  sugar  solution 
and  filtered  through  filter-paper.  The  large  corpuscles  were  retained  by  the  meshes 
of  the  filter-paper  and  the  clear  fluid  which  came  through  slowly  underwent  coagulation. 


THE  COAGULATION  OF  THE  BLOOD  893 

The  beginning  of  our  modern  ideas  on  the  subject  must  be  ascribed  to  Buchanan, 
though  many  of  the  facts  discovered  by  this  observer  escaped  general  recognition  and 
were  later  re-discovered  by  Alexander  Schmidt.  Buchanan  worked  chiefly  on  hydrocele 
fluid  and  showed  that  this  could  be  made  to  yield  fibrin  by  treatment  with  fresh  blood 
or  by  adding  it  to  the  washings  of  a  blood  clot.  He  compares  the  action  of  the  latter 
to  that  of  rennet  on  the  protein  of  milk.  His  experiments  showed  that  "  fibrin  has 
not  the  least  tendency  to  deposit  itself  spontaneously  in  the  form  of  a  coagulum,  that, 
like  albumin  and  casein,  fibrin  often  coagulates  under  the  influence  of  suitable  reagents, 
and  that  the  blood,  like  most  other  liquids  of  the  body  which  appear  to  coagulate 
spontaneously,  only  do  so  in  consequence  of  their  containing  at  once  fibrin  and  sub- 
stances capable  of  reacting  upon  it  and  so  occasioning  coagulation."  He  held  therefore 
that  the  coagulation  of  the  blood  is  due  to  the  conversion  of  a  soluble  constituent  of 
( he  fl'/uor  sanguinis  into  fibrin  by  an  action  exerted  probably  by  the  colourless  corpuscles 
and  comparable  to  the  action -which  rennet  exerts  in  effecting  the  coagulation  of  milk. 
Furthermore  the  liquid  winch  accumulates  in  certain  serous  sacs  may  be  made  to  yield 
a  coagulum  of  fibrin  when  subjected  to  the  action  of  liquids  or  solids  rich  in  the  cellular 
elements  with  which  the  coagulent  action  appeared  to  be  associated  (Gamgee). 

Denis  in  1856  attempted  to  separate  this  precursor  of  fibrin.  He  received  the  blood 
into  one-sixth  of  its  volume  of  saturated  sodium  sulphate,  allowed  the  corpuscles  to 
settle,  and  filtered  off  the  supernatant  plasma.  On  saturating  this  with  sodium  chloride 
a  precipitate  was  produced  which  Denis  designated  '  plasmine.'  This  precipitate,  on 
in  in  water,  slowly  underwent  coagulation  and  was  apparently  split  into  two 
substances — a  solid  fibrin  and  a  soluble  protein.  Clotting  therefore,  according  to  Denis, 
was  dependent  on  the  splitting  of  a  single  protein  into  two  different  proteins,  one  of 
which  was  insoluble.  A  few  years  later  the  subject  was  taken  up  by  Alexander  Schmidt, 
who  devoted  the  remaining  thirty  years  of  his  life  to  the  investigation  of  the  coagulation 
of  the  blood.  Working  first,  as  Buchanan  had  done,  on  fluids  obtained  from  serous 
cavities,  he  noticed  that  these  could  be  made  to  clot  by  the  addition  of  serum,  and  he 
concluded  that  coagulation  was  due  to  the  interaction  or  combination  of  two  different 
proteins,  one  fibrinogen,  contained  in  the  serous  fluid,  and  the  other  '  fibrinoplastin,' 
which  was  contained  in  the  serum  and  could  be  precipitated  by  acidification  or  by 
dilution  and  passage  of  a  stream  of  carbon  dioxide.  This  fibrinoplastin  was  identical 
with  what  we  should  nowadays  call  paraglobulin,  but  had  adherent  to  it  fibrin  ferment. 
Schmidt  later  on  found  that  in  many  cases  it  was  not  sufficient  to  mix  these  two  sub- 
stances together,  but  that  a  third  factor  was  necessary,  which  could  be  obtained  either 
from  serum  or  from  blood  clot  which  had  been  coagulated  by  alcohol.  This  third 
factor  he  compared  to  a  ferment,  so  that  the  theory  put  forward  by  Schmidt  in  1872 
was  that  coagulation  depends  on  the  interaction  of  two  substances — fibrinogen  and 
oplastin — under  the  influence  of  a  third  substance,  fibrin  ferment  or  thrombin. 
A  few  years  later  Hammarsten,  of  Upsala,  in  a  very  carefid  series  of  experiments, 
proved  conclusively  that  the  fibrinoplastin  of  Schmidt  was  not  a  necessary  factor. 
Hammarsten  discovered  the  method  which  we  use  at  the  present  time  for  separation 
of  fibrinogen,  namely,  precipitation  by  half-saturation  with  common  salt,  and  showed 
that  the  fibrinogen  obtained  in  this  way  and  purified  by  repeated  precipitation  and 
resolution  would  yield  a  clot  of  fibrin  on  the  addition  of  fibrin  ferment  prepared  by 
Schmidt's  process.  According  to  Hammarsten  therefore,  clotting  was  due  to  the 
conversion  of  the  fibrinogen  present  in  the  circulating  plasma  into  fibrin  by  the  action 
of  fibrin  ferment,  which  was  probably  yielded  by  the  disintegration  of  the  white  blood 
corpuscles.  Schmidt's  later  work  was  directed  chiefly  to  determining  the  mode  of 
origin  of  the  fibrin  ferment.  Though  his  researches  yielded  a  number  of  important 
facts,  especially  as  to  the  part  played  by  tissue  cells  in  furnishing  the  precursors  of  I  he 
ferment  or  in  influencing  the  processes  of  clotting,  they  did  not  result  in  clarifying  the 
views  of  physiologists  generally  on  the  subject  of  clotting.  Perhaps  their  most  useful 
effect  was  tu  demonstrate  the  complexity  of  the  processes  which  occur  in  the  blood 
after  it  leaves  the  vessels,  and  to  show  that  in  the  maintenance  of  the  fluid  condition 
in  the  vessels  as  well  as  in  the  production  of  a  clot  outside  the  vessels,  there  must  be  an 
interaction  between  the  opposing  factors,  some  of  which  hinder  and  some  of  which 


894 


PHYSIOLOGY 


favour  the  occurrence  of  coagulation.  According  to  Schmidt  the  plasma  is  itself 
derived  from  the  cells  of  the  body,  the  fibrinogen  being  formed  through  the  stages  of 
paraglobulin  and  cytoglobulin.  The  thrombin  is  derived  from  a  precursor  prothrombin 
under  the  action  of  a  zymoplastie  substance  also  derived  from  the  cells.  In  the  presence 
of  the  proper  concentration  of  salts  the  thrombin  acts  upon  fibrinogen  to  produce  fibrin. 
His  views  may  bo  roughly  expressed  by  the  following  schema  given  by  Howell : 


Cells 

1 

1 
Plasma 

1 

Cytoglobulin 

Zymoplastie 
substance 

1 
Prothrombin 

Paraglobulin 

1 
Fibrinogen 

Thrombin 

Soluble  fibrin  —  Salts  =  Fibrin 

Some  important  light  was  thrown  on  the  subject  by  the  researches  of  Wooldridge. 
Working  chiefly  with  peptone  plasma,  he  showed  in  the  first  place  that  such  plasma 
contained  all  the  factors  necessary  for  the  production  of  fibrin,  and  therefore  that  the 
co-operation  of  leucocytes  was  not  a  necessary  part  of  the  process.  Peptone  plasma, 
separated  entirely  from  leucocytes  and  red  corpuscles,  could  be  made  to  clot  by  dilution, 
by  the  passage  of  a  stream  of  carbon  dioxide  or  filtration  through  a  clay  cell.  This 
power  of  clotting  without  addition  of  any  other  substances  depended  on  the  presence  in 
the  plasma  of  a  substance  called  by  Wooldridge  '  A-fibiinogen,'  which  was  thrown 
down  as  a  disc-like  precipitate  on  cooling  to  0°  C.  On  separating  this  precipitate, 
which  he  regarded  as  equivalent  to  the  blood  platelets,  by  means  of  the  centrifuge, 
the  remaining  plasma  would  clot  only  on  the  addition  of  extracts  of  tissues.  Since 
neither  the  original  plasma  nor  the  plasma  after  separation  of  the  A-fibrinogen  would 
clot  on  the  addition  of  fibrin  ferment,  Wooldridge  thought  that  the  fibrinogen  of 
Hammarsten  was  absent  from  such  plasma,  which  contained  only  two  fibrinogens, 
A-  and  B-fibrinogen.  Clotting  therefore  consisted  essentially  in  an  interaction  between 
A-  and  B-fibrinogen,  and  was  inaugurated  by  the  appearance  of  A-fibrinogen  as  a  disc- 
like  precipitate.  In  this  interaction  he  showed  that  ferment  was  produced,  and  the 
weakest  part  of  his  theory  was  that  it  gave  practically  no  office  to  the  ferment  pro- 
duced during  the  first  steps  of  the  process  imagined  by  him.  The  B-fibrinogen  could 
be  thrown  down  by  the  action  of  dilute  acid  or  of  salt  from  the  plasma  after  separation 
of  the  A-fibrinogen.  After  precipitation  and  re-solution  two  or  three  times  it  would 
clot  with  fibrin  ferment,  and  was  coagulated  at  a  temperature  of  56°  C,  and  was  there- 
fore the  typical  fibrinogen  of  Hammarsten.  According  to  Wooldridge  therefore, 
previous  observers  had  been  working,  not  with  the  fibrinogens  of  the  plasma,  but  with 
a  fibrinogen  altered  by  repeated  precipitation  and  re-solution.  One  fact  discovered 
by  him,  which  at  once  attained  universal  recognition,  was  the  production  of  intravascular 
clotting  by  the  injection  of  tissue  extracts.  These  tissue  extracts  contained  tissue 
fibrinogens  which  he  compared  with  A-fibrinogen.  According  to  him  clotting  could 
be  inaugurated  either  by  the  action  of  A-fibrinogen  on  the  B-fibrinogen,  or  by  the 
action  of  tissue  fibrinogen  on  the  B-fibrinogen  of  the  plasma.  In  every  ease  fibrin 
ferment  resulted  and  could  therefore  effect  the  conversion  of  any  C-fibrinogen  of 
Hammarsten  which  might  be  present  in  the  fibrin.  It  will  be  seen  that  this  theory  of 
Wooldridge  presents  a  striking  similarity  to  that  which  is  generally  accepted  at  the 
present  day.  If  we  change  the  names  of  A-fibrinogen  to  thrombokinase,  of  B-fibrinogen 
to  thrombogen,  we  see  that  the  only  difference  between  Wooldridge's  theory  and  that 


THE  COAGULATION  OF  THE  BLOOD  895 

of  Morawitz  is  that  the  former  ignored  the  importance  of  lime  salts  in  the  process  and 
imagined  that  the  interaction  of  thronibokinase  and  thrombogen  resulted  in  the  direct 
production  of  fibrin  as  well  as  ferment,  instead  of  recognising  that  the  interaction  of  the 
two  substances  was  simply  a  first  stage  and  that  thrombin  was  formed  in  this  process 
for  the  subsequent  conversion  of  the  fibrinogen  into  fibrin. 

Attention  however  was  largely  diverted  from  Wooldridge's  work  by  the  discovery 
of  the  necessity  of  calcium  salts  for  clotting.  Green  had  already  shown  that  the  clotting 
of  many  forms  of  salt  plasma  could  be  hastened  by  the  addition  of  calcium  sulphate, 
whereas  the  coagulation  of  serous  fluid  was  not  affected  by  this  salt.  Green  suggested 
that  possibly  a  zymogen  of  the  ferment  was  activated  by  the  calcium  salt.  The  absolute 
necessity  for  the  presence  of  this  salt  was  first  demonstrated  by  Arthus  and  Pages  (1890) 
on  oxalate  and  fluoride  plasma.  At  first  Arthus  was  inclined  to  regard  the  part  played 
by  calcium  salts  in  the  coagulation  of  the  blood  as  analogous  in  all  respects  to  that  played 
in  the  coagulation  of  milk  by  rennet,  and  suggested  that  the  conversion  of  fibrinogen 
into  fibrin  was  actually  the  combination  of  fibrinogen  with  calcium  salts,  the  combina- 
tion being  effected  by  the  agency  of  the  ferment.  It  was  shown  however  by  Pekel- 
haring  that  the  power  of  linie  salts  to  produce  clotting  in  oxalate  plasma  was  annulled 
if  the  body  precipitable  by  cold  had  been  previously  removed,  and  Hanimarsten  proved 
conclusively  that  the  action  of  calcium  salts  was  on  the  prothrombin  and  not  on  the 
fibrinogen,  careful  analyses  of  fibrinogen  and  fibrin  respectively  giving  practically 
equal  figures  for  calcium.  Hammarsten  pointed  out  moreover  that  fibrin  ferment 
would  convert  fibrinogen  into  fibrin  in  the  total  absence  of  soluble  calcium  salts  and 
even  in  the  presence  of  a  slight  excess  of  oxalate. 

Later  experiments  have  had  reference  chiefly  to  the  nature  of  the  prothrombin 
precipitate  and  to  the  question  of  the  origin  of  the  fibrin  ferment  from  the  blood  plasma. 
Recent  advances  in  the  subject  were  much  facilitated  by  the  discovery  by  Delezenne 
that  bird's  blood  could  be  ]  ire  von  ted  from  clotting  by  the  simple  expedient  of  collecting 
it  free  from  any  contact  with  the  tissues.  A  careful  study  of  this  blood  and  a  comparison 
of  its  behaviour  with  that  of  other  forms  of  uncoagulablo  plasma  by  Fuld  and  Spiro, 
and  especially  by  Morawitz,  have  resulted  in  the  further  separation  of  the  precursor 
of  fibrin  into  two  substances,  thrombokinase  and  thrombogen.  Further  investigations 
by  Nolf  have  dealt  especially  with  the  question  of  the  interaction,  which  is  continually 
taking  place  between  the  vessel  wall  and  the  contained  blood  and  which  may  result, 
according  to  the  circumstances,  in  the  diminution  or  increase  in  the  coagulability  of 
the  blood.  According  to  Nolf  the  essential  factors  in  the  production  of  blood  clotting 
are  three  proteins,  namely,  fibrinogen,  thrombogen,  and  thrombozym.  The  two  former 
are  produced  in  the  liver,  while  the  thrombozym  is  formed  from  the  leucocytes.  The 
clotting  depends,  not  on  a  ferment  action,  but  on  a  mutual  interaction  and  precipitation 
of  colloids  with  as  a  result  either  fibrin  or  thrombin.  Thrombin  differs  from  fibrin 
merely  in  containing  less  fibrinogen.  For  this  reaction  to  take  place  the  presence  of 
calcium  is  necessary  as  well  as  certain  thromboplastic  substances  which  act  as  centres 
of  precipitation.  The  fluid  condition  of  the  blood  in  the  vessel  depends  on  the  presence 
of  an ti thrombin  formed  in  the  liver.  Nolf  thus  agrees  with  Wooldridge  in  regarding 
thrombin  as  a  product  of  coagulation  rather  than  a  cause.  Thrombin,  according  to 
him,  is  merely  an  unsaturated  compound  which  is  capable  of  taking  up  or  uniting  with 
more  fibrinogen  to  form  fibrin.  Nolf  would  regard  the  formation  of  fibrin  as  an  import- 
ant preparatory  step  in  the  nutrition  of  the  cells.  He  compares  these  actions  occurring 
in  the  blood  to  the  actions  of  digestive  ferments  on  proteins.  Just  as  casein  is  first 
precipitated  and  then  digested  by  pepsin,  so  fibrinogen  is  first  precipitated  as  fibrin  by 
union  with  thrombozym  and  thi'ombogen.  This  fibrin  is  then  hydrolysed  and  dissolved 
by  the  further  action  of  the  thrombozym,  which  he  regards  as  essentially  proteolytic 
in  character.  That  the  whole  blood  does  not  coagulate  within  the  vessels  he  explains 
by  assuming  that  the  cells  of  the  blood  and  tissues  are  covered  normally  with  an  ultra- 
microscopic  layer  of  fibrin.  This  forms  a  neutral  surface,  like  a  paraffined  vessel, 
which  has  no  thromboplastic  effect  upon  the  plasma.. 

According  to  Mellanby  the  prothrombin  in  the  plasma  is  constantly  associated  with 
the  fibrinogen.     It  may  be  converted  to  thrombin  either  by  the  action  of  calcium  and 


896  PHYSIOLOGY 

thrombokinase,  or  bj  the  action  of  calcium  and  alkali,  or  possibly  by  the  action  of 
calcium  alone.  The  latest  mnk  cm  the  subject  by  Rettger  has  tended  somewhat  to 
the  simplification  of  this  extremely  complex  problem.  In  the  first  place,  he  regards 
the  formation  of  fibrin  as  non-fermentative  in  character,  thus  agreeing  with  Nolf, 
fibrin  being  produced  by  the  simple  union  of  fibrinogen  and  thrombin,  though  a  very 
small  amount  of  thrombin  may  produce  a  much  larger  amount  (about  200  times  its 
weight)  of  fibrin.  He  finds  no  evidence  of  the  pre-existenee  in  the  blood  of  a  thrombin 
or  pro-ferment,  and  is  inclined  to  regard  the  action  of  so-called  kinases,  which  can  be 
extracted  from  animal  tissues,  as  similar  to  that  of  such  agents  as  dust,  threads  of  linen, 
which  can  produce  a  similar  coagulating  effect  in  birds'  blood.  The  thrombin  he 
regards  as  derived  from  the  formed  elements  at  the  moment  of  their  rapid  disintegra- 
tion when  placed  under  abnormal  circumstances.  For  the  formation  of  active  thrombin 
a  minimal  amount  of  calcium  salts  must  enter  into  the  molecular  complex.  We  thus 
return  to  the  simpler  expression  of  the  processes  of  coagulation  as  given  by  Pekelharing 
and  Hammarsten,  the  prothrombin  which  is  formed  from  the  platelets  and  leucocytes 
by  secretion  or  process  of  disintegration  being  activated  to  thrombin  by  the  calcium 
salts  present,  and  the  thrombin  so  formed  combining  quantitatively  with  the  fibrinogen 
to  form  fibrin.  The  prothrombin  is  not  readily  destroyed ;  it  may  remain  in  calcium 
free  serum  for  days  and  when  activated  form  thrombin  quickly.  Thrombin,  on  the 
other  hand,  disappears  very  rapidly  from  active  serum  in  consequence  of  combining 
with  some  of  the  proteins  of  the  scrum.  This  property  of  combining  with  the  fibrinogen 
and  disappearing  from  the  serum  is  not  shared  by  the  prothrombin. 


SECTION  V 

THE   QUANTITY  AND    COMPOSITION    OF   THE 
BLOOD    IN    MAN 

A.     THE   TOTAL   QUANTITY   OF   BLOOD   IN   THE   BODY 

The  amount  of  blood  contained  in  the  body  can  be  estimated  by  Welcker's 
method.  It  is  not  sufficient  simply  to  open  one  of  the  blood  vessels  and 
allow  the  animal  to  bleed  to  death,  because  it  is  not  possible  in  this  way 
to  obtain  the  whole  of  the  blood  present  in  the  body,  and  the  blood  which 
is  obtained  gradually  becomes  more  dilute  in  consequence  of  absorption 
from  the  tissue  spaces  as  bleeding  continues.  A  small  sample  of  blood  is 
therefore  taken  from  a  blood  vessel  and  diluted  100  times  with  distilled 
water  to  serve  as  a  standard  of  comparison.  The  animal  is  then  bled  from 
a  cannula  placed  in  a  large  artery,  while  at  the  same  time  normal  salt 
solution  is  led  into  a  vein  so  as  to  maintain  the  vascular  system  as  full  as 
possible  and  allow  of  its  being  washed  out  by  the  action  of  the  heart.  When 
the  heart  ceases  to  beat,  the  blood  vessels  are  thoroughly  washed  out  by 
a  stream  of  normal  salt  solution  from  the  aorta.  The  animal  is  then  minced 
up  thoroughly  and  extracted  with  distilled  water,  so  as  to  dissolve  out 
the  haemoglobin  still  adherent  to  the  tissues  and  especially  contained  in 
the  red  marrow.  These  washings  are  filtered  and  mixed  with  the  whole 
diluted  blood  and  the  strength  of  the  mixture  in  haemoglobin  is  compared 
with  that  of  the  standard  solution,  In  this  way  it  is  possible  to  estimate 
the  total  haemoglobin  present  in  the  body  in  terms  of  the  sample  and  so 
find  the  total  amount  of  circulating  fluid.  It  has  been  found  that  the  dog 
contains  about  7-7  per  cent,  of  his  body  weight  as  circulating  blood,  and 
although  smaller  figures  were  obtained  on  other  animals,  such  as  the  rabbit, 
the  number  of  one-thirteenth  has  been  taken  as  applicable  to  man  on  the 
basis  of  two'  observations  made  long  ago  on  executed  criminals.  According 
to  Haldane  this  estimate  is  too  high,  the  average  amount  of  blood  in  man 
being  only  about  4-9  per  cent,  of  the  body  weight,  i.  e.  about  one-twentieth; 
in  some  cases,  as  in  fat  individuals,  it  may  be  as  little  as  one-thirtieth.  Since 
the  determination  of  the  total  volume  of  the  circulating  blood  plays  an 
important  part  in  the  consideration  of  the  pathology  of  certain  diseases 
such  as  anaemia  and  heart  disease,  the  ingenious  method  adopted  by  Haldane 
for  this  determination  in  the  living  animal  may  be  here  described.  The 
method  depends  on  the  fact  that  carbon  monoxide  gas  when  inhaled 
57  897 


898  PHYSIOLOGY 

combines  with  haemoglobin,  expelling  the  oxygen  from  the  oxyhemoglobin. 
If  we  allow  a  man  to  breathe  a  certain  volume  of  carbon  monoxide  until 
it  is  entirely  absorbed  and  then  find  that  one-fifth  of  the  haemoglobin  in  his 
blood  is  saturated  with  carbon  monoxide,  we  know  that  the  whole  blood 
could  take  up  five  times  the  bulk  of  carbon  monoxide  which  the  man  has 
inspired.  In  this  way  we  determine  the  total  '  carbonic  oxide  capacity  ' 
of  the  blood,  and  since  CO-haemoglobin  contains  the  same  volume  of  carbon 
monoxide  as  oxyhemoglobin  does  of  oxygen,  the  same  figure  gives  us  the 
total  '  oxygen  capacity.'  The  total  oxygen  capacity  enables  us  to  deter- 
mine the  total  amount  of  haemoglobin  in  the  bodv,  and  if  we  know  the 


Fia.  3S0.     Haldane's  CO  method  for  determining  total  blood  volume  in  man. 


percentage  amount  of  haemoglobin  in  the  blood  it  is  easy  to  calculate  the 
total  volume  of  circulating  fluid. 


Before  the  carbonic  oxide  is  administered,  the  percentage  oxygen  capacity,  i.  e.  the 
volume  of  oxygen  capable  of  being  taken  up  by  the  ha'moglobin  of  100  c.c.  of  the  blood, 
is  determined  as  follows :  The  oxygen  capacity  of  a  sample  of  fresh  ox  blood  is  accurately 
measured  by  the  ferricyanide  method  (v.  p.  902).  The  ox  blood  is  then  compared 
colorimetrically  with  blood  obtained  in  the  ordinary  way  by  means  of  a  hasrnoglobin- 
ometer  needle  from  the  finger  of  the  subject  of  the  experiment,  and  the  oxygen  capacity 
of  the  latter  blood  calculated  from  the  result  of  the  comparison.  The  subject  is  now 
made  to  breathe  through  a  mouthpiece  A  (Fig.  380)  into  a  bladder  B  of  about  2  litres 
capacity.  The  carbon  dioxide  produced  during  the  experiment  is  absorbed  by  the  soda 
lime  vessel  between  the  mouthpiece  and  the  bladder.  The  oxygen  as  it  is  used  up  is 
replaced  from  an  oxygen  cylinder  through  the  tube  C.  D  is  a  graduated  vessel  contain- 
ing pure  carbonic  oxide  gas.  While  the  subject  is  breathing  in  and  out  of  the  bag,  a 
given  volume  of  carbon  monoxide  is  admitted  into  the  bag,  being  driven  out  from  the 
tube  D  by  allowing  water  to  flow  through  the  tap  E.  The  required  volume  of  carbon 
monoxide  is  gradually  driven  in  from  the  measuring  cylinder  at  the  rate  of  about  30  c.c. 
every  two  minutes.  When  the  required  quantity  has  been  driven  in  and  pushed  forward 
by  the  oxygen,  an  interval  of  two  or  three  minutes  is  allowed  to  elapse.  After  this  a 
drop  of  blood  is  taken  for  analysis.     It  contains  a  certain  amount  of  CO-ha>moglobin. 


QUANTITY  AND   COMPOSITION  OF  THE   BLOOD   IN  MAN    899 


The  relative  saturation  of  the  blood  in  carbon  monoxide  is  determined  by  the  colorimetric 
method.  A  number  of  narrow  test-tubes  of  exactly  equal  diameter  and  each  holding 
about  6  c.c.  are  taken,  and  2  c.c.  of  water  saturated  with  air  measured  off  into  each. 
Two  cubic  millimetres  of  the  blood  of  the  subject  are  measured  off  in  the  ordinary  way 
by  means  of  a  ha?moglobinometer  pipette  into  each  of  the  six  tubes,  the  solutions  being 
well  mixed.  Four  cubic  millimetres  of  this  blood  are  thoroughly  saturated  with  coal 
gas  and  placed  in  another  shorter  tube,  which  is  filled  full  and  tightly  corked.  In  this 
tube  the  haemoglobin  is  completely  saturated  with  carbon  monoxide.  After  the  subject 
has  breathed  the  carbon  monoxide,  a  sample  of  his  blood  is  taken  and  diluted  as  before. 
The  solution  in  this  tube  is,  of  course,  pinker  than  those  in  the  other  tubes.  A  standard 
solution  of  carmine  is  now  added  from  a  narrow  burette  to  one  of  the  tubes  of  normal 
blood  solution  until  its  tint  is  the  same  as  that  of  the  blood  taken  after  the  inhalation. 
Addition  of  the  carmine  is  then  continued  until  the  tint  is  equal  to  that  of  the  blood 
solution  which  is  entirely  saturated  with  carbon  monoxide.  Supposing  that  0-45  c.c. 
of  carmine  was  required  to  produce  equality  of  tint  with  that  of  the  blood  taken  during 
the  experiment  and  2-5  c.c.  to  produce  equality  of  tint  with  that  of  the  saturated  blood, 
then  as  2'5  c.c.  of  carmine  in  45  c.c.  of  liquid  were  required  to  produce  saturation  tint, 
and  only  0-45  c.c.  of  carmine  in  2-45  c.c.  of  liquid  to  produce  the  tint  of  the  blood  under 
examination,  the  percentage  saturation  of  the  latter  could  be  calculated  by  the  following 
sum  : 


100:* 


2-5    j45 
f5    2^45 

.-.  x  =  331 


Although  this  method  requires  careful  execution  in  order  to  avoid 
fallacies,  it  is  possible  to  attain  results,  as  has  been  shown  by  Douglas, 
closely  agreeing  with  Welcker's  method.  The  error  is  probably  not  greater 
than  10  per  cent.,  which  is  negligible  in  comparison  with  the  large  changes 
in  total  blood  volume  which  have  been  found  to  occur  in  certain  cases  of 
disease.  The  total  record  of  two  such  observations  by  Haldane  and  Lorrain 
Smith  may  be  here  quoted  : 


Body  weight 
in 

kilogrammes. 
72-9 
89-0 


Normal  Individual 

Volume  of  dry  CO.  Percentage 

absorbed  in  c.c.  saturation  of 

at  0°  C  Hb  with  CO. 

116              .  18-9 


116 


Oxygen  capacity  Total  amount 

per  100  c.c.  of  of  blood 

blood  in  c.c.  in  grammes. 

18-7  .  3455 


18-2 


2970 


22-7 

Grammes  of  blood 

per  100  gnu.  of 

body  weight. 

4-75 

3:34 


Dry  oxygen 
capacity  of 
blood  in  c.c. 

014 

511 

C.c.  of  oxygen 
per  100  grm.  of 
body  weight. 

0-84 

0-57 


In  applying  this  method  in  cases  of  disease  it  is  important  not  to  give  too 
large  a  dose  of  carbonic  oxide  gas.  In  a  normal  individual  30  per  cent, 
of  the  haemoglobin  may  be  combined  with  carbon  monoxide  before  any 
oxygen  hunger  is  felt,  and  it  is  possible  to  saturate  half  the  haemoglobin 
with  this  gas,  though  with  considerable  discomfort  to  the  individual.  In 
cases  such  as  heart  disease,  where  the  patient  is  at  the  very  margin  of  his 
resources,  even  30  per  cent,  diminution  of  the  oxygen  capacity  of  the  blood 
may  have  serious  results,  and  the  carbon  monoxide  inspired  must  be  there- 
fore kept  at  the  lowest  limit  at  which  it  is  possible  to  carry  out  a  reliable 
determination  of  the  relative  carbonic  oxide  saturation  of  the  blood  sample. 


900  PHYSIOLOGY 

A  simpler  method  of  determining  the  total  blood  volume  has  been  worked  out  by 
Keith,  Rowntree  and  Geraghty.  The  method  consists  in  injecting  a  non-toxic,  non- 
diffusible  dye  substance  into  the  blood  stream  and  estimating  its  dilution.  The  dye 
used  is  '  vital  red,'  a  chemical  compound  belonging  to  the  triphenyl-methane  series. 
In  performing  the  test  6  to  8  c.c.  of  blood  are  removed  from  an  elbow  vein.  From 
10  to  18  c.c.  of  a  1-5  per  cent,  solution  of  the  dye  in  distilled  water  is  then  slowly  injected 
by  the  same  needle.  Five  minutes  later  a  second  specimen  of  blood  is  withdrawn  into 
a  third  syringe.  The  blood  samples  are  prevented  from  clotting  by  the  addition  of 
potassium  oxalate.  A  part  of  this  is  drawn  into  a  hasmatocrit  tube  and  centrifuged 
for  'twenty  minutes  at  a  high  speed  in  order  to  determine  the  relative  volume  of  cor- 
puscles and  plasma.  The  rest  of  both  samjiles  of  blood  are  centrifuged  in  order  to 
obtain  the  plasma.  Samples  of  plasma  before  and  after  are  then  compared  in  the 
following  mixture  : 

[  1  part  of  the  diluted  dye  solution. 
Standard-  1  part  of  the  plasma  before  dye  injection. 
[2  parts  0-8  per  cent.  NaCl  solution. 


Test 


1  part  of  plasma  after  dye  injection. 
3  parts  0-8  per  cent.  NaCl  solution. 


The  two  solutions  are  compared  in  a  colorimeter  and  the  test  solution  read  off  as  a 
percentage  of  the  standard.     The  following  formula  will  give  us  the  plasma  volume  : 

If  R  be  the  percentage  reading  of  test  solution. 

-       X  c.c.  dye  injected  X  100  =  c.c.  plasma. 
R 

The  blood  volume  is  calculated  from  the  hematocrit  reading. 

100  X  c.c.  plasma 

Total  blood  volume  =  —  -. — - — ; — =-. — r- 

percentage  plasma  in  blood. 

The  total  blood  volume  probably  varies  appreciably  with  alterations 
in  the  condition  of  the  animal,  and  may  be  found  different  on  two  suc- 
ceeding days.  It  is  certainly  influenced  by  the  height  of  the  blood  pressure 
as  well  as  by  the  oxygen  tension  in  the  air  breathed,  and  therefore  alters 
with  the  altitude.  Some  of  these  variations  we  shall  have  to  consider  more 
fully  in  a  later  section.  Any  lowering  of  blood  pressure  causes  an  absorp- 
tion of  fluid  from  the  tissues  into  the  blood,  so  that  the  latter  becomes  more 
dilute.  The  blood  content  during  the  last  stages  of  bleeding  may  contain 
little  more  than  50  or  60  per  cent,  of  the  haemoglobin  which  was  present 
in  the  first  samples  of  blood,  pointing  to  a  corresponding  dilution  of  the 
blood  during  these  few  minutes  by  means  of  tissue  lymph.  By  this  means, 
i.  e.  the  absorption  of  fluid  from  tissues,  the  volume  of  circulating  blood 
after  a  limited  haemorrhage  is  rapidly  brought  up  to  normal,  so  that  there 
is  a  circulation  of  a  fluid  impoverished  in  corpuscles.  The  latter  are  made 
up  in  the  course  of  a  few  weeks  as  a  result  of  increased  activity  in  the 
bone-marrow. 

Relative  Amount  of  Plasma  and  Corpuscles.  The  relative  amount  of  corpuscles 
in  a  given  sample  of  blood  is  most  easily  determined  by  Blix's  method.  The 
blood  is  mixed  with  a  definite  amount  of  2-5  per  cent,  potassium  bichromate,  and 
the  mixture  is  put  into  small  graduated  capillary  tubes,  which  are  then  placed  in 
a  centrifuge  revolving  about  10,000  times  per  minute.  The  corpuscles  rapidly 
accumulate  in  an  almost  solid  mass  at  the  bottom  of  the  tube,  and  their  volume 


QUANTITY  AND   COMPOSITION   OF  THE  BLOOD   IN  MAN    901 

can  be  directly  read  off.  It  is  often  possible  by  working  quickly  to  receive  blood  into 
such  graduated  capillary  tubes  and  to  centrifuge  it  rapidly  before  it  has  had  time 
to  coagulate.  The  corpuscles  are  hurried  down  to  the  bottom  of  the  tube  within 
two  or  three  minutes  and  their  volume  can  be  in  this  way  directly  determined. 
An  indirect  method  for  the  same  purpose  was  devised  by  Hoppe-Seyler.  The  total 
proteins  of  defibrinated  blood  are  determined  and  compared  with  the  total  proteins 
of  the  washed  corpuscles  and  of  the  serum.  Thus  in  one  experiment  100  gmi.  of 
defibrinated  pig's  blood  contained  18-90  grm.  protein  plus  haemoglobin.  The  blood 
corpuscles  of  100  grm.  of  the  same  blood  contained  15-07  grm.  proteins  plus  haemo- 
globin; therefore  the  serum  of  the  same  100  grm.  of  blood  contained  18-90  —  15-07  = 
3-83  grm.  proteins.  One  hundred  grammes  of  serum  contained  6-77  grm.  protein.  From 
these  figures  the  amount  of  serum  in  the  100  grm.  of  defibrinated  blood  may  be 
computed  as  follows  : 

—     .  100  =  56-6  per  cent,  serum. 
6-77  ^ 

100  —  56-6  =•  43-4  per  cent,  blood  corpuscles. 

The  average  volume  of  corpuscles  in  human  blood  can  be  taken  as  50  per 
cent,  of  the  total  amount,  different  estimations  having  given  figures  varying 
from  48  to  54  per  cent.  In  the  horse  the  volume  of  corpuscles  is  53  per 
cent.,  in  the  dog  36  per  cent. 

•  The  Enumeration  of  the  Corpuscles.  In  order  to  enumerate  the  red 
corpuscles,  the  blood  is  diluted  with  a  known  amount  of  an  isotonic 
fluid  and  the  number  is  counted  in  a  measured  volume  of  the  mixture. 
The  average  number  of  red  corpuscles  is  about  5,000,000  per  cubic  milli- 
metre in  adult  men  and  rather  fewer,  about  4,500,000,  in  adult  women. 
The  enumeration  of  corpuscles  is  subject  to  considerable  errors,  probably 
not  less  than  10  per  cent.  Moreover  different  conditions  of  the  cir- 
culation may  cause  variations  in  the  relative  distribution  of  plasma  and 
corpuscles  respectively  in  different  parts  of  the  circulation,  so  that  the 
blood-count  of  a  specimen  from  the  capillaries  of  the  finger  or  lobe  of  the 
ear  may  vary  considerably  from  a  similar  count  of  the  corpuscles  in  blood 
obtained  directly  from  a  minute  vein  or  artery.  More  important  therefore 
is  the  determination  of  the  haemoglobin.  For  this  purpose  a  measured 
quantity  of  the  blood,  2  to  5  c.mm.,  is  obtained  in  a  capillary  pipette  and 
mixed  with  a  given  volume  of  water.  The  red  fluid  thus  obtained  is  com- 
pared with  a  standard.  This  latter  in  von  Fleischl's  instrument  is  a  prism 
of  coloured  glass.  In  Oliver's  instrument  the  standard  consists  of  a  series 
of  tinted  glasses,  one  of  which  represents  the  colour  of  a  measured  quantity 
of  normal  blood  diluted  with  water  and  placed  in  a  flat  glass  cell  of  a  certain 
size,  while  the  others  represent  percentages  of  hsemoglobin  below  and  above 
the  normal.  The  most  accurate  method  is  that  due  to  Hoppe-Seyler  and 
Haldane,  namely,  the  conversion  of  the  blood  sample  into  CO-hsemoglobin 
and  its  comparison  with  a  standard  specimen  of  CO-haeinoglobin,  which  is 
stable  in  solution  and  can  therefore  be  kept  in  a  sealed  glass  vessel  for  any 
length  of  time. 

The  Gxygen  Capacity  of  the  Blood.  Instead  of  determining  the  haemo- 
globin we  may  measure  directly  the  oxygen  capacity  of  the  blood,  since 


902 


PHYSIOLOGY 


the  oxygen-binding  power  of  this  fluid  is  entirely  dependent  on  the 
amount  of  haemoglobin  it  contains.  For  this  purpose  we  may  make  use 
of  the  fact  discovered  by  Haldane,  that  the  combined  oxygen  in  oxy- 
haemoglobin  is  liberated  rapidly  and  completely  on  addition  of  a  solution 
of  potassium  ferricyanide  to  laked  blood,  and  may  thus  be  easily  measured 
with  the  help  of  an  apparatus  similar  to  that  used  for  determining  urea  in 
urine  by  the  hypobromite  method. 

The  following  description  of  the  method  is  given  by  Haldane  : 

'  Twenty  cubic  centimetres  of  the  oxalated  or  defibrinated  blood,  thoroughly 
saturated  with  air  by  swinging  it  round  in  a  large  flask,  are  measured  out  from  a  pipette 
into  the  bottle  a,  which  has  a  capacity  of  about  120  c.c.     As  it  is  important  to  avoid 


^ 


Fig.  381.     Haklane's  method  for  determining  the  oxygen  capacity  of  tho  blood. 

blowing  expired  air  into  the  bottle,  the  last  drops  of  blood  are  expelled  from  the  pipette 
by  closing  the  top  and  warming  the  bulb  with  the  hand.'  Thirty  cubic  centimetres 
are  then  added  of  a  solution  prepared  by  diluting  ordinary  strong  ammonia  solution 
(sp.  gr.  0-SS)  with  distilled  water  to  ^^j.  The  ammonia  prevents  carbonic  acid  from 
coming  off,  while  the  distilled  water  lakes  the  corpuscles.  The  blood  and  ammonia 
solution  are  thoroughly  mixed  by  shaking,  and  at  the  end  of  this  operation  the  solution 
should  appear  perfectly  transparent  when  tilted  up  against  the  sides  of  the  bottle.1 
About  4  c.c.  of  a  saturated  solution  of  potassium  ferricyanide  are  then  poured  into  the 
small  tube  B  (the  length  of  which  should  slightly  exceed  the  width  of  the  bottle)  and 
placed  upright  in  A.  The  rubber  stopper,  which  is  provided,  as  shown,  with  a  bent 
glass  tube  connected  with  the  burette  by  stout  rubber  tubing  of  about  1  mm.  bore,  is 


1  If  the  solution  were  not  transparent  this  would    indicate  that  the  taking  was 
incomplete,  and  more  ammonia  solution  would  need  to  be  added. 


QUANTITY  AND  COMPOSITION   OF  THE   BLOOD    IN  MAN    903 

then  firmly  put  in,  and  the  bottle  placed  in  the  vessel  of  water  c,  the  temperature  of 
which  should  be  as  nearly  as  possible  that  of  the  room  and  of  the  blood  and  water  in 
the  bottle.  If  the  stopper  is  not  heavy  enough  to  sink  the  bottle,  the  latter  should  be 
weighted.  By  opening  to  the  outside  the  three-way  tap  (or  T-tube  and  clip)  on  the 
burette,  and  raising  the  levelling  tube  which  is  held  by  a  spring  clamp,  the  water  in 
the  burette  is  brought  to  a  level  close  to  the  top.  The  tap  is  then  closed  to  the  outside, 
and  the  reading  of  the  burette  (which  is  graduated  to  •05  c.e.,  and  may  be  read  to  -01  c.c.) 
taken  after  careful  levelling. 

The  water-gauge  (which  has  a  bore  of  about  1  mm.)  attached  to  the  temperature 
and  pressure-control  tube  is  now  accurately  adjusted  to  a  definite  mark.  This  is 
easily  accomplished  by  sliding  the  rubber  tube  backwards  or  forwards  on  the  piece 
of  glass  tubing  D.  The  control  tube  is  an  ordinary  test-tube  containing  some  mercury 
to  sink  it,  and  connected  with  the  gauge  by  stout  rubber  tubing  of  about  1  mm. 
bore. 

As  soon  as  the  reading  of  the  burette  is  constant,  which  it  will  probably  be  within 
two  or  three  minutes,  the  bottle  is  tilted  so  as  to  upset  b,  and  is  shaken  as  long  as  gas  is 
evolved.  During  this  operation  b  should  be  repeatedly  emptied,  as  otherwise  the 
oxygen  dissolved  in  its  liquid  might  not  be  completely  given  off.  When  the  evolution 
of  oxygen  has  ceased  the  bottle  is  replaced  in  the  water.  If,  as  is  probable,  the  pressure- 
gauge  indicates  an  alteration  in  the  temperature  of  the  water,  cold  water  from  the  tap, 
or  warmed  water,  is  added  till  the  original  temperature  has  been  re-established  and  the 
reading  of  the  burette  noted  as  soon  as  it  is  constant.  The  bottle  is  again  shaken,  etc., 
until  a  constant  result  is  obtained,  for  which  about  fifteen  minutes  from  the  beginning 
of  the  operations  are  required.  The  temperature  of  the  water  in  the  jacket  of  the 
burette,  and  the  reading  of  the  barometer,  are  now  taken,  and  the  gas  evolved  is  reduced 
to  its  dry  volume  at  0°  and  7C0  mm.  To  calculate  the  oxygen  evolved  from  100  c.c.  of 
blood,  allowance  must  be  made  for  the  fact  that  a  20  c.c.  pipette  does  not  deliver  20  c.c. 
of  blood,  but  only  about  19-6  c.c.  The  actual  amount  of  shortage  for  a  given  pipette 
can  easily  be  determined  by  weighing  the  pipette  after  water,  and  again  after  blood, 
has  been  delivered  from  it.  A  further  slight  correction  is  necessary  on  account  of  the 
fact  that  the  air  in  the  bottle  at  the  end  of  the  operation  is  richer  in  oxygen  than  at  the 
beginning,  so  that,  as  oxygen  is  about  twice  as  soluble  as  nitrogen,  slightly  more  gas  will 
be  in  solution.  With  a  bottle  of  120  c.c.  capacity  and  20  per  cent,  of  oxygen  in  the  blood, 
the  air  in  the  bottle  at  the  end  will  evidently  contain  about  27  per  cent,  of  oxygen,  so 
that,  assuming  that  the  coefficients  of  absorption  of  oxygen  and  nitrogen  in  the  54  c.c. 
of  liquid  within  the  bottle  are  nearly  the  same  as  in  water,  the  correction  will  amount 
at  15°  C.  to  -06  c.c.  in  the  reading  of  the  burette,  or  +  0-30  per  cent,  in  the  result. 

The  Specific  Gravity  of  the  Blood.  The  specific  gravity  of  the  blood 
may  be  determined  by  directly  weighing  a  sample,  or  more  conveniently 
by  collecting  blood  in  a  capillary  tube  and  discharging  drops  of  it  into 
a  series  of  vessels  containing  glycerin  and  water  mixed  in  varying  pro- 
portions. When  it  is  found  that  the  drop  of  blood  as  it  leaves  the 
capillary  vessel  neither  rises  nor  falls  in  the  glycerin  and  water  mixture, 
we  know  that  the  specific  gravity  of  the  blood  is  identical  with  that  of 
the  mixture.  A  graduated  series  of  these  mixtures  is  kept  in  bottles 
and  their  specific  gravity  is  generally  determined  before  the  experiment. 
Hammerschlag's  method  consists  in  placing  a  drop  of  blood  in  a  mixture 
of  chloroform  and  benzene  and  then  adding  chloroform  or  benzene,  as 
the  case  may  be,  until  the  drop  neither  rises  nor  falls.  The  specific 
gravity  of  the  mixture  is  then  taken.  The  specific  gravity  varies  in  man 
between  1057  and  1066,  and  in  woman  from  1051  to  1061.  It  is  increased 
by  loss  of  water,  as  after  profuse  perspiration,  or  by  passive  congestion 


904  PHYSIOLOGY 

of  the  part-  from  which  the  sample  is  taken.  It  is  also  increased  as  a 
result  of  any  operation  upon  a  serous  cavity  in  consequence  of  exuda- 
tion of  plasma  in  the  inflamed  or  irritated  part.  It  is  diminished  as  the 
result  of  bleeding.  The  specific  gravity  of  serum  is  1028  to  1032,  of  cor- 
puscles about  1090.  It  is  interesting  to  note  that  the  specific  gravity  of 
the  blood  is  highest  in  the  foetus  at  full  term,  when  it  amounts  to  1066, 
contrasting  with  that  of  the  mother  at  the  same  time,  the  specific  gravity 
of  whose  blood  is  only  1050.  The  specific  gravity  rapidly  falls  to  the 
latter  figure  after  birth. 

THE   REACTION   OF   THE   BLOOD 

The  blood  has  long  been  described  as  alkaline  owing  to  the  fact  that  it 
turns  neutral  litmus  paper  blue.  This  fact  can  be  demonstrated  by  allowing 
a  drop  to  flow  on  a  piece  of  glazed  litmus  paper  and  then  wiping  away  the 
blood  with  a  piece  of  linen  moistened  with  distilled  water  or  neutral  saline 
solution.  The  alkalinity  of  the  blood  was  determined  by  mixing  a  small 
definite  quantity  with  sulphate  of  soda  solution  containing  a  definite  amount 
of  tartaric  acid.  The  acid  was  then  titrated  against  a  decinormal  solution 
of  sodium  hydrate  until  a  drop  of  the  mixture  gave  a  blue  stain  and  was 
placed  on  blue  litmus  paper.  It  must  be  noted  however  that  this  method 
gave,  not  the  alkalinity,  but  a  measure  of  the  alkaline  reserve — i.  e.  of  the 
total  amount  of  soda  in  combination  with  weak  acids  which  can  be  replaced 
by  the  tartaric  acid.  This  alkaline  reserve  consists  almost  exclusively  of 
sodium  bicarbonate,  and  the  method  indicated  above  is  a  means  of  estimating 
the  total  amount  of  this  salt  in  the  blood. 

In  van  Slyke's  method  the  alkaline  reserve  of  the  plasma  is  determined  by  finding 
out  how  much  C02is  evolved  from  a  given  volume  of  the  oxalated  plasma  (1  e.c),  when 
this  is  treated  with  5  per  cent,  sulphuric  acid  so  as  to  convert  all  the  bicarbonate  into 
sulphate.  Since  the  amount  of  carbonic  acid  taken  up  depends  on  the  partial  pressure 
of  the  C02  in  the  atmosphere  to  which  the  plasma  is  exposed,  the  plasma  is  first  shaken 
up  with  alveolar  air  provided  by  the  experimenter  himself,  which  always  contains  about 
5-5  per  cent,  of  CO^ 

Normal  human  blood  plasma  treated  in  this  way  yields  between  0'6  and  0-7  c.c.  of 
C02  per  cubic  centimetre. 

The  reaction  of  the  fluid,  strictly  speaking,  depends  on  the  relative  pro- 
portions of  the  H  and  OH  ions  present.  Pure  distilled  water  owes  its 
neutrality  to  the  fact  that  it  contains  equal  amounts  of  H  and  OH  ions. 
If  the  H  ions  increase  and  the  OH  ions  diminish,  the  reaction  becomes  acid. 
The  relative  concentration  of  H  and  OH  ions  in  a  fluid  can  be  measured 
electrically.  In  this  method  the  potential  difference  is  measured  between 
the  fluid  and  a  platinum  electrode  immersed  in  it,  which  is  kept  saturated 
with  hydrogen.  In  determining  the  reaction  of  the  blood  by  this  means, 
care  must  be  taken  to  make  the  estimation  at  the  body  temperature,  and 
also  to  keep  a  tension  of  5  per  cent,  of  an  atmosphere  of  C02  in  the  gaseous 
mixture  in  contact  with  the  blood  or  blood  plasma.     If  blood  is  raised  from 


QUANTITY  AND  COMPOSITION  OF  THE  BLOOD  IN  MAN    905 

15°  to  38°  C,  the  alkalinity  increases  fourfold;  moreover,  since  the  reaction 
depends  upon  the  relation  of  the  free  carbonic  acid  to  the  bases  which  are 
present  in  the  fluid,  any  escape  of  C02  from  the  blood  will  diminish  the 
hydrogen  ions  present  and  increase  the  alkalinity.  An  easier  method  than 
the  electrical  is  to  employ  indicators  which  vary  in  their  sensitiveness  to 
changes  of  reaction.  By  previous  experiment  it  has  been  determined  what 
concentration  of  hydrogen  ions  is  sufficient  to  cause  a  change  of  colour  in  the 
different  indicators.  In  the  following  Table,  taken  from  a  paper  by  Boaf, 
are  given  the  colours  of  a  number  of  different  indicators  and  the  degree 
of  acidity — i.  e.  the  hydrogen  ion  concentration  which  just  suffices  to  change 
their  colours. 


Indicator 

Acid  colour 

Transitional 
colour 

Alkaline  colour 

Hydrogen  ion  concen- 
tration at  which  colour 

change  begins 

Dimethylamidc 
azobenzol 

"       |      Red 

Orange 

Yellow 

IX  10-3 

Congo  red 

Blue      [ 

Purple  and 
brown 

|      Red 

IX  10-4 

Vesuvin  brown 

Brown 

— 

Yellow 

1  x  io-4 

Gallein     . 

Colourless 

Pink 

Red 

IX  lo-4 

Na  alizarine 
sulphonate 

1    Yellow 

Orange 

Red 

lx  io-4 

Lacmoid  . 

Red 

Purple 

Blue 

ix  io-4-ix  io-8 

Rosolic  acid 

Yellow 

Orange 

Red 

lx  io-5 

Litmus     . 

Red 

Purple 

Blue 

ix  io- s-  lx  10 -8 

Neutral  red 

Red 

Orange 

Yellow 

IX  IO-8 

Alizarine 

Yellow 

Orange 

Red 

lx  IO-8 

Phenolphthaleii 

l          Colourless 

Pink 

Red 

IX  IO-9 

It  should  be  remembered  that  in  distilled  water  of  the  highest  state  of  purity  the 
concentration  of  H  and  OH  ions  respectively  is  about  1  X  10  _  7. 


By  these  methods  the  hydrogen  ion  concentration  of  the  blood  at  38° 
is  found  to  be  04  x  10  ~  7  so  that  it  is  just  on  the  alkaline  side  of  neutrality. 
It  might  be  thought  that  with  such  a  feeble  alkalinity  the  merest  trace  of 
acid  added  to  the  blood  would  suffice  to  make  it  acid.  It  is  found  however 
that  a  relatively  large  proportion  of  an  acid  must  be  added  to  the  blood  in 
order  to  produce  an  appreciable  change  in  its  reaction.  This  is  due  to  the 
fact  that  the  sodium  bicarbonate  acts  as  a  '  buffer  ' — i.  e.  a  substance  which 
can  take  up  acid  or  alkali  with  a  minimal  change  of  reaction.  Thus,  if  some 
acid  be  added  to  the  plasma,  it  combines  with  the  sodium  and  the  equivalent 
amount  of  C02  escapes,  so  that  if  the  concentration  of  the  latter  gas  be 
retained  constant  in  the  atmosphere  to  which  the  plasma  is  exposed,  the 
reaction  remains  almost  the  same  as  before.  In  the  same  way,  if  some  alkali 
be  added  to  blood  in  contact  with  an  atmosphere  containing  5  per  cent. 
C02,  it  combines  with  the  C02  to  form  sodium  bicarbonate,  and  the  reaction 
is  again  practically  unaltered.    This  property  of  the  blood  of  retaining  a 


906  PHYSIOLOGY 

constant  reaction,  even  though  fixed  acids  are  added  to  it,  is  of  immense 
importance  in  the  economy  of  the  body.  All  cellular  functions  are  acutely 
sensitive  to  changes  in  reaction,  and,  as  we  shall  see  later,  the  activity  of 
the  respiratory  centre  is  primarily  dependent  on  the  livdrogen  ion  con- 
centration of  the  blood  with  which  it  is  bathed.  This  hydrogen  ion  con-, 
centration  depends  in  the  normal  animal  on  the  partial  pressure  of  the  C02 
in  the  medium  with  which  the  blood  is  in  contact,  so  that  the  slightest  rise 
in  the  C02  tension  in  the  alveolar  air  of  the  lungs  causes  at  once  a  corre- 
sponding increase  in  the  H  ion  concentration  of  the  blood,  to  which  the 
centre  responds  by  increased  activity.  On  the  other  hand,  considerable 
quantities  of  lactic  acid,  for  instance,  can  be  produced  by  the  muscles  and 
poured  into  the  blood  without  affecting  more  than  a  transitory  alteration 
in  the  activity  of  the  respiratory  centre. 

The  alkaline  reserve  of  the  blood  is  significant,  since  any  diminution 
indicates  in  all  probability  the  production  of  fixed  acids  in  the  tissues,  and 
a  progressive  reduction  will  precede  the  point  at  which  the  '  buffer '  action 
of  the  sodium  bicarbonate  is  lost,  and  the  blood  then  responds  to  any  addition 
of  acid  hy  an  appreciable  change  in  reaction.  It  is  only  when  the  alkaline 
reserve  has  been  reduced  to  a  minimum  that  a  true  condition  of  '  acidosis,' 
with  its  rapidly  fatal  effects,  can  come  into  being. 

THE   OSMOTIC   PRESSURE   OF   THE   BLOOD 

Since  the  blood  serves  as  a  circulating  medium,  by  means  of  which 
the  composition  of  the  tissues  juices  forming  the  immediate  environment 
of  all  the  cells  of  the  body  is  maintained  constant,  its  osmotic  pressure 
must  be  of  considerable  importance  in  regulating  the  normal  exchanges 
of  the  cells  with  their  surrounding  fluid.  The  osmotic  pressure  of  the 
blood  depends  on  its  molecular  concentration  and  can  be  determined  by 
any  of  the  methods  mentioned  earlier  (p.  125).  Of  these  the  most  con- 
venient is  the  determination  of  the  freezing-point.  The  depression  of 
freezing-point,  A,  of  mammalian  blood  is  about  0-56  and  varies  between 
0-54  and  0-60.  The  depression  of  the  freezing-point  observed  in  blood 
is  equal  to  that  of  a  0-9  per  cent,  sodium  chloride  solution,  which  is  there- 
fore taken  as  isotonic  with  the  blood.  .  Since  the  corpuscles  are  in  osmotic 
equilibrium  with  the  plasma,  their  osmotic  pressure  must  be  equal  to  that 
of  the  plasma,  and  laking  the  blood  does  not  alter  its  freezing-point  or  its 
osmotic  pressure.  The  blood  of  the  frog  has  a  lower  osmotic  pressure, 
the  normal  saline  fluid  for  the  frog's  tissues  being  equivalent  to  0-65  per 
cent,  sodium  chloride  solution. 


THE   ELECTRICAL   CONDUCTIVITY   OF   THE   BLOOD 

In  a  solution  it  is  only  the  dissociated  ions  which  have  the  power  of 
carrying  electric  discharges.  The  conductivity  of  a  solution  of  pure  urea 
or  pure  glucose  would  not  differ  appreciably  from  that  of  distilled  water, 


QUANTITY  AND  COMPOSITION  OF  THE  BLOOD   IN  MAN    907 

since  neither  of  these  substances  is  ionised  in  solution.  The  conductivity 
of  blood  serum  is  therefore  determined  almost  entirely  by  its  content  in 
salts.  Since  this  is  approximately  constant,  the  conductivity  of  serum 
varies  within  very  narrow  limits.  The  conductivity  of  blood  varies  how- 
ever within  wide  limits,  since  the  outer  limiting  layer  of  the  corpuscles 
is  impermeable  to  many  of  the  ions  of  the  salts  of  the  serum.  The  corpuscles 
present  a  resistance  to  the  passage  of  the  charged  ions  and  therefore  of  the 
electric  current  through  them,  so  that  the  larger  the  number  of  corpuscles 
contained  in  a  given  specimen  of  blood  the  lower  will  be  the  conductivity 
of  the  latter.  Stewart  has  made  use  of  this  fact  as  a  basis  for  a  method  of 
determining  the  relative  volume  of  corpuscles  and  plasma. 

The  relative  amount  of  serum  can  be  given  by  the  formula  : 
p  =  M6)     (174 -X  (6)) 

where  p  is  the  number  of  c.c.  of  serum  in  100  o.c.  of  blood ;  A.  (6),  X  (s),  the  conductivity 
respectively  of  the  blood  and  serum  (both  measured  at  or  reduced  to  5"  C.  and  expressed 
in  reciprocal  Ohms  X  108).  A  reciprocal  Ohm  is  the  conductivity  of  a  mercury  column 
1063  metres  long  and  1  square  millimetre  in  section. 


THE  GENERAL  COMPOSITION  OF  THE  BLOOD 

The  general  composition  of  the  blood  has  been  determined  by  Karl 
Schmidt  hi  man,  and  by  Abderhalden  in  the  horse  and  bullock.  The 
results  are  given  in  the  Tables  on  pages  908  and  909. 

The  important  points  to  be  drawn  from  these  analyses  may  be  sum- 
marised as  follows.  Human  blood  contains  from  rather  over  one-third  to 
one-half  of  its  weight  of  corpuscles.  It  contains  from  20  per  cent,  to  25  per 
cent,  solids.  Blood  plasma  is  resolved  by  clotting  into  serum  and  fibrin. 
The  fibrin  forms  only  0-2  to  0-4  per  cent,  of  the  total  weight  of  blood.  The 
serum  contains  in  100  parts  8  to  9  parts  of  solids,  of  which  7  to  8  parts 
consist  of  proteins,  while  the  salts  make  up  about  1  part.  The  chief  salt 
present  in  the  serum  is  sodium  chloride,  which  constitutes  60  per  cent, 
of  the  ash.  Next  to  this  comes  sodium  carbonate,  about  30  per  cent., 
and  besides  these  two  we  find  traces  of  potassium,  sodium,  and  calcium 
chlorides  and  phosphates.  Traces  of  fats,  cholesterin,  lecithin,  dextrose, 
urea,  and  other  nitrogenous  extractives  are  constantly  found  in  the  serum. 
The  fats  are  much  increased  after  a  meal  rich  in  them  and  may  give  the 
serum  a  milky  appearance.  The  red  corpuscles  contain  from  30  to  40  per 
cent,  total  solids.  Of  the  solid  constituents  haemoglobin  forms  nine-tenths ; 
the  other  tenth  corresponds  to  the  stroma  consisting  of  stroma  protein 
(nucleo-protein),  lecithin,  cholesterin,  and  salts.  There  is  a  striking  con- 
t  rast  between  the  salts  of  the  corpuscles  and  those  in  the  serum,  the  former 
consisting  chiefly  of  potassium  phosphate,  the  latter  of  sodium  chloride 
which  in  some  animals  is  entirely  wanting  in  the  corpuscles. 


908 


PHYSIOLOGY 


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QUANTITY  AND  COMPOSITION   OF  THE  BLOOD   IN  MAN    909 


Blood  of  a  Man  Twenty-five  Years  of  aoe 
One  thousand  Grammes  of  Blood  contain 
513-02  Blood  corpuscles. 

349-69 


water     .... 
Substances    not    vaporising 

at 

ottrvv 

120°     .          .          .          . 

163-33 

7-70           (including  0-512  iron) 

Hxmatin 

'  Blood-casein,'  etc.    . 

151-89 

Inorganic  constituents 

3-74          (excluding  iron) 

Chlorine 

0-898\ 

Chloride  of  potassium 

,    1-887 

Sulphuric  acid 

0-031 

Sulphate  of  potassium 

.    0-068 

Phosphoric- acid 

0-695 

Phosphate  of  potassium 

.    1-202 

Potassium 

1-586 

Phosphate  of  sodium  . 

.    0-325 

Sodium  .... 

0-241 

Soda 

.    0-175 

Phosphate  of  lime    . 

0-048 

Phosphate  of  lime 

.    0048 

Phosphate  of  magnesium  . 

0-031 

Phosphate  of  magnesium 

.    0-031 

Oxygen  .... 

0-206/ 



Total 

.    3-736 

486-98  Interstitial  Fluid  (Plasma). 

Water            " . 

439-02 

Substances    not    vaporising 

at 

120°     .... 

47-96                                         -      . 
3-93 

Fibrin     .... 

'  Albumen,'  etc. 

39-89 

Inorganic  constituents 

4-14 

Chlorine 

l-722\ 

Sulphate  of  potassium 

.    0-137 

Sulphuric  acid 

0-063 

Chloride  of  potassium 

.    0-175 

Phosphoric  acid 

0-071 

Chloride  of  sodium 

.    2-701 

Potassium 

0-153 

Phosphate  of  sodium  . 

.    0-132 

Sodium   .... 

1-661 

Soda 

.    0-746 

Phosphate  of  lime     . 

0145 

Phosphate  of  lime 

.    0-145 

Phosphate  of  magnesium  . 

0-106 

Phosphate  of  magnesium 

.    0-106 

Oxygen  .... 

0-221 



Total 

.    4-142 

Specific  gra 

vit 

y  =  1-0599 

THE   PROTEINS   OF   THE   PLASMA 

The  plasma  is  generally  described  as  containing  a  number  of  different 
proteins  belonging  to  the  class  of  coagulable  proteins.  No  albumoses  or 
peptones  are  present.  Since  the  plasma  in  clotting  gives  rise  to  fibrin 
and  serum,  we  may  divide  its  protein  constituents  into  those  which  are 
the  precursors  of  fibrin  and  those  which  are  still  contained  in  the  serum. 

The  Precursors  of  Fibrin.  Most  of  these  have  been  dealt  with  in 
discussing  the  causation  of  coagulation.  It  remains  for  us  here  only  to 
mention  some  of  the  chemical  features  of  fibrinogen  and  its  product 
fibrin.  Fibrinogen  is  best  separated  by  Hanunarsten's  method,  namely, 
half -saturation  with  sodium  chloride,  or  by  the  use  of  ammonium  sulphate. 


910  FHYSIOLOGY 

Fibrinogen  is  precipitated  between  13  and  28  per  cent,  saturation  with 
ammonium  sulphate,  whereas  no  other  globulins  are  precipitated  until 
the  saturation  amounts  to  29  per  cent,  of  ammonium  sulphate.  Fibrinogen 
obtained  in  either  of  these  ways  can  be  purified  by  re-solution  and  re- 
precipitation,  but  loses  its  solubility  in  the  process,  so  that  every  time  it 
is  precipitated  some  of  the  substance  becomes  insoluble.  The  insoluble 
fibrinogen  resembles  fibrin  in  many  characters,  but  does  not  swell  in  the 
presence  of  dilute  acids  as  fibrin  does.  Fibrinogen  is  soluble  in  dilute 
alkali,  from  which  it  may  be  precipitated  by  careful  neutralisation.  Fib- 
rinogen in  salt  solution  coagulates  at  56°  C.  A  small  amount  however 
remains  in  solution  and  is  not  coagulated  until  65°  C.  is  reached.  Fibrinogen 
can  be  therefore  described  as  a  globulin  occurring  in  the  plasma  and  con- 
verted on  coagulation  into  fibrin.  The  other  precursors  of  fibrin,  namely, 
those  involved  in  the  production  of  thrombin  and  called  thrombokinase 
and  thrombogen,  seem  to  be  phosphorus-containing  proteins,  perhaps 
belonging  to  the  class  of  nucleo-proteins.  Their  chief  characteristics  have 
already  been  dealt  with. 

FIBRIN.  Fibrin  is  easily  obtained  by  whipping  blood  as  it  flows  from 
the  vessels  with  a  bundle  of  wires  or  twigs,  and  then  washing  the  stringy 
threads  so  obtained  under  a  stream  of  water.  As  prepared  in  this  way 
it  always  contains  fragments  of  leucocytes,  blood  platelets,  and  stromata, 
which  have  become  entangled  in  its  meshes.  In  order  to  prepare  fibrin 
in  a  pure  state,  it  is  necessary  to  get  it  by  the  action  of  fibrin  ferment  on 
a  pure  solution  of  fibrinogen.  Fibrin  is  a  white  stringy  substance  insoluble 
in  water  and  in  dilute  salt  solutions.  It  slowly  dissolves  in  5  per  cent, 
solutions  of  sodium  chloride,  sodium  sulphate,  potassium  nitrate,  etc., 
but  is  converted  in  this  process  into  soluble  globulins.  It  is  probable 
that  its  solution  is  effected  by  the  agency  of  minute  traces  of  proteolytic 
ferment  present  in  the  blood  and  adherent  to  the  fibrin  as  it  is  precipitated. 
This  probability  is  strengthened  by  the  fact  that  a  certain  amount  of 
album'oses  is  always  foiuid  in  the  fluid  along  with  the  soluble  globulins. 
In  dilute  acid,  such  as  0-2  per  cent,  hydrochloric  acid,  fibrin  swells  into  a 
clear  jelly  which  very  slowly  undergoes  solution  with  the  formation  of  acid 
albumen  and  proteoses. 

THE  PROTEINS  OF  THE  SERUM.  The  serum  proteins  are  generally 
grouped  in  two  classes,  namely,  the  serum  albumens  and  the  serum  globulins. 
All  the  proteins  are  completely  precipitated  by  saturation  with  ammonium 
sulphate.  By  half-saturation  with  this  salt  only  the  globulins  are  pre- 
cipitated and  can  be  separated  from  the  serum  albumens  by  filtration. 
The  proportion  of  globulin  to  albumen  as  determined  in  this  way  is  known 
as  the  '  protein  quotient.'  It  varies  in  different  animals,  but  in  the  same 
individual  it  is  almost  constant  in  the  blood,  serum,  lymph,  and  serous 
transudations,  though  the  total  amounts  of  protein  in  these  may  be  very 
different. 

SERUM  ALBUMEN.  Serum  albumen  remains  in  the  serum  after  half- 
saturation  with  ammonium  sulphate.     It  can  be  precipitated  from  this  by 


QUANTITY  AND  COMPOSITION  OF  THE  BLOOD  IN  MAN     911 

complete  saturation  with  ammonium, sulphate  or  sodio-magnesium  sulphate, 
or  in  the  crystalline  form  by  slight  acidification,  as  in  Hopkins'  method 
described  on  p.  73.  Serum  albumen  is  soluble  in  distilled  water.  Its 
solutions  therefore  can  be  dialysed  indefinitely  without  any  precipitation 
taking  place. 

THE  GLOBULINS.  The  globulins  of  serum,  known  as  paraglobulin  01 
serum  globulin,  are  obtained  by  half -saturation  with  ammonium  sulphate. 
Their  solutions  in  salt  coagulate  at  about  75°  C.  Since  globulin  is  insoluble 
in  distilled  water,  it  is  precipitated  on  dialysing  serum  against  distilled 
water.  The  precipitate  obtained  in  this  way  is  not  however  so  great  in 
extent  as  that  obtained  on  half -saturation,  and  on  this  account  the  globulin 
fraction  of  the  serum  proteins  has  been  divided  into  two  fractions,  namely, 
cuglolmlin.  precipitable  by  dialysis,  and  pseudo-globulin,  not  precipitable  by 
dialysis,  but  thrown  down  on  half-saturation  with  ammonium  sulphate. 

A  thorough  study  of  serum  globulin  by  Hardy  has  shown  that  this  body  forms 
adsorption  combinations  with  acids,  alkalies,  or  neutral  salts.  With  acids  and  alkalies 
the  globulin  forms  '  salts  "  which  ionise  in  solution  so  that  in  an  electric  field  the  entire 
mass  of  protein  moves.  These  salts  cannot  be  precipitated  by  dialysis.  In  them  the 
globulin  acts  much  more  strongly  as  an  acid  than  as  a  base,  so  that  a  weak  acid,  such  as 
acetic  acid,  has  a  much  smaller  dissolving  power  over  globulin  than  has  the  equivalent 
amount  of  hydrochloric  acid,  and  boracic  acid  has  a  very  slight  power  indeed.  The 
weak  basic  character  of  globulin  causes  its  salt  in  weak  acids  to  undergo  hydrolysis 
with  separation  of  globulin,  so  that  in  order  to  reach  the  same  grade  of  solution  with 
a  weak  acid  as  with  a  strong  acid  a  great  excess  of  the  acid  is  necessary.  Owing  to  the 
much  stronger  acid  character- of  globulin  it  is  found  that  weak  ammonia  dissolves  it 
almost  as  well  as  strong  alkalies.  With  neutral  salts  globulins  form  molecular  com- 
pounds which  are  soluble,  but  are  readily  decomposed  by  water  with  liberation  of  the 
insoluble  globulin.  They  are  therefore  stable  only  in  the  presence  of  a  comparatively 
large  excess  of  salt.  The  globulins  differ  from  the  albumens  of  the  serum  in  containing 
constantly  organic  phos]morus  as  an  integral  part  of  their  molecule.  In  all  its  solutions 
globulin  is  present  in  large  molecular  aggregates,  so  that  it  is  impossible  to  filter  a  globulin 
solution  through  a  porous  clay  cell. 

THE   CONDITION   OF   THE   PROTEINS   IN   THE   BLOOD  SERUM 

Although  it  is  easy  by  such  simple  means  as  the  addition  or  removal 
of  neutral  salts  to  separate  one  or  more  different  forms  of  protein  from 
serum,  we  have  strong  evidence  that  these  proteins  do  not  exist  side  by 
side  in  the  serum,  but  are  combined  to  form  what  we  may  term  serum 
protein,  which  acts  as  a  whole  and  differs  in  its  qualities  from  many  of 
those  of  its  constituent  globulins  or  albumens.  When  a  current  is  passed 
through  blood  serum  no  movement  of  protein  takes  place  (Hardy).  Alkali 
globulin  therefore  cannot  be  present.  Salt  globulin  might  be  assumed 
to  be  present  since  it  does  not  ionise  in  solution,  but  sertun  is  not  preci- 
pitated by  simple  addition  of  acid,  which  would  readily  precipitate  salt 
globulin  in  alkaline  solution.  Moreover  serum  can  be  readily  filtered 
through  a  porous  cell,  and  this  method  is  adopted  for  obtaining  it  free 
from  contamination  by  micro-organisms.  Globulin  in  any  of  its  solutions 
will  not  pass  through  a,  porous  cell.     If  globulin  he  present  as  such  in  the 


912  PHYSIOLOGY 

serum,  it  is  therefore  not  ionised,  but  the  agent  which  dissolves  it  must  be 
something  more  than  alkali  or  salt,  since  either  alone  or  together  they  will 
not  produce  a  solution  which  will  pass  through  a  porous  cell.  Serum  has 
still  the  power  of  taking  up  globulin  and  will  dissolve  almost  its  own  volume 
of  precipitated  globulin,  though  in  oxalate  serum  there  is  not  a  trace  of 
alkali  globulin  nor  of  any  ionised  protein.  We  are  justified  therefore  in 
concluding  that  serum  protein  may  be  regarded  as  a  complex  unit.  By 
simple  means,  such  as  dialysis,  dilution,  or  addition  of  salt,  this  unit  can 
be  broken  up  with  the  separation  of  the  various  proteins  which  we  have 
designated  as  serum  albumen  and  serum  globulin,  etc.  The  question 
naturally  suggests  itself  whether  in  plasma  we  have  not  a  similar  com- 
bination of  all  its  varied  colloidal  constituents  to  form  one  labile  mass  of 
fluid  protoplasm. 


CHAPTER  XIII 
THE   PHYSIOLOGY   OF   THE   CIRCULATION 
SECTION  I 
GENERAL    FEATURES    OF   THE    CIRCULATION 

In  order  that  the  nutrition  of  the  tissues  may  be  properly  carried  out,  and 
that  they  may  receive  a  continual  supply  of  nourishment  from  the  ali- 
mentary canal,  and  of  oxygen  from  the  lungs,  and  be  able  to  free  themselves 
of  their  waste  products,  the  blood  which  flows  through  them  must  be 
continually  renewed.  For  this  purpose  every  part  of  the  body  is  supplied 
with  tubes — blood  vessels — of  various  sizes  and  structures. 

In  the  tissues  the  blood  is  passing  continuously  through  a  thick  mesh- 
work  of  capillaries,  hair-like  vessels  with  walls  consisting  of  a  single  layer 
of  delicate  endothelial  cells,  which  permit  of  a  free  interchange  of  material 
by  diffusion  between  the  blood  within  and  the  tissue  fluid  outside  the 
vessel.  The  movement  of  the  blood  is  maintained  by  a  hollow  muscular 
organ,  the  heart,  placed  in  the  chest,  the  blood  being  brought  from  the 
heart  to  the  tissues  by  thick-walled  tubes,  the  arteries,  and  being  carried 
back  from  the  tissues  to  the  heart  by  a  system  of  thin-walled  vessels,  the 
veins. 

In  all  the  vertebrates  the  vascular  system  is  closed,  i.  e.  communicates  at  no  point 
with  the  tissue  spaces  or  ccelomic  cavity.  It  is  found  in  its  simplest  form  in  fishes 
(Fig.  382,  a),  where  the  heart  consists  of  one  auricle  and  one  ventricle.  The  blood  is 
'1  from  the  great  veins  into  the  auricle.  The  walls  both  of  auricle  and  ventricle 
contract  rhythmically.  By  the  contraction  of  the  auricle  the  blood  is  forced  into  the 
ventricle,  and  this,  when  it  contracts,  sends  the  blood  on  into  t lie  bulbus  arteriosus. 
From  the  bulbus  the  blood  passes  through  the  branchial  arteries  into  the  gills,  where 
it  takes  up  oxygen  from  the  surrounding  water,  and  then  flows  on  into  the  aorta,  by 
Which  it  is  distributed  to  the  various  organs  of  the  body.  From  the  capillaries  of  these 
organs  the  blood  is  i  ollected  by  the  veins  and  is  carried  once  more  back  to  the  auricle. 
She  fish  heart  is  thus  entirely  on  the  venous  side  of  the  vascular  system. 

In  amphibia,  such  as  the  frog,  the  heart  consists  of  two  auricles  and  one  ventricle. 
The  right  auricle  receives  venous  blood  from  the  body  by  means  "I  the  venae  cavse  and 
forces  it  by  its  contraction  into  the  ventricle.  From  the  ventricle  the  blood  passes 
into  the  aorta,  whence  it  is  carried  partly  by  the  pulmonary  artery  to  the  lungs,  partly 
by  arteries  to  the  different  organs  of  the  body.  The  blood,  which  has  passed  through 
the  lungs  and  been  arterialised,  flows  through  the  pulmonary  veins  to  the  left  auricle, 
whence  it  passes  into  the  ventricle  and  mixes  with  the  venous  blood  which  is  arriving 
from  the  right  auricle.  The  pulmonary  circulation  is  thus  merely  a  branch  of  the 
general  01  systemic  circulation.  The  bulbus  aortae  in  the  frog  is  divided  into  two  parts 
58  913 


914 


PHYSIOLOGY 


by  means  of  a  spiral  valve,  by  which  a  partial  separation  of  the  blood  coming  from  the 
right  and  left  auricles  is  effected,  and  the  venous  blood  from  the  right  auricle  directed 
especially  into  the  pulmonary  artery. 

In  birds  and  mammals  the  heart  has  become  entirely  divided  into  two  halves,  right 
and  left,  which  have  no  communication  with  one  another  except  by  way  of  the  blood 
vessels  and  capillaries.  The  right  auricle  receives  the  venous  blood  from  all  parts  of 
the  body  and  sends  it  on  to  the  right  ventricle,  whence  it  is  forced  into  the  lungs  along 
the  pulmonary  artery.  In  the  lungs  it  takes  up  oxygen  and  becomes  arterial  and  is 
returned  by  the  pulmonary  veins  to  the  left  auricle  and  so  to  the  left  ventricle.  The 
rhythmic  contractions  of  the  left  ventricle  then  force  the  blood  into  the  aorta,  whence 
by  the  branching  arteries  it  is  carried  to  all  parts  of  the  body. 

A  B  C 


Fia.  382.     Diagram  of  circulatory  system  in  A,  fish;  B,  amphibian  (frog);  C,  mammal. 

v,  ventricle;    a,  auricle;    K,  gill  capillaries;    A,  aorta;  c,  systemic  capillaries; 

L,  lung  capillaries;  r,  I,  right  and  left  auricles;  rV,  IV,  right  and  left  ventricles. 

The  whole  vascular  system  is  distensible  and  elastic,  so  that  its  capacity 
will  increase  with  the  pressure  of  the  blood  contained  in  it.  Since  the 
driving  force  is  furnished  by  the  heart,  the  pressure  which  causes  the  flow 
of  blood  through  the  system  must  decline  as  we  pass  from  the  arterial  to  the 
venous  side.  The  chief  function  of  the  large  arteries  is  to  serve  as  elastic 
conduits,  whereas  the  small  arteries  or  arterioles  leading  from  the  arteries 
to  the  capillaries  have  in  addition  the  function  of  regulating  the  amount  of 
blood  flowing  through  the  capillary  area  of  the  organs  which  they  supply. 
The  veins  have  the  function  of  conducting  blood  at  a  low  pressure  from 
capillaries  to  heart  and  of  storing  up  any  excess  of  blood  which  is  not 
immediately  taken  up  by  the  heart. 

Corresponding  to  this  difference  in  function  we  find  variations  in  the  structure  of  the 
blood  vessels  according  to  their  situation  in  the  circuit.  The  vessels  which  carry  the 
blood  from  the  heart  to  the  tissues,  the  arteries,  are  thick-walled,  and  contain  an 
abundance  of  muscular  and  elastic  elements  in  their  walls.     The  typical  medium-sized 


GENERAL   FEATURES   OF   THE   CIRCULATION 


915 


artery  is  described  as  consisting  of  three  coats  (Fig.  383) :  an  Mima  lined  by  a  continuous 
layer  of  flattened  endothelial  cells,  which  rest  on  a  well-marked  lamina  of  yellow  elastic 
tissue;  a  media  composed  of  unstr.'ated  muscular  fibres  arranged  longitudinally  and 
circularly;  and  an  external  coat  or  adventitia  of  fibrous  tissue,  with  a  number  of  longi- 
tudinal elastic  fibres.     Near  the  heart,  in  the  great  vessels  such  as  the  aorta  and  its 


Fig.  3?o.     Transverse  section  of  part  of  the  wall  of  the  posterior 

tibial  artery  (  X  75). 

a,  endothelial  and  sub-endothelial  layers  of  intima;  6,  lamina  of  elastic  tissue; 

.  c,  media  consisting  of  muscle  fibres ;  d,  adventitia.     (Schafer.) 

larger  branches,  there  is  a  preponderance  of  elastic  tissue  as  compared  to  the  muscular ; 
and  we  find  in  the  media  alternate  layers  of  muscle  fibres  and  fenestrated  elastic  mem- 
branes. In  the  smallest  arteries  on  the  other  hand,  the  arterioles,  the  elastic  element 
entirely  disappears,  so  that  the  wall  consists  of  muscle  fibres,  chiefly  circular,  fined  by 
the  endothelium.  In  the  latter  vessels  a  contraction  of  their  walls  may  result  in  an 
entire  obliteration  of  the  lumen,  so  shutting  off  altogether  the  supply  of  blood  to  the 
capillaries  beyond.  In  the  veins  the  same  three  coats  can  be  distinguished  as  in  the 
typical  artery,  but  the  wall  of  the  vessel  is  much  thinner  in  proportion  to  the  lumen. 
In  the  vein  moreover  there  is  a  preponderance  of  the  fibrous  tissue  elements,  the  mus- 
cular and  elastic  tissue  being  but  little  marked.  On  this  account  the  vein  collapses 
unless  it  is  distended  by  some  internal  pressure. 

Capacity  in  c.c. 


_____ 

7 

- 

' 

— : 

/ 

120        130        140        150        160 


nun.  Hg. 
Fio.  3S4.     Curves  of  distensibility  of  an  artery  (thick  line)  and  of  a  vein  (thin  line).     The 
figures  at  the  left  side  of  the  diagram  represent  the  capacity  of  a  section  of  the  vessel 
when  distended  under  a  certain  pressure,  expressed  by  the  figures  on  the  base  line  in 
mm.  Hg.     (Constructed  from  figures  given  by  Roy.) 

The  histological  difference  between  veins  and  arteries  is  of  considerable 
importance  for  the  understanding  of  the  distribution  of  pressures  in  the 
vascular  system,  since  the  distensibility  and  reaction  to  pressure  of  these 
vessels  are  conditioned  by  their  structure.    In  Fig.  384  is  represented  the 


916  PHYSIOLOGY 

distensibility,  i.e.  the  increase  in  capacity  of  an  artery  and  a  vein  under 
gradually  increasing  internal  pressure.  It  will  be  seen  that  an  artery,  which 
has  a  certain  capacity  at  zero  pressure,  gradually  distends  with  increasing 
pressure.  The  increase  in  capacity  is  small  at  first,  and  becomes  most 
rapid  between  90  and  100  mm.  Hg.  After  this  point  every  increment  of 
pressure  brings  about  a  gradually  diminishing  increment  of  capacity.  Thus 
a  change  of  internal  pressure  causes  the  greatest  change  in  capacity  when 
the  pressure  in  the  artery  corresponds,  as  we  shall  see,  to  the  average  arterial 
pressure  in  the  normal  animal.  In  the  vein,  on  the  other  hand,  the  capacity, 
which  is  nothing  at  zero  pressure,  becomes  considerable  on  raising  the 
pressure  to  1  mm.  Hg.  A  further  rise  of  pressure  to  10  mm.  Hg.  causes  a 
considerable  increase  in  volume,  but  from  this  point  the  increments  of  volume 
with  rising  pressure  rapidly  diminish.  Whereas  the  artery  is  most  distensible 
at  about  100  mm.  Hg.,  the  vein  has  its  limits  of  optimum  distensibility 
between  0  and  10  mm.  Hg. 

As  the  arteries  branch,  although  each  branch  is  smaller  than  the  parent 
vessel,  the  total  area  of  the  two  branches  into  which  the  vessel  divides  is 
greater.  Thus  there  is  a  continual  increase  in  the  cross  area  of  the  bed 
of  the  blood  stream  as  we  pass  from  the  heart  towards  the  periphery. 
This  increase  is  especially  marked  at  the  junction  between  the  capillaries 
and  the  arterioles  on  one  side  and  the  venules  on  the  other,  so  that  the 
total  area  of  the  bed  iu  the  region  of  the  capillaries  can  be  taken  as  about 
800  times  that  of  the  area  of  the  aorta  where  the  blood  leaves  the  heart. 

On  cutting  through  an  artery,  blood  escapes  from  the  central  end,  i.  e. 
that  nearest  the  heart,  with  great  force  and  in  a  series  of  jerks,  each  of 
which  corresponds  to  a  contraction  of  the  ventricles.  This  manner  of 
escape  shows  that  in  the  arteries  the  blood  is  at  a  high  pressure,  and  that 
the  flow  from  the  heart  to  the  periphery  is  a  pulsatory  one.  The  same 
lesson  may  be  learnt  by  connecting  a  long  tube  with  the  central  end  of  a 
divided  artery.  This  experiment,  which'  was  first  performed  by  the  Rev. 
Stephen  Hales,  may  be  described  in  his  own  words  : 

"  In  December  I  caused  a  mare  to  be  tied  down  alive  on  her  back ;  she  was  fourteen 
hands  high,  and  about  fourteen  years  of  age,  had  a  Fistula  on  her  Withers,  was  neither 
very  lean,  nor  yet  lusty  :  Having  laid  open  the  left  crural  Artery  about  three  inches 
from  her  belly,  I  inserted  into  it  a  brass  Pipe,  whose  bore  was  one  sixth  of  an  inch  in 
diameter;  and  to  that,  by  means  of  another  brass  Pipe  which  was  fitly  adapted  to  it, 
I  fixed  a  glass  Tube,  of  nearly  the  same  diameter,  which  was  nine  feet  in  length  :  Then 
untying  the  Ligature  on  the  Artery,  the  blood  rose  in  the  Tube  eight  feet  three  inches 
perpendicular  above  the  level  of  the  left  Ventricle  of  the  heart :  But  it  did  not  attain 
to  its  full  height  at  once;  it  rushed  up  about  half  way  in  an  instant,  and  afterwards 
gradually  at  each  Pulse  twelve,  eight,  six,  four,  two,  and  sometimes  one  inch  :  When 
it  was  at  its  full  height,  it  would  rise  and  fall  at  and  after  each  Pulse  two,  three,  or  four 
inches ;  and  sometimes  it  would  fall  twelve  or  fourteen  inches,  and  have  there  for  a 
time  the  same.  Vibrations  up  and  down  at  and  after  each  Pulse,  as  it  had,  when  it  was 
at  its  full  height;   to  which  it  would  rise  again,  after  forty  or  fifty  Pulses." 

The  method  adopted  by  Hales  of  measuring  the  lateral  pressure  of 
blood  in  the  vessels  offers  very  considerable  drawbacks.     The    manipula- 


GENERAL   FEATURES   OF   THE   CIRCULATION 


917 


tion  of  such  long  tubes  is  awkward,  and  the  blood  which  escapes  into  the 
tubes  very  soon  clots  and  renders  further  observation  impossible.  It  is 
therefore  customary  when  we  desire  to  gain  an  idea  of  the  average  pressure 
in  any  blood  vessel,  especially  in  an  artery,  to  use  a  mercurial  manometer 
for  this  purpose. 

This  instrument,  which  was  first  applied  to  physiological  purposes  by  Ludwig,  con- 
sists of. a  U-tube  with  two  vertical  limbs  about  eighteen  inches  in  height,  which  is  half- 
filled  with  clean  mercury.  On  the  surface  of  the  mercury  of  one  limb  is  a  float  of 
vulcanite  from  which  a  stiff  fine  rod  of  straw,  glass,  or  steel  rises,  bearing  on  its  upper 
end  the  writing-point.  This  point  may  be  adjusted  so  as  to  write  on  the  blackened 
glazed  surface  of  a  moving  sheet  of  paper  (Fig.  385).  (The  arrangement  for  imparting 
a  continuous  movement  to  a  sheet  of 
glazed  paper  is  known  as  a  kymograph.) 
Instead  of  smoking  the  paper,  a  pen  may 
Ijc  fitted  to  the  end  of  a  rod  and  its 
excursions  recorded  in  ink  on  a  moving 
band  of  white  paper.  The  other  limb 
of  the  manometer  is  connected  by  a 
flexible  inextensible  tube  with  a  small 
tube  or  cannula  which  is  tied  into  the 
central  end  of  an  artery,  a  clip  being 
previously  placed  on  the  artery  so  as 
to  prevent  the  escape  of  blood  during 
the  insertion  of  the  cannula.  To  the 
manometer  is  connected  a  three-way 
tap  by  means  of  which  the  manometer 
can  be  placed  in  communication  with 
the  artery  alone,  or  with  the  artery  and 
a  pressure  bottle.  By  means  of  the 
latter  the  whole  system  is  filled  with 
magnesium  sulphate  solution  (25  per 
cent.)  or  a  half -saturated  solution  of 
sodium  sulphate,  at  a  pressure  of  150 
mm.  Hg.  The  pressure  bottle  is  then 
cut  off  so  that  the  manometer  remains 
in  connection  only  with  the  cannula,  the 
mercury  in  one  linib  being  150  milli- 
metres above  that  in  the  other.  The 
clip  is  then  taken  off  the  artery.     The 

pressure  in  the  cannula  being  greater  than  that  in  the  artery,  a  small  amount  of  the 
fluid  used  to  fill  the  tubes  rims  into  the  circulation.  The  mercury  in  the  manometer 
drops  to  a  height  of  100  to  120  mm.  Hg.  and  stays  about  that  level,  rising  and  falling 
slightly  with  each  heart  beat  (Fig.  387).  The  blood  which  enters  the  cannula  at  each 
heart  beat  does  not  clot  for  a  considerable  time  owing  to  its  admixture  with  the  saline 
fluid  used  for  filling  the  cannula  and  connecting  tubes. 


Fia.  385.     Arrangement  of  an  apparatus  for 

taking  blood-pressure  tracing. 

a,    artery    (carotid);    c,    cannula;     d,  threo 

way  cock;  m,  mercurial  manometer;  6,  drum 

covered  with  smoked  paper;  r,  tube  to  pressure 

bottle. 


If  a  vein  be  ligatured,  it  swells  up  on  the  distal  side  of  the  ligature. 
In  the  vein  be  cut  across,  blood  escapes  chiefly  from  the  peripheral  end, 
and  instead  of  spurting  out  to  a  considerable  distance  with  each  heart 
beat  it  flows  steadily,  but  with  very  little  force,  so  that  light  pressure  by 
a  bandage  is  sufficient  to  restrain  the  hemorrhage.  If  a  mercurial  mano- 
meter be  connected  with  the  vein,  the  pressure  in  its  interior  is  found  to 
amount  to  onlv  a  few  mm .  Hg. 


918 


PHYSIOLOGY 


By  taking  the  pressure  at  different  parts  of  the  circulation,  we  obtain 
a  distribution  which  is  represented  roughly  in  the  accompanying  diagram 
(Fig.  386).  The  blood  pressure,  which  is  about  100  to  120  mm.  Hg.  in 
the  large  arteries  near  the  heart,  falls  only  slowly  in  these  arteries,  so  that 


Fig.  38G.     Scheme  of  blood  pressure  in — A,  the  arteries;  c,  capillaries;  and  v,  veins. 

oo,  line  of  no  pressure;  lv,  left  ventricle;  ka,  right  auricle;  bp,  height  of 

blood  pressure. 


ii\  the  radial  artery  it  is  not  very  much  below  that  in  the  aorta.  Between 
the  medium-sized  arteries  and  capillaries  there  is  a  very  extensive  fall  of 
pressure  as  the  blood  passes  through  the  arterioles,  so  that  in  the  capillaries 
the  pressure  on  an  average  may  be  taken  as  20  to  40  mm.  Hg;  from  the 
capillaries  to  the  veins  the  blood  pressure  falls  steadily  imtil  in  the  big 
veins  near  the  heart  it  may  be  negative. 


SECTION  II 

THE   BLOOD   PRESSURE   AT   DIFFERENT   PARTS 
OF  THE  VASCULAR   CIRCUIT 

THE  ARTERIAL  BLOOD  PRESSURE.     The  arterial   blood  pressure  as 
recorded  by  a"  mercurial  manometer  exhibits  a  series  of  pulsations  corre- 
sponding to  each  heart  beat  (Fig.  387).    These  pulsations  are  due  to  the 
fact  that  the"  artery  becomes  fuller  each  time  the  ventricle  forces  more 
blood  into  it  during  its  systole.      Between  the 
beats  of  the  heart,  i.  e.  during  diastole,  the  aortic 
valves  are  closed,  and  blood  escapes  from  the 
arteries  into  the  capillaries  and  veins,  so  that 
the  blood  pressure  falls.    The  mercurial  mano- 
meter does  not  register  these  rapid  changes  of 
pressure,  in  the  artery  with  any  accuracy.    The 
inertia  of  the  mercury  is  such  that  it  takes  some 
time  to  be  set  into  movement  by  the  rise  of   I 
pressure  in  the  artery,  and  before  it  has  attained   I 
its  full  height  the  pressure  in  the  artery  has    Fig.    387.    Blood-pressure 
i        ii-  r  n       -vir-j.1.  -j     j.    -u   j         tracing  taken  with  mer- 

already  begun  to  fall.    With  a  very  wide-tubed       curiai  manometer  (from 

manometer  the  oscillations  may  be  almost  irn-       carotid  of  rabbit), 
perceptible  owing  to  the  mass  of  mercury  that       A'  •b"5i£jM  of  no 
has  to  be  moved  at  each  heart  beat.    Such  a 

manometer  gives  a  true  record  of  what  is  known  as  the  '  mean  arterial 
pressure.'  In  order  to  determine  the  true  course  of  the  pressure  in  the 
heart,  it  is  necessary  to  diminish  to  the  utmost  possible  extent  the  inertia 
of  the  moving  parts  of  the  recording  instrument,  and  to  employ  some 
manometer  such  as  that  of  Hurthle  or  of  Frank,  in  which  the  pressure  is 
measured  by  recording  the  stretching  of  an  elastic  membrane.  Such 
instruments  will  be  described  later  in  dealing  with  the  changes  of  pressure 
in  the  ventricle  during  contraction. 

In  the  living  animal  the  variation  in  the  arterial  pressure  at  each  heart 
beat  is  much  greater  than  would  be  anticipated  from  an  inspection  of  the 
tracing  given  by  the  mercurial  manometer.  The  highest  pressure  which 
occurs  while  blood  is  passing  from  the  heart  into  the  aorta  is  called  the 
systolic  arterial  pressure ;  the  pressure  at  the  end  of  diastole,  just  before 
the  heart  begins  to  force  a  fresh  quantity  of  blood  into  the  aorta,  is  the 
diastolic  pressure  ;    and  the  range  between  these  two  extremes  is  known 

919 


920  PHYSIOLOGY 

as  the  pulse  pressure.  Thus  in  the  dog,  with  a  mean  pressure  of  about 
120  mm.  Hg.  in  the  aorta,  the  systolic  pressure  may  be  as  much  as  160, 
while  the  diastolic  pressure  is  only  Kid  mm.  In  this  case  the  pulse  pressure 
would  be  (io  mm.  Hg.  In  man  the  systolic  pressure,  as  measured  in  the 
brachial  artery,  is  under  normal  conditions  about  110  mm.,  while  the 
diastolic  pressure  is  only  65  to  75  mm.,  so  that  the  pulse  pressure  is  about 
15  nun.  Hg.  As  we  pass  outwards  towards  the  periphery  the  pulse  pressure 
becomes  less  and  less  marked,  until  finally  in  the  capillaries  and  veins 
there  is  no  pulse  wave  perceptible. 

THE   DETERMINATION   OF   THE   BLOOD   PRESSURE   IN   MAN 

It  is  important  for  clinical  purposes  to  be  able  to  determine  even  approximately  the 
blood  pressure  in  the  different  parts  of  the  vascular  system  in  man,  and  various  methods 
have  been  devised  for  this  purpose.  The  determination  of  the  systolic  blood  pressure 
in  the  arteries  is  easily  carried  out  by  the  use  of  Riva  Rocci's  sphygmomanometer. 
This  apparatus  (Fig.  388)  consists  of  a  leather  or  canvas  band  about  10  cm.  wide,  which 


b^    a    *m 


Fig.  388.     Riva  Rocci's  sphygmomanometer.  Flo.  389. 

(C.  J.  Martin's  pattern.     Hawksley.) 

can  be  buckled  closely  round  the  upper  arm.  Inside  this  band  is  a  rubber  bag  of  the 
same  shape,  which  communicates  by  a  rubber  tube  with  a  mercurial  manometer  and  by 
a  three-way  tap  with  a  pressure  bulb  or  bicycle  pump,  or  with  the  external  air.  The 
band  is  buckled  round  the  arm  and  the  fingers  of  the  observer  are  placed  on  the  radial 
pulse.  The  bag  is  then  distended  with  air  so  that  it  exercises  a  pressure  on  the  arm, 
the  pressure  being  indicated  on  the  mercurial  manometer.  Air  is  forced  in  until  the 
radial  pulse  disappears.  By  means  of  the  three-way  tap  the  air  is  then  let  slowly  out 
of  the  bag  until  the  radial  pulse  is  just  perceptible.  The  height  of  the  mercurial  mano- 
meter at  this  moment  is  equal  to  the  systolic  pressure  in  the  main  arterial  trunk  from 
which  the  brachial  artery  takes  origin.  The  principle  of  this  method  will  be  made 
clear  by  reference  to  the  diagram  (Fig.  389).  If  we  imagine  A  as  a  segment  of  the  brachial 
artery  passing  through  the  tissues  which  are  surrounded  by  the  rubber  bag,  we  see  that 
so  long  as  the  pressure  in  the  interior  of  the  artery  is  greater  than  that  exerted  by  the 
tissues  on  the  exterior,  the  artery  will  be  patent  and  the  pulse  can  pass  through.  If 
however  the  pressure  in  the  tissues  becomes  greater  than  the  maximum  pressure 
inside  the  artery  at  any  time  of  the  heart  beat,  the  segment  of  artery  will  collapse  (as 
in  b),  thus  stopping  the  transmission  of  blood  and  of  the  pulse  wave.  If  we  exclude  the 
elasticity  of  the  tissues  themselves,  we  may  take  the  pressure  in  the  bag  as  representing 
the  pressure  in  the  tissue  fluids  surrounding  the  artery,  so  that  the  pulse-obliterating 
pressure  in  the  bag  will  correspond  to  the  maximum  or  systolic  pressure  in  the  artery. 
By  a  slight  modification  of  the  apparatus  it  is  possible  to  determine  also  the  diastolic 
pressure.  For  this  purpose  the  rubber  bag  is  connected  also  with  a  manometer  of  small 
inertia,  giving  a  true  representation  of  the  actual  changes  of  pressure.     It  is  evident 


BLOOD   PRESSURE  AT  PARTS  OF  VASCULAR   CIRCUIT    921 

that,  when  the  pressure  in  the  bag  and  in  the  tissues  surrounding  the  artery  exactly 
corresponds  to  the  diastolic  pressure,  the  artery  will  be  completely  collapsed  when  the 
pressure  arrives  at  its  lowest  point  and  will  then  dilate  almost  to  the  utmost  with  the 
systolic  rise  of  pressure.  If  we  are  taking  a  record  of  the  pressure  changes  in  the  bag 
in  this  way,  the  pulse  waves  as  recorded  by  the  manometer  will  slowly  increase  in  size 
as  the  pressure  in  the  bag  is  gradually  raised.  At  one  point  the  waves  rapidly  increase 
and  reach  a  maximum,  marking  the  pressure  at  which  the  artery  is  just  completely 
collapsed  at  the  lowest  point  of  each  pulse  wave  (the  diastolic  pressure).  As  the  pressure 
is  still  further  raised,  the  excursions  of  the  manometer  tend  to  diminish  in  size,  first 


Fig.  390.     Erlanger's  apparatus  for  recording  systolic  and  diastolic 
blood  pressures. 


I  ln\\  ly  and  then  rapidly,  and  the  point  of  rapid  diminution  corresponds  to  the  systolic 
pressure.  Above  this  point  the  manometer  still  shows  small  oscillations,  due  to  the 
impact  of  the  unoccluded  stump  of  the  artery  on  the  upper  bolder  of  the  india-rubber 
bag. 

Many  different  methods  have  been  introduced  for  the  purpose  of  recording  the 
pressure  oscillations  in  the  ba<_'.  In  Erlanger's  apparatus  the  lubber  bag  is  put  into 
connection  with  a  thick-walled  rubber  ball  rs  contained  in  a  glass  chamber.  The 
chamber  (Fig.  390)  communicates  with  a  sensitive  tambour  and  also,  by  means  of  a 
capillary  opening  provided  with  a  stop-cock,  with  the  cxteinal  air.  By  this  means  the 
slow  expansion  of  the  ball  PS  is  not  recorded  by  the  tambour,  which  moves  only  with 
the  sudden  oscillations  of  pressure  due  to  each  heart  beat.  With  this  instrument  it 
is  ea6y  to  read  on  the  accompanying  mercurial  manometer  the  point  at  which  the 


922 


PHYSIOLOGY 


oscillations  of  pressure  in  the  bag  suddenly  become  maximal,  and  so  to  determine 
approximately  the  diastolic  pressure  in  the  artery. 

VENOUS  PRESSURE.  To  determine  the  venous  pressure  in  man  we  may  use 
some  modification  of  von  Recklinghausen's  method.  A  circular,  disc-shaped,  incom- 
plete rubber  bag  (Fig.  391)  is  made  by  cementing 
together  at  the  circumference  two  rubber  discs, 
each  of  which  has  a  hole  in  the  centre.  This  is 
placed  over  a  peripheral  vein  and  a  glass  plate 
laid  on  the  top  (Fig.  392).  A  tube  leads  from 
the  interior  of  the  annular  rubber  bag  to  a  water 
manometer  and  to  a  bicycle  pump  or  bellows  for 
the  injection  of  air.  On  blowing  air  into  the  bag 
the  pressure  in  its  interior  rapidly  increases.  If  the 
skin  and  glass  plate  have  been  previously  smeared 
with  glycerin,  the  air  does  not  escape  but  distends 
the  bag,  pressing  it  against  the  skin  on  the  one 
hand  and  the  glass  plate  on  the  other.  Through 
the  hole  in  the  rubber  bag  it  is  easy  to  see  the 
pressure  at  which  the  vein  collapses — that  is  to  say, 
the  point  at  which  the  pressure  in  the  bag  is  equal 
to  the  pressure  within  the  vein.  By  a  similar  method,  using  a  smaller  bag,  we  may 
determine  the  pressure  which  is  just  sufficient  to  obliterate  the  capillaries  in  any  given 
area  of  the  skin,  so  causing  a  blanching  of  the  skin  lying  under  the  bag. 


EJ 


Fig.  391. 


The  following  Table  may  serve  to  give  an  idea  of  the  average  height 
of  the  mean  blood  pressure  (not  systolic)  at  different  parts  of  the  vascular 
system  in  man,  in  the  horizontal  position.  The  pressures  are  all  subject 
to  considerable  variations  according  to  the  activity  of  the  individual  and 
the  physiological  activity  of  the  various  parts  and  organs  of  the  body : 


Large  arteries  (e.  g.  carotid) 

Medium  arteries  (e.  g.  radial) 

Capillaries 

Small  veins  of  arm  . 

Portal  vein     . 

Inferior  vena  cava 

Large  veins  of  neck 


.     90  mm.  mercury  (65-1 10). 
85  mm.         „ 
about       15  to  40  mm.  mercury. 
9  mm.  mercury. 
10  mm.         „ 
3  mm.         „ 
from         0  to  -8  mm.  mercury.    - 


The  cause  of  these  peculiarities  in  the  circulation  in  different  parts  of  the  vascular 
system  will  be  rendered  clearer  by  a  study  of  a  flow  of  fluid  through  a  tube  of  uniform 
bore  (Fig.  393).  If  the  tube  AG  be  connected  with  the  reservoir  e,  fluid  will  flow  from 
A  to  G  under  the  influence  of  the  pressure  difference  between  the  fluid  in  the  reservoir 
and  that  at  o.  The  pressure  on  the  fluid  at  each  part  of  the  tube  can  be  measured  by 
attaching  at  a  series  of  points — e.  g.  at  b,  c,  d,  e,  r — vertical  tubes  in  which  the  fluid 
will  rise  to  a  height  corresponding  to  the  lateral   pressure  existing  at  these  several 


BLOOD  PRESSURE  AT  PARTS  OF  VASCULAR  CIRCUIT    923 

points.  When  fluid  is  flowing  from  A  to  a,  it  will  be  found  that  the  heights  of  the  fluid 
in  the  tubes  show  a  continuous  descent,  so  that  the  line  joining  the  tops  of  the  fluid 
in  the  various  tubes  is  a  straight  one.  The  movement  of  the  fluid  from  b  to  c  can  be 
regarded  as  due  to  the  difference  of  the  pressure  between  B  and  c,  i.  e.  P2-IV  It  will 
be  noticed  in  the  diagram  that  the  straight  line  joining  the  tops  of  the  fluid  does  not 
strike  the  surface  of  the  fluid  in  R,  but  falls  a  little  below  it.  Of  the  total  pressure  in  R, 
H,  the  large  portion  h'  is  employed  in  overcoming  the  resistance  of  the  tube  AG,  while  a 
small  portion  h  represents  the  force  necessary  to  give  to  the  fluid  as  it  leaves  the  reservoir 


at  a  a  certain  velocity.  If  the  flow  of  fluid  be  diminished  by  partially  clamping  the 
end  at  G,  the  rate  of  fall  of  the  pressures  will  be  diminished.  The  same  effect  will  be 
produced  either  by  raising  the  level  of  G  or  by  lowering  the  level  of  the  reservoir  and  so 
the  pressure  at  a. 

The  difference  of  pressure  between  any  two  points,  i.  e.  between  d  and  e,  may  be 
led  as  that  pressure  which  is  necessary  to  maintain  a  certain  velocity  of  the  fluid 


against  the  resistance  offered  by  the  friction  of  the  fluid  in  contact  with  the  walls  of 
the  tube.  This  friction,  and  therefore  the  resistance  to  the  flow,  can  be  altered  by 
6!iminishing  the  diameter  of  the  tube,  when  a  larger  difference  of  pressure  will  be 
necessary  in  order  to  maintain  the  same  velocity  of  flow.  This  can  be  shown  by  in- 
troducing a  resistance  between  d  and  e  by  partially  clamping  the  tube  at  this  point 
(Fig.  394).  The  continuity  of  the  fall  of  pressures  in  the  vertical  tube  is  at  once  abolished. 
Between  A  and  d  there  is  a  continuous  fall,  which  is  succeeded  by  a  steep  fall  between 
D  and  E,  and  this  again  by  a  gradual  fall  between  E  and  G.  In  any  system  of  tubes 
therefore  through  which  fluid  is  flowing,  the  fall  of  pressure  between  any  two  points 


924  PHYSIOLOGY 

will  be  proportional  to  the  velocity  of  the  flow  between  these  two  points.  The  velocity, 
on  the  other  hand,  will  vary  directly  as  the  difference  of  pressures,  and  inversely  as  the 
resistance  between  the  two  points.     These  relations  may  be  expressed  by  the  formula 

it. 

In  the  vascular  system,  while  the  circulation  is  maintained,  the  largest 
difference  of  pressure  exists  between  the  arteries  on  the  one  side  and  the 
small  veins  on  the  other,  a  great  fall  occurring  between  the  arteries  and 
the  capillaries  themselves.  This  distribution  of  pressure  points  to  the 
chief  resistance  in  the  vascular  system  as  being  situated  in  the  arterioles. 
The  resistance  presented  by  these  vessels  is  due  to  the  fact  that  they  are 
maintained  in  a  state  of  tonic  contraction  by  the  agency  of  the  central 
nervous  system.  The  total  bed  of  the  stream  in  the  region  of  the  arterioles, 
while  greater  than  that  of  the  arteries,  is  considerably  less  than  that  of 
the  rich  meshwork  of  capillaries,  while  the  difference  between  the  diameters 
of  arterioles  and  capillaries  is  not  very  great.  On  this  account  the  velocity 
of  the  blood  in  the  arterioles  is  very  much  greater  than  that  obtaining  in 
the  capillaries,  and  since  friction  and  therefore  the  resistance  varies  as  the 
square  of  the  velocity,  the  resistance  to  the  flow  of  blood  through  the 
arterioles  must  be  much  greater  than  that  presented  by  the  capillaries. 
The  large  part  taken  by  the  arterioles  in  determining  the  difference  of 
pressure  between  the  arteries  and  veins  is  shown  by  the  fact  that  this 
difference  can  be  diminished  to  one-half  by  any  means  which  causes  a 
dilatation  of  the  arterioles,  as,  for  example,  destruction  of  the  vasomotor 
centre. 

THE   CONVERSION   OF   AN   INTERMITTENT   INTO   A 
CONSTANT    FLOW 

■  Not  only  is  the  blood  pressure  in  the  veins  much  lower  than  in  the 
arteries,  but  the  flow  of  blood  has  been  converted  on  its  passage  through  the 
peripheral  resistance  from  a  pulsatory  into  a  continuous  flow.  This  change 
is  connected  with  the  distensible  elastic  nature  of  the  arterial  walls. 

Since  this  is  a  purely  mechanical  question  it  will  be  more  easily  under- 
stood by  a  simple  illustration.  The  heart  may  be  regarded  as  a  pump, 
forcing  a  certain  amount  of  blood  (in  man  about  60  c.c.)  into  the  circulation 
at  each  stroke.  If  a  pump  be  connected  with  a  rigid  tube,  every  time 
that  a  certain  amount  is  forced  into  the  beginning  of  the  tube  an  exactly 
equal  quantity  will  be  forced  out  at  the  other  end.  Increasing -the  peri- 
pheral resistance  by  partial  closure  of  the  end  of  the  tube  will  not  affect 
the  intermittent  character  of  the  flow,  but  will  merely  serve  to  diminish 
the  quantity  thrown  in,  as  well  as  the  quantity  which  escapes  at  the  other 
end  of  the  tube,  supposing  that  the  work  done  by  the  pump  is  equal  in 
both  cases.  If  instead  of  a' rigid  tube  we  employ  an  elastic  tube  and  the 
end  be  left  open  so  that  no  resistance  is  offered  to  the  outflow  of  the  fluid, 
the  effect  will  be  the  same  as  when  we  used  the  rigid  tube ;  the  outflow  will 
correspond  exactly  to  the  inflow  and  will  be  just  as  intermittent.     But 


BLOOD  PRESSURE   AT   PARTS  OF  VASCULAR  CIRCUIT      925 

now,  if  the  end  of  the  elastic  tube  be  clamped  so  as  to  increase  the  resist- 
ance to  the  outflow,  there  will  be  a  marked  difference  from  the  residts 
obtained  when  the  rigid  tube  was  partially  obstructed.  Each  stroke  of 
the  pump  forces  a  certain  amount  of  fluid  iuto  the  tube.  Owing  to  the 
peripheral  resistance  this  cannot  all  escape  at  once,  and  so  part  of  the 
force  of  the  pump  is  spent  in  distending  the  walls  of  the  tube,  and  part 
of  the  fluid  that  was  forced  in  remains  in  the  tube.  The  distended  elastic 
tube  tends  to  empty  itself  and  forces  out  the  fluid  which  over-distends 
it  before  the  next  stroke  of  the  pump  occurs.  So  now  the  outflow  may  be 
divided  into  two  parts,  one  part  which  is  forced  out  by  the  immediate 
effect  of  the  stroke  of  the  pump,  and  another  part  which  is  forced  out  by 
the  elastic  reaction  of  the  tube  between  the  strokes.  If  the  strokes  be 
rapidly  repeated  before  the  tube  has  time  to  empty  itself  thoroughly,  it 
will  get  more  and  more  distended.  Greater  distension  means  stronger 
elastic  reaction,  and  therefore  stronger  outflow  of  the  fluid  between  the 
beats.  This  distension  goes  on  increasing  till  the  fluid  forced  out  between 
the  strokes  by  the  elastic  reaction  of  the  wall  of  the  tube  is  exactly  equal  to 
that  entering  at  each  stroke,  and  the  flow  thus  becomes  continuous. 

The  same  thing  occurs  in  the  living  body.  A  man's  heart  at  each  beat 
oi  contraction  forces  about  60  c.c.  of  blood  into  the  already  distended 
aorta.  The  first  effect  of  this  is  to  distend  the  aorta  still  further.  The 
elastic  reaction  of  the  walls  drives  on  another  portion  of  blood,  which 
distends  the  next  segment  of  the  arterial  wall,  and  so  the  wave  of  distension 
is  transmitted  with  gradually  decreasing  force  along  the  arteries.  This 
wave  of  distension  is  what  we  feel  on  the  radial,  artery,-  or  any  exposed 
artery,  as  the  pulse.  After  each  heart  beat  the  arteries  tend  to  return 
to  their  original  size,  and  drive  the  blood  on  through  the  arterioles  (the 
peripheral  resistance)  into  the  capillaries  and  so  into  the  veins.  By  the  time 
the  blood  has  reached  the  veins.  ;ill  trace  of  the  heart  beat  has  disappeared 
and  the  pressure  has  fallen  to  a  few  millimetres  of  mercury. 


INFLUENCE   OF   THE   CAPACITY   OF   THE   VASCULAR   SYSTEM 
ON   THE   CIRCULATION 

So  far  we  have  only  considered  the  influence  of  changes  of  pressure 
and  resistance  in  a  system  of  tubes  with  a  head  of  pressure  at  one  end  and 
a  free  outflow  at  the  other.  In  the  body  however  the  vascular  system 
is  a  closed  circuit  of  elastic  tubes  presenting  varying  resistances  to  the 
flow  of  blood,  and  of  varying  distensibility  at  different  parts  of  their  course. 
In  this  e]i. seil  system  is  inserted  a  pump,  the  heart,  with  the  function  of 
driving  the  blood  through  the  system.  Since  all  the  blood  vessels  are 
elastic  and  distensible,  the  capacity  of  the  system  is  not  fixed,  but  must 
vary  with  the  internal  pressure  to  which  the  vessels  are  subjected.  More- 
over the  position  of  the  different  parts  of  the  circulation  must  have  an 
influence  on  the  capacity  of  the  system,  since  the  dependent  vessels  will 
be  distended,  not  only  by  the  average  pressure  of  the  fluid  throughout  the 


926 


PHYSIOLOGY 


system,  but  also  by  the  hydrostatic  pressure  due  to  the  weight  of  the  column 
of  fluid  pressing  on  them.  The  elasticity  of  the  tubes  is  also  a  varying 
factor  and  can  be  considerably  altered  by  the  contraction  of  the  muscular 
coats  of  the  vessels,  or  by  pressure  on  the  vessels  exerted  by  the  surrounding 
muscular  and  elastic  structures. 


Fig.  395.  Artificial  schema  to  demonstrate  the  main  features  of  the  circulation. 
The  heart  is  an  enema  syringe  with  valves  at  v  and  v.  The  artery  is  a  thick-walled 
rubber  tube.  On  the  venous  side  is  placed  a  length  of  wido  thin-walled  tubing, 
to  represent  the  large  thin-walled  distensible  veins.  The  arterioles  and  capillaries 
(peripheral  resistance)  are  represented  by  wide  glass  tubes  packed  with  sponges. 
By  opening  the  clamp  on  the  tube  D  ('  splanchnic  area  arterioles  ')  the  peripheral 
resistance  can  be  removed,  and  a  free  passage  of  fluid  allowed  from  arterial  to 
venous  side. 

It  will  simphfy  the  discussion  of  "the  main  factors  of  the  circulation 
in  a  closed  system  if,  for  the  present,  we  neglect  the  variable  factors  and 
see  what  would  take  place  in  such  a  system  of  elastic  tubes  all  situated 
on  one  horizontal  plane.  Such  a  system  is  represented  in  the  diagram 
(Fig.  396),  and  a  working  model  of  it  in  Fig.  395. 
The  heart  h  is  interpolated  at  one  part  of  the 
circuit,  while  the  free  outflow  of  the  fluid  from  B 
to  d  is  impeded  by  the  presence  of  a  peripheral 
resistance  at  c.  Such  a  system  would  have  a 
definite  capacity  at  zero  internal  pressure,  but 
a  very  much  greater  amount  of  fluid  might  be 
forced  into  it  imder  a  positive  pressure.  We  will 
assume  that  the  pressure  throughout  the  system 
is  equal  to  10  mm.  Hg.,  i.  e.  the  elastic  tubes  are 
all  slightly  distended.  If  the  heart  h  now  begins 
to  contract,  it  will  pump  fluid  from  e  into  A. 
The  pressure  in  e  will  fall  from  10  mm.  to  0  mm.,  while  that  in  a  will  rise 
to  a  corresponding  extent,  the  resistance  at  c  preventing  the  free  escape 
of  fluid  from  b  to  d  and  so  causing  the  heart  to  pile  up  the  fluid  which  it 
has  taken  from  e  into  a. 

If  the  texture  of  the  tubes  were  uniform  throughout  the  system,  it  is 


BLOOD  PRESSURE  AT  PARTS  OF  VASCULAR  CIRCUIT     927 

evident  that  the  rise  of  pressure  in  a  would  approximate  very  nearly  to 
the  fall  of  pressure  in  e.  In  the  vascular  system  the  veins  are  however 
much  more  easily  distended  than  the  arteries.  In  Fig.  384  (p.  915)  is 
shown  the  dist eligibility  of  corresponding  sections  of  arteries  and  veins 
under  gradually  increasing  internal  pressures.  An  artery  has  a  certain 
capacity  even  at  zero  pressure.  As  the  pressure  in  its  interior  is  increased, 
the  artery  is  distended,  and  its  capacity  rises  first  slowly  and  then  more 
rapidly,  the  increment  in  capacity  being  greatest  between  90  and  110  mm. 
Hg.  The  vein,  on  the  other  hand,  is  collapsed  when  there  is  no  distending 
force  in  its  interior,  so  that  at  zero  pressure  its  capacity  is  nothing.  The 
slightest  rise  of  pressure,  even  of  1  mm.  Hg.  causes  a  considerable  increase 
in  its  capacity,  and  the  capacity  rises  rapidly  with  increasing  pressure  up  to 
about  20  mm.  Hg.  "Whereas  the  artery  is  most  distensible  at  100  mm.  Hg., 
the  vein  is  at  its  optimum  distensibility  at  about  10  mm.  Hg.  If  therefore 
the  tubes  at  e  are  made  of  thin-walled  rubber  tubing,  they  will  be  consider- 
ably distended  under  a  pressure  of  10  mm.  Hg.,  which  has  practically  no 
influence  on  the  thicker-walled  arterial  tube  a. 

A  small  amount  of  fluid  taken  from  e  would  cause  very  little  fall  of 
pressure  on  this  side.  A  considerable  force  will  be  necessary  to  send  this 
fluid  into  the  more  resistant  arterial  tube,-  so  that  on  pumping  a  given 
amount  of  fluid  from  e  to  a,  the  pressure  in  e  may  fall  5  mm.,  while  the 
pressure  in  a  has  to  be  raised  from  50  to  100  mm.  Hg.  in  order  to  distend 
the  arteries  to  such  an  extent  that  they  will  accommodate  the  fluid  taken 
from  e. 

In  such  a  system,  when  the  heart  is  at  rest,  the  pressure  all  over  the 
sj'stem  will  be  *  uniform,  and  in  the  example  we  have  chosen  the  mean 
systematic  pressure  was  10  mm.  Hg.  When  the  heart  contracts,  it  takes 
up  fluid  from  the  venous  side  and  piles  it  up  on  the  arterial  side  until  the 
pressure  on  the  arterial  side  is  sufficient  to  cause  exactly  the  same  amount 
of  fluid  to  flow  through  the  peripheral  resistance  into  the  veins  as  is  taken 
by  the  heart  from  the  veins  at  each  beat.  This  rise  of  pressure  in  the 
arteries  may  be  many  times  greater  than  the  fall  of  pressure  in  the  veins. 
If  more  fluid  is  injected  into  the  system  when  the  heart  is  at  rest,  the  whole 
system  will  be  more  distended  and  the  mean  systemic  pressure  will  rise. 
When  the  heart  contracts,  it  will  raise  the  pressure  on  the  arterial  side  and 
lower  that  on  the  venous  side  as  before,  but  it  is  evident  that,  according 
to  the  force  of  the  heart  heat,  the  arterial  pressure  may  be  less  than,  equal 
to,  or  greater  than  the  pressure  attained  before  the  introduction  of  fluid. 
Since  however  the  mean  systemic  pressure  is  raised,  the  increased  amount 
of  fluid  must  be  accommodated  somewhere,  so  that  if  the  arterial  pressure 
is  as  great  as  before,  the  venous  pressure  must  be  greater.  In  the  same 
way  the  withdrawal  of  a  certain  amount  of  fluid  may  lower  the  mean 
systemic  pressure,  say  from  10  to  5  mm.  Hg.  It  is  still  possible  for 
the  pump  to  maintain  an  arterial  pressure  equal  to  that  produced  when  the 
mean  systemic  pressure  was  10  mm.  Hg.,  but  to  produce  this  effect  the 
relative  distribution  of  blood  must  be  altered  and  the  veins  must  be  more 


928  PHYSIOLOGT 

empty  than  fchej  were  previously.  The  maintenance  of  a  constant  arterial 
pressure  with  varying  amount  of  fluid  in  the  system  can  therefore  be  accom- 
plished either  by  alterations  in  the  work  of  the  heart  or  by  alterations  in 
the  peripheral  resistance,  and  therefore  in  the  ease  with  which  the  blood  is 
allowed  to  escape  from  the  arterial  to  the  venous  side. 

Alterations  of  the  capacity  of  the  system  will  have  the  inverse  effect 
to  alterations  of  its  contents.  Thus  diminution  in  the  volume  of  veins, 
such  as  might  be  caused  in  the  living  body  by  the  contraction  of  their 
walls  and  which  may  be  imitated  in  our  model  by  pressure  on  the  veins 
from  without,  will  drive  the  fluid  into  other  parts  of  the  system  and  there- 
fore raise  the  mean  systemic  pressure.  This  rise  of  pressure  may  be  con- 
fined to  the  arteries  by  increased  action  of  the  heart,  or  it  may  be  confined 
to  the  veins  by  diminished  action  of  the  heart  or  decreased  constriction  of 
the  arterioles  forming  the  peripheral  resistance. 

Similar  change  in  capacity  may  be  brought  about  if  we  bring  in  the 
effects  of  hydrostatic  pressure.  If  in  the  model  illustrated  (Fig.  395)  we 
allow  the  thin-walled  vein  to  hang  over  the  edge  of  the  table,  the  pressure 
of  the  column  of  fluid  within  it  causes  it  to  dilate  and  therefore  to  accom- 
modate more  fluid,  and  this  increased  capacity  might  be  so  great  that  the 
pressure  in  the  section  of  the  ■  vein  nea~r  the  heart  might  sink  to  nothing 
and  the  heart  receive  no  blood  when  it  started  to  contract.  The  whole 
arterial  system  might  in  this  way  be  allowed  to  drain  under  the  influence 
of  gravity  into  the  distensible  dependent  segment  of  the  venous  tube. 

All  the  conditions  in  our  artificial  schema  have  their  exact  analogue  in 
the  living  body.  The  determination  of  the  mean  systemic  pressure  in 
the  living  body  is  difficult  to  carry  out  with  accuracy.  If,  for  instance, 
we  stop  the  heart,  which  we  can  do  by  stimulation  of  the  vagus  nerve,  the 
arteries  will  gradually  empty  themselves  through  the  peripheral  resistance 
into  the  veins,  and  this  process  will  tend  to  go  on  until  the  pressures  are 
identical  throughout  the  system.  Before  this  equilibrium  is  arrived  at 
however,  reaction  takes  place  on  the  part  of  the  animal,  tending  to  restore 
the  failing  circulation.  Thus  the  vessels  contract  strongly,  so  diminishing 
the  capacity.  Movements  take  place,  causing  pressure  on  the  veins  of  the 
abdomen  and  the  suction  of  the  blood  into  the  big  veins  of  the  thorax. 
Moreover  the  vessels  in  an  animal  are  not  all  on  one  plane  and,  if  the  animal 
is  in  a  vertical  position,  the  hydrostatic  pressure  of  the  column  of  blood 
between  the  heart  and  the  dependent  parts  of  the  body  may  distend  the 
veins  to  such  an  extent  that  the  whole  of  the  blood  is  taken  up  in  these 
veins  and  none  returned  to  the  heart.  The  fact  that,  after  stoppage  of  the 
heart,  the  pressure  is  positive  at  all  parts  of  the  vascular  system  in  the 
animal  with  open  thorax  shows  that  there  is  actually  a  mean  systemic 
pressure,  i.  e.  under  normal  circumstances,  when  the  animal  is  in  a  hori- 
zontal position,  all  parts  of  the  system  are  slightly .  distended.  Direct 
measurement  shows  that  this  mean  systemic  pressure  is  about  10  mm.  Hg. 
The  smallness  of  this  figure  shows  moreover  that,  under  the  influence  of 
gravity  alone,  the  pressure  will  be  easily,  reduced  to  nothing  at  all  in  the 


BLOOD    PRESSURE   AT    PARTS   OF    VASCULAR    CIRCUIT      929 

upper  parts  of  the  body.  In  a  man  in  the  vertical  position,  in  the  absence 
of  the  nervous  reactive  mechanism  which  we  shall  consider  later  on,  the 
whole  of  the  blood  would  accumulate  in  the  abdomen  and  lower  parts  of 
t  iic  body,  and  the  circulation  would  come  to  a  standstill.  On  the  other 
hand,  the  pressure  may  be  altered  in  any  part  of  the  vascular  system  in 
any  of  the  following  ways  : 

(1)  Alteration  of  capacity  of  the  total  system  either  by  contraction  of 
walls  of  the  vessels  or  by  pressure  on  them  from  without. 

(2)  Alteration  of  the  total  volume  of  the  circulating  fluid. 

Either  of  these  two  factors  would  affect,  in  the  first  place,  the  mean 
systemic  pressure.  The  distribution  of  pressure,  i.  e.  the  relative  pressure 
in  the  arteries  and  veins,  will  be  determined  by 

(•$)  Alteration  in  the  output  of  the  heart. 

(1)  Alteration  in  the  peripheral  resistance  and  therefore  in  the  ease  with 
which  the  blood  can  escape  from  arterial  to  venous  side. 

In  any  change  either  in  arterial  or  venous  pressure  at  least  two  of  these 
factors  are  involved.  Every  constriction  of  arterioles  causes  not  onlv  an 
in,  ri  ase  in  the  peripheral  resistance  but  also  a  diminished  capacity  of  the 
whole  system,  so  that  the  arterial  pressure  is  raised  at  the  same  time  as 
i  he  mean  systemic  pressure.  Nearly  always  such  a  change  will  involve 
immediate  consequence  some  corresponding  alteration  in  the  heart 
beat,  so  that  at  least  three  factors  will  co-operate  in  the  production  of  the 
rise  or  fall  of  blood  pressure.  We  shall  have  occasion  to  deal  with  many 
examples  of  these  complex  conditions  when  we  are  discussing  the  reactions 
of  the  vascular  system  as  a  whole. 


THE   DEPENDENCE   OF   ARTERIAL   PRESSURE   ON    OUTPUT 
OF   HEART 

The  importance  of  the  heart  beat  in  determining  arterial  pressure  is 
connected  with  its  output  in  a  given  time.  The  arterial  pressure  is  due 
to  the  fact  that  the  heart  is  taking  up  fluid  from  the  venous  side  and  pumping 
it  into  the  arterial  side.  The  pressure  on  the  latter  side  must  rise  so  lonf 
as  the  rate  at  which  the  fluid  is  put  into  the  arterial  system  by  the  heart 
ater  than  that  by  which  it  escapes  through  the  peripheral  resistance. 
Arterial  pressure  therefore  is  a  resultant  of  the  two  effects  : 

(a)  The  amount  of  blood  entering  the  arterial  system  from  the  heart; 

(b)  The  amount  of  blood  leaving  the  arterial  system  through  the  peri- 
pheral resistance. 

It  is  evident  that  the  pressure  will  be  altered  by  altering  either  of  tin- 
two  factors —peripheral  resistance  or  output  of  the  heart.  The  cardiac 
output  will  depend  on  the  amount  of  blood  .contained  in  the  heart  at  the 
lie-inning  of  each  contraction,  on  the  strength  with  which  the  heart  beats, 
and  on  the  number  of  contractions  of  the  heart  in  any  given  period 
of  time.  The  filling  of  the  heart  at  the  begmning  of  each  beat  is 
in  its  turn  dependent  on  the  amount  of  blood  which  is  available  to  fill  the 
59 


930  PHYSIOLOGY 

cavities  and  therefore  on  the  pressure  in  the  great  veins.  Increased  fre- 
quency of  heart  beat  need  not  therefore  necessarily  increase  the,  total 
output  of  the  heart  into  the  arterial  system.  If  the  heart  is  beating  with 
optimum  rate  and  force,  it  will  keep  the  venous  system,  at  any  rate  that 
part  nearest  the  heart,  practically  empty,  and  it  is  not  possible  for  it  to 
obtain  more  blood  to  put  into  the  arterial  side,  however  frequently  it  may 
beat.  There  will  be  an  optimum  frequency  of  the  heart  beat  which  will 
depend  on  the  state  of  filling  of  the  great  veins.  Tire  fuller  these  are  the 
more  rapidly  the  heart  may  beat  and  increase  the  total  output.  On  the 
other  hand,  in  a  normal  animal  with  the  heart  beating  at  its  optimum  rate 
and  with  effective  contraction  of  its  muscular  walls,  while  slowing  the 
heart  rate  will  dimmish  the  total  output  and  therefore  the  arterial  pressure 
increase  in  the  frequency  of  the  beat  cannot  raise  the  arterial  pressure  to 
any  appreciable  extent,  though  the  heart  may  tend  to  wear  itself  out  by 
beating  at  a  greater  rate  than  the  optimum. 


SECTION  III 

THE    VELOCITY    OF   THE    BLOOD   AT    DIFFERENT 
PARTS    OF   THE    VASCULAR    SYSTEM 

When  fluid  is  flowing  through  a  tube  of  uniform  diameter,  the  amount 
passing  be1  ween  any  two  points  is  practically  in  proportion  to  the  difference 
of  pressure  between  these  two  points,  and  varies  inversely  as  the  resistance 
fe  be  overcome.  If  the  tube  is  of  unequal  bore,  as  represented  in  Kg  397 
sine,  the  amount  of  fluid  passing  a  during  a  given  interval  of  time  must  be 
equal  lo  the  amount  passing  t-where  the  bed  of  the  stream  is  wide-— the 
veloc.t.N  „l  ( be  flow  must  be  smaller  at  b  than  at  a.  The  same  dependency 
ol   velocity  on  the  total  bed  must 

fcppiy    in    any    closed    system    of (  [ 

tubes.     Thus   in   a   closed   circuit ,  — *.  ______ 

(Fig.  396)  with  a  steady  flow  from         °         I 

the    arterial   to    the    venous   side,  h 

the    amount    of   fluid   leaving   the  Fw.  397. 

heart   and  passing  a  during  a  minute  must  be  exactly  equal  to  the  total 

amount   of   fluid   passing  from   arteries   to   veins   through  the   peripheral 

pfesistance  b. 

The  total  area  at  c  i.s  probably  one  thousand  times  that  of  the  aorta  at  a 

and  we  should  expect  therefore  a  proportionate  slowing  of  the  blood  stream' 

matter  of  fact,  while  the  velocity  of  the  blood  in  the  aorta  of  alarge 

al  may  be  taken  as  about  half  a  metre  per  second,  the  velocity  of  the 

b] l  m  thc  capillaries  is  about  half  a  millimetre  per  second.    Moreover 

Snnce  ,he  total  cross-section  of  the  big  veins  near  the  heart  under  a  normal 
distending  pressure  is  about  twice  that  of  the  first  part  of  the  aorta  the 
velocity  of  the  blood  in  the  great  veins  is  only  about  half  of  that  found  in 
rta.  In  such  a  closed  circuit  increased  output  of  the  heart  will  increase 
the  average  velocity  round  the  system,  and  the  same  effect  may  be  produced 
by  diminution  of  the  peripheral  resistance. 

In  the  living  body  a  great  dilatation  of  the  arterioles,  causing  a  fall  of 
the  peripheral  resistance,  generally  increases  the  total  capacity  of  the  system 
The  arterial  relaxation  therefore  not  only  gives  rise  to  an  easier  outflow 
B»m  arteries  to  veins  but  also  causes  a  diminished  dilatation  of  the  , 
and  therefore  decreased  filling  of  the  heart  during  diastole  The  heart 
output  is  therefore  also  lessened,  so  that  a  final  result  of  a  dilatation  of  the 
Arterioles  may  be  a  diminished  instead  of  an  increased  velocity  throughout 
the  system.  ° 

931 


932  PHYSIOLOGY 

The  foregoing  discussion  of  the  factors,  which  determine  the  average 
velocity  across  a  given  cross-section  of  the  whole  vascular  system,  musl 
not  be  applied  directly  to  the  changes  in  the  velocity  following  on  local 
all  nations  in  the  resistance  presented  by  some  particular  vascular  area. 
In  this  case  the  local  changes  are  insufficient  to  affect  the  general  arterial 
blood  pressure,  and  the  effect  of  diminution  of  peripheral  resistance  is  to 
furnish  a  short  cut  for  a  small  portion  of  the  total  output  of  the  heart  from 
the  arterial  to  the  venous  side.  Thus  dilatation  of  the  vessels  of  the  sub- 
maxillar gland,  while  not  altering  the  general  blood  pressure  as  registered 
in  the  carotid  artery,  causes  the  blood  flow  through  the  gland  to  be  increased 
six  to  eight  times;  and  the  peripheral  resistance  in  the  gland  may  be  so  far 
diminished  that  the  blood  passes  through  the  capillaries  into  the  veins 
without  losing  the  pulsatile  force  imparted  to  it  by  each  heart  beat.  The 
pressures  therefore  in  arterioles,  capillaries,  and  veins  are  all  increased  by 
this  local  vaso-dilatation.  On  the  other  hand,  constriction  of  the  arterioles 
of  any  given  part  will  diminish  the  velocity  of  the  blood  through  this  part 
and  also  the  pressure  in  its  capillaries. 

The  larger  the  area  affected  by  the  change  in  the  peripheral  resistan.  e, 
the  more  difficult  it  is  to  predict  a  priori  what  will  be  the  result  on  the 
velocity  of  the  blood  and  on  the  circulation  as  a  whole,  or  in  the  parts 
specially  affected.  Thus  section  of  one  splanchnic  nerve  in  the  dog  causes 
an  increased  flow  of  urine  from  the  kidney  on  the  same  side,  the  paralysis  of 
the  vessels  in  this  organ  causing  an  increased  flow  of  blood  through  it  and 
an  increased  pressure  in  its  capillaries.  Section  of  the  corresponding  nerve 
of  the  rabbit  may  cause  a  diminution  rather  than  an  increase  in  the  amount 
of  urine  secreted,  owing  to  the  fact  that  the  total  area  supplied  by  the 
splanchnic  nerve  is  much  greater  relatively  hi  the  rabbit  than  in  the  dog. 
Thus  section  of  this  nerve  may  cause  such  a  wide- 
spread dilatation  that  the  blood  pressure  falls;  and 
although  the  vessels  in  the  kidney  are  relaxed,  the 
arterial  pressure  is  not  sufficient  to  drive  through 
these  relaxed  vessels  as  much  blood  as  was  previously 
/      \    /    \        driven  through  the  normally  contracted  arterioles. 

METHODS   OF   MEASURING  THE  VELOCITY 
OF    THE    BLOOD 

The  velocity  in  an  artery  is  measured  by-  placing  some 
apparatus  in  the  path  of  the  blood  without  intercepting  its 
flow;  such  an  apparatus  may  be  used  to  give  the  quick 
v  %qr  IV  <  nm  of  variations  in  the  velocity  which  occur  in  the  course  of  each 
LudwS  '  fiSkr.'  heart  beat,  or  the  average  flow  of  blood  through  the  cross- 
section  of  the  artery  in  a  given  space  of  time.  For  the  latter 
purpose  Ludwig's  Stromuhr,  or  current  clock  (Fig.  398),  has  been  most  used.  This 
instrument  consists  of  two  bulbs  of  equal  size,  a  and  6,  communicating  with  one 
another  above;  their  lower  ends  arc  clamped  in  the  disc  c,  which  is  pierced  by  two 
openings  serving  to  connect  the  lower  orifices  of  the  bulbs  with  the  tubes  t,  I,  cemented 
into  the  lower  disc  ab. 

An  artery  such  as  the  carotid,  being  clamped  at  its  central  end  and  divided,  a  is 


VELOCITY  OF  BLOOD   AT  PAETS  OF  VASCULAR  SYSTEM    933 

inserted  into  its  central  end.  and  5  into  its  peripheral  eut  end.     The  tube  a  is .filled  witii 
'        V  sal solution  or  defibrinated  blood.     On  damping  the  artery,  blood flow* 

,;  :l,nd  oSves  the  contained  oil  over  into  6  the  contents  o  I  being n.anw nle  for    d 

into  the  peripheral  end  of  the  artery.     When  blood  has  completely  filled  the  bulb  «.  the 

t0  mills  are  Versed,  and  the  blood  now  entering  the  artery  displace, ^dm. 

and  forces  the  blood  which  had  entered  a  on  into  the  peripheral  end  of  the  artery. 
I  '„,  Lacity  of  the  bulbs  and  the  number  of  times  it  has  been  necessary  to 

SSita  the  couL,  say.  of  one  minute,  we  know  also  the  amount  of  blood  wluch 

has  passed  across  the  section  of  the  artery  under  experiment 

I  ,  order  to  determine  from  this  volume  the  velocity  of  the  blood  across  the  section, 

i  e  thro  ughtiie  artery,  the  total  volume  passing  in  the  minute  must  be  divided  by  the 

.:,,;, s Son.    Tins  ,,11  give  the  velocity  per  minute.    Many  modifications  of  tins 


Fig.  399.     Diagram  showing  the 
ruction    of    Ghauveau's 
hEemadromograph. 


Fig.  400.  Diagram  to  show  principle  of 
construction  of  Cybulski's  photoha:mata- 
chometcr. 


apparatus  have  been  devised,  but  none  give  any  information  of  the  rapid  changes 
occurring  in  the  velocity  of  the  blood  during  a  single  pulse  wave.  For  this  purpose  we 
must  have  recourse  to  some  instrument  such  as  Chauveau's  hsemadromograph  or 
Cybulski's  photohamatachometer.  The  Ticemadromograph  (Fig.  399)  consists  of  a 
pendulum  which  is  hung  in  a  tube,  through  which  flu-  blood  is  allowed  to  flow  placed 
in  the  course  of  the  artery.  The  deviation  of  I  his  pendulum  from  the  vertical  will  be 
in  proportion  to  the  velocity  of  the  current,  and  if  its  upper  end  be  connected,  as  in  the 
diagram  with  a  tambour,  the  variations  in  velocity  can  be  recorded  on  a  blackened 
surface  by  means  of  a  lever.  The  photohcematacfumeter  is  based  on  an  interesting 
application  of  Pitot's  tubes.  If  a  current  of  blood  be  directed  along  the  tube  ab  pos- 
sessing two  vertical  side  tubes  c  and  d  (Fig.  4<K>).  the  pressure  at  c  will  be  greater  than 
■that  at  d,  since  at  c  the  momentum  of  the  moving  mass  of  blood  is  added  to  the 
lateral  pressure  of  the  fluid.  A  tube  of  this  shape  is  connected  with  an  artery,  such 
as  the-  carotid,  and  the  tubes  h  and  V  are  attached  at  the  points  c  and  d.     These  two 


031 


PHYSIOLOGY 


tubes  are  united  at  their  upper  extremities.  In  this  ease  so  long  as  the  blood  flows 
from  a  to  b,  the  fluid  in  h  will  rise  higher  t  hail  in  /<'.  and  the  difference  in  height  of  the 
fluid  in  the  two  tubes  will  be  proportional  to  the  velocity  of  the  blood.  A  graphic  record 
of  this  difference  of  pressure  is  obtained  by  allowing  a  narrow  beam  of  light  to  throw  an 
image  of  the  menisci  of  the  two  columns  of  fluid  through  a  slit  on  to  a  moving  photo- 
graphic plate.  Such  a  record  is  given  in  Fig.  401.  The  width  of  the  black  space  at  any 
point  is  proportional  to  the  velocity  of  the  blood  at  the  moment  at  which  this  part  of 


Fig.  401.     Record  of  blood  velocity  in  the  carotid  artery  of  the  rabbit.     (C'ybulski.) 

the  record  was  being  taken.  Of  course  this  instrument  has  to  be  calibrated  if  we  wish  to 
determine  the  velocity  of  the  blood  in  absolute  measure.  In  Fig.  401  the  velocity  at  the 
points  1  and  1',  corresponding  to  the  cardiac  systole,  was  248  mm.  per  second.  At  2  and 
%',  corresponding  to  the  dicrotic  elevation,  the  velocity  was  also  248  mm.  At  3  and  3', 
towards  the  end  of  diastole  the  velocity  sank  to  127  mm. 

The  velocity  of  the  blood  in  the  capillaries  can  be  measured  by  direct  observation 
of  the  capillaries  under  the  microscope,  and  noting  the  time  it  takes  for  a  blood  corpuscle 
to  move  from  one  edge  of  the  field  to  the  other. 


THE    VELOCITY    IN    DIFFERENT   PARTS    OF    THE 
VASCULAR    SYSTEM 

During  systole  the  velocity  of  the  blood  in  any  part  of  the  arterial  system 
must  lie  greater  than  during  diastole;  thus  in  the  carotid  of  the  horse  the 
following  figures  were  found  : 


During  systole 
During  diastole 


Velocity  per  second 
520  mm. 
150  mm. 


The  following  figures  of  the  average  velocity  have  been  obtained   from 
experiments  on  dogs  (Tigerstedt.)  : 


Body 
weight 

Artery 

Volume 
per  second 

Linear 

velocity  per 

second 

Diameter 
of  artery 

B.P. 

Remarks 

kg. 

14-6 
141 

('rural. 

Crural. 
Carotid. 

c.c. 
0-63 

1-69 

1-95 

nun. 
128 

275 
241 

2-5 

2.8 
3-3 

mm.  !!•,'. 
77 

88 
93 

Nerves  un- 
injured. 
Nerves  cut 
Nerves  un- 
injured 

SECTION  IV 

THE   MECHANISM   OF   THE   HEART    PUMP 

In  the  mammal  the  two  sides  of  the  heart  are  in  communication  only  by 
means  of  the  blood  vessels  of  the  systemic  and  pulmonary  area.  Each 
side  ((insists  of  an  auricle  into  which  the  veins  open,  and  a  ventricle  which 
receives  the  blood  from  the  auricle  and  discharges  it  into  the  arterial  trunk — ■ 
either  aorta  or  pulmonary  artery.  Since  the  auricles  have  to  act  merely 
as  a  receptacle  for  -part  of  the  blood  which  enters  during  the  relaxation  or 
diastole  of  the  heart,  their  cavities  are  smaller  than  those  of  the  ventricles, 
and  their  -vails  are  thin,  corresponding  to  the  small  amount  of  work  thrown 
on  them  in  propelling  blood  into  the  relaxed  ventricle.  The  ventricles  have 
the  oitice  of  carrying  on  the  main  work  of  the  circulation  and  of  forcing 
blood  through  the  peripheral  resistance.  Their  walls  are  much  thicker 
than  those  of  the  auricles.  The  right  ventricle  has  a  wall  which  is  only  about 
one-fourth  the  thickness  of  the  left  ventricle,  in  conformity  with  the  much 
heavier  work  to  be  done  by  the  hitter.  On  cutting  a  section  through  the 
two  ventricles  in  a  contracted  condition,  the  thin  wall  of  the  right  ventricle 
is  seen  to  lie  in  the  form  of  a  crescent  round  the  circular  left  ventricle.  The 
capacity  of  both  ventricles  is  approximately  equal,  and  amounts  in  man 
to  about  1 10  c.c.  for  each  ventricle  when  the  heart  is  completely  relaxed. 

The  auricles  are  separated  from  the  ventricles  by  a  fibrotendinous  ring. 
From  this  ring  tab  origin  most  of  the  muscular  fibres  of  the  heart  walls. 
The  muscular  fibres  of  the  auricles  run  in  both  circular  and  longitudinal 
directions,  the  circular  fibres  being  continued  round  both  auricles,  and 
special  rings  of  circular  fibres  surrounding  the  openings  of  the  great  veins. 
From  the  fibrotendinous  ring  between  the  auricle  and  the  left  ventricle  and 
Erom  the  sides  of  the  aorta,  the  muscular  fibres  forming  the  superficial  layer 
of  the  ventricular  wall  pass  obliquely  downwards  to  the  left  towards  the 
apex  of  the  ventricle.  Here  they  loop  round  into  the  interior  of  the  ventricle 
and  pass  up  near  its  inner  surface  to  end  either  in  the  papillary  muscles  or 
in  the  auriculo-ventricular  ring  of  fibrous  tissue.  Between  these  two  layers 
we  find  a  third  median  layer  of  muscular  fibres  which  is  in  the  form  of  a 
muscular  cone.  The  fibres  of  this  layer  form  complete  loops  round  the  left 
ventricle.  The  middle  layer  is  connected  by  many  strands  of  muscular 
Bbres  with  both  inner  and  outer  layers. 

Mall  divides  the  muscular  fibres  of  the  mammalian  heart  into  four  groups,  two  super- 
ficial and  two  deep,  as  follows  : 

(1)  The  superficial  bulbo-spiral  fibres.  These  arise  from  the  conns  arteriosus,  the 
left  side  of  the  aorta  and  the  left  side  of  the  auriculo-ventricular  ring,  and  take  an 

935 


93fi 


rTTYSIOLOCJY 


oblique  course  to  the  apex,  where  fchey  make  a  Bpiral  turn  (the-  vortex)  and  reach  the 
interior  of  the  left  ventricle,  ending  for  the  tnosl  pari  in  the  intraventricular  septum 
and  the  papillary  muscles. 

(2)  The  superficial  sino-spiral  fibres  rise  on  the  dorsal  side  of  the  heart  from  the  right 
auriculo-ventricular  ring  and  run  obliquely  on  the  anterior  surface  of  the  right  vent  ricle 
to  the  apex,  where  they  also  turn  inwards,  forming  the  anterior  hom  of  the  '  vortex,' 
and  end  chiefly  in  the  papillary  muscles  of  the  right  ventricle. 

(3)  The  deep  bulbo-spiral  fibres  form  a  complete  cylinder  around  the  left  ventricle, 
and  are  attached  chiefly  to  the  dorsal  side  of  the  aorta. 


Fig.  402.     View  of  the  heart  from  behind,  to  show  the  course  of  the  chief 

strands  of  muscle  fibres.     (Maix.) 
The  black  lines  represent-  the  bulbo-spiral  fibres,  the  grey  fines  the  sino- 
spiral  fibres. 

(-1)  The  deep  sino-spiral  fibres  arc  attached  to  the  dorsal  aspect  of  the  left  auriculo- 
ventricular  ring,  whence  they  enter  the  right  ventricle  and  turn  upwards  towards  tin- 
base.  The  uppermost  of  these  Sbres  form  circular  rings  round  the  conu.i  arteriosus  at 
the  base  of  the  pulmonary  artery. 

The  fact  that  the  muscular  fibres  are  continuous  over  both  auricles  and 
over  both  ventricles  respectively  ensures  the  practically  simultaneous  con- 
traction of  each  of  these  parts  of  the  heart.  Although  on  coarse  dissection 
there  seems  to  be  absolute  division  between  the  muscular  tissue  of  auricles 
and  ventricles,  it  has  been  shown  by  Kent,  His,  and  others  that  there  is 
continuity  of  muscular  tissue  between  the  two  parts  of  the  heart  by  a  special 
band  of  muscular  fibres,  '  the  bundle  of  His,'  which  rises  in  the  wall  of  the 
right  auricle  and  passes  beneath  the  foramen  ovale  and  across  the  auriculo- 


THE  MECHANTSM  OF  THE  HEART  PUMP 


937 


ventricular  junction  into  the  inter- ventricular  septum.     The  exact  course 
of  these  fibres  and  their  significance  will  be  considered  later. 

The  normal  direction  of  the  blood  flow  through  the  heart  is  determined 
mainly  by  the  valves  which  guard  the  auriculo-ventricular  orifices  and  the 
openings  of  the  aorta  and  pulmonary  artery.  The  auriculo-ventricular 
valves  are  tubular  membranes  attached  round  the  entire  circumference  of 
the  auriculo-ventricular  ring.      They  are  composed  of  fibrous  and  elastic 


Fig.  403. 


Left  auricle  and  ventricle,  with  outer  side  cut  away  to  show  chief  points 
in  anatomy  i>f  heart.     (Testtjt.) 
1,  aorta;  2,  pulmonary  artery;  3,  ant.  coronary  vessels;  5,  5',  pulmonary  veins; 
6,  Id!  auricle;  7.  auricular  appendage;  10,  cavity  of  left  ventricle;  11,  12,  mitral 
valves;  13,  14.  papillary  muscles;  1(1,  arrow  pointing  to  aortic  orifice. 

tissue,  covered  on  each  side  with  endocardium,  and  project  downwards  into 
tin'  cavities  of  the  ventricles.  On  each  side  the  membrane  is  divided  by 
deep  incisions  into  large  Haps,  three  in  number  mi  the  right  side  (the  tricuspid 
valves)  and  two  in  number  on  the  left  side  (the  mitral  valves).  The  sail-like 
margins  of  these  valves  are  connected  by  thin  tendinous  cords  to  the  papil- 
lary muscles,  which  are  nipple-shaped  projections  of  the  muscular  walls  of 
the  ventricles.  By  this  means  the  edges  of  the  valves  are  kept  close  togel  her 
and  prevented  from  eversion  under  the  strong  pressure  exerted  by  the  con- 
tracting ventricle.  By  the  downward  pull  of  the  papillary  muscles  on  the 
valves  during  the  contraction  of  the  ventricles,  closure  is  rendered   more 


938  PHYSIOLOGY 

complete,  the  inner  surface  of  the  valves  being  apposed  over  a  considerable 
area.  The  action  of  the  valves  is  aided  by  the  contraction  of  the  fibres 
surrounding  the  base  of  the  heart,  so  that  the  auriculo-ventricular  orifice 
is  much  smaller  during  systole  than  during  diastole. 

From  a  purely  mechanical  standpoint  the  valves  guarding  the  arterial 
orifices  are  much  more  perfect  than  those  just  described,  which  depend  for 
their  efficiency  on  the  proper  contraction  of  the  ventricular  wall  and  of  the 
musculi  papiUares.  Each  orifice  is  provided  with  three  valves,  each  of 
which  is  semilunar  in  shape  and  attached  by  its  convex  borders  to  the 
arterial  wall,  and  presents  in  the  middle  of  its  free  border  a  small  fibro- 
cartilaginous nodule,  the  corpus  Arantii,  from  which  fine  elastic  fibres  pass 
to  all  parts  of  the  valve.  The  extreme  margin  of  the  valve,  the  lunula, 
on  each  side  of  the  corpus  Arantii  is  very  thin,  beinu  formed  of  little  more 
than  the  endocardium.  Whenever  the  pressure  in  the  arteries  is  greater 
than  that  in  the  ventricles,  these  valves  are  closed,  and  the  thin  margins 
come  in  contact  with  similar  portions  of  the  adjacent  valves,  so  .preventing 
the  reflux  of  a  single  drop  of  blood.  The  borders  of  the  valves  under  these 
circumstances  come  together  in  the  form  of  a  star  composed  of  three  hnes 
at  angles  of  120°,  the  three  corpora  Arantii  being  pressed  together  at  the 
centre  of  the  star. 

No  valves  are  found  at  the  orifices  of  the  great  veins  into  the  auricles, 
a  reflux  of  blood  in  this  situation  during  contraction  of  the  heart  being 
limited  by  the  contraction  of  the.  muscular  rings  round  the  veins,  which 
always  accompanies  the  auricular  contraction. 

The  heart  and  the  roots  of  the  great  vessels  he  almost  free  in  a  special 
cavity,  the  wall  of  which  is  formed  by  a  tough  fibrous  membrane,  the 
pericardium.  This  is  attached  below  to  the  central  tendon  of  the  diaphragm, 
and  above  to  the  arterial  trunks.  It  is  fined  by  a  layer  of  endothelium 
continuous  with  a  similar  layer  covering  the  surface  of  the  heart.  The 
two  surfaces  are  kept  continually  moist  by  the  pericardial  fluid,  so  that 
the  heart  can  move  freely  within  the  pericardium  without  friction.  One  of 
the  chief  functions  of  the  pericardium  appears  to  be  to  check  an  excessive 
dilatation  of  the  heart  during  conditions  attended  by  a  great  rise  of  venous 
pressure. 


THE   SEQUENCE   OF   EVENTS   IN   THE   CARDIAC   CYCLE 

On  opening  the  chest  of  an  anaesthetised  animal,  while  artificial  respira- 
tion is  maintained,  the  heart  is  seen  contracting  rhythmically  within  the 
pericardium.  On  incising  this  sac  its  restraining  power  on  the  dilatation 
of  the  heart  is  shown  by  the  fact  that  during  diastole  the  wall  of  the  heart 
bulges  through  the  opening,  and  the  increased  diastolic  filling,  consequent 
on  the  removal  of  this  restraining  influence,  is  at  once  apparent,  if  in  any 
way  the  frequency  of  the  contractions  of  the  heart  be  diminished  so  as  to 
prolong  the  diastolic  period. 

Each  beat  of  the  heart  begins  l>v  a  simultaneous  contraction  of  both 


THE  MECHANISM  OF  THE  HEART  PUMP      939 

auricles,  associated  with  a  retraction  of  the  auricular  appendages,  which 
become  pale  and  bloodless.  After  a  pause  of  not  more  than  a  tenth  of  a 
second,  the  contraction  of  the  auricles  is  followed  by  that  of  the  ventricles, 
and  blood  is  thrown  out  into  the  large  arteries.  The  contraction  of  the 
auricles  lasts  about  a  tenth  of  a  second,  that  of  the  ventricles  about  three- 
tenths  of  a  second.  The  period  of  relaxation  or  diastole  lasts  about  four- 
tenths  of  a  second.  During  this  cycle  of  changes  the  following  events  are 
taking  place  within  the  heart  : 

In  the  diastolic  period  the  aortic  valves  are  closed  and  the  arterial 
system  is  open  only  towards  the  capillaries.  In  consequence  of  the  high 
pressure  established  within  the  arteries  by  the  previous  heart  beats,  the 
blood  flows  steadily  through  the  arterioles,  capillaries,  and  veins  into  the 
rigHt  heart,  and  similarly  the  pressure  in  the  pulmonary  artery  causes  a 
partial  emptying  of  this  vessel  with  its  branches  through  the  pulmonary 
capillaries  into  the  left  heart.  The  flow  into  the  heart  is  assisted  by  the 
elastic  retraction  of  the  lungs,  which  causes  a  negative  pressure  in  the 
structures  between  them  and  the  chest  wall,  s<>  that  the  blood  is  sucked  from 
the  other  parts  of  the  body  towards  the  thorax.  During  diastole  there  is 
a  continuous  flow  of  blood  from  veins  into  auricles  and  from  auricles  into 
ventricles  and,  as  the  walls  of  both  these  cavities  are  relaxed,  there  is  no 
impediment  to  the  inflow  of  the  blood  until  the  dilating  heart  begins  to 
stretch  the  pericardium. 

Under  normal  circumstances  the  diastole  comes  to  an  end  before  the 
restraining  influence  of  the  pericardium  can  be  effective.  The  contraction 
of  tlie  auricles  diives  their  contents  into  the  ventricles  and  so  still  farther 
increases  their  distension,  no  resistance  being  offered  by  the  widely  dilated 
auriculo-ventricular  orifices  or  by  the  flaccid  wall  of  the  ventricles.  As  the 
Mood  rushes  from  auricle  into  ventricle  through  the  funnel-shaped  opening 
of  the  membranous  tube  formed  by  the  valves,  eddies  are  set  up  in  the 
ventricle  tending  to  close  the  valves,  so  that  they  are  held,  as  the  resultant 
oi  the  two  opposing  currents,  in  a  condition  midway  between  closure  and 
opening.  The  onset  of  the  ventricular  contraction  is  extremely  rapid. 
There  is  a  quick  rise  ,,f  pressure  in  the  ventricle,  which  presses  together 
the  flaps  of  the  mitral  or  tricuspid  valves,  while  the  bases  of  these  valves 
.tie  approximated  by  the  contraction  of  the  circular  fibres  at  the  base  of 
the  ventricles.  As  the  heart  shortens  in  systole  the  papillary  muscles  also 
shorten,  so  thai  the  valves  are  prevented  from  eversion  into  the  auricles, 
while  the  blood  is  pressed,  so  to  speak,  between  the  cone  of  the  ventricular 
wall  and  the  cone  formed  by  the  tubular  valves. 

The  outflow  of  blood  from  the  ventricles  does  not  however  commence 
immediately.  Whereas  at  the  beginning  of  systole  the  pressure  in  the, 
ventricle  cavity  is  quite  small  (only  2  or  3  mm.  Hg.),  there  is  a  pressure  in 
the  aorta  of  50  to  80  mm.  Hg.  Before  the  semilunar  valves  separating  the 
lumen  of  the  aorta  from  the  ventricular  cavity  can  be  opened,  the  pressure 
in  the  left  ventricle  must  rise  to  a  point  which  is  greater  than  that  in  the 
aorta,  and  similarly  on  the  right  side  of  the  heart.     As  soon  as  this  happens 


940  PHYSIOLOGY 

the  valves  open  and  the  outflow  of  blood  commences,  and  continues  so 
long  as  the  pressure  in  the  ventricles  is  higher  than  thai  in  the  great  arteries. 
Directly  however  the  ventricular  pressure  falls  below  the  arterial  pressure, 
the  valves  must  close  and  the  output  of  blood  come  to  an  end. 

In  order  to  obtain  an  accurate  idea  of  the  exact  duration  of  each  of  these 
events  in  the  cardiac  cycle,  it  is  necessary  to  study  the  changes  occurring 
in  the  pressure  within  the  auricles  and  ventricles  during  the  various  phases 
of  the  heart  beat. 

THE    ENDOCARDIAC    PRESSURE 

A  manometer  which  shall  register  accurately  the  changes  in  the  pressure 

within  the  heart  must  he  capable  of  responding  to  very  rapid  changes.  Thus 
in  the  left  ventricle  at  the  beginning  of  the  systole,  there  may  be  a  rise  of 
130  mm.  Hg.  in  •<)(>  sec,  i.  c.  2170  mm.  Hg.  per  sec.  In  a  heart  beating 
rapidly  and  forcibly  under  the  action  of  adrenalin,  the  rise  may  be  still  more 


Fig.  404.      Diagram  of  Marey's  cardiac  'sound,'  consisting  of  a  Ion?:  tube  ah, 
terminating  at  one  end  in  the  ampulla   /«,  which  is  covered  with  an  elastic 

mbrane.      The  side-piece  r  serves  to  indicate  the  position  of  the,anipulla 

alter  it  has  been  introduced  into  the  vessels. 

rapid,  e.g.  150  mm.  Hg.  in  -025  sec.  A  mercurial  manometer  with  its  great 
inertia  would  be  quite  unequal  to  registering  such  rapid  changes  of  pressure. 
a7id  would  moreover  tend  to  enter  into  oscillations  which  would  quite  deform 
the  curve.  We  require  an  instrument  with  very  small  weight  of  moving 
parts,  so  as  to  possess  small  inertia  and  be  capable  of  registering  a  rapid  rise 
of  pressure  without  entering  into  oscillations  of  its  own. 

Several  methods  have  been  adopted  for  this  purpose.  In  one  (<  Ihauveau  and  Marey) 
a  cardiac  'sound  '  (Fig.  404)  is  passed  down  the  jugular  vein  into  the  right  auricle  or 
ventricle,  or  down  the  carotid  artery  into  the  left  ventricle.     The  cardiac  sound  is  a 


Fig.  405.     Marey 's  tambour. 

a,  axis  of  lever:  h.  metal  tray  covered  with  rubber  membrane,  and  communi- 
cating by  tube  /  with  free  end  of  cardiac  sound. 

stiff  tube  having  an  elastic  bulb  or  ampulla  at  the  end  which  is  to  be  inserted  into  the 
heart.  The  bulb  is  supported  by  a. steel  frame,  so  that  it  is  not  completely  compressible 
by  external  pressure.  The  free  end  of  the  tube  is  connected  with  a  writing  tambour 
(Fig.  405),  a  small  round  metal  tray  covered  with  a  delicate  clastic  membrane.     To 


THE  MECHANISM  OF  THE  HEART  PUMP  94] 

the  top  of  the  membrane  a  lever  is  attached  by  which  any  change  of  pressure  on  the 
ampulla  may  be  recorded  on  a  moving  smoked  surface.  The  large  size  of  these  sounds 
makes  it  difficult  bo  use  them  on  any  animal  smaller  than  the  ass  or  horse.  In  smaller 
animals,  such  as  the  dog,  the  question  has  been  investigated  by  the  use  of  a  manometer 
such  as  that  of  Hiirthle.     In  this  instrument  (Fig.  406)  the  changes  of  pressure  are 


Fig.  406.     Diagram  to  show  construction  of  Hiirthle's  membrane  manometer. 

recorded  by  the  oscillations  of  a  thick  rubber  membrane  which  covers  a  very  small 
tambour.  The  tambour  is  filled  with  magnesium  sulphate  solution,  which  is  also  used 
to  till  the  tube  connecting  with  the  heart.  This  tube  can  be  inserted  in  the  same  way 
as  Maivv's  cardiac  sound. 

Even  Hiirthle's  instrument  is  inadequate  to  give  a  correct  representation  of  the  very 
rapid  changes  of  pressure  occurring  in  the  contracting  ventricle.  A  study  of  the  theory 
of  recording  instruments  by  Otto  Frank  has  enabled  him  to  lay  down  certain  funda- 
mental requirements  of  such  a  recording  instrument.  In  order  that  an  instrument 
may  reproduce  correctly  rapid  changes  of  pressure,  the  mass  moved  must  be  as  small  as 
possible  in  order  to  reduce  the  momentum,  and  therefore  the  tendency  to  overthrow  of 
the  instrument,  to  the  greatest  possible  extent.  Moreover  the  movement  of  fluid  into 
and  out  of  the  instrument,  which  accompanies  each  change  of  pressure,  must  occur  with 
the  smallest  possible  friction.  This  is  accomplished,  as  in  Hurtlile's  instrument,  by 
using  a  very  small  tambour,  covered  with  a  strong,  tightly  stretched  membrane  connected, 
by  as  short  and  wide  a  tube  as  is  feasible,  with  the  heart  or  blood  vessel  where  it  is 
desired  to  register  changes  of  pressure.  A  lever  is  entirely  got  rid  of,  the  minute  oscilla- 
tions of  the  membrane  being  recorded  by  means  of  a  beam  of  light  which  impinges  on 


EF 


Fig.  407.     Diagram  of  Piper's  manometer. 

a  mirror  attached  to  the  rubber  membrane  and  reflected  on  to  a  moving  photographic 
surface.  In  Fig.  407  is  represented  the  construction  of  Piper's  manometer,  built  on 
the  principles  laid  down  by  Frank. 

It  cimsists  of  a  tube  armed  with  a  stiletto,  A,  which  tits  it  accurately.  At  c  is  a  tap 
which,  when  opened,  will  permit  the  passage  of  the  stiletto,  and  can  close  the  tube 
entirely  when  the  stilette  is  withdrawn.  About  2  cms.  above  the  lower  extremity  of  the 
tube  is  a  small  drum-like  enlargement,  closed  on  one  side  by  a  thick  membrane,  E. 
On  the  edge  of  this  membrane  is  fixed  by  means  of  shellac  a  minute  mirror,  F,  1  mm.  in 
diameter.  With  the  stilette  protruding,  the  manometer  is  thrust  directly  into  the 
cavity  of  the  heart,  and  tixed  in  position  by  a  purse-string  suture  through  the  super- 
ficial part  of  the  heart  muscle,  tied  tightly  round  the  end  of  the  manometer.  The  stilet  te 
is  then  withdrawn  and  the  tap  turned  off,  but  alterations  in  pressure  in  the  cavity  of  the 
heart  cause  minute  oscillations  of  the  membrane,  which  can  be  recorded  and  magnified  to 
any  desired  extent  by  means  of  a  beam  of  light  reflected  from  the  mirror  on  to  a  moving 


<J12 


PHYSIOLOGY 


photographic  plate  or  paper.  The  advantage  of  this  optical  method  of  registration  is 
that  the  magnification  can  be  increased  to  any  extent  without  alt*  ring  I  he  mass  moved. 
The  '  figure  of , 'merit '  of  this  manometer,  i.  e.  its  own  period  of  vibration,  when  filled 
with  fluid,  is  about  250  per  second  with  a  thick  membrane,  so  that  it  can  record  with 
perfect  accuracy  all  such  rapid  changes  of  pressure  as  may  occur  even  in  (he  left  ventricle. 


Fig.  408.     Endocardiac  pressure  tracings,  taken  with_  Piper's  manometer. 
A,  Simultaneous  tracings  from  left  ventricle  and  left  auricle.     To  bo  read  from  left 
to  right.     B  and  C  taken  from  loft  ventricle,  C  at  a  faster  rate  of  recording  surface 
than  B.     To  be  read  from  right  to  left.     Kt  =  closure  of  A.V.  valves ;  S„  opening 
of  aortic  valves;  S2,  elastic  oscillation  or  wave;  K,,  opening  of  A.V.  valvos. 


THE  MECHANISM  OF  THE  HEART  PUMP 


943 


On  registering  the  endocardiac  pressure  by  the  opti6al  method,  it  is 
found  that  the  curves  vary  in  form  according  to  the  condition  of  the  heart. 
In  order  to  interpret  these  curves,  we  must  utilise  the  knowledge,  obtained 
from  a  simultaneous  record  of  the  pressures  in  the  auricle  and  ventricle, 
or  in  the  ventricle  and  aorta.  Fig.  408  represents  the  different  forms  of 
curve  obtained  from  the  left  ventricle.  Very  often,  as  in  A,  the  curve 
is  not  unlike  a  single  muscle  twitch  or  the  curve  of  contraction  of  the  frog's 
heart  muscle.  Nearly  always  however  it  is  possible  to  see  on  the  upstroke 
one  or  two  elevations,  the  most  noticeable  being* the  elevation  marked  Sx. 
This  can  be  shown  to  correspond  to  the  opening  of  the  aortic  valves.  This 
is  still  better  marked  in  B,  where  the  heart  was  beating  very  forcibly  and 


Aorta 


1  2     3  4  5  67 

Via.  409. 

rapidly  under  the  influence  of  adrenalin,  and  is  also  very  evident  in  c.     In 

some  eases,  as  in  a,  the  rise  of  pressure  occurs  distinctly  more  slowly  after 
Sx  than  before.  Jn  b  there  is  a  further  rapid  rise  of  pressure  after  Sx  before 
the  curve  begins  to  slope  away  and,  at  the  change  of  velocity  of  rise,  there 
is  a  second  wave  at  the  point  S2.  This  is  also  marked  in  C.  The  slope 
of  the  curve  after  Sj  or  S2  varies  considerably  according  to  the  amount 
of  blood  the  heart  is  sending  out.  In  c  the  intraventricular  pressure  curve 
runs  almost  horizontal  for  a  time,  and  this  part  of  the  curve  is  known  as 
the  systolic  plateau,  but,  as  is  evident  from  A,  a  plateau  in  the  strict  sense 
of  the  term  is  not  always  present.  At  the  end  of  the  '  plateau  '  the  pres- 
sure rapidly  falls,  and  the  period  where  the  lines  thin  out,  i.e.  the  point 
at  which  the  fall  is  occurring  most  rapidly,  corresponds  to  the  closure  of  the 
aortic  valves. 

j.  The  average  course  of  the  changes  of  pressure  in  the  heart  during  each 
beat  is  shown  diagrammatically  in  Fig.  409  (Piper).     The  cardiac  cycle 


944  PHYSIOLOGY 

begins  with  the  contraction  of  the  auricle  at  1,  which  mayor  may  not  give 
rise  to  a  slight  rise  of  pressure  in  the  ventricles.  As  the  auricular  contrac- 
tion dies  away,  the  ventricular  contraction  begins  at  2.  This  causes  a  very 
rapid  rise  of  pressure.  Almost  immediately  after  the  beginning  of  the  rise, 
or  sometimes  synchronously,  the  auriculo-ventricular  valves  close  at  the 
point  marked  3.  The  pressure  then  rises  rapidly  in  the  ventricular  cavity. 
Directly  it  exceeds  the  pressure  in  the  aorta,  the  aortic  valves  open  at  the 
point  marked  4,  and  the  aortic  pressure  thereafter  rises  with  the  ventricular 
pressure.  During  the  whole  duration  of  the  ventricular  contraction,  the 
aortic  pressure,  remains  somewhat  below  the  ventricular  pressure,  showing 
that  blood  is  flowing  continuously  from  ventricle  into  aorta.  The  rise  of 
pressure  in  the  aorta  may  be  at  first  rapid  and  then  slow  off  gradually. 
With  the  change  of  velocity  of  the  rise  of  pressure,  vibrations  may  be  set  up 
at  5  especially  in  the  aorta  and  also,  but  to  a  less  extent,  in  the  ventricle. 
These  vibrations  are  however  often  absent.  At  the  end  of  the  plateau 
the  pressure  in  the  ventricle  falls  rapidly  as  this  organ  begins  to  relax.  Its 
pressure  therefore  falls  below  that  of  the  aorta,  and  the  aortic  valves  close, 
the  closure  of  the  valves  being  followed  by  the  so-called  dicrotic  elevation 
or  incisure  at  7.  The  pressure  in  the  ventricles  then  continues  to  fall,  first 
rapidly  and  then  more  slowly,  until  it  reaches  the  line  of  zero  pressure,  and 
remains  at  or  near  this  line  during  the  greater  part  of  diastole.  With  a  big 
inflow  there  may  be  a  slight  rise  towards  the  end  of  diastole,  which  may 
be  accentuated  by  the  auricular  contraction.  If  the  chest  is  opened  the 
pressure  in  the  ventricle  never  sinks  below-  zero  during  any  part  of  diastole. 
The  time  relations  of  these  events  naturally  varies  with  the  frequency  of 
contraction  of  the  heart.  In  a  dog's  heart  beating  about  100  times  a  minute, 
the  following  phases  in  the  ventricular  tracing  were  determined  by  Hurthle. 

(1)  A  small  rise  of  pressure,  due  to  contraction  of  the  auricles,  lasting 
about  -05  second. 

(2)  A  very  steep  ascent,  rather  above  the  middle  of  which  the  aortic 
valves  open.  The  beginning  of  the  rise  is  generally  marked  by  a  sharp 
secondary  wave  or  by  a  sudden  change  in  the  direction  of  the  curve.  This 
point  is  about  -02  to  -04  second  after  the  beginning  of  the  ventricular 
contraction. 

(3)  A  prolonged  stage,  lasting  about  two-tenths  of  a  second  during 
which  the  ventricle  is  contracting.  During  this  time  the  tracing  may  show 
a  flattened  top,  the  '  plateau,'  or  a  rounded  summit.  Near  the  beginning 
of  this  plateau,  a  second  wave  may  make  its  appearance  if  the  rate,  at  which 
the  pressure  rises,  falls  off  suddenly.  This  second  wave  is  therefore  most 
marked  with  a  considerable  output  and  a  heart  which  beats  forcibly  and 
rapidly. 

(4)  A  rapid  fall,  due  to  the  relaxation  of  the  ventricular  muscle.  Near 
the  upper  part  of  this  fall  the  aortic  valves  close ;  but  it  is  generally  difficult, 
without  comparison  with  the  simultaneous  aortic  pressure  curve,  to  make 
out  the  exact  point  of  closure  on  the  ventricular  pressure  curve. 

(5)  A  period  lasting  about  two-tenths  of  a  second  during  which  the 


THE  MECHANISM'  OF  THE  HEART  PUMP  945 

ventricle  remains  relaxed  and  the  pressure  is  approximately  zero,  in  some 
cases  rising  slightly  towards  the  end. 

The  period  of  outflow  of  blood  lasts  from  the  moment  at  which  the 
aortic  valves  open  to  the  moment  at  which  in  the  relaxing  ventricle  the 
pressure  falls  below  that  in  the  aorta  and  the  aortic  valves  close.  It  there- 
fore corresponds  with  the  duration  of  that  part  of  the  curve  which  has  been 
called  the  '  plateau.'  The  maximum  pressure  attained  in  the  left  ventricle 
naturally  depends  on  the  height  of  the  aortic  pressure  and  is  always  greater 
than  this.  Under  normal  conditions  in  the  dog,  with  an  average  aortic 
pressure  of  loo  mm.  Hg.,  the  pressure  in  the  ventricle  may  be  130  or  150  mm. 
Hg.  The  difference  between  the  average  pressure  in  the  aorta  and  the 
maximum  pressure  attained  during  contraction  of  the  ventricle  will  naturally 
be  greater  the  larger  the  amount  of  blood  which  is  thrown  out  at  each 
contraction.  Thus  in  one  case  in  a  dug  of  111  kilos.,  with  an  average  aortic 
pressure  of  Km  mm.  Hg.,  the  maximum  pressure  in  the  left  ventricle  was 
llo  mm.  Kg.  with  an  output  of  2040  c.c.  per  minute,  and  115  mm.  Hg.  with 
an  output  of  650  c.c.  per  minute.  On  the  right  side  the  maximum  pressure 
is  much  less,  corresponding  to  the  low  resistance  of  the  pulmonary  system 
of  blood  vessels.  Otherwise  the  general  course  of  the  curves  is  very  similar 
on  the  two  sides  of  the  heart.  The  maximum  pressure  in  the  right  ventricle 
may  be  taken  as  varying  between  25  and  35  mm.  Hg.  under  ordinary 
conditions. 

CHANGES   OF   PRESSURE   IN   THE   AURICLES 

Owing  to  the  absence  of  valves  between  the  right  auricle  and  the  venae 
ca  \  se,  changes  of  pressure  within  this  cavity  are  transmitted  along  the  veins. 
The  venous  pulsation  is  especially  marked  in  circumstances  which  give  rise 
to  high  venous  pressure,  so  that  the  veins  are  not  entirely  emptied  at  any 
part  of  the  cardiac  cycle.  The  most  superficial  observation  shows  that  the 
jugular  vein  pulsates  twice  for  each  heart  beat.  The  exact  form  of  the 
pressure  tracing  in  the  auricles  varies  considerably  according  to  the  inflow 
of  blood  and  the  state  of  filling  of  their  cavities.     A  typical  tracing  with 

derate  inflow  of  blood  is  given  in  Fig.  408  A,  p.  942,  and  in  this  figure 

the  relations  of  the  different  elevations  in  the  auricular  tracing  to  the  intra- 
ventricular events  can  be  made  out.  A  somewhat  different  curve  is  given 
in  Fig.  400,  but  it  will  be  noted  that  the  essential  features  of  the  curves  are 
identical.     In  every  case  the  auricle  curve  presents  the  following  features  : 

(1)  The  first  positive  wave  (pre-systohc  wave)  corresponding  to  the 
auricular  systole. 

(2)  The  second  positive  wave  k  (first  systolic  wave)  occupying  the  begin- 
ning of  the  ventricular  systole.  This  is  caused  by  the  sharp  closure  of  the 
mitral  valve. 

(3)  A  third  positive  wave  (second  systolic  wave)  which  may  present 
secondary  undulations.  This  rise  of  pressure  is  due  to  the  gradual  filling  of 
the  auricles  while  the  auriculo-ventricular  valves  are  still  shut. 

(f)  A  negative  wave  which  corresponds  to  the  '  post -systolic  vacuum' 
60 


946  JM1YS10L0GY 

(it  ('hauveau  and  iMaicy.     At  this  point  (he  ventricle  is  entirely  relaxed  and 
the  auriculo-ventricular  valves  open,  so  allowing  the  blood  to  flow  freely 

1 1  he  auricle  into  the  ventricle.     This  negative  wave  is  not  always  well 

marked,   and    is    represented    only   by    a   series   of  small   undulations   in 
Fig.  408  A. 

The  pressure  uses  in  the  left  auricle  somewhat  higher  thai1  in  the  right 
auricle,  In  the  latter  ease  the  big  veins  act  as  a  supplementary  reservoir 
to  the  auricle,  so  that  in  no  period  of  the  cardiac  cycle  need  the  pressure  in 
the  latter  chamber  rise  to  any  extent.  In  both  the  auricular  tracings  given 
the  heart  sounds  are  apparent  as  small  oscillations  in  the  curve. 


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Fig.  410.     Curve  of  pressures  in  left  auricle  of  cat.     (Stbaub.) 
I,  II,  III  Ton  =  1st,  2nd,  and  3rd  heart  sounds. 

NEGATIVE  PRESSURE.  When  the  flow  of  blood  through  a  tap  is  suddenly 
interrupted,  the  momentum  of  the  fluid  tends  to  make  it  continue  its  movement  so  that 
a  diminution  of  pressure  is  produced  in  the  rear  of  the  moving  column.  In  the  tracings 
obtained  (by  means  of  the  older  instruments,  such  as  those  of  Hurthle,  the  lever  at  the 
end  of  the  ventricular  systole  descended  even  below  the  base  line,  thus  suggesting 
that  for  a  short  period  of  time  there  was  actually  a  negative  pressure  in  the  ventricles. 
If  the  manometer  be  connected  with  the  heart  by  a  tube  provided  with  a  valve  alio  whig 
the  movement  of  fluid  only  in  one  direction,  it  becomes  a  maximum  or  minimum  mano- 
meti  i  according  to  the  direction  of  the  valve.  This  tube  however  increases  the  inertia 
of  the  whole  system,  so  that  the  use  of  the  minimum  manometer  tends  to  exaggerate 
the  apparent  negative  pressure.  According  to  some  statements  there  may  be  a  negative 
pressure  of  40  to  60  mm.  Hg.  in  the  ventricle  at  some  period  during  the  cardiac  cycle. 
Many  explanations  were  put  forward  to  account  for  this  negative  pressure,  but  they  are 
all  rendered  unnecessary  by  the  fact  revealed  by  more  perfect  graphic  methods  that  at 
no  period  in  the  cardiac  cycle  is  there  a  negative  pressure  in  the  ventricles.  Naturally 
under  normal  conditions  the  pressure  in  the  chest  outside  the  heart  is  negative  owing 
to  the  elastic  retraction  of  the  lungs,  and  may  vary  from  -3  to  -30  mm.  Hg.,  according 
as  it  is  measured  during  normal  expiration  or  during  forced  inspiration.  This  negative 
pressure  may  be  transmitted  to  the  interior  of  the  heart,  but  the  pressure  within  the 
ventricles  never  falls  below  the  pressure  obtaining  outside  the  heart. 


CHANGES  IN  FORM  OF  THE  HEART 

As  the  heart  walls  are  perfectly  flaccid  during  diastole,  the  shape  of  this 
organ  as  a  whole  will  depend  upon  the  position  in  which  the  heart  is  lying 


THE  MECHANISM  OF  THE  HEART  PUMP      917 

and  the  direction  of  its  support.  Thus  if  the  chest  and  the  pericardium  be 
opened  and  the  animal  be  in  the  supine  position,  the  heart  during  diastole 
will  be  flattened  from  before  backwards  as  a  result  of  the  simple  weight  of 
its  contents.  In  this  position  therefore,  systole  will  be  accompanied  by  a 
shortening  in  the  lateral  and  vertical  directions  and  a  lengthening  in  the 
sagittal  direction.  During  systole,  when  the  heart  becomes  tense  and  all 
its  fibres  are  firmly  contracted,  the  heart,  whatever  its  previous  condition, 
takes  the  form  of  a  truncated  cone.  Under  normal  circumstances  the  heart 
in  the  unopened  chest  lies  in  the  pericardium,  which  is  attached  above  to 
the  great  vessels  and  lielow  to  the  central  tendon  of  the  diaphragm.  It  is 
supported  laterally  by  the  lungs  which  however,  owing  to  their  elasticity, 
bave  very  little  influence  on  its  shape  during  diastole. 

When  the  heart  is  freed  from  the  pericardium,  the  obliquity  of  its  fibres 
causes  the  apex  to  move  forwards  and  to  the  right  during  systole;  this 
movement  is  normally  prevented  by  the  attachment  of  the  pericardium  to 
the  central  tendon  of  the  diaphragm,  so  that  the  most  movable  part  of  the 
heart  comes  to  he  the  base.  If  three  needles  be  passed  through  the  chest 
wall  so  that  their  points  He,  one  in  the  base,  one  about  the  centre  of  the 
ventricles,  and  one  in  the  apex  of  the  ventricles,  each  ventricular  systole  is 
Eound  to  be  accompanied  by  a  movement  of  the  needle  in  the  base  of  the 
heart  downwards,  a  slighter  movement  in  the  same  direction  of  the  needle 
in  the  middle  of  the  ventricles,  and  practically  no  movement  at  all  of  the 
needle  which  is  thrust  into  the  apex.  During  systole  the  base  of  the  heart 
-  downwards  towards  the  apex.  This  movement  is  determined  partly 
by  the  shortening  of  the  fibres  of  which  the  ventricular  wall  is  composed, 
partly  by  the  lengthening  of  the  great  arteries  as  blood  is  forced  into  them 
under  pressure  from  the  ventricles. 

The  changes  in  the  shape  of  the  cavities  of  the  heart  during  contraction 
have  been  studied  in  the  stage  of  extreme  contraction  produced  by  heat 
rigour.  In  such  hearts  it  is  found  that  the  cavities  are  never  entirely 
obliterated,  though  the  right  ventricle  is  reduced  to  a  narrow  slit  widening 
out  slightly  in  the  neighbourhood  of  the  auriculo-ventricular  orifices,  while 
in  the  left  ventricle  a  distinct  cavity  is  left  between  the  mitral  valves  and 
the  free  ends  of  the  papillary  muscles.  During  normal  activity  it  is  probable 
that  the  emptying  of  the  cavities  rarely  proceeds  to  so  great  an  extent. 

THE   APEX   BEAT     ' 

The  movement  of  the  heart  at  each  contraction  is  communicated  to  the 
chest  wall,  over  a  limited  area  of  which  it  may  be  felt  and  seen,  except  in 
fat  individuals.  The  region  where  the  pulsation  of  the  chest  wall  is  most 
marked  lies  in  the  fifth  intercostal  space,  a  little  to  the  median  side  of  the 
left  nipple.  The  pulsation  is  spoken  of  as  the  '  apex  beat,'  and  was  formerly 
thought  to  be  due  to  the  twisting  forward  of  the  apex  at  each  systole.  The 
apex  of  the  heart  is  really  situated  lower  down  and  as  we  have  already 
seen,  so  long  as  the  pericardium  is  intact,  is  relatively  motionless.  During 
diastole  the  ventricles  form  a  flabby  flattened  cone  Lying  against  the  chest 


948 


PHYSIOLOGY 


wall  and  slightly  deformed  by  the  latter.  In  systole  the  ventricles  contract 
forcibly  on  the  contained  fluid  and  become  hard  and  rigid,  assuming  the 
form  of  a  rounded  cone.  This  sudden  recovery  of  shape  and  hardening  of 
the  ventricular  wall  pushes  out  that  part  of  the  chest  wall  in  immediate 
proximity  to  the  ventricles  and  so  gives  rise  to  the  '  apex  beat.' 

The  cardiac  impulse  may  be  registered  by  means  of  a  cardiograph.  In  nearly  all 
forms  of  this  instrument  a  button  resting  on  the  chest  wall  transmits  the  movement  of 
the  latter  to  a  tambour,  which  again  is  connected  by  a  tube  to  a  registering  tambour. 
One  such  instrument  is  shown  in  Fig.  411. 


Fia.  411.  A  cardiograph.  This  is  strapped  round  the  chest,  the  central  button  is 
applied  to  the  '  apex  beat,'  and  its  pressure  on  the  chest  wall  regulated  by 
means  of  the  three  screws  at  the  sides.  The  tube  at  the  upper  part  of  the 
instrument  serves  to  connect  the  drum  of  the  cardiograph  with  a  registering 
tambour  such  as  that  shown  in  Fig.  405. 

The  curves  so  obtained,  which  are  known  as  cardiograms,  may  vary  considerably 
in  the  same  subject  according  to  the  pressure  employed  and  the  exact  spot  at  which 
the  tambour  is  applied.  Their  interpretation  often  presents  difficulties  owing  to  the 
fact  that  their  form  is  conch  tioned  by  two  factors,  viz.  (1 )  the  actual  size  (antero-posterior 


Fig.  412.     Cardiogram.     (Huktiile. 


diameter)  of  the  ventricles;  (2)  the  resistance  to  distortion  (i.  e.  the  tension)  of  the 
ventricular  wall;  this  factor  will  increase  in  importance  with  increasing  pressure  of  the 
cardiograph  button  on  the  chest  wall.  Fig.  412  represents  a  cardiographic  tracing 
or  cardiogram  which  may  be  spoken  of  as  typical.  In  order  to  interpret  this  curve 
we  must  record  at  the  same  time  either  the  intraventricular  pressure  in  animals  or  the 
heart  sounds  in  man.  This  cardiogram  presents  considerable  similarities  to  the  endo- 
cardiac  pressure  curve;  in  both  there  is  an  ascending  limb,  a  plateau,  and  a  descending 
limb,  and  in  many  cases  a  small  elevation  occurs  at  the  beginning  of  a  curve  during  the 
contraction  of  the  auricle.  The  exact  point  at  which  the  auricular  passes  into  the 
ventricular  contraction  varies  from  case  to  case  and  may  be  altered  by  altering  the 
degree  of  pressure  put  on  the  recording  button.  In  the  first  figure  given  the  auricular 
systole  finishes  before  the  main  rise  of  the  lever  occurs.  In  many  cases  however,  the 
elevation  due  to  the  auricular  systole  may  take  up  the  greater  part  of  the  ascending 
limb  of  the  curve,  as  in  Fig.  413. 


THE  MECHANISM  OP  THE  HEART  PUMP      949 

In  the  experiment  from  which  this  figure  was  taken,  the  heart  sounds  were  recorded 
at  the  same  time  as  the  apex  beat.  It  will  be  seen  that  the  first  heart  sound,  correspond- 
ing to  the  ventricular  systole,  begins,  not  at  the  commencement  of  the  rise  of  the  cardio- 
gram but  at  the  notch  near  the  top  of  the  ascent.  The  first  part  of  the  ascent  is  therefore 
caused  by  the  increase  in  the  volume  of  the  ventricle,  due  to  the  sudden  contraction  of 
the  auricles,  the  ventricular  systole  being  marked  by  the  notch  near  the  top  of  the 
curve.  Owing  to  the  co-operation  of  the  volume  and  pressure  factors  in  the  production 
of  the  cardiogram,  the  curve  generally  begins  to  decline  with  the  diminution  in  volume 
which  follows  the  sudden  opening  of  the  aortic  valves.  Here  again  however,  the  effect 
will  vary  with  the  pressure  of  the  button.  If  an  actual  deformation  of  the  ventricular 
muscle  can  be  effected,  as  in  thin  patients,  the  plateau  of  the  curve  may  last  during  the 
whole  of  the  cardiac  cycle.  Other  forms  of  curves  may  be  obtained  which  show 
considerable  deviation  from  the  endocardiac  pressure  tracing;  these  are  spoken  of  as 
atypical,  and  are  generally  conditioned  by  a  faulty  jiosition  of  the  cardiograph,  the 
button  being  applied  to  the  chest  wall  in  the  immediate  vicinity  of  the  apex  beat- 
instead  of  to  the  apex  beat  itself. 


T'ig.  413.     Cardiogram  (b)  with  simultaneous  record  of  heart  sounds  (a). 
(HtJRTHXE.) 

1.   position  of  first  heart  sound;  2,  position  of  second  heart  sound. 


THE    HEART   SOUNDS 

If  we  apply  our  ear  to  the  front  of  a  person's  chest  (it  is  more  convenient 
to  use  the  stethoscope  for  the  purpose),  we  hear  two  distinct  sounds  accom- 
panying each  beat  of  the  heart,  followed  by  a  pause  corresponding  to  the 
diastole.  The  sounds  are  compared  to  the  syllables  lubb,  dup,  the  first 
sound  being  low-pitched  and  prolonged,  the  second  sound  high  and  sharp. 
Thus  the  heart  sounds^  may  be  represented  :  lubb.  dup  (pause),  lubb,  dup 
(pause). 

The  causation  of  the  second  sound  is  very  simple  and  may  be  considered 
first.  It  is  heard  just  over  the  second  right  costal  cartilage,  i.  e.  the  place 
where  the  aorta  lies  nearest  the  surface.  It  comes  at  the  end  of  the  systole, 
as  determined  by  the  hardening  of  the  apex  of  the  heart,  felt  as  the  apex 
beat,  and  can  be  shown  to  be  synchronous  with  the  closure  of  the  aortic 
valves.  It  is  in  fact  caused  by  the  sudden  shutting  and  stretching  of 
these  valves,  that  occur  directly  the  heart  ceases  to  contract  and  to  force 
the  blood  into  the  aorta.  If  the  valves  be  hooked  back  in  an  animal  by 
means  of  a  wire  passed  down  a  carotid  artery,  the  second  sound  disappears 
and  is  replaced  by  a  murmur  caused  by  the  blood  rushing  back  into  the 
ventricle  at  the  end  of  the  systole.     The  same  disappearance  of  the  normal 


950  PHYSIOLOGY 

second  sound  is  observed  in  eases  where  the  valves  are  prevented  from 
closing  by  diseased  conditions. 

The  pulmonary  and  aortic  valves  generally  close  simultaneously.  In 
some  eases  however,  the  aortic  may  close  slightly  before  the  pulmonary, 
giving  rise  to  a  '  reduplicated  second  sound."  The  pulmonary  element  of 
this  sourTd  is  best  heard  over  the  second  left  cartilage,  or  in  the  second 
left  intercostal  space. 

The  first  sound  has  probably  a  twofold  origin,  viz.  from  the  sudden 
closure  of  the  auriculo-ventricular  valves  and  from  the  contraction  of  the 
thick  muscular  wall  of  the  ventricle. 

If  the  veins  going  to  the  heart  be  clamped  so  that  the  heart  can  no  longer 
be  distended  with  blood  nor  the  valves  put  on  the  stretch,  the  first  sound 
is  altered  in  character,  but  not  abolished.'  The  first  sound  may  indeed 
be  heard  on  listening  with  a  stethoscope  to  the  beat  of  an  excised  heart. 
It  is  said  that  two  notes  may  be  detected  in  the  first  sound — a  high  note 
of  short  duration  due  to  closure  of  the  valves,  and  a  low-pitched  note  due 
to  the  muscular  contraction.  The  muscular  element  of  the  first  sound  has 
the  same  pitch  as  the  soimd  produced  by  contracting  voluntary  muscle, 
and  therefore  as  the  resonance  tone  of  the  ear.  This  consideration  prevents 
our  arguing  from  the  tone  that  a  cardiac  contraction  is  a  tetanus.  As  we 
shall  show  later  on,  each  ventricular  contraction  is  analogous  to  a  simple 
muscle  twitch  and  not  to  a  tetanus. 

THE  THIRD  HEART  SOUND.  A  number  of  observers  have  described  a  third 
heart  sound  as  occurring  in  certain  individuals  during  the  diastole,  a  short  time  after 
the  second  sound.  It  is  softer  and  of  a  lower  pitch  than  the  second  sound,  and  is  heard 
most  distinctly  over  the  apex  beat.  It  is  probably  due  to  the  vibrations  set  up  in  the 
fluid  itself  or  in  the  auriculo-ventricular  valves  by  the  sudden  inrush  of  blood  from 
auricles  to  ventricles  at  the  beginning  of  the  diastole.  The  sound  is  shown  objectively 
by  the  vibrations  on  the  endocardial;  pressure  curve  given  in  Fig.  410  (Straub).  It  has 
also  been  registered  electrically  by  Einthoven. 

CARDIAC   MURMURS 

When  a  fluid  escapes  through  a  narrow  orifice  into  a  wider  space,  vibra- 
tions are  set  up  in  the  fluid  and  may  be  transmitted  by  any  clastic  medium 
to  the  ear,  giving  rise  to  the  sensation  of  sound.  Such  a  sound  is  produced 
when  water  is  allowed  to  run  from  a  tap  into  a  vessel  of  water,  or  when 
air  is  blown  out  between  the  .partially  closed  lips.  The  formation  of  such 
vibrations  forms  indeed  the  basis  for  the  construction  of  many  musical 
instruments.  The  same  sort  of  vibration  may  be  set  up  in  the  large  vessels 
or  in  the  heart,  whenever  the  blood  passes  rapidly  through  a  narrow  orifice 
into  a  wider  space. 

In  the  normal  individual  sounds  produced  in  this  way  are  so  slight 
that  they  may  be  neglected;  under  abnormal  conditions,  as  after  diseases 
affecting  the  valvular  orifices  of  the  heart,  this  vibration  may  occur  during 
every  heart  cycle  and  be  heard  with  ease  on  applying  the  car  to  the  chest. 
These  murmurs,  or  bruits  as  they  are  called,  are  of  paramount  importance 
in  enabling  the  medical  man  to  form  a  judgment  as  to  the  condition  of  the 


THE  MECHANISM  OF  THE  HEART  PUMP      951 

different  valves  of  the  heart.  Thus  injury  to  an  aortic  valve,  so  as  to  allow 
of  leakage  during  diastole,  involves  the  squirting  of  a  small  amount  of  fluid 
under  high  pressure  from  the  aorta  into  the  relaxed  ventricle.  On  listening 
to  the  chest  of  a  man  with  such  a  lesion,  this  regurgitation  during  diastole  is 
heard  as  a  rushing  sound  occurring  in  the  place  of  or  continuing  the  second 
sound  up  to  the  beginning  of  the  next  first  sound,  which  denotes  the  com- 
mencement of  systole. 

In  many  cases  the  disease  which  occasions  the  inadequacy  of  the  valve 
is  followed  by  processes  of  repair  and  cicatrisation  in  which  the  valves 
become  puckered  and  contracted  and  perhaps  adherent,  so  that  the  orifices 
can  never  become  thoroughly  patent  or  thoroughly  closed.  Under  such 
circumstances  vibrations  will  be  set  up  in  the  current  of  blood  as  ft  escapes 
through  the  narrow  orifice  into  the  aorta  during  systole,  and  on  listening  to 
the  chest  over  the  second  right  costal  cartilage,  a  '  to  and  fro  '  bruit  is 
heard  composed  of  a  systolic  immediately  followed  by  a  diastolic  murmur. 
In  the  same  way  incompetency  of  the  mitral  valve,  or  dilatation  of  the  mitral 
orifice  in  consequence  of  weakness  of  the  cardiac  muscle,  gives  rise  to  a 
murmur  which  lasts  during  the  whole  of  the  ventricular  contraction  and 
is  therefore  systolic  in  character.  Such  a  murmur  is  heard  best  over  the 
apex  beat,  and  is  also  transmitted  backwards  so  that  it  can  be  heard  on 
listening  at  the  back  of  the  patient.  A  narrowing  of  the  mitral  orifice  in 
consequence  of  contraction  of  the  valves  will  set  up  a  resistance  to  the 
flow  of  blood  from  left  auricle  to  left  ventricle.  The  auricle  becomes  hyper- 
brophied,  its  contraction  prolonged,  and  the  escape  of  blood  through  the 
contracted  orifices  gives  rise  to  a  murmur  which  is  heard  on  listening  over 
the  apex  heat  as  a  presystolic  bruit.  This  bruit  is  easily  distinguished  from 
a  systolic  murmur  by  noticing  that  it  runs  unto  and  ends  with  tin' 
apex  beat,  whereas  a  systolic  murmur  does  not  begin  until  the  elevation  of 
the  apex  coram)  nces. 

Several  physiologists  have  succeeded  in  recording  heart  sounds  graphically.  Hurthle's 

method  consists  in  an  application  of  tin-  mioropl e.     A  special  form  of  stethoscope  is 

so  arranged  that  by  its  means  the  vibrations  corresponding  to  the  heart  sounds  are 
transmitted  to  ,i  contact  between  silver  and  carbon.  A  strong  current  is  passing 
through  this  contact,  as  well  as  through  an  electro  magnet,  which  attracts  an  iron 
disc  attached  to  (he  membrane  of  a  Marey's  tambour.  Any  vibration  transmitted  to 
the  carbon-silver  contact  alters  its  resistance,  and  so  the  strength  of  the  current  passing 
through  the  electro-magnet.  In  this  way  the  heart  sounds  can  affect  (he  pullexerted 
by  the  electro  magnet  on  the  membrane  of  the  tambour,  and  (lie  change  in  the  volume 
of  the  contained  airis  recorded  l\\  means  of  an  ordinary  registering  tambour. 

Similar  results  have  been  obtained  bj   Einthoven,  who  has  allowed  the  van 
in  the  current  passing  through  (he  microphone  to  be  recorded  directly  by  means  of  a 
very  delicate  capillary  or  string  electrometer. 

TIME  RELATIONS 

The  time  relations  of  the  various  events  oi  I  be  cardiac  cycle  are  indicated 
in  tin'  accompanying  diagram  (Fig  414).  In  man  the  heart  beats  on  tin' 
average  about  seventy-two  times  in  the  minute,  so  (Imt  each  cardiac  cycle — ■ 


952 


PHYSIOLOGY 


i.  e.  systole  plus  diastole— can  be  rewarded  as  occupying  0-8  sec.  During 
five-tenths  of  a  second  the  ventricles  are  relaxed  ;  during  the  first  four- 
tenths  of  this  period,  which  corresponds  to  the  diastole  of  the  heart  as  a 
whole,  blood  is  flowing  in  a  steady  stream  from  the  veins  through  the  auricles 
into  the  ventricles,  so  that  the  heart  is  gradually  increasing  in  size.  The 
systole  of  the  auricle  then  occurs  and  lasts  about  0-1  sec.  This  is  followed 
by  the  ventricular  systole,  the  immediate  effect  of  which  is  to  close  the 
auriculo-ventricular  valves  on  both  sides  of  the  heart.  The  whole  ventricu- 
lar contraction  lasts  0-3  sec;  during  the  first  period  of  this  the  ventricle 
is  getting  up  pressure,  the  pressure  rapidly  rising  until  it  equals  the  aortic 
pressure.  This  period,  during  which  the  ventricle  is  simply  contracting 
isometric*ally  on  its  contents  without  any  flow  of  blood  occurring,  lasts 


Piastole. 

g 

a 

^P 

1 

*. 

Blood 

Iowint 

systole 

in 

o  auri 
vent 
from 

cles  a 
icles 
veins 

A 

of 
Aur- 
icles 

V 

stole 
ntric 

of 

Dia 

tnle 

1 

1       C 

■i       0 

3       0 

i       I 

5 

0 

i        0 

7       0 

s       o 

a     i 

M 


ilff 


aup 

Fig.  414. 


I.nlil.- dup 

Diagram  of  events  constituting  a  cardiac  cycle. 


between  -02  and  -04  sec,  and  is,  of  course,  longer  the  higher  the  pressure 
in  the  aorta.  Directly  the  intraventricular  pressure  rises  above  this  point 
the  aortic  valves  open  and  blood  is  driven  into  the  aorta.  The  outflow  of 
blood  continues  throughout  the  whole  of  the  ventricular  systole,  and  may 
be  taken  as  lasting  about  0-2  sec.  The  ventricle  then  suddenly  relaxes, 
the  period  of  relaxation  occupying  about  0-5  sec;  the  'plateau'  of  the 
endocardiac  pressure  curve  on  the  average  lasts  about  0-18  sec,  and  accord- 
inf  to  the  condition  of  the  heart-  and  the  peripheral  resistance  may  present 
a  gradual  ascent  or  descent.  Directly  relaxation  commences,  the  ventricular 
pressure  falls  below  the  aortic  pressure  or  the  pulmonary  pressure,  and  the 
semilunar  valves  close,  giving  rise  to  the  second  sound.  Systole  is  now  at 
an  end  and  the  diastolic  period  of  filling  recommences.  The  first  sound  is 
synchronous  with  the  commencement  of  the  ventricular  contraction,  and 
the  same  event  is  signalled  by  the  occurrence  of  the  apex  beat. 

Although  the  pulse  frecpiently  may  undergo  considerable  variations 
according  to  the  condition  of  the  individual,  being  higher  during  activity 
or  imder  conditions  of  mental  excitement,  the  greater  part  of  the  difference 
in  duration  of  the  cardiac  cycle  thereby  induced  falls  upon  the  diastolic 
period.    Thus  to  take  wide  limits  the  pulse  rate  may  vary  between  32 


THE  MECHANISM  OF  THE   HEART  PUMP  953 

and  124  beats  in  the  minute,  while  under  the  same  circumstances  the  period 
occupied  by  the  systole  varies  only  between  0-382  and  0-190  sec. — and  these 
of  course  are  extreme  limits.  Variation  therefore  in  the  time  occupied  by 
each  cardiac  cycle  is  determined  mainly  by  variation  in  the  time  occupied 
by  the  diastole. 

FILLING   OF   THE   HEART   IN   DIASTOLE 

Since  the  heart  is  perfectly  flaccid  during  diastole  it  is  unable  to  exert 
any  suction  force  on  the  blood  in  the  veins.  Its  filling  during  diastole 
depends  on  the  existence  of  a  positive  pressure  within  the  veins,  or  at  any 
rate  of  a.  pressure  greater  than  that  in  the  auricles  and  ventricles;  the 
greater  the  pressure  within  the  large  veins  the  more  rapidly  will  the  blood 
enter  the  heart  during  diastole  and  the  larger  the  amount  of  blood  in  this 
viscus  when  it  begins  its  contraction.  In  this  process  an  important  part 
is  played  by  the  mechanical  conditions  existing  in  the  thoracic  cavity. 
Owing  to  the  elasticity  of  the  lungs  and  the  fact  that  they  are  constantly 
tending  to  contract,  the  pressure  in  the  thorax  is  less  than  that  of  the 
external  atmosphere  by  the  amount  which  is  required  to  distend  the  lungs 
to  fill  the  cavity . 

At  the  end  of  expiration  this  difference  amounts  to  about  5  mm.  Hg. 
rising  to  9  mm.  Hg.  at  the  end  of  inspiration  and  to  30  mm.  Hg.  at  the 
end  of  a  forced  inspiration.  On  the  other  hand,  the  veins  outside  the  thorax 
are  exposed  to  a  pressure  which  is  a  little  above  that  of  the  atmosphere. 
When  the  thorax  is  at  rest,  the  veins  and  auricles  are  therefore  expanded 
and  the  flow  of  blood  into  them  rendered  more  easy.  The  respiratory 
movements,  by  causing  an  alternating  suction  on  the  walls  of  the  great 
veins,  act  like  an  accessory  pump  and  cause  an  aspiration  of  blood  into 
the  veins  of  the  thorax  with  each  inspiration. 

It  is  evident  that,  if  the  pressure  within  the  thorax  be  sufficiently  raised 
so  as  to  cause  a  positive  pressure  on  the  big  veins  and  auricles,  the  return 
flow  of  blood  to  the  heart  must  come  to  an  end.  Thus  during  extreme 
muscular  efforts  the  glottis  is  fixed  and  a  positive  pressure  is  produced  in 
the  thorax.  The  deficient  circulation  and  the  deficient  aeration  of  the 
blood  thereby  induced  are  shown  by  the  engorgement  of  the  superficial 
veins  and  the  blueness  of  the  surface.  Weber  showed  that  by  a  forcible 
expiration,  with  the  glottis  closed,  the  pulse  might  disappear  at  the  wrist 
and  the  circulation  be  brought  for  a  time  to  a  standstill,  so  that  even  loss 
of  consciousness  might  supervene. 

Since  the  heart  during  its  systole  diminishes  its  own  volume  by  the  expulsion  of 
blood  from  the  thorax,  it  becomes  smaller,  and  the  space  thus  provided  in  the  chest 
cavity  is  taken  up  by  an  expansion  of  the  veins,  auricles,  and  lungs.  To  this  systolic 
diminution  of  intrathoracic  pressure  is  due  the  '  cardio-pneumatic  '  movements. 
These  are  recorded  l>y  attaching  one  nostril  to  a  delicate  tambour  by  means  of  a  tube, 
while  the  other  nostril  and  the  mouth  are  kept  closed.  If  a  carotid  pulse  tracing  be 
taken  at  the  same  time,  it  will  lie  found  that  there  is  a  fall  of  the  lever  attached  to  the 
nasal  cavity,  synchronous  with  the  rise  of  the  pressure  in  the  arteries  and  due  to  the 
expulsion  of  blood  from  the  heart. 


954  PHYSIOLOGY 

The  normal  filling  of  the  heart  during  diastole  can  be  prevented  by 
anything  which  hinders  its  expansion,  such  as  the  presence  of  fluid  in  the. 
pericardial  cavity.  The  same  effect  may  be  produced  experimentally.  If  oil 
be  allowed  to  flow  into  the  pericardium,  when  the  pressure  of  the  oil  rises 
to  about  60  mm.,  the  pressure  of  the  vena  cava  rises  to  a  height  just  above 
that  obtaining  in  the  pericardial  cavity.  On  increasing  the  pressure,  a 
point  is  finally  reached  at  which  no  more  blood  can  be  driven  from  the  veins 
to  the  heart,  so  that  the  arterial  blood  pressure  falls  to  zero  and  death  ensues. 

In  order  to  maintain  the  arterial  pressure  it  is  necessary  that  the  amount 
of  blood, driven  into  the  arterial  system  by  the  contraction  of  the  left  ventricle, 
should  be  exactly  equal  to  that  leaving  the  arteries  to  pass  into  the  capillaries 
during  the  period  which  elapses  between  each  systole. 

Over-filling  of  the  heart  is  prevented  to  a  certain  extent  by  the  resistance 
of  its  walls.  The  danger  of  over-filling  is  therefore  most  marked  in  the 
right  ventricle.  An  important  part  is  played  moreover  by  the  pericardium 
in  this  regard.  Even  when  beating  normally,  the  heart  during  diastole 
tends  to  protrude  through  a  slit  made  in  the  pericardium,  and  Barnard 
has  shown  that  the  right  auriculo-ventricular  valve  ceases  to  be  entirely 
efficient  when  the  pericardium  has  been  freely  opened,  the  closure  of  this 
valve  being  dependent  on  the  support  afforded  to  the  heart  by  the 
pericardium. 

SYSTOLIC   OUTPUT   OF   THE   HEART 

The  amount  of  blood  which  passes  through  the  whole  body  and  is  avail- 
able for  the  metabolic  exchanges  of  all  the  tissues  depends  on  the  amount 
of  blood  which  leaves  the  heart  each  minute.  The.  height  of  the  arterial 
pressure  also  depends  on  the  relation  between  the  amount  of  blood  leaving 
the  arterial  system  by  the  capillaries  and  that  entering  from  the  heart. 
The  determination  of  the  output  of  the  left  ventricle  is  therefore  one  of 
the  most  important  problems  in  physiology.  The  output  of  the  right  ventricle 
must  be  equal  to  that  from  the  left  ventricle,  otherwise  the  blood  would 
accumulate  on  one  or  other  side  of  the  heart  and  bring  the  circulation  to 
a  standstill.  It  is  therefore  immaterial  on  which  side  of  the  heart  the 
output  be  determined. 

The  methods  which  have  been  devised  for  determining  the  cardiac 
output  fall  into  two  classes.  In  the  first  class  it  is  sought  to  determine 
the  total  volume  of  blood  leaving  the  right  or  left  ventricle  in  the  course 
of  a  given  time,  say  one  minute.  If  this  amount  be  divided  by  the  number 
of  heart  beats  in  the  same  time,  the  output  of  each  ventricle  per  beat  is 
at  once  obtained.  A  second  method  consists  in  the  determination  of  the 
volume  changes  in  the  ventricles  at  each  beat  of  the  heart.  During  diastole 
the  ventricles  are  receiving  blood  and  increase  in  volume,  during  systole 
they  expel  blood  and  therefore  diminish  in  volume.  The  change  in  volume 
at  each  beat  nives  therefore  the  combined  output  of  right  and  left  ventricles 
and  must  be  divided  by  half  in  order  to  give  the  output  of  either  ventricle 
separately. 


THE  MECHANISM  OF  THE  HEART  PUMP      955 

METHODS  OF  DETERMINING  OUTPUT.  In  a  method  devised  by  the  author 
it  is  possible  to  determine  the  output  of  the  left  ventricle  under  all  manner  of  conditions 
and  to  vary  at  will  the  arterial  resistance,  the  venous  pressure,  the  filling  of  the  heart, 
or  the  temperature  of  the  blood  supply  to  the  heart.  The  arrangement  of  the  apparatus 
is  shown  in  Fig.  415.  Artificial  respiration  being  maintained,  the  chest  is  opened  under 
an  anaesthetic.  The  arteries  coming  from  the  arch  of  the  aorta — in  the  cat,  the  innomi- 
nate and  the  left  subclavian — are  then  ligatured,  thus  cutting  off  the  whole  blood  supply 
to  the  brain,  so  that  the  anaesthetic  can  be  discontinued.  Cannula?  are  placed  in  the  inno- 
minate artery  and  the  superior  vena  cava.  The  cannulae  are  filled  beforehand  with  a  solu- 
tion of  hirudin  in  normal  salt  solution  so  as  to  prevent  clotting  of  the  blood  during 
the  experiment.     The  descending  aorta  is  closed  by  a  ligature.     The  only  path  left  for 


lie:.  416.  Arrangement  of  apparatus  for  working  on  the  isolated  mammalian 
beait.  ('Heart-lung  preparation.*)  The  different  parts  are  not  drawn  to 
scale,  and  the  lungs  are  not  shown.     (Starling.) 

the  blood  is  by  the  ascending  aorta  and  the  cannula  CA  in  the  innominate  artery. 
The  arterial  cannula  communicates  by  a  T-tube  with  a  mercurial  manometer  M'  to 
record  the  mean  arterial  pressure,  and  passes  to  another  T-tube,  v,  one  limb  of  which 
projects  into  a  teat-tube  B.  The  air  in  this  test-tube  will  be  compressed  with  a  rise 
of  pressure  and  will  serve  as  a  driving  force  for  the  blood  through  the  resistance.  It 
thus  takes  the  part  of  the  resilient  arterial  wall.  The  other  limb  of  the  T-tube  passes 
to  the  resistance  R.  This  consists  of  a  thin  -walled  rubber  tube  (e.  g.  a  rubber  finger- 
stall) which  passes  through  a  wide  glass  tube  provided  with  (wo  lateral  tubulures  w,  v. 
One  of  these  is  connected  with  a  mercurial  manometer  M'  and  the  other  with  an  air 
reservoir  into  which  air  can  be  pumped.  When  air  is  injected  into  the  outer  tube,  the  tube 
E  collapses,  and  will  remain  collapsed  until  the  pressure  of  the  blood  within  it  is  equal 
or  superior  to  the  pressure  in  the  air  surrounding  it.  It  is  thus  possible  to  vary  at  VI  ill 
the  resistance  to  the  outflow  of  the  blood  from  the  arterial  side.  From  the  peripheral 
end  of  R  the  blood  passes  a1  a  Lovi  pressure  through  a  spiral  immersed  in  warm  water 
into  a  large  glass  reservoir.  From  the  reservoir  a  wide  india-rubber  tube  leads  to  a 
cannula,  which  is  placed  in  the  superior  vena  cava  SVG,  all  the  branches  of   which 


956  PHYSIOLOGY 

have  beon  tied.  This  cannula  ia  provided  with  a  thermometer  to  show  tho  temper- 
ature of  the  blood  supplied  to  the  heart.  A  tube  placed  in  the  inferior  vena  cava  and 
connected  with  a  water  manometer  shows  the  pressure  in  the  right  auricle.  On  the  record- 
ing surface  we  thus  have  a  record  of  the  arterial  pressure,  and  of  the  pressure  within  the 
right  auricle.  The  output  of  the  whole  system  can  be  measured  at  any  time  by  opening 
the  tube  X,  clamping  F,  and  allowing  the  blood  to  flow  for  a  given  number  of  seconds 
into  a  graduated  cylinder. 

This  method,  although  of  considerable  importance  in  giving  information  as  to  the 
conditions  which  determine  the  output  of  the  left  ventricle  and  the  maximum  capacity 
of  the  heart  as  a  pump,  tells  us  nothing  as  to  the  output  of  the  left  ventricle  under 
normal  conditions  in  the  intact  animal.  For  this  purpose  some  indirect  means  must 
be  adopted  which  can  be  used  on  the  intact  animal  and  if  possible  on  man  himself, 
so  that  the  output  can  be  measured  under  different  conditions  of  rest  and  activity. 
Moreover  the  output  as  measured  on  the  other  side  of  the  artificial  arterial  resistance 
represents  the  ventricular  output  minus  the  blood  flow  through  the  coronary  arteries. 
It  is  possible  however  to  insert  a  cannula  into  the  coronary  sinus,  and  so  to  measure 
the  blood  flow  through  the  heart  muscle.  The  coronary  circulation  must  be  added 
to  the  flow  through  the  arterial  resistance  in  order  to  arrive  at  the  correct  total  output 
of  the  left  ventricle.  The  two  chief  methods  for  the  determination  of  the  ventricular 
out  put  in  the  intact  animal  are  those  of  Zuntz  and  of  Krogh. 

ZUNTZ'S  METHOD.  This  is  based  on  a  comparison  of  the  differences  in  gases 
contained  in  the  arterial  and  venous  blood  and  the  actual  amount  of  oxygen  taken 
from  the  air  in  the  lungs.  Thus  in  one  ease  he  found  that  in  a  horse  weighing  3(50 
kilos.  2733  c.c.  of  oxygen  were  taken  up  in  the  lungs  per  minute,  while  the  arterial 
blood  contained  10-33  per  cent,  more  oxygen  than  the  venous  blood.  Since  therefore 
every  100  c.c.  of  blood  that  passed  through  the  lungs  had  taken  up  10-33  c.c.  of  oxygen, 
and  2733  c.c.  had  been  taken  up  in  the  course  of  a  minute,  it  is  evident  that 


100  X  2733 
10-33 


20,457  c.c. 


of  blood  must  have  passed  through  the  lungs  in  the  time.  This  therefore  was  the  output 
of  blood  by  the  right  ventricle  in  a  minute  and  was  equivalent  to  -00122  of  the  body 
weight  per  second. 

In  a  similar  experiment  on  a  dog  the  output  per  second  of  the  right  ventricle  was 
found  to  be  -00157  of  the  body  weight.  In  order  to  get  the  output  at  each  beat  it  will 
be  necessary  to  divide  the  output  per  minute  by  the  number  of  heart  beats  in  the  same 
time.  From  the  results  of  determinations  made  in  this  way  Zuntz  concluded  that  the 
output  of  the  right  ventricle  in  man  at  each  beat  varies  between  50  and  100  c.c.  and 
may  be  taken  on  an  average  at  60  c.c. 

KROGH 'S  METHOD.  In  Krogh's  method  an  endeavour  is  made  to  determine 
the  volume  of  blood  flowing  through  the  lungs  in  a  given  time  by  finding  out  how 
much  nitrous  oxide  is  taken  up  from  a  mixture  of  nitrous  oxide  and  air,  with  which 
tin1  lungs  are  filled.  Nitrous  oxide  is  chosen  because  it  can  be  breathed  in  considerable 
proportions  without  injury,  and  is  itself  very  soluble  in  water  or  in  the  blood.  The 
estimation  is  carried  out  in  the  following  way.  A  small  recording  spirometer  is  filled 
with  about  4J  litres  of  a  gas  mixture  containing  10  to  25  per  cent.  N20  and  20  to  25 
per  cent,  oxygen.  The  subject,  seated  in  a  chair  or  on  a  bicycle  ergometer,  expires  to 
the  greatest  possible  extent,  and  then  takes  a  deep  inspiration  from  the  spirometer. 
He  holds  his  breath  for  five  to  fifteen  seconds,  breathes  out  sharply  into  the  spirometer, 
expiring  at  least  one  litre.  At  the  end  of  this  sharp  expiration,  a  sample  of  his  alveolar 
air  is  taken  by  connecting  the  tube  from  his  face-piece  with  an  evacuated  glass  bulb, 
as  in  Haldane's  method  of  determining  alveolar  air.  The  breath  is  now  held  for  a 
period  varying  between  six  and  twenty-five  seconds.  He  then  makes  a  final  sharp 
ample  expiration  into  the  spirometer,  a  sample  of  his  alveolar  air  being  taken  at  the 
end  of  this  expiration.  The  excursions  of  the  spirometer  indicate  exactly  what  volume 
of  air  he  has  breathed  in  and  breathed  out  at  each  part  of  the  experiment.     These  are 


THE  MECHANISM  OF  THE  HEART  PUMP      957 

recorded  on  a  travelling  surface,  so  that  the  duration  of  the  experiment  is  represented 
by  the  horizontal  distance  between  the  lines  showing  the  moments  of  sampling  (Fig. 
416). 

By  comparison  of  the  composition  of  ordinary  alveolar  air  with  the  alveolar  air  ob- 
tained after  the  first  sharp  expiration,  the  amount  of  residual  alveolar  air  is  determined, 
so  that  the  total  volume  of  gas  contained  in  the  lungs  at  each  part  of  the  experiment 
is  also  known.  During  the  time  when  the  breath  is  being  held,  nitrous  oxide  is  being 
taken  up  in  solution  by  the  blood  as  it  passes  through  the  lungs,  its  solubility  being  such 
that  1  c.c.  of  blood,  if  exposed  to  an  atmosphere  of  pure  nitrous  oxide,  will  take  up 
0-43  c.c.  of  this  gas.  From  the  data  obtained  in  this  way,  the  amount  of  blood  passing 
t  hrough  t  he  lungs  during  the  period  between  the  two  expirations  can  be  calculated.  The 
following  record  of  one  experiment  may  serve  as  an  example.  The  volume  of  air  in 
the  lungs  at  the  beginning  of  the  experiment  was  3-25  litres  and  contained  12  per  cent, 
nit  runs  oxide,  so  that  the  total  quantity  of  nitrous  oxide  in  the  air  of  the  lungs  was 
3250  c.c.  X  11,,"fy  =  390  c.c.  At  the  end  of  the  period  the  total  volume  of  air  in  the 
lungs  was  three  litres,  containing  only  10  per  cent,  nitrous  oxide,  so  that  the  lungs 


28/  sec 
I   5  sec 


Fig.  416.     (Kiioan.) 

now  contained  only  300  c.c.  nitrous  oxide,  90  c.c.  nitrous  oxide  having  been  taken  up 
by  the  blood.     This  90  c.c.  was  taken  up  from  an  air  in  which  the  mean  pressure  of 

this  gas  was     --  =11  per  cent.      During  the  period  of  observation,  from  a  gas 

containing  ;it   atmospheric  pressure  11  per  cent,  of  nitrous  oxide,  each  c.c.  of  blood 

will  take  up         — =  0-047  c.c.      In  order  to  take  up  90  c.c.  therefore.  1-9  litres  of 

100 
blood  must  have  passed  through  the  lungs  during  the  time  of  the  observation.     The 
erperimenl   lasted  twenty-eight  seconds.     The  amount  of  blood  passing  through  the 
lungs  per  minute  was  therefore  4-2  litres.     This  figure  represents  the  output  from  the 
right  ventricle  during  one  minute,  and  if  the  pulse  rate  is  70  per  minute,  the  output 

ner  heat  will  be    -  '  —  =  60  c.c.  per  beat.     The  figure,  arrived  at  in  this  way  for  the 
1  70 

a  \  erage  out  put  of  each  ventricle  in  man  during  rest,  thus  agrees  with  the  figure  obtained 
by  Zuntz.     The  output  of  both  ventricles  is  of  course  the  same. 

According  to  Krogh,  the  ventricular  output  per  minute  in  man  may  vary  from  2-8 
litres  to  21  litres  of  blood  per  minute.  The  latter  is  an  extreme  figure  and  was  obtained 
in  a  powerful  athlete  doing  hard  work.  In  the  case  of  Krogh  himself,  the  maximum 
output  was  about  12  litres  per  minute.  It  is  interesting  to  note  that  the  same  perform- 
ance may  be  obtained  from  a  dog's  heart  in  the  heart-lung  preparation,  allowing  for 
the  difference  in  size  between  the  hearts  of  the  dog  and  man  respectively. 

CARDIOMETRIC  METHOD.  Of  the  various  methods  which  have  been  devised  for 
recording  plethysmographically  the  changes  in  the  volume  of  the  heart  at  each  beat  (as 
tirst  carried  out  by  Roy),  the  simplest  is  that  devised  by  Henderson.  The  chest  and 
pericardium  being  opened,  a  glass  cardiometer,  of  the  shape  shown  in  Fig.  417,  is  slipped 
over  the  heart.  This  cardiometer  consists  of  a  glass  sphere  with  a  wide  opening.  To 
the  margin  of  the  opening  is  tied  a  rubber  diaphragm  with  a  hole  in  it,  which  accurately 
fits  the  heart  as  it  lies  in  the  auriculo-ventricular  groove.     The  tube  of  the  cardiometer  is 


958  PHYSIOLOGY 

connected  with  some  form  of  pisl icorder  or  a  tambour  with  a  slack  membrane. 

The  disadvantage  of  this  method  is  that  the  graphic  record  of  rapid  and  am  pic  changes 
in  volume  is  one  of  the  mosl  difficult  problems  in  experimental  physiology,  the  inerl  ia 
and  friction  of  the  moving  piston  tending  to  deform  the  shape  of  the  curve  obtained. 
Straub  has  therefore  used  a  soap  bubble  as  the  volume  measurer,  photographing  its 
edge  and  using  the  record  as  an  index  to  the  change  in  volume.  It  is  possible  how- 
ever to  obtain  a  piston  recorder  moving  sufficiently  freely  to  give  a  fairly  correct 
reproduction  of  the  volume  changes  of  the  heart,  provided  that  these  do  not  occur  with 
too  great  rapidity.  It  has  been  suggested  by  Piper  to  convert  the  volume  changes 
into  small  pressure  changes,  and  to  record  these  latter  by  one  of  the  methods  described 
above. 

The  factors  which  determine  the  output  of  the  left  ventricle  are  bust 
■studied  in  the  heart-lung  preparation.  In  this  it  can  be  shown  that,  pro- 
vided the  venous  inflow  remains  constant,  the  output  is  also  constant  and 
is  unaffected  by  considerable  alterations  of  arterial  resistance  and  of  the 


Fro.  417.     Henderson's  glass  cardiometer. 

rate  of  the  heart.  Thus  with  a  moderate  venous  inflow  the  output  remains 
constant  whether  we  maintain  the  average  arterial  pressure  at  60  mm.  Hg. 
or  at  160  mm.  Hg.  It  is  also  unaffected  by  altering  the  rate  of  the  heart 
from  80  beats  per  minute  up  to  160,  or  even  200,  beats  per  minute.  On 
the  other  hand,  the  output  is  at  oiice  altered  by  alterations  in  the  venous 
inflow  and,  as  already  stated,  can  be  altered  in  a  heart  weighing  50  gms. 
from  a  few  c.c.  up  to  3000  c.c.  per  minute.  The  only  essential  in  this 
preparation  is  that  the  output  from  the  left  ventricle  shall  be  sufficient 
to  maintain  a  circulation  through  the  coronary  vessels  and  so  keep  the 
active  muscle  properly  supplied  with  blood. 

With  increasing  inflow  of  blood  into  the  heart  the  large  veins,  auricles, 
and  ventricles  naturally  become  more  filled  during  diastole,  and  during 
systole  of  the  ventricles,  when  the  auriculo-ventricular  valves  are  closed, 
the  blood  rushing  in  from  the  venous  system  must  accumulate  in  the  big 
veins  and  auricles  to  a  still  greater  extent.  The  venous  pressure  therefore 
rises  with  increased  venous  inflow.  In  so  far  as  venous  pressure  is  an 
index  of  venous  inflow,  we  may  say  that  the  output  of  the  heart  increases 
with  the  venous  pressure  so  long  as  the  heart  is  functionally  capable  of 
dealing  with  the  blood  it  receives  during  diastole.  But  although  the 
ventricular  output  is  practically  independent  of  the  frequency  of  the  heart 
beat  and  a  constant  venous  inflow,  the  venous  pressure  tends  to  fall  as 


THE  MECHANISM  OF  THE  HEART  PUMP      959 

the  heart  beat  Increases  in  rate.  The  optimum  venous  pressure  is  that 
which  fills  the  ventricle  during  its  diastole  to  the  maximum  extent  to 
which  it  is  able  to  respond.  As  the  rate  of  the  heart  increases,  the  inflow 
of  blood  can  also  be  increased  without  causing  over-distension  of  the 
ventricles.  The  increase  of  heart  rate  therefore  is  an  important  factor 
hi  enabling  this  organ  to  deal  with  the  maximum  amount  of  blood.  Although 
increase  of  rate  does  not  alter  the  output  with  constant  venous  inflow,  it 
does  increase  the  maximum  amount  of  inflowing  blood  which  the  heart  is 
able  to  expel. 

We  thus  see  that  alterations  in  the  vigour  of  the  circulation  depend  in 
the  first  instance  on  the  venous  circulation.  The  greater  volume  of  the 
blood  that  is  brought  up  to  the  heart  by  the  accessory  factors  of  the  cir- 
culation, the  greater  will  be  the  output  of  this  organ.  The  changes  in  rate 
and  force  of  the  heart  which  accompany  its  increased  activity  and  increased 
output,  e.g.  during  exercise,  represent  merely  the  means  by  which  this 
organ  is  able  to  deal  in  the  most  advantageous  manner  with  the  increased 
inflow. 

THE  WORK   OF   THE   HEART 

The  energy  of  the  ventricular  contraction  is  expended  in  two  ways  : 

first,  in  forcing  a  certain  amount  of  blood  into  the  already  distended  aorta 

against    the    resistance    presented    by  the    arterial   blood  pressure,  which 

itself  is  directly  conditioned  by  the  resistance  in  arterioles  and  capillaries ; 

and  secondly,  in  imparting  a  certain  velocity  to  the  mass  of  blood  so  thrown 

out.      Thus  the  energy  of  the  muscular  contraction  is  converted  partly 

into  potential  energy  in  the  form  of  increased  distension  of  the  arterial  wall 

and  partly  into  the  kinetic  energy  represented  by  the  momentum  of  the 

moving  column  of  blood.     The  work  done  at  each  beat  may  be  calculated 

from  the  formula  : 

wV2 

W  =  QR  +  — 

2g 

where  \\  stands  for  work,  to  for  the  weight,  and  Q  for  the  quantity  (volume 

in  c.c.)  of  blood  expelled  at  each  contraction;    R  is  the  average  arterial 

resistance  or  pressure  during  the  outflow  of  blood  from  the  heart,  and  V  is 

the  velocity  of  the  blood  at  the  root  of  theaorta.     In  this  equation  QR  is 

vJV2 . 
the  work  done  in  overcoming  the  resistance,1  and  —      is  the  energy  expended 

in  imparting  a  certain  velocity  to  the  blood. 

If  we  take  Ho  c.c.  as  the  average  output  of  each  ventricle.  Km  mm.  Hg. 
as  the  average  pressure  at  the  beginning  of  the  aorta,  and  500  mm.  per 

1  This  expression,  QR,  is  only  approximately  correct.  Supposing  the  pressure  in 
the  aorta  at  the  beginning  of  systole  is  50  mm.  Hg.  and  at  the  end  of  systole  150  mm., 
the  work  could  not  be  deduced  accurately  from  the  average  pressure,  but  would  need  a 
simple  application  of  the  integral  calculus  for  its  determination.  The  expression 
employed  above  deviates  from  the  real  value  by  at  most  10  per  cent.,  and  is  thereforo 
sufficiently  accurate  for  our  purpose. 


960  PHYSIOLOGY 

second  as  the  velocity  imparted  bo  the  blood  thrown  into  the  aorta,  we  can 
calculate  the  work  done  by  the  human  heart  at  each  beat. 

QR  =  60  X  0-100  m.  X  13-6  =  81-6  grammetres, 

or  roughly  80  grammetres.     On  the  other  hand,  the  expression 

» 

wW-       60  X  (0-5)2       n  _  . 

—  =  —  -  =  0-7  grammetres. 

2<7  2  •   9-8 

It.  is  evident  that  this  latter  factor  is  negligible,  and  that  for  all  practical 
purposes  we  may  regard  the  work  of  the  heart  as  proportional  to  the  output 
multiplied  by  the  average  arterial  blood  pressure.  Taking  tin'  average 
pressure  in  the  pulmonary  artery  at  20  mm.  Hg.,  the  work  of  the  right 
ventricle  at  each  beat  would  amount  to  about  16  grammetres,  a  total  for 
the  two  ventricles  of  about  100  grammetres  per  beat,  which  is  equivalent 
to  about  10,000  kilogrammetres  in  twrenty-four  hours  for  a  man  at  rest. 

During  muscular  work  this  figure  would  be  largely  increased.  Not  only 
does  QR  become  much  larger,  but  the  velocity  factor  is  no  longer  negligible, 
since  the  work  done  in  imparting  velocity  to  the  blood  increases  as  the 
cube  of  the  output  per  minute.  If  we  take,  as  an  example,  a  maximum 
effort  on  the  part  of  an  athlete,  we  may  assume  an  output  per  beat  of  180  c.c. 
and  a  pulse  rate  of  180  per  minute  (an  output  per  minute  of  32-4  litres) 
and  an  average  arterial  pressure  of  120  mm.  Hg. 

Then 

QR  =  180  X  -120  X  13-6  =  294  grammetres. 

To  determine  the  velocity  of  output,  we  assume  that  180  c.c.  of  blood 
are  thrown  out  into  the  aorta  during  §  of  J  second,  the  time  of  outflow 
being  about  §  of  each  cardiac  cycle  This  gives  a  velocity  of  2-3  metres 
per  second,  assuming  a  cross  section  of  625  mm.2  at  the  root  of  the  aorta. 
Therefore 

wV°-       180  x  (2-3)2       .  , 

=  *  =  5  grammetres. 

2;/  2  x  9-8 

The  total  work  of  both  sides  of  the  heart  will  be  : 

294  -\-  5  -\-   59  +  5  =  363  grammetres  per  beat,  or  65  kilogrammetres  per 
Left  side.  Eight  side.  minute. 

This  rati'  of  work  could  probably  not  be  maintained  for  more  than  a  few 
minutes. 

This  work  is  done  by  a  contraction  of  the  muscle  fibres  surrounding  the  cavities 
of  the  ventricles.  It  is  important  to  remember  that  the  strain  or  tension,  winch  is 
thrown  on  these  "fibres  and  which  resists  their  contraction,  will  be  determined  not  only 
by  the  blood  pressure  which  has  to  be  overcome,  but  also  by  the  size  of  the  ventricle 
cavities.  Since  the  pressure  in  a  fluid  acts  in  all  directions,  the  tension  caused  by  any 
given  pressure  on  the  walls  of  a  hollow  vessel  will  increase  with  the  diameter  of  the 
vessel.  Thus  if  we  take  a  sphere  with  a  radius  of  10  cm.  filled  with  fluid  at  a  pressure 
of  10  cm.  Hg.,  there  will  be  a  pressure  on  each  square  centimetre  of  the  inner  surface 
of  the  sphere  of  136  grm.  The  total  distending  force,  i.  e.  the  pressure  on  the  whole  of 
the  inner  wall  of  the  sphere,  will  be  equal  to  this  pressure  multiplied  by  the  area, 


THE  MECHANISM  OF  THE  HEART  PUMP      961 

i.  e.  to  136  X  47rr2  =  136  X  47r  X  100.  If  by  a  contraction  of  the  walls  the  radius 
be  reduced  to  5  cm.,  the  total  pressure  on  the  internal  surface  will  be  reduced  to 
136  X  4r  X  25,  i.  e.  will  be  one  quarter  of  the  previous  amount.  Moreover  in  the 
case  of  the  heart,  with  increasing  distension  the  wall  becomes  thinner  and  the  number 
of  muscle  fibres  in  a  given  area  fewer,  so  that  the  larger  the  heart  the  more  strongly 
will  each  fibre  have  to  contract  in  order  to  produce  a.  given  tension  in  the  contained, 
lluid.  At  the  beginning  of  systole  the  distended  heart  must  therefore  contract 
more  strongly  than  at  the  end  of  the  systole,  in  order  to  raise  the  blood  it  contains  to 
a  pressure  sufficient  to  overoome  that  in  the  aorta. 

It  is  evident  that  an  unrestricted  diastolic  filling  of  the  heart  is  not  of 
unqualified  advantage  to  this  organ.  If  during  diastole  the  heart  be  too 
forcibly  distended,  as  may  easily  occur  after  opening  the  pericardium,  or 
in  cases  of  enfeeblement  of  the  heart's  action  by  chloroform  poisoning  or 
otherwise,  the  muscle  fibres  of  the  heart  may  be  quite  unable  to  contract 
against  the  distending  force  represented  by  a  pressure  in  the  heart  equal 
to  that  in  the  aorta.  Under  such  conditions  we  may  have  sudden  heart 
failure,  which  can  be  relieved  only  by  diminishing  the  diastolic  distension, 
as,  e.  g.  by  letting  blood  from  the  veins  opening  into  the  heart. 


61 


SECTION   V 

'  THE    FLOW   OF   BLOOD   THROUGH  THE   ARTERIES 

THE  PULSE.  Owing  to  the  elasticity  and  distensibility  of  the  arterial  wall, 
the  rhythmic  rise  of  pressure  corresponding  to  each  heart  beat  causes  an 
expansion,*  which  can  be  felt  by  the  finger  placed  on  any  exposed  artery, 
such  as  the  radial,  and  is  spoken  of  as  the  pulse.  Just  as  the  blood  pressure 
diminishes  from  heart  to  periphery,  so  the  amplitude  of  the  pulse  decreases 
as  we  go  farther  away  from  the  heart. 

If  the  arterial  system  were  perfectly  rigid,  the  increased  pressure  due 
to  the  forcing  of  the  blood  into  the  arterial  system  at  each  ventricular 
systole  would  occur  practically  simultaneously  at  every  point.  The  arteries 
are  however  elastic  and  distensible,  so  that  the  first  effect  of  the  flow  of 
blood  into  the  aorta  is  to  distend  the  section  of  the  aorta  nearest  to  the 
heart.  The  elastic  reaction  of  this  forces  a  portion  of  the  blood  into  the 
nearest  section,  so  that  the  increased  pressure  is  transmitted  from  segment 
to  segment  of  the  arteries  in  the  form  of  a  wave  at  the  velocity  of  about 
seven  metres  per  second. 

It  is  important  not  to  confuse  the  velocity  of  the  pulse  wave  with  that 
of  the  blood  flow;  the  latter  is  never  greater  than  0-5  metre  per  second, 
and  is  very  much  less  than  this  in  the  smaller  arteries.  Perhaps  the  differ- 
ence between  the  two  quantities  may  be  marie  clearer  by  illustration  : 
If  the  hindmost  of  a  row  of  billiard  balls  be  struck  sharply  with  a  cue,  the 
foremost  ball  flies  off  and  the  others  stop  still;  in  this  case  the  energy 
imparted  to  the  first  ball  by  the  stroke  has  been  transmitted  from  ball  to 
ball,  just  as  the  effect  of  the  ventricular  contraction  is  transmitted  from 
section  to  section  of  the  arterial  bloodstream.  If  the  balls  are  struck  s<> 
that  the  cue  continues  pressing  on  the  hindmost  after  the  stroke  is  delivered, 
the  front  ball  flies  off,  while  the  others  move  slowly  along  in  the  direction 
of  the  stroke.  Li  the  arteries  this  continuous  pressure  is  furnished  by 
the  elastic  reaction  of  the  arterial  wall,  and  we  see  how  the  impact  of  the 
blood  may  travel  quickly  as  a  wave  of  increased  pressure,  while  the  blood 
itself  is  moving  slowly  along,  impelled  by  the  reaction  of  the  arterial  wall. 
If  we  imagine  a  rigid  tube  ab  (Fig.  418)  provided  with  a  piston  at  the 
end  a,  and  filled  with  an  incompressible  fluid,  an  inward  movement  of 
the  piston  at  A  will  cause  a  simultaneous  outflow  of  fluid  at  the  end  B.  If 
the  end  B  is  closed,  the  piston  at  A  cannot  be  moved  at  all.  Pressure  applied 
to  the  piston  will  raise  the  pressure  simultaneously  at  all  points  in  the 
tube  ab.  The  increased  pressure  applied  at  A  is  therefore  transmitted 
with  practically  no  loss  of  time  to  all  parts  of  the  tube  ab  This  immediate 
spread  of  the  wave  of  pressure  apphes  only7  to  an  incompressible  fluid 
within  a  rigid  tube.     If  the  fluid  were  compressible,  if  it  consisted,  e.  g.  of 

962 


THE  FLOW  OF   BLOOD   THROUGH  THE  ARTERIES      963 

air,  a  sudden  movement  inwards  of  the  piston  at  A  would  not  be  felt  imme- 
diately at  B.  The  propagation  of  the  wave  of  pressure  from  a  to  B  would 
take  a  finite  period  of  time,  its  velocity  being  identical  with  that  of  the 
velocity  of  propagation  of  a  wave  of  sound  in  air,  i.  e.  1100  feet  per  second. 

A 

=1 


s 


The  same  retarding  effect  will  be  produced  if  we  have  an  incompressible 
fluid  within  a  tube  whose  wall  is  distensible  and  elastic.  If  we  imagine 
(Fig.  il'J)  an  elastic  tube  bc  filled  and  distended  with  water  and  connected 
at  b  to  a  rigid  tube,  which  is  provided  with  a  piston,  the  first  effect  of  a 
rapid  movement  of  fluid  driven  in  by  the  piston  will  be  a  rise  of  pressure 
at  the  point  immediately  in  front  of  the  piston,  viz.  at  a.  The  wall  being 
distensible,  and  pressure  being  propagated  along  the  fluid  in  every  direction, 
the  rise  of  pressure  at  a  -will  be  spent  partly  on  the  particles  of  fluid    in 


front  of  it .  viz.  at  b,  but  also  on  the  walls  of  the  tube,  so  that  this  is  stretched 
and  the  cross-section  of  the  tube  enlarged.  The  distended  segment  at  a 
will  then  exert  a  pressure  on  the  contained  fluid,  driving  this  backwards 
and  forwards.  The  fluid  on  its  side  towards  the  piston  will  tend  to  come 
to  a  stop,  while  that  towards  the  distal  end  of  the  tube  will  be  accelerated. 
The  distended  wall  therefore  returns  to  its  original  diameter,  and  the  next 
segment  at  6  is  stretched  in  its  turn,  so  that  a  wave  of  increased  pressure 
is  propagated  along  the  tube  in  the  direction  of  the  arrow. 

The  velocity  with  which  this  wave  is  propagated  depends  on  the  density  of  the 

fluid,  i.  e.  its  inertia,  and  on  the  resistance  of  the  walls  of  the  tube  to  distension,  since 

this   will  determine  the  rapidity  of  its  recovery.     The  velocity  of  propagation  of  the 

of  increased  pressure,  or  the  wave  of  expansion  of  the  artery,  is  expressed  by  the 

following  formula  : 


fgea 

v  =  *V  T>d 


where  v  is  the  velocity  per  second, 

</,  t  he  acceleration  due  to  gravity, 
e,  the  elastic  coefficient  of  the  wall, 
a,  the  thickness  of  the  wall, 
d,  the  diameter  of  the  tube, 
I),  the  density  of  the  fluid, 
k,  a  constant. 


PHYSIOLOGY 


If  the  end  c  of  the  tube  is  closed,  the  wave  of  a  positive  pressure  on 
arriving  at  b  will  be  reflected  back  as  a  positive  reflected  wave.  If  a 
tracing  be  taken  of  the  oscillations  or  variations  of  pressure  in  the  tube, 
two  waves  at  least  are  seen,  one  of  which  is  the  primary  wave  due  to  the 


Jil^-^^ 


5ovV\KaAA/v\1a/v\/vuv\  a  j 


Fiq.  420.  Pulse  curves  described  by  a  series  of  sphygniographic  levers  placed 
at  intervals  of  20  cm.  from  each  other  along  an  elastic  tube,  into  which  fluid  is 
forced  by  the  sudden  stroke  of  a  pump.  The  pulse  valve  is  travelling  from 
left  to  right,  as  indicated  by  the  arrows  over  the  primary  (a)  and  secondary 
(b,  c)  pulse  waves.  The  dotted  vertical  lines,  drawn  from  the  summit  of  the 
several  primary  waves  to  the  tuning-fork  curve  below,  each  complete  vibration 
of  which  occupies  5',T  sec,  allow  the  time  to  be  measured  which  is  taken  up  by  the 
wave  in  passing  along  20  cm.  of  the  tubing.  The  waves  (a')  are  waves  repeeled 
from  the  closed  distal  end  of  the  tubing ;  this  is  indicated  by  the  direction  of 
tho  arrows.  It  will  be  observed  that  in  the  more  distant  lever  (VI)  the  reflected 
wave,  having  but  a  slight  distance  to  travel,  becomes  fused  with  the  primary 
wave,  so  that  the  rise  of  pressure  in  VI  is  actually  greater  than  that  in  V. 
(From  Foster,  after  Makey.) 

movement  of  fluid  caused  by  the  piston ;  the  other  is  the  secondary  wave 
reflected  back  from  the  periphery.  The  fact  that  the  secondary  wave  is 
a  reflected  one  is  shown  by  the  fact  that  the  nearer  to  the  peripheral  resist- 
ance the  pulse  is  recorded,  the  nearer  is  the  secondary  to  the  primary  wave, 
as  is  seen  in  Fig.  420. 


THE  FLOW  OF  BLOOD  THROUGH  THE  ARTERIES       965 

If  the  tube  bc  be  widely  opened  a  reflected  wave  is  also  observed,  but 
this  time  of  reversed  sign,  i.  e.  the  wave  is  one  of  negative  pressure.  The 
production  of  this  wave  is 
dependent  on  the  momentum 
of  the  moving  column  of  fluid. 
If  in  the  tube  ab,  with  a  tap 
at  c  and  a  manometer  m 
(Fig.  421),  the  current  of  fluid 
be  suddenly  checked  by  turn- 
ing the  tap  c,  the  column  in    _^ 

front    of    the    tap,    having    a     

certain  momentum,  will  tend  FIG  42i. 

to  go  on  moving  and  therefore 

produce  a  suction  or  negative  pressure  behind  it.  When  a  wave  of  positive 
pressure  arrives  at  the  open  end  of  a  tube,  there  is  a  sudden* increase  in 
the  velocity  of  output,  and  the  momentum  of  the  mass  of  fluid  which  is 
thrown  out  causes  a  similar  suction  or  negative  pressure,  which  travels  back 
the  whole  length  of  the  tube.  If  the  end  of  the  tube  is  only  partially 
closed,  every  primary  positive  wave  will  be  transformed  into  a  reflected 
one  which  is  partly  positive  and  partly  negative.  Since  both  these  reflected 
waves  travel  through  the  tube  with  the  same  velocity  and  will  mutually 
interfere,  the  result  may  be  either  a  positive  or  a  negative  wave  or  nothing 
at  all,  according  to  the  degree  of  constriction. 

In  a  branching  system  of  tubes,  such  as  the  arterial  system,  reflection 
of  waves  must  take  place  at  every  dividing  place.  All  the  conditions  for 
the  origin  of  reflected  waves  and  interference  of  such  waves  are  present 
in  the  arterial  system.  It  is  impossible  a  priori  however  to  say  whether 
any  reflected  wave  will  form  a  marked  feature  on  the  pulse  tracing.  It  is 
possible  that  the  multitudinous  reflections  which  must  occur  in  every  part 
of  I  lie  arterial  system  may  interfere  with  one  another  to  such  an  extent  that 
they  mutually  annul  each  other.  The  origin  of  any  secondary  wave  in 
the  pulse  tracing  must  therefore  be  determined  by  experiment. 

To  study  the  pulse  more  fully  it  is  necessary  to  obtain  a  graphic  record 
of  the  expansion  of  the  arteries  or,  what  comes  to  the  same  thing,  of  the 
exact  changes  in  pressure  which  produce  this  expansion.  The  curve 
obtained  with  the  mercurial  manometer  shows  elevations  corresponding 
to  the  pulse;  but  the  instrument  is  far  too  sluggish  to  record  the  finer 
variations  of  pressure.  For  this  purpose  a  manometer  which  has  very 
little  inertia,  such  as  Hiirthle's  or  Piper's,  must  be  used.  The  expansion 
of  1  he  artery  is  registered  by  means  of  a  lever,  which  may  be  made  to  rest 
more  or  less  heavily  upon  the  artery,  and  the  movements  of  which  are 
recorded  on  a  blackened  surface.  Such  an  instrument  is  called  a  sphjgmo- 
graph.  Of  the  many  forms  of  sphymographs,  Marey's  or  Dudgeon's  is 
ips  the  most  convenient  for  clinical  purposes. 

The  principle  of  Marey's  sphygmograph  is  shown  in  Fig.  422.     Tho  button  b  is 
adjusted  so  as  to  press  on  the  radial  artery.     Its  movements  are  transmitted  to  a  lever 


966  PHYSIOLOGY 

m.  The  screw  on  this  works  on  a  small  cogged  wheel  at  o,  which  is  also  the  axis  of  the 
wiiting  lever  I.  The  movements  of  the  button  b  thus  transmitted  to  a  point  near  the 
axis  of  I  are  reproduced  by  this  lever  highly  magnified,  and  as  such  are  recorded  on  a 
blackened  surface.     The  pressure  on  the  artery  can  be  adjusted  by  means  of  a  screw. 

Dudgeon's  sphygmograph  (Fig-  423)  is  rather  easier  to  use  than  Marey's,  and  is  there- 
fore largely  employed  for  clinical  purposes.  It  is  provided  with  a  dial  by  which  the 
pressure  on  the  artery  can  be  graduated,  and  has  a  small  clockwork  arrangement  for 


Fio.  422. 

moving  along  the  slip  of  smoked  paper  on  which  the  records  are  taken.  The  arrange- 
ment of  the  levers  in  this  form  of  sphygmograph  is  shown  in  Fig.  424,  where  f  is  the 
(adjustable)  spring  bearing  by  its  button  P  on  the  artery.  The  up-and-down  move- 
ments of  P  are  transmitted  to  s,  being  much  magnified  and  converted  into  side-to-side 
movements.  The  point  of  S  rests  on  the  blackened  surface  represented  in  section  at  A, 
and  scratches  on  this,  when  moving,  a  magnified  record  of  the  expansion  of  the  artery 
under  the  knob  P. 


Fig.  423.     Dudgeon's  sphygmograph,  showing  its  mode  of  application  to 
the  radial  artery. 

In  all  these  sphygmographs,  even  the  most  perfect,  the  moving  parts  have  a  con- 
siderable amount  of  inertia,  so  that  the  curve  they  gi  ve  is  always  more  or  less  deformed. 
This  fact  must  be  borne  in  mind  when  comparing  the  pulse  curves  obtained  by  means 
of  a  sphygmograph  with  those  given  by  the  more  perfect  forms  of  manometer,  such  as 
Frank's  or  Piper's. 

Either  form  of  sphygmograph  is  generally  applied  to  the  radial  artery 
since  this  is  near  the  surface  and  is  supported  by  bone,  and  the  arm  is  well 
adapted  for  the  application  of  the  sphygmograph.  The  pulse  curve  obtained 
by  means  of  a  sphygmograph  varies  according  to  the  artery  employed  and 
the  force  with  which  the  lever  presses  on  the  artery,  but  all  the  curves 
present  the  same  general  features. 


THE  FLOW  OF  BLOOD  THROUGH  THE  ARTERIES       067 


Fiq.  425.     Pulse  curve  from  radial  artery. 


The  velocity  of  the  pulse  can  be  measured  by  taking  simultaneous 
tracings  from  two  arteries  separated  by  some  distance  from  one  another, 
such  as  the  femoral  artery  and  the  dorsalis  pedis,  or  from  the  carotid  and 
radial  arteries.     In  a  healthy  individual 
the  velocity  varies  between  7  and  10 
metres    per   second.     The    more    rigid 
the   arteries   the   greater  will   be   the 
velocity,    so    that    the     velocity    of 
propagation    gradually   increases    with 
advancing   age,   and   is   higher  in   the 
arteries     of     the     lower     extremities 
than    in  the  more  distensible  arteries 
of  the  arm. 

The  length  of  the  pulse  wave  can 
be  found  by  multiplying ;  the  velocity  Fl^g  ™T£  $%££?$££. 
of  transmission  by  the  time  occupied  graph, 
by  the  wave  in  passing  any  given 
point.  The  duration  of  the  wave  at 
any  point  corresponds  to  the  time 
of  a  cardiac  cycle,  viz.  0-8  sec,  so 
that  if  the  velocity  of  transmission 
be  taken  as  7  metres  per  second,  the 
length  of  the  wave  is  about  5-6  metres. 

The  pulse  wave  thus  reaches  the  periphery  long  before  it  has  been  com- 
pleted in  the  aorta.  Fig.  425  represents  a  pulse  curve  taken  from  the  radial 
artery.  The  elevation  due  to  the  expansion  of  the  artery  is  rapid  and 
uninterrupted.  We  have  already  explained  that  this  is  due  to  the  sudden 
pumping  of  blood  into  the  first  part  of  the  aorta,  whence  the  impulse  is 
transmitted  as  a  wave  along  the  arteries.  The  curve  descends  gradually 
till  the  next  beat  occurs,  since  the  elastic  reaction  of  the  arteries,  which 
tends  to  keep  up  the  pressure,  acts  more  constantly  and  steadily  than 
the  heart  beat.  On  this  descending  part  of  the  curve  occur  two  or  three 
secondary  elevations  :  h  is  the  primary  or  '  percussion  '  wave,  c  the  pre- 
dicrotic  or  '  tidal '  wave,  and  e  the  dicrotic  wave.  Elevations,  which  are 
called  post-dicrotic  waves,  may  occur  on  the  curve  after  e.  It  is  better  to 
class  the  elevations  before  the  dicrotic  notch  d  as  systolic  elevations,  and 
those  afterwards,  including  the. dicrotic  elevation  itself,  as  diastolic. 

For  the  exact  understanding  of  these  elevations  it  is  necessary  to  com- 
pare the  pulse  tracings  taken  from  a  small  artery  with  the  variations  in 
pressure,  which  occur  at  the  same  time  in  the  aorta  and  in  the  left  ventricle 
(Fig.  426).  We  are  enabled  in  this  way  to  dissociate  the  waves  caused  by 
the  ventricular  systole  from  those  which  have  their  origin  in  the  arterial 
system,  hi  Fig.  426  are  given  somewhat  diagrammatically  typical  tracings 
of  the  intra-auricular,  intraventricular,  and  aortic  pressures  during  one 
heart  beat.  The  dotted  lines  represent  approximately  the  sort  of  curve 
which  would  In-   given    by  a  sphygmograph  applied  to  the  aorta,  taking 


968 


1MIYST0L0GY 


into  account  the  greater  inertia  of  the  latter  instrument.  The  auricular 
systole  begins  at  the  ordinate  1.  It  gives  a  slight  rise  of  pressure  in  the 
ventricle,  but  as  a  rule  is  not  transmitted  to  the  aorta,  though  often  some 
small  traces  of  it  can  be  seen.  As  the  auricular  contraction  is  dying  away, 
the  ventricular  contraction  begins  at  2.  The  first  effect  of  this  rise  of 
pressure  is  to  close  the  auriculo-ventricular  valves,  as  is  shown  by  the 
elevation  at  3  in  the  auricular  curve,  and  the  shock  of  the  closure  is  occa- 
sionally transmitted  to  the  aorta.  The  pressure  in  the  ventricles  then 
rapidly  rises.  At  the  point  4  it  surpasses  the  pressure  in  the  aorta  and 
then  rapidly  rises  above  it.  Since  the  aortic  valves  offer  no  resistance  to 
the  flow  of  blood  from  ventricles  to  aorta,  they  must  open  as  soon  as  the 


Aorta 


I'entricle 

Auricle 


intraventricular  exceeds  the  aortic  pressure,  and  this  is  shown  by  the  rise 
of  pressure  in  the  aorta  at  5.  The  shock  of  the  inrush  of  blood  may  give 
rise  to  a  distinct  secondary  wave  at  this  point.  The  pressure  then  con- 
tinues for  a  time  to  rise  rapidly  both  in  the  ventricle  and  in  the  aorta,  blood 
flowing  from  the  heart  into  the  arterial  system.  As  the  first  rush  of  blood 
diminishes  and  as  the  blood  begins  to  escape  more  rapidly,  under  the  influence 
of  the  rise  of  pressure,  from  the  peripheral  end  of  the  arterial  system,  the 
rise  of  pressure  in  the  ventricle  and  aorta  slows  off,  and  the  junction  between 
these  two  periods  at  5.  where  the  rise  of  pressure  becomes  suddenly  slower, 
may  be  marked  in  the  aortic  curve  by  one  or  two  secondary  waves.  It  must 
be  remembered  however  that  all  these  secondary  waves  shown  on  the  aorta 
at  4  and  5  may  be  absent,  the  one  at  5  being  the  one  which  is  most  frequently 
seen.  From  6  to  7  the  ventricle  is  still  contracting  and  forcing  blood  into 
the  aorta.  The  curve  of  pressure  is  generally  rounded.  It  may  present  a 
flat  top,  the  plateau,  or  the  top  may  be  rounded  with  an  inclination  to  fall 


THE  FLOW  OF  BLOOD  THROUGH  THE   ARTERIES       969 

or  to  rise  (cf.  Fig.  408).  At  6  the  ventricle  relaxes,  the  intraventricular  pres- 
sure falls  rapidly,  and  at  7  falls  below  the  aortic  pressure.  The  aortic  valves 
must,  now  close  since  the  pressure  is  greater  on  their  aortic  side.  The  pressure 
in  the  ventricle  now  continues  to  fall  until  it  becomes  zero.  In  the  aorta 
however  there  is  a  sharp  elevation  immediately  after  7,  i.  e.  immediately 
after  the  closure  of  the  aortic  valves.  This  is  known  as  the  dicrotic  elevation, 
the  previous  depression  being  the  dicrotic  notch  or  incisure.  It  is  at  this 
point  that  the  second  sound  of  the  heart  is  heard  and  is  evidently  due  to  the 
vibrations  which  are  represented  graphically  in  the  record  of  intra-aortic 
pressure. 

There  are  several  factors  at  work  tending  to  produce  a  secondary  wave 
at  this  point.  With  the  sudden  cessation  of  the  inflow  of  blood  from  the 
ventricles  at  the  end  of  the  ventricular  contraction,  a  negative  wave  must 
be  produced  at  the  beginning  of  the  aorta  which,  transmitted  along  the 
arterial  system,  will  tend  to  produce  a  reflux  of  blood  towards  the  heart. 
The  movement  so  caused  is  reinforced  by  the  elastic  reaction  of  the  arterial 
wall  so  that  the  returning  blood  is  driven  up  against  the  aortic  valves, 
closing  them  tightly  and  putting  them  on  the  stretch.  Even  in  a  rigid 
tube  the  sudden  cessation  of  flow  causes  a  negative  wave,  followed  by  a 
positive  wave  in  the  opposite  direction  in  the  aorta;  this  positive  wave 
is  increased  by  the  elastic  reaction  of  the  stretched  aortic  valves.  The 
blood  is  driven  up  against  them  by  the  wave  of  positive  pressure  and  then 
rebounds,  like  a  billiard  ball  from  the  elastic  cushion,  and  gives  rise  to  the 
dicrotic  elevation. 

The  predicrotic  waves  in  the  pulse  tracing  are  evidently  due  to  the 
instrumental  exaggeration  of  the  wave,  which  may  occasionally  be  seen 
even  in  a  perfect  pressure  tracing  at  5.  The  rapid  rise  of  pressure  in  the 
or  in  the  more  peripheral  artery,  which  follows  the  opening  of  the 
aortic  valves,  sets  up  a  tendency  to  secondary  oscillations  at  this  point. 
The  greater  the  inertia  of  the  instrument,  the  greater  is  the  exaggeration 
of  these  waves.  As  is  shown  by  the  dotted  line  in  Fig.  426,  the  lever  of 
the  sphygmograph  is  jerked  up,  practioally  leaving  the  artery,  and  then 
falls  and  rebounds  again,  so  that  the  simple  rounded  top  becomes  resolved 
by  instrumental  error  into  a  curve  with  two  waves,  which  have  been  called 
the  percussion  wave  and  the  predicrotic  wave.  In  the  same  way  the  inertia, 
of  the  instrument  will  tend  to  exaggerate  the  dicrotic  elevation  and 
possibly  to  give  rise  to  slight  post-dicrotic  waves. 

It  would  seem  that  the  pulse  curve,  as  recorded  in  the  aorta  and  the 
arterial  trunks  given  off  from  the  aortic  arch,  can  be  referred  entirely  to 
events  taking  place  in  the  heart  during  systole  or  at  the  beginning  of  the 
aorta  at  the  commencement  of  diastole ;  and  there  seems  no  reason  to  assume 
the  co-operation  of  waves  reflected  from  the  periphery  to  explain  the  pro- 
duction of  any  of  the  secondary  waves  observed  on  the  pulse.  A  considerable 
difference  is  however  noticeable  between  the  pulse  as  recorded  in  the  aorta 
and  that  recorded  in  the  brachial  or  femoral  arteries,  or  in  the  radial  at  the 
wrist .     The  effect  of  the  propagation  along  an  endless  system  of  elastic  tubes 


970 


PHYSIOLOGY 


of  the  sudden  wave  of  pressure  started  in  the  aorta  must  be  to  diminish  the 
rapidity  of  onset  of  each  primary  wave,  and  therefore  to  diminish  the 
secondary  vibrations  of  the  curve.  In  an  elastic  system  of  tubes  such  as 
the  arterial  system,  there  are  factors  at  work  analogous  in  many  respects 
to  those  responsible  for  the  deformation  of  the  curve  given  by  an  imperfect 
manometer.  These  would  be  of  two  kinds — viz.  oscillations  of  the  column 
of  fluid  within  the  stretched  arterial  wall,  and  the  reflection  of  waves  from 
different  points  in  the  periphery.  Many  of  these  reflections  will  interfere 
with  and  annul  one  another.     But  in  the  arterial  system  there  are  certain 


-J""*" 


Fir;.  427.     Pulse-pressure  curves  taken  by  means  of  Frank's  manometer  (Frank). 

a,  B,  c,  aortic  pressure  curves  at  different  rates  of  the  heart;  D  and  E,  aortic 
pressure  curve,  D,  compared  with  simultaneous  record  of  the  pressure  in  the  femoral 
artery  E. 

points  where  distinct  reflections  of  waves  can  be  expected—  e.  g.  in  the  circle 
of  Willis,  at  the  bifurcation  of  the  aorta  into  the  two  iliac  arteries,  and  in 
the  superficial  and  deep  arterial  arches  in  the  hand  and  the  foot.  We  have 
distinct  evidence  that  such  waves  are  set  up  and  modify  the  form  of  the 
pulse  in  the  femoral  and  brachial  arteries  and  their  branches.  Thus  in 
the  Fig.  427  e,  the  primary  rise  of  pressure  in  the  femoral  artery  is  higher 
than  even  the  primary  rise  in  the  aorta.  This  condition  of  things  is  ex- 
plicable only  on  the  assumption  of  a  reflected  wave  passing  back  along  the 
artery  just  after  the  passage  of  the  primary  wave,  so  that  the  two  are 
summated.  In  the  same  way,  although  the  dicrotic  depression  in  the  curve, 
427  E,  is  no  doubt  mainly  the  propagated  effect  of  the  incisure  observed  in 
the  aortic  pulse,  it  is  probably  deformed  and  the  subsequent  elevation 
exaggerated  as  a  result  of  reflection  of  the  post-dicrotic  wave  from  the  peri- 


THE  FLOW  OF  BLOOD   THROUGH  THE  ARTERIES      971 

phery.  The  occurrence  of  reflected  waves  serves  to  explain  why  the  systolic 
pressure  in  the  femoral  artery  is  found  higher  and  the  diastolic  pressure  lower 
than  in  the  brachial.  The  femoral  artery  being  more  rigid  than  the  brachial 
and  the  peripheral  resistance  more  definitely  localised,  reflected  waves  occur 
in  the  artery  at  so  short  a  time  after  the  primary  wave  has  passed  down 
that  there  is  summation  of  the  two  waves,  with  production  of  a  higher  maxi- 
mum and  a  lower  minimum  than  was  present  in  the  waves  as  started  in  the 
aorta.  If  the  leg  be  plunged  into  hot  water,  so  as  to  dilate  all  its  arterioles, 
this  difference  between  the  arm  and  the  leg  systolic  pressures  disappears. 
The  varying  development  of  reflected  waves  on  the  two  sides  also  explains 
why  the  systolic  pressures  in  the  two  arms  are  rarely  found  to  be  identical. 

The  general  form  of  the  pulse  curve  varies  with  changes  in  the  heart, 
in  (he  arteries,  and  in  the  peripheral  resistance.  Thus  some  curves  may 
present  secondary  elevations  on  the  ascending  part,  and  are  called  anacrotic, 
while  in  others  all  secondary  elevations  occur  on  the  descending  part.  The 
latter  type  is  called  catacrotic,  and  is  the  tracing  usually  obtained  from  a 
normal  radial  artery.  By  comparing  these  two  types  of  curves  with  the 
corresponding  intraventricular  pressures,  we  find  that  in  both  cases  blood 
is  flowing  into  the  aorta  during  the  whole  time  from  the  beginning  of  the 
primary  elevation  to  the  notch  just  before  the  dicrotic  elevation.  This  is 
shown  by  the  fact  that  the  intraventricular  pressure  is  all  thi^  time  slightly 
higher  than  the  aortic  pressure.  So  long  as  this  is  the  case  blood  must 
flow  from  ventricle  into  aorta.  (This  fact  proves  that  there  is  normally 
no  part  of  the  cardiac  cycle  during  which  the  ventricle  remains  contracted 
and  empty,  the  ventricle  in  all  cases  relaxing  before  it  has  completely  emptied 
itself  of  blood.) 

Now  it  is  easy  to  see  the  conditions  which  determine  whether  the  systolic 
plateau  shall  be  ascending  or  descending,  and  therefore  when  the  pulse 
shall  be  anacrotic  or  catacrotic.  If,  after  the  first  sudden  rise  of  pressure 
in  the  aorta,  the  blood  can  escape  more  rapidly  through  the  peripheral 
resistance  than  it  is  thrown  into  the  beginning  of  the  aorta,  the  'systolic 
plateau  '  will  sink,  and  a  catacrotic  pulse  tracing  is  obtained.  If,  on  the 
other  hand,  the  peripheral  resistance  is  high,  or  an  extra  large  amount  of 
blood  be  thrown  into  the  aorta  at  each  stroke  of  the  heart  (e.g.  by  pro- 
longation of  the  diastole),  the  aortic  pressure  will  rise  so  long  as  blood  is 
flowing  in,  and  we  get  an  ascending  systolic  plateau  and  an  anacrotic  pulse. 
Thus  we  obtain  an  anacrotic  pulse  in  old  people  with  Bright's  disease,  in 
whom  the  peripheral  resistance  is  very  high,  and  also  in  animals  when  the 
heart  is  slowed  by  vagus  action. 

The  production  of  the  dicrotic  elevation  is  favoured  by  any  influence 
which  increases  the  elastic  resiliency  of  the  arteries  or  causes  the  primary 
elevation  of  the  pulse  to  be  rapid  and  sharp.  Thus  it  is  much  more  pro- 
nounced in  young  people  than  in  old  people,  whose  arteries  have  become 
rigid.  When  the  peripheral  resistance  is  low  through  relaxation  of  the 
arterioles,  and  the  heart  is  beating  forcibly,  as  in  manj  case  oi  fever  and 
also  to  some  extent   after  a  good  meal  with  alcohol,  the  dicrotic  elevation 


972  PHYSIOLOGY 

becomes  very  marked.  Under  such  circumstances  it.  may  be  easily  felt 
with  the  linger  at  the  wrist,  and  in  many  cases  the  mistake  has  been  com- 
mitted of  taking  the  dicrotic  wave  for  a  normal  beat,  and  so  doubling  the 
rate  of  the  pulse.  There  can  be  little  doubt'  that,  in  the  production  of  such 
a  marked  dicrotism,  reflection  from  the  periphery  plays  an  important  part. 
With  a  high  blood  pressure  and  rigid  arteries,  a  reflected  wave  will  travel 
back  very  quickly  and  will  tend  to  add  itself  to  the  primary  wave.  With 
a  low  blood  pressure,  dilated  arteries,  and  the  output  of  the  heart  thrown 
rapidly  into  a  relatively  empty  arterial  system,  the  primary  wave  will 
rise  and  fall  very  rapidly  and  the  reflected  wave  will  travel  back  along  the 
arteries  more  slowly,  so  that  its  main  effect  will  be  to  add  to  the  dicrotic 
elevation  normally  proceeding  outwards  from  the  heart  towards  the  peri- 
phery. The  figure  420  VI  represents  the  condition  as  it  is  found  in  the 
femoral  artery  under  normal  circumstances,  when  the  reflected  wave  adds 
to  the  height  of  the  primary  wave.  In  420  V  the  reflected  wave  '  a  ' 
would  tend  to  add  to  any  dicrotic  elevation  present  at  this  point,  and  prob- 
ably represents  the  relation  existing  in  the  arterial  system  with  relaxed 
arteries  and  a  heart,  beating  forcibly  but  throwing  out  only  a  small  amount 
of  blood  at  each  beat. 

From  time  immemorial  the  physician  has  sought  by  feeling  the  pulse 
to  come  to  some  idea  as  to  the  condition  of  the  circulation.  A  number  of 
different  qualities  have  therefore  been  distinguished.  According  to  the 
number  of  beats  per  minute  the  pulse  is  designated  as  fr&juent  or  rare. 
The  size  of  the  pulse  has  reference  to  the  amplitude  of  excursions  of  each 
beat  and  the  pulse  is  distinguished  as  large  or  small.  The  velocity  of  the 
pulse  expresses  the  speed  with  which  the  excursion  is  accomplished.  The 
quick  pulse  is  one  in  which  the  artery  presses  against  the  finger  suddenly 
and  then  disappears  suddenly,  while  in  the  slow  pulse  the  period  during 
which  pressure  can  be  felt  is  more  prolonged.  The  hardness  of  the  pulse 
is  determined  chiefly  by  the  blood  pressure.  If  the  pulse  is  compressible 
it  is  spoken  of  as  soft;  if  it  can  only  be  obliterated  with  difficulty  it  is  hard. 
Certain  combinations  of  these  qualities  are  also  described.  Thus  a  large 
and  hard  pulse  is  spoken  of  as  strong,  a  iveak  pulse  being  both  small  and  soft. 
A  small  hard  pulse  is  called  contracted.  If  the  rhythm  of  the  heart  beat 
is  irregular  the  pulse  is  also  irregular.  An  intermittent  pulse  is  one  in  which 
one  heart  beat  is  dropped  occasionally,  i.  e.  once  in  every  four  or  eight  beats, 
and  may  be  due  to  the  interposition  of  a  ventricular  contraction  which  is 
too  weak  to  send  the  pulse  along  so  far  as  the  radial  artery. 

Judgments  as  to  the  conditions  of  the  heart  and  circulation  from  the 
feeling  of  the  pulse  oscillations  must  however  be  made  with  extreme 
caution.  The  pulse  curve  may  indeed  give  approximate  information  as 
to  the  condition  both  of  the  heart  and  the  arterial  system.  Thus  the  period 
between  the  beginning  of  the  primary  elevation  and  the  dicrotic  notch 
corresponds  to  the  outflow  of  blood  from  ventricle  to  aorta.  A  large  pulse 
curve  does  not  necessarily  indicate  a  big  output,  since  the  expansion  of  the 
artery  is  determined  not  only  by  events  occurring  in  the  aorta  but  also  by 


THE  FLOW  OF  BLOOD  THROUGH  THE  ARTERIES       973 

the  tonus  of  the  artery  under  the  finger  and  the  resistance  in  the  peripheral 
brandies. 

Perhaps  the  best-marked  condition  of  the  pulse  is  that  known  as  the 
'  water-hammer '  pulse,  which  is  observed  in  cases  where  the  aortic  valves 
are  injured  or  diseased  so  as  to  allow  of  regurgitation  into  the  ventricle. 
The  systolic  rise  of  pressure  in  the  arterial  system  is  followed  by  an  extremely 
rapid  fall,  so  that  towards  the  end  of  diastole  the  pressure  in  the  arteries 
may  be  insufficient  to  keep  the  arterial  system  filled.  Under  such  con- 
ditions, if  the  arm  be  held  above  the  head  and  the  wrist  of  the  patient 
be  grasped,  the  pulse  in  the  arteries  of  the  wrist  is  felt  as  a  smart  blow 
coinciding  with  each  beat  of  the  heart. 


THE   CIRCULATION   THROUGH   THE   CAPILLARIES 

The  capillary  circulation  is  most  easily  studied  by  examining  under 
the  microscope  the  tongue  of  the  frog  or  the  web  of  the  frog's  foot. 
Under  a  power  of  about  150  to  180  diameters  a  network  of  vessels  is  seen, 
consisting  of  small  arteries,  capillaries,  and  veins.  The  direction  of  flow 
in  the  arteries  is  opposite  to  that  in  the  veins.  In  the  capillaries  the  flow 
is  from  arteries  to  veins,  though,  on  account  of  the  reticular  arrangement 
of  these  vessels,  the  direction  of  the  stream  through  them  is  not  quite 
constant  and  may  occasionally  be  reversed.  The  flow  of  blood  in  the 
arteries  is  rapid,  whereas  in  the  veins  it  is  generally  possible  to  distinguish 
the  individual  blood  corpuscles.  Through  the  capillaries  the  flow  is  very 
inconstant.  If  a  group  of  capillaries  be  watched  for  some  time,  the 
blood  may  at  first  hurry  through  a  number  of  them  with  great  rapidity ; 
the  flow  then  becomes  slower  and  may  quicken  up  to  a  moderate  pace 
again.  These  variations  in  the  capillary  flow  are  probably  associated 
with  spontaneous  alterations  in  the  condition  of  contraction  of  the  small 
arteries  supplying  the  group  of  capillaries.  It  is  easy  to  observe  that  the 
arterial  flow  is  pulsatile,  the  pulsation  disappearing  in  the  capillaries  and 
veins.  Another  difference  between  the  circulation  in  these  three  kinds 
of  vessels  is  to  be  found  in  the  condition  of  the  peripheral  zone.  In  the 
arteries  the  blood  stream  is  divided  into  two  parts,  the  peripheral  stream 
— about  -01  mm.  wide,  consisting  only  of  colourless  plasma  with  occasionally 
a  stray  leucocyte — and  an  axial  stream,  in  which  all  the  red  blood  corpuscles 
are  being  hurried  along.  Li  the  veins  there  is  a  similar  peripheral  plas- 
matic zone,  but  here  we  find  regularly  scattered  leucocytes  which  travel 
rather  more  slowly  than  the  axial  stream  of  red  corpuscles.  The  fori) 
of  this  axial  zone  is  purely  mechanical,  and  may  be  imitated  in  any  fluid 
containing  in  suspension  particles  whose  specific  gravity  is  somi 
higher  than  that  of  the  fluid.  Li  the  capillaries  there  is  no  separation  of 
the  two  zones,  since  the  lumen  of  these  vessels  as  a  ride  allows  the  passage 
only  of  one  or  two  corpuscles  abreast,  so  that  they  are  everywhe 
contact  with  the  wall.  The  corpuscles  are  evidently  elastic  structures, 
and  may  be  seen  to  bend  if  they  impinge  on  the  dividing  point  of  two 


!i;i  PHYSIOLOGY 

capillaries  before  they  are  finally  swept  off  by  the  stream  into  one  or  the 
other. 

The  capillary  wall  is  composed  of  a  single  layer  of  elongated  flattened 
cell  i  which  presenl  little  resii  tance  to  the  passage  through  them  by  diffusion 
of  dissolved  substances,  suck  as  sugar,  salts,  oxygen,  or  carbon  dioxide. 
In  this  way  the  tissue  cells  obtain  oxygen  from  the  red  blond  corpuscles 
and  nutriment  from  the  plasma,  and  give  off  to  the  circulating  blood  carbon 
dioxide  and  other  effete  substances  as  the  products  of  their  metabolism. 
There  is  evidence  that  in  some  situations  the  cells  forming  the  capillary 
wall  may  be  contractile.  According  to  Strieker  and  others,  the  cell  sub- 
stance is  arranged  in  strands  running  from  the  nuclei  around  the  capillary. 
By  the  contraction  of  these  strands  the  vessel  may  be  narrowed  to  oblitera- 
tion. These  phenomena  have  been  observed  in  the  nictitating  membrane 
of  the  frog,  but  it  is  doubtful  how  far  they  may  be  extended  to  the  other 
capillary  systems  of  the  body.  If  the  contractile  power  is  at  all  universally 
present,  it  must  play  an  important  part  in  determining  the  amount  of  blood 
flow  through  the  capillaries  of  an  organ,  and  will  doubtless  be  largely  affected 
by  chemical  substances  produced  as  the  result  of  the  metabolism  of  the 
surroimding  tissues. 

The  average  length  of  a  capillary  is  between  0-4  and  0-7  mm.      The 
velocity  of  blood  flow  can  be  directly  determined  by  observing  under  the 
microscope  the  time  taken  by  any  given  corpuscle  to  travel  a  measured 
distance  on  the  microscope  stage.    The  mean  velo- 
city determined  in  this  way  varies  from  about  0-5 
to  0-8  mm.  per  second.- 

The  blood  pressure  in  the  capillaries  may  be 
measured  approximately  by  applying  pressure  to 
the  outer  surface  of  the  skin  or  mucous  membrane, 
and  noticing  the  point  at  which  blanching  of  the 
surface  is  produced. 

In  vim  Kries'  method  a  small  glass   plate,  from  2  to 

•r>  sq.  mm.  in  area,  is  placed  on  the  last  joint  of  the  finger. 

Fig.    42S.      Apparatus   of      Attached  to  this  glass  plate  is  a  small  scale  pan  on  which 

von  Kxies  for  measuring       weights  are  placed  until  the  pressure  is  just  sufficient  to 

capillary  blood  pressure.        blanch  the  underlying  skin.     In  using  this  method  the 

calculation  of  the  capillary  pressure  is  made  as  follows  : 

Supposing  that  the  size  of  the  glass  plate  is  4  sq.  mm.  and  1  grm.  in  the  scale  pan  is 

just  sufficient  to  cause  a  change  of  colour  in  the  skin,  then 

a  weight  of  1  grm.  =  1  c.c.  H,0  =  1000  c.mm.  H20 

is  present  on  an  area  of  4  sq.  mm.  The  height  of  the  column  of  water  supported  by 
1  sq.  mm.  is  therefore  =  250  mm.  H,0.     The  errors  of  this  method  are  consider- 

able, since  the  pressure  thus  determined  is  not  the  total  capillary  pressure,  but  this 
minus  the  pressure  in  the  tissue  spaces  on  the  outer  side  of  the  capillary  wall.  The 
result  will  therefore  vary  not  only  with  capillary  pressure  but  also  with  the  tension  of 
the  skin  and  the  amount  of  fluid  in  the  tissue  spaces. 

The  pressure  in  the  capillaries  as  found  by  this  method  necessarily  varies  with  the 


THE  FLOW  OF   BLOOD   THROUGH  THE  ARTERIES      975 

position  of  the  part  under  investigation,  i.  e.  with  the  hydrostatic  pressure  of  the  column 
of  blood  between  it  and  the  heart.     The  following  figures  were  found  by  von  Kries  : 


Finger  :      Mm.  H20 

Distance  of  finger 
below  head 

328 
329 
513 

73S 

B 

0  mm. 
205  mm. 
490  mm. 
840  mm. 

20  mm.  Hg. 

of  Babbits  :  33  nun.  Hg. 
Frog's  Web  (Roy) :    100-150  mm. 

H.O. 

Capillary  venous  pressure  of  brain  (Hill)  : 

(1)  Animal  in  horizontal  position  :  10  mm.  Hg. 

(2)  ,,        ,,  feet-down  position  :  zero  or  less. 

(3)  During  strychnine  convulsions  :  50  mm.  Hg. 

Owing  to  the  fact  that  a  varying  and  unknown  resistance — that  of 
the  arterioles—  lies  between  the  capillaries  and  the  arteries,  the  pressure  in 
the  capillaries  must  stand  in  much  closer  relationship  to  that  in  the  veins 
than  to  that  in  the  arteries.  One  cannot  therefore  argue  that  a  fall  of 
arterial  pressure  necessarily  involves  a  fall  of  capillary  pressure  in  all  parts 
of  the  body.  We  can  only  judge  of  changes  in  the  capillary  pressure  by 
taking  simultaneously  the  pressures  in  both  the  afferent  and  efferent 
:1s.  If  these  both  rise  or  fall  together  -we  may  be  certain  thai  the 
capillary  pressure  also  rises  or  falls.  Where  the  arterial  and  venous 
pressures  move  in  opposite  directions,  it  is  difficult  to  say  what  alterations, 
if  any,  will  be  produced  in  the  capillary  pressure. 

The  resistance  to  the  flow  of  blood  through  the  capillaries  is  determined 
by  the  internal  friction,  i.e.  the  viscosity  of  the  blood;  this  varies  in 
different  animals  between  three  and  five  times  that  of  water.  It  has  been 
calculated  that  the  fall  of  pressure  undergone  by  the  blood  in  passing 
through  any  given  capillary  area  is  only  about  20  to  60  nun.  of  blood,  and 
at  the  most  is  never  more  than  150  mm.  blood,  ('.  e.  about  10  nun.  Hg.  This 
bears  out  the  conclusion  to  which  we  have  already  come,  viz.  that  the 
chief  seat  of  the  resistance  in  the  vascular  system  is  in  the  arterioles,  and 
it  is  in  this  region  that  the  chief  fall  of  pressure  occurs. 

No  part  of  the  circulation  however  shows  greater  variations  than  the 
capillary  system.  We  must  think  of  this  as  a  vast  irrigation  system  of 
canals  -the  greater  part  of  which  are  closed  under  normal  circumstances. 
and  open  only  when  t  he  chemical  changes  in  the  tissue  require  a  large  increase 
in  the  supply  of  blood.  In  muscle  the  capacity  of  this  irrigation  system  ma] 
be  increased  750  times  during  activity.  A  similar  opening  up  of  capillary 
channels  may  be  observed  in  the  skin  and  connective  tissues  as  a  result  of 
irritation  or  injury.  It  seems  probable  that  such  changes  will  affect  arterial 
pressure  by  their  influence  on  the  total  capacity  of  the  vascular  system  (if  of 
wide  enough  occurrence)  rather  than  by  alterations  thereby  produced  in 
the  peripheral  resistance 


SECTION  VI 

THE    FLOW   OF    BLOOD    IN    THE   VEINS 

In  the  veins  there  is  a  constant  decrement  of  pressure  as  we  pass  from  the 
periphery  towards  the  heart.  This  decrement  of  pressure  is  the  conse- 
quence of  the  pumping  action  of  the  heart,  so  that  the  flow  through  the 
veins  must  be  ascribed  to  the  same  force  as  that  which  determines  the 
flow  through  the  arteries,  viz.  the  heart  beat.  Owing  to  the  fact  that  no 
appreciable  resistance  lies  between  the  veins  and  the  heart,  the  difference 
of  pressure  necessary  to  maintain  a  constant  flow  through  these  vessels 
is  very  small.  Thus  in  the  horizontal  position  the  pressure  in  the  femoral 
veins  may  be  from  5  to  10  mm.  Hg.,  and  in  the  inferior  vena  cava  from 
1  to  5  mm.  The  pressure  in  the  great  veins  near  the  heart  is  generally 
negative  owing  to  the  aspiration  of  the  thorax,  and  this  negative  pressure 
is  naturally  increased  during  inspiration.  Opening  the  thorax  therefore 
causes  a  rise  of  pressure  in  all  the  large  veins.  In  the  latter  the  pressure 
depends  chiefly  on  the  heart  activity,  being  lowered  by  vigorous  action 
of  the  heart  pump  and  raised  when  this  fails  irr  any  way.  In  the  peri- 
pheral veins  the  pressure  is  more  dependent  on  the  flow. through  the  corre- 
sponding arteries.  If  an  artery  of  a  lirnb  be  ligatured,  the  pressure  in  the 
small  veins  of  the  lirub  sinks  until  it  is  reduced  to  the  pressure  in  the  nearest 
large  trunk  in  which  a  flow  of  blood  continues. 

Each  cardiac  cycle  causes  variations  in  the  pressure  in  the  great  veins 
next  the  heart  in  two  ways  : 

(1)  By  the  transmission  along  the  veins  of  the  alterations  in  the  intra- 
auricular  pressure. 

(2)  By  the  diminution  in  the  volume  of  the  heart  in  consequence  of  the 
expulsion  of  its  blood  along  the  arteries  with  each  heart  beat. 

On  this  account  the  jugular  veins  show  pulsations  with  each  heart  beat 
which  are  somewhat  complex  in  character  and  resemble  closely  those 
occurring  in  the  auricle  (vide  p.  946.)  In  Fig.  429  a  tracing  from  the 
wall  of  the  jugular  vein  is  given.  It  will  be  seen  that  each  heart  beat 
gives  rise  to  three  variations  in  pressure  within  the  veins.  These  three 
undulations  are  evidently  exactly  analogous  to  those  given  in  Fig.  410 
as  occurring  in  the  auricular  tracing.  We  should  therefore  regard  a  as  the 
auricular  contraction,  c  as  the  elevation  due  to  the  closure  of  the  auricilo- 
ventricular  valves,  v  as  the  elevation  due  to  the  accumulation  of  blood 
in  the  auricles  during  the  ventricular  systole.     The  curve  c  is  often  spoken 

976 


THE  FLOW  OF  BLOOD  IN  THE  VEINS  977 

of  ae  the  carotid  elevation,  and  has  been  ascribed  by  Mackenzie  to  direct 
propagation  to  the  jugular  vein  from  the  underlying  carotid  artery.  He 
has  come  to  this  conclusion  because  he  has  not  found  it  in  tracings  of  the 
liver  pulse  hi  cases  of  incompetent  tricuspid  valves.  There  is  no  doubt 
however  that  the  elevation  cau  be  seen  on  tracings  from  the  inferior  vena 
cava.  The  explanation  of  its  absence  from  liver  tracings  is  probably  to 
be  ascribed  to  the  fact  that  the  great  mass  of  the  liver  substance  is  unable 
to  transmit  the  very  rapid  oscillation  of  pressure  due  to  the  closure  of 
the  auriculo-ventricular  valves.  These  venous  pulsations  are  much  more 
marked  in  cases  of  heart  disease, where  there  is  partial  failure  of  the  heart 
pump  and  overfilling  of  the  venous  system,  often  combined  with  incom- 
petence of  the  auriculo-ventricular  valves. 

Besides  the  favourable  influences  exercised  on  the  circulation  through 
the  veins  by  the  aspiration  of  the  thorax,  a  considerable  part  is  played  in 
the  venous  circulation  by  the  contraction  of  the  muscles  of  the  body  as 
well  as  by  the  passive  movements  of  different  parts.    The  adjuvant  effect 


Jug.  V. 
Rod.  art. 


Fio.  429.     Venous  pulse  tracing  from  jugular  vein  compared  with  the 
arterial  pulse  tracing  from  the  radial  artery. 

of  passive  or  active  movement  on  the  circulation  through  the  veins  is  ren- 
dered possible  by  the  existence  in  these  vessels  of  valves,  which  are  semilunar 
folds  of  the  intima  projecting  into  their  lumen,  and  so  arranged  that  they 
allow  the  passage  of  blood  only  towards  the  heart.  Two  such  valves  are 
as  a  rule  situated  opposite  to  each  other.  Every  movement  of  a  limb, 
active  or  passive,  causes  an  external  pressure  on  the  veins  and  therefore 
empties  them  towards  the  heart.  Thus  in  walking,  each  time  the  thigh  is 
moved  backwards  the  femoral  vein  becomes  empty  and  collapses,  and  fills 
again  as  soon  as  the  leg  is  brought  forward  to  its  former  position  or  is  flexed 
in  front  of  the  body.  When  muscular  movements  become  general,  as  in 
walking  or  running,  the  active  compression  of  the  veins  thus  brought  about 
plays  an  important  part-  in  hurrying  the  blood  into  the  right  heart,  so  that  the 
output  of  this  organ  is  increased  and  the  arterial  blood  pressure  is  raised. 

Since  the  blood  in  the  vessels  is  subject  to  the  influence  of  gravity,  we 
should  expect  to  find  that  the  pressure  in  the  veins  of  the  foot  was  equal 
to  the  pressure  hi  the  veins,  say,  of  the  hand  at  the  level  of  the  heart  plus 
the  pressure  equivalent  to  the  column  of  blood  between  these  veins  and 
the  heart,  i.e.  about  a  metre  of  blood.  On  measuring  the  pressure  by 
von  Recklinghausen's  or  by  Hill's  method  in  these  veins,  this  is  not  found 
62 


978  PHYSIOLOGY 

to  be  the  case.    The  pressure  indeed  in  the  veins  of  the  Eoot   is  but  little 
higher  than  that  in  the  veins  of  the  hand.     Von    Recklinghausen   found 

that,  after  subtracting  the  distance  between   the   l and  the  heart,  the 

pressure  in  the  veins  was  negative  by  as  much  as  40  cm.  In  the  same 
way.  as  Hill  has  shown,  the  pressure  in  the  capillaries  of  the  foot  is  about 
the  same  as  in  the  capillaries  of  the  hand.  When  a  man  assumes  the 
upright  position,  the  arteries  of  the  leg  and  foot  contract  until,  under  the 
combined  influence  of  the  heart's  contraction  and  gravity,  the  blood 
supply  to  the  capillaries  is  sufficient  only  to  keep  the  pressure  in  these 
vessels  at  a  certain  moderate  height.  The  return  of  the  blood  from  the 
dependent  parts  cannot  be  ascribed  to  the  heart  beat  a1  all.  but  is  due  to 
the  extrinsic  mechanism  of  circulation  through  the  veins,  i.e.  the  contrac 
tions  of  the  muscles  of  the  limb  which  press  all  the  deep  and  superficial 
veins,  and  in  virtue  of  the  valves  force  the  blood  contained  therein  by 
Poupart's  ligament  into  the  abdomen.  The  fact  that  circulation  through 
the  legs  is  dependent  on  the  contractions  of  their  muscles  explains  why 
it  is  so  difficult  to  stand  still  for  any  length  of  lime  without  moving,  and 
emphasises  the  need  of  moderate  exercise  for  the  maintenance  of  a  normal 
circulation. 


SECTION   VII 

THE    PULMONARY    CIRCULATION 

In  the  Lungs  there  is  an  extensive  system  of  wide  capillaries  presenting 
very  little  resistance  to  the  flow  of  blood.  The  arterioles  are  wide  and  have 
only  a  slight  amount  of  muscular  fibre  in  their  walls,  so  that  a  slight  pressure 
suffices  to  drive  the  blood  from  the  right  to  the  left  heart.  The  determina- 
tion of  the  normal  average  pressure  in  the  pulmonary  artery  presents  con- 
siderable difficulties,  but  it  probably  does  not  exceed  15  to  20  mm.  Hg., 
i.  e.  about  one-sixth  of  the  mean  aortic  pressure. 

The  capillaries  of  the  lungs  may  vary  passively  in  size  according  to  the 
condition  under  which  they  may  be  placed.  Thus,  whereas  at  the  height  of 
inspiration  the  blood  contained  in  the  lungs  is  about  one-twelfth  of  the 
whole  blood  in  the  body,  this  amount  is  diminished  during  expiration  to 
between  one-fifteenth  and  one-eighteenth,  and  by  forcible  artificial  inflation 
of  the  lungs  may  be  lessened  to  one-sixtieth.  These  changes  exercise  a 
considerable  effect  on  the  systemic  blood  pressure  and  are  largely  responsible 
for  the  respiratory  variations  observed  therein.  On  the  other  hand,  the 
distensibility  of  the  lung  capillaries  may  play  an  important  part  in  enabling 
the  lungs  to  act,  so  to  speak,  as  a  reservoir  for  the  left  side  of  the  heart. 
If,  in  consequence  of  raised  arterial  pressure  or  other  factor,  there  is  a 
temporary  excess  of  output  on  the  right  side  that  cannot  be  dealt  with  at 
once  by  the  left  heart,  the  excess  is  taken  up  for  a  time  in  the  lung 
capillaries. 

Ya  so-motor  fibres  to  the  lung  vessels  have  been  described  as  running  in 
the  anterior  roots  of  the  third,  fourth,  and  fifth  dorsal  nerves.  Their  action 
is  however  of  little  importance,  and  their  very  existence  is  questioned 
by  some  observers.  The  fact,  that  injection  of  adrenaline  causes  some  vaso- 
constriction in  the  lungs,  points  to  the  presence  of  a  vaso-motor  sympathetic 
supply  to  those  organs. 

If  we  examine  a  tracing  of  the  arterial  blood  pressure,  we  notice  that  it 
presents  certain  periodic  oscillations  which  accompany  the  movements  of 
respiration.  With  each  inspiration  the  blood  pressure  rises;  with  each 
expiration  it  falls.  The  synchronism  of  the  rise  and  fall  with  the  respiratory 
movements  is  not  exact,  since  the  rise  continues  for  a  short  time  after  the 
beginning  of  expiration  before  it  begins  to  fall,  and  the  fall  continues  right 
into  the  beginning  of  the  next  inspiration,  so  that  the  highest  point  of 
the  curve  occurs  at  the  beginning  of  expiration  and  the  lowest  point  at  the 
beginning  of  inspiration.  During  the  fall  which  accompanies  expiration  the 
heart  beats  may  become  less  frequent.  This  change  of  rate  is  marked  in 
the  dog,  but  is  by  no  means  constant  in  man.     On  dividing  both  vagi, 

979 


980  PHYSIOLOGY 

this  difference  in  the  pulse  rate  during  inspiration  and  expiration  disappears, 
but  the  main  features  of  the  blood  pressure  curve  remain  the  same;  so  thai  we 
must  look  for  some  mechanical  explanation  of  the  respiratory  undulations. 

We  have  already  seen  thai  under  normal  conditions  the  lungs  arc  in  a 
state  of  over-distension,  and  that  in  consequence  of  this  condition  they  arc 

c stantly  tending  to  collapse,  and  are  therefore  exerting  a  pull  on  the  chesl 

wall.  As  soon  as  we  admit  air  into  the  pleural  cavity  by  perioral  ing  the  chest 
wall,  the  kings  collapse.  The  force  with  which  the  lungs  tend  to  collapse 
amounts  to  6  mm.  Hg.  at  the  end  of  a  quiet  expiration,  so  we  say  that  in  the 
pleura]  cavity  there  is  normally  a  negative  pressure  of  G  mm.  Hg.  As  the 
chest  expands  in  inspiration  it  drags  the  lungs  still  more  open.  As  these 
become  more  distended,  their  pull  on  the  chest  wall  becomes  greater,  and 
hence  the  negative  pressure  iir  the  pleura  may  be  increased  during  forcible 
inspiration  to  30  mm.  Hg.  It  must  be  remembered  that  the  heart  and  great 
veins  and  arteries  are  in  the  thorax  separated  from  the  pleural  cavity  only 
by  a  thin  yielding  membrane,  so  that  they  are  practically  exposed  to  any 
pressure,  positive  or  negative,  which  may  exist,  in  the  pleural  cavity.  Hence 
even  at  the  end  of  inspiration  the  heart  and  large  vessels  are  subjected  to  a 
negative  pressure  of  6  mm.  Hg.  Outside  the  thorax  all  the  vessels  are 
exposed  to  a  positive  pressure,  conditioned  in  the  neck  by  the  elasticity 
of  the  tissues  and  in  the  abdomen  by  the  contractions  of  the  diaphragm 
and  abdominal  muscles. 

Blood,  like  any  other  fluid,  will  always  flow  from  a  point  of  higher  to 
a  point  of  lower  pressure.  There  must  thus  be  a  constant  aspiration  of  blood 
from  peripheral  parts  into  the  thorax.  This  aspiratory  force  will  not 
influence  arteries  and  veins  alike.  The  arteries,  having  thick,  comparatively 
nou-distensible  walls,  will  be  very  little  affected  by  the  negative  pressure 
obtaining  in  the  thoracic  cavity,  whereas  the  thin-walled  distensible  veins 
will  be  largely  influenced  by  the  same  factor.  The  total  result  then  of  the 
negative  pressure  in  the  pleural  cavities  is  to  increase  the  flow  of  blood  from 
the  veins  into  the  heart  without  affecting  to  any  appreciable  degree  the 
outflow  of  blood  from  the  heart  into  the  arteries.  The  more  pronounced  the 
negative  pressure  in  the  thorax,  the  greater  will  be  the  amount  of  blood 
sucked  into  the  heart  from  the  veins.  During  inspiration  therefore  the 
heart  will  be  better  supplied  with  blood  than  during  expiration,  and  this 
factor  in  itself  will  tend  to  raise  the  arterial  blood  pressure.  The  inspiratory 
descent  of  the  diaphragm  wall  moreover  tend  to  increase  the  inflow  into  the 
heart  by  raising  the  positive  pressure  in  the  abdomen,  so  that  blood  is  pressed 
out  of  the  abdominal  veins  and  sucked  into  the  heart  and  the  thoracic  veins. 

Another  factor  which  must  play  some  part  is  the  influence  of  the  respiratory  move- 
ments on  the  circulation  through  the  lungs.  In  trying  to  understand  this  influence,  it 
must  be  remembered  that  the  pulmonary  capillaries  lie  in  a  certain  amount  of  elastic 
and  connective  tissue  and  are  separated,  on  the  one  side  by  the  alveolar  epithelium 
from  air  at  the  ordinary  atmospheric  pressure,  and  on  the  other  by  the  pleural  endothe- 
lium from  the  pleural  cavity,  where  the  pressure  varies  from  6  to  30  mm.  Hg.  below 
the  atmospheric  pressure.  We  may  therefore  consider  the  pulmonary  capillaries  as 
lying  between,  and  attached  to,  two  concentric  elastic  bags,     Under  normal  conditions, 


THE   PULMONARY  CIRCULATION  981 

since  these  bags  are  always  tending  to  collapse,  the  inner  one  must  be  pulling  away  from 
the  outer  one.  and  the  outer  one  from  the  chest  wall.  Hence  there  must  be  a  negative 
pressure  in  the  tissues  between  these  two  bags — a  negative  pressure  which  in  the  expira- 
tory condition  will  be  something  between  0  and  -  6  mm.  Hg.,  and  in  the  inspiratory 
condition  between  0  and  -  30  mm.  Hg.  H  we  regard  the  average  pressure  within 
the  pulmonary  capillaries  as  constant,  these  capillaries  must  be  more  dilated  in  the 
inspiratory  than  in  the  expiratory  condition.  This  dilatation  of  the  pulmonary  capil- 
laries will  have  two  effects.  Their  capacity  will  be  increased  and  the  resistance  they 
present  to  the  flow  of  blood  will  be  diminished. 

Let  us  now  consider  what  effect  these  changes  will  have  on  the  general  arterial 
blood  pressure.  We  will  assume  that  during  expiration  the  pulmonary  vessels  have 
a  capacity  of  25  c.c.  and  that  the  beat  of  the  right  heart  is  forcing  through  them  10  c.c. 
of  blood  per  second.  So  long  as  the  chest  remains  in  the  expiratory  condition  10  c.c. 
of  blood  will  be  flowing  into  the  left  heart  and  into  the  aorta,  so  that  the  systemic  blood 
pressure  will  remain  constant.  Now  let  us  suppose  that  an  inspiratory  enlarge- 
ment of  the  thorax  takes  place,  the  negative  pressure  in  the  pleura  is  increased,  the  two 
walls  of  the  lungs  are  pulled  farther  away  from  one  another,  and  there  is  a  general  enlarge- 
ment of  the  pulmonary  capillaries.  We  will  assume  that  this  enlargement  increases  the 
capacity  of  the  pulmonary  capillaries  from  25  to  30  c.c.  Owing  to  this  increased  capacity, 
the  first  5  c.c.  of  blood  which  flows  into  the  lungs  after  the  beginning  of  inspiration  will 
not  flow  out  through  the  pulmonary  vein,  but  will  simply  serve  to  bring  the  capillaries 
into  the  same  state  of  distension  as  before.  Hence  at  tlie  beginning  of  inspiration  the 
flow  through  the  pulmonary  vein  will  be  diminished;  there  will  be  less  blood  discharged 
into  the  left  heart,  and  therefore  a  fall  in  systemic  pressure.  As  soon  however  as  the 
increased  capacity  of  the  pulmonary  vessels  is  made  up,  the  dilating  effect  of  the  inspira- 
tory movement  of  these  vessels  wiil  aid  the  flow  through  the  lungs,  in  consequence  of 
the  diminution  of  resistance,  so  that  the  same  force  of  the  right  heart  which  drove  10  c.c. 
of  blood  per  second  through  the  former  resistance  during  expiration  will  now  drive 
more,  say  12  c.c.  of  blood.  There  is  thus  more  blood  entering  the  left  heart,  and  there- 
fore a  rise  of  systemic  pressure  during  the  last  three-quarters  of  the  inspiratory  move- 
ment. Expiration  will  have  exactly  the  reverse  effect.  At  the  beginning  of  expiration 
there  is  a  diminution  of  capacity  in  the  pulmonary  vessels  from  30  to  25  c.c.  Hence 
daring  (lie  first  second  of  expiration  the  outflow  of  blood  from  the  pulmonary  vein  into 
the  left  heart  will  be  17  c.c.  (12  c.c.  +  5  c.c).  After  this,  the  increased  resistance  in 
the  pulmonary  capillaries  in  consequence  of  their  constriction  will  come  into  play,  and 
the  flow  of  blood  through  them  will  fall  once  more  from  12  c.c.  to  10  c.c.  Hence  at  the 
beginning  of  expiration  the  inflow  of  blood  from  the  pulmonary  vein  into  the  left  heart 
is  greater  than  at  any  period.  The  arterial  pressure  will  therefore  rise  to  its  greatest. 
height  at  the  beginning  of  expiration,  and  will  fall  during  the  last  three-quarters  of 
expiration,  but  will  attain  its  minimum  only  at  the  beginning  of  the  next  inspiration. 

Li  this  way  the  effect  of  tin1  respiratory  movements  on  the  systemic 
blood  pressure  could  be  entirely  explained  by  the  influence  they  exert  on 
the  lung  vessels  or  lesser  circulation.  On  the  other  hand,  Lewis  regards  the 
pericardial  pressure,  i.  e.  the  direct  influence  of  the  thoracic  movements  on  the 
heart,  as  playing  a  much  more  important  part  than  changes  in  the  pulmonary 
circulation  in  the  production  of  the  respiratory  undulations  in  the  M  >od 
pressure.  Ee  shows  moreover  that  in  man  the  effect  of  respiration  on 
J  blood  pressure  may  vary  according  to  the  type  of  respiratory 
movement,  a  deep  intercostal  inspiration  (not  prolonged)  causing  a  pure 
fall,  while  a  deep  diaphragmatic  inspiration  gives  a  pure  rise  of  blood 
pressure.  In  expiration  the  reverse  effects  hold.  He  concludes  that  in 
man  it  is  not  possible  to  make  any  general  statement  as  to  the  nature  of 
the  blood  pressure  response  to  a  particular  respiratory  act. 


SECTION  VIII 

THE  CAUSATION  OF  THE  HEART  BEAT 

If  the  heart  be  cut  out  of  the  body  of  a  cold-blooded  animal,  such  as  the 
frog  or  tortoise,  it  will  continue  to  beat  with  the  normal  sequence  of  its 
different  chambers  for  hours,  or  even  days,  provided  that  it  be  kept  cool  and 
moist.  In  the  case  of  a  warm-blooded  animal,  the  heart  is  similarly  capable 
of  continuing  its  rhythmic  contractions  for  some  little  time  after  excision. 
The  period  of  survival  of  the  heart  is  less  in  warm-blooded  than  in  cold- 
blooded animals.  The  fact  that  in  both  cases  the  heart  will  continue  to  beat 
after  removal  from  all  its  connections  with  the  central  nervous  system,  and 
when  blood  is  no  longer  flowing  through  it,  shows  that  the  causation  of  the 
heart  beat  is  to  be  sought  in  the  walls  of  the  heart  itself. 

The  heart  wall  consists  of  a  muscular  tissue  resembling  in  many  respects 
voluntary  muscle ;  like  this,  it  presents  longitudinal  and  transverse  striations ; 
like  this,  it  is  capable  of  contracting  in  response  to  direct  stimulation. 
Normally  voluntary  muscle  contracts  only  in  response  to  impulses  from  the 
central  nervous  system.  When  Remak  described  the  existence  of  collections 
of  ganglion  cells  in  the  sinus  venosus,  it  was  natural  that  physiologists  should 
ascribe  to  these  collections  of  nerve  cells  the  same  automatic  rhythmic 
functions  that  had  been  found  by  Flourens  and  others  to  be  associated  with 
the  grey  matter  of  the  medulla  oblongata  in  connection  with  the  maintenance 
of  the  respiratory  movements. 

ANATOMY  OF  THE  FROG'S  HEART 

The  hearts  of  the  frog  and  of  the  tortoise  have  figured  so  largely  in  the  researches  on 
the  causation  of  the  heart  beat  that  it  may  be  profitable  to  mention  briefly  the  main 
points  of  their  anatomy. 

The  frog's  heart  consists  of  the  sinus  venosus,  which  receives  the  anterior  and 
posterior  venae  cava?,  two  auricles,  one  ventricle,  and  the  bulbus  arteriosus,  which  opens 
into  the  two  aorta?.  The  venous  blood  from  the  body  flows  into  the  sinus  venosus  by 
the  three  venae  cavae,  and  thenoe  into  the  right  auricle,  while  the  left  auricle  receives 
the  blood  from  the  lungs.  The  ventricle  thus  receives  mixed  arterial  and  venous 
blood,  the  arterial  blood  being  directed  by  the  spiral  valve  of  the  bulbus  aortas  so 
as  to  flow  chiefly  towards  the  head. 

The  muscular  fibres  of  the  heart  are  less  highly  developed  than  those  of  the  mamma- 
lian heart.  They  are  spindle-shaped,  and  only  dimly  cross-striated.  The  cross-striation 
becomes  more  distinctly  marked  as  we  proceed  from  sinus  to  ventricle,  the  sinus  muscle 
fibre  representing  the  most  primitive  condition.  There  is  complete  muscular  con- 
tinuity between  all  the  cavities  of  the  heart.  The  circular  ring  of  muscle  at  the  junction 
of  sinus  with  auricles  and  of  auricles  with  ventricles  presents  only  slight  traces  of  cross- 
striation  (Gaskell). 

The  heart  is  well  supplied  with  nerve  fibres  and  ganglion  cells.  The  two  vagi  enter 
982 


THE   CAUSATION   OF  THE  HEART  BEAT 


983 


the  sinus  venosus  and  branch  just  under  the  pericardium.  Here  they  become  con- 
nected with  a  collection  of  nerve  cells,  known  as  Remak's  ganglion.  From  the  sinus 
the  two  vagi,  now  called  septal  nerves,  pass  down  in  the  interauricular  septum,  one  in 
front  and  the  other  behind.  Near  the  auriculo-ventricular  groove  they  enter  two  collec- 
tions of  ganglion  cells,  called  Bidder's  ganglia.  From  these  ganglia  non-medullated 
fibres  are  distributed  to  surrounding  parts  of  the  auricle  and  to  the  whole  of  the  ventricle. 
In  the  upper  third  of  the  ventricle  occur  scattered  ganglion  cells  attached  to  the  nerve 
These  are  quite  absent  in  the  lower  half  or  two-thirds. 
In  the  tortoise  (Fig.  431)  the  two  auricles  are  bound  together  by  a  flat  band  of 
t  issue,  which  serves  also  to  connect  the  sinus  with  the  ventricle.     The  septum  between 


Fro.  430.  Diagram  of  frog's  heart.  (After 
Cyon.) 
v.  ventricle:  E.A,  L.A,  right  and  left  auricles 
(atrium);  s.V,  sinus  venosus;  P. v.  pulmonary 
veins;  L.v.c.s  and  R.v.c.s.  left  and  right  su- 
perior vena  cava;  v.c.i,  vena  cava  inferior; 
tt.a,  truneus  arteriosus. 


Fio.  431,  Tortoise's  heart  (after 
Gaskell)  as  it  appears  when  sus- 
pended for  registering  the  auricu- 
lar and  ventricular  contractions. 
N,  nerve-trunk  with  fibres  con- 
necting Remak's  and  Bidder's 
ganglia ;  cob.  V,  coronary  vein. 


the  auricles  arises  from  the  central  line  of  this  junction  wall.     The  two  vagus  nerves 

nlo  a  large  accumulation  of  ganglion  cells  in  the  sinus,  and  thence  along  the  basal 

wa  11  to  the  auriculo-ventricular  groove,  lying  just  under  the  pericardium.     In  the  groove 

i  hey  pass  into  a  collection  of  ganglion  cells,  whence  fibres  are  given  off  to  both  auricles 

and  ventricle.     As  they  leave  the  sinus,  a  branch  is  always  given  off  by  the  right  nerve 

■  nipany  the  coronary  vein,  which  conveys  blood  from  the  ventricular  wall  to  the 

Thus  the  nerves  of  the  tortoise's  heart  are  altogether  more  accessible  than  those 

of  (lie  frog's  heart.     In  other  points  the  tortoise's  heart  is  similar  to  the  frog's  heart, 

i  <  msiderably  larger. 


THE    AUTOMATIC   CONTRACTION    OF    THE   FROG'S   HEART 

The  frog's  heart  in  the  body,  or  when  removed  from  the  body  intact, 
beats  regularly,  the  contraction  starting  in  the  sinus,  then  travelling  to 
auricles,  ventricle,  and  bulbus.  If  however  the  heart  be  removed  by 
cutting  it  across  the  sino-auricular  junction,  or  if  the  auricles  be  functionally 
separated  from  the  sinus  by  a  ligature  round  this  junction  (Stannius'  liga- 
ture), the  auricles  and  ventricle  stop  in  an  uncontracted  condition  (diastole), 
while  the  sinus  goes  on  boating  regularly.  After  the  lapse  of  a  period  varying 
from  five  minutes  to  half  an  hour,  the  detached  part  of  the  heart  begins  to 
beat,  at  first  slowly  and  then  more  rapidly,  but  never  attaining  the  rate  of  the 
sinus.  The  auricles  beat  first,  and  then  the  ventricle.  If  now  the  ventricle 
be  cut  away  by  ait  incision  in  the  auriculo-ventricular  groove  from  the  auricles, 
the  latter  go  on  beating;  while  the  former,  after  a  few  beats  due  to  the 
excitation  of  the  incision,  stops  beating,  and  only  after  a  considerable  time 
may  begin  again  to  contract  very  slowly. 

On  the  other  hand,  a  ventricle-apex  preparation  (that  is  to  say,  the  lower 


984  PHYSIOLOGY 

two-thirds  of  the  ventricle  separated  functionally  from  the  rest  of  tlnv  heart), 
never  beats  again  under  normal  circumstances.  To  single  stimuli  it  responds 
with  a  single  beat,  not  with  a  series  of  beats  as  the  whole  heart  does.  If  the 
lower  third  of  the  ventricle  be  separated  functionally  in  the  living  frog  by 
crushing  the  ring  of  tissue  between  it  and  the  upper  third,  it  never  gives  a 
spontaneous  beat  again,  although  it  is  under  the  most  normal  conditions  pos- 
sible in  the  circumstances.  There  is  thus  a  descending  scale  of  automatic 
power  in  the  different  parts  of  the  frog's  heart — from  the  sinus,  where  it 
•  is  highest,  to  the  lower  parts  of  the  ventricle,  where  it  is  apparently  absent. 
From  this  fact  it  has  been  thought  that  the  automaticity  of  the 
frog's  heart  is  dependent  on  the  ganglia  present  in  it.  The  contraction  was 
supposed  to  be  started  by  impulses  proceeding  from  the  sinus  ganglion. 
If  this  were  cut  off,  Bidder's  ganglia  or  the  scattered  cells  in  the  upper 
third  of  the  ventricle  could,  it  was  thought,  take  up  its  task  of  originating 
impulses.  The  muscle  cells  under  this  hypothesis  act  as  the  servants  of  the 
ganglion  cells",  just  as  the  voluntary  muscles  wait  on  the  commands  of  the 
cells  in  the  spinal  cord  and  brain. 

The  view  that  the  ganglion  cell  sends  out  rhythmic  impulses  had  how- 
ever to  be  discarded  when  it  was  discovered  that  the  muscle  forming  the 
lower  third  of  the  ventricle  either  of  the  frog  or  the  tortoise,  though  free  from 
ganglion  cells,  could  be  excited  by  various  means  to  rhythmic  contractions. 
Thus  it  could  be  set  into  rhythmic  action  when  supplied  with  salt  solution 
under  pressure  through  a  perfusion  cannula,  or  when  excited  by  the  passage 
of  a  constant  current  or  of  weak  induction  shocks.  The  fact  that  the  heart 
muscle  responded  to  continuous  stimulation  by  a  rhythmic  discharge  sug- 
gested that  the  function  of  the  ganglion  cells  was  to  furnish  a  constant 
stimulation  to  the  muscle  cells  and  so  maintain  these  hi  rhythmic  activity. 

The  theory  of  the  ganglionic  origin  of  the  cardiac  rhythm  was  seriously 
affected  by  a  series  of  researches  carried  out  by  Gaskell  and  by  Engelmann. 
The  arguments  against  the  '  neurogenic  '  hypothesis  may  be  summarised 
as  follows : 

(a)  The  cardiac  muscle,  free  from  any  ganglion  cells  whatsoever,  can  be 
excited  by  various  means  to  rhythmic  contraction.  When,  in  the  living  frog, 
the  apex  of  the  ventricle  is  crushed  off  from  the  base  so  as  to  leave  only 
material  continuity  between  the  two  parts,  the  circulation  of  the  blood  is 
maintained  by  the  contraction  of  all  the  parts  of  the  heart  except  the  apex, 
which  never  resumes  its  activity.  If  however  the  intraventricular  pressure 
be  raised  by  clamping  the  aorta,  the  apex  begins  to  beat  at  its  own  rhythm, 
which  is  independent  of  the  rhythm  of  the  rest  of  the  heart.  Moreover  a. 
strip  free  from  ganglion  cells  can  be  cut  from  the  apex  of  the  tortoise's 
ventricle  (Fig.  432)  which,  on  keeping  in  a  moist  chamber  and  moistening 
occasionally  with  normal  salt  solution,  enters  into  rhythmic  contractions. 

(b)  In  the  frog  it  is  possible  to  excise  the  interauricular  septum  with 
its  ganglia,  and  a  considerable  portion  of  the  ganglia  in  the  sinus  venosus  and 
at  the  base  of  the  ventricles,  without  interfering  in  any  way  with  the  cardiac 
rhythm.    This  experiment  is  still  easier  to  carry  out  in  the  tortoise's  heart 


THE  CAUSATION  OF  THE  HEART  BEAT 


985 


where  the  nerves  and  ganglia  run  in  the  basal  portion  of  the  auricles.  This 
can  be  excised,  leaving  the  two  auricular  appendages  in  connection  with  the 
sinus  venosus  and  with  the  ventricles. 

(c)  The  heart  in  the  developing  chick  can  be  seen  beating  at  a  time  when 
it  is  quite  free  from  nerve  cells,  which  only  extend  into  it  at  a  later  date. 

(d)  Remak's  ganglia  are  situated  at  the  point  where  the  two  vagus  nerves 
enter  the  heart,  and  under  the  microscope  can  be  seen  to  be  connected  with 
the  fibres  of  these  nerves.  We  have  now,  from  the  discovery  of  Langley  and 
Dickinson,  a  means  of  judging  of  the  action  of  ganglion  cells  in  the  drug 
nicotine,  which  first  stimulates  and  then  paralyses  nerve  cells  themselves, 
or  the  synapses  between  the  cells 

and  the  nerve  fibres  in  connection 
with  them.  Direct  application 
of  nicotine  to  the  heart,  after  a 
primary  period  of  slowing,  leaves 
the  heart  beat  practically  iui--4 
altered,  the  normal  sequence  of 
beat  in  the  various  cavities  being 
unaffected.  After  the  application 
of  the  drug  however,  stimulation 
of  the  trunk  of  the  vagus  is  with- 
out effect,  though  slowing  or  stop- 
page of  the  heart  may  still  be 
produced  by  excitation  of  the 
post-ganglionic  nerve  fibres  of 
the  vagus,  which  arise  from  the 
cells  of  Remak's  ganglia.    These 

iglia  must  therefore  be  re- 
garded not  as  a  motor  centre  for 
the  heart,  but  merely  as  a  distri- 
buting centre  for  the  inhibitory 
fibres  of  the  vagus.    Since  tetani- 

sation  of  the  heart  with  weak  currents  also  causes  local  inhibition,  it  would 
seem  that  the  finer  nerve  fibres  ramifying  throughout  1  he  muscular  substance, 
are,  to  a  large  extent  at  all  events,  inhibitory  in  their  function.  This  is 
confirmed  by  the  fact  that  atropine,  which  paralyses  the  inhibitory  fibres 
of  the  vagus,  also  abolishes  the  direct  inhibitory  effect  of  tetanisation  on  the 
heart  muscle.  Gaskell  and  Engelmann  therefore  came  to  the  conclusion 
that  the  source  of  the  cardiac  rhythm  was  to  be  found,  not  in  the  ganglia 
scattered  about  its  cavities,  but  in  the  muscular  cells  themselves. 

The  normal  sequence  of  events— i.  e.  the  subordination  of  the  ventricle  to 
auricles  and  auricles  to  sinus  so  that  the  beal  always  follows  in  the  order, 
sinus,  auricles,  ventricle,  bulbus— can  be  ascribed  to  the  difference  be 
the  natural  rhythms  of  these  different  cavities.  It  is  possible  to  record  the 
contractions  of  each  of  these  parts  of  the  heart  separately,  after  having  divided 
them  either  functionally  by  crushing  the  intervening  tissue   or   by  actual 


Fig.  432.  Tortoise's  heart  from  dorsal  surface. 
(Gaskell.) 
S,  simis;  J,  sino-auricular  junction;  A,  auri- 
cles; C,  coronary  vein;  V,  ventricle  (The 
dotted  line  shows  how  a  strip  may  be  cut  from 
the  ventricle  apex.) 


98G 


PHYSIOLOGY 


section.  Under  such  conditions  it,  is  found  that  there  is  a  descending  scale 
of  rhythm  from  sinus  to  bulbus,  the  contractions  of  the  sinus  being  most 
frequent,  those  of  the  ventricle  and  bulbus  the  least  frequent.  Thus  it  is 
impossible  for  the  ventricle  to  beat  at  its  own  rhythm,  since  before  it  is  ready 
to  beat  again  after  performing  one  beat,  it  receives  an  impulse  from  the 
auricles  causing  an  excited  beat.  That  the  normal  sequence  of  contractions 
is  dependent  simply  on  the  natural  rhythm  of  the  sinus  is  shown  by  the  fact 
that,  by  exciting  the  ventricle  by  means  of  induction  shocks  repeated  at  a 
rhythm  slightly  quicker  than  that  of  the  sinus.it  is  possible  to  excite  a  reversed 
rhythm,  the  order  of  the  beat  being  now  ventricle,  auricles,  sinus  venosus. 

The  dependence  of  the  ven- 
tricular rhythm  on  the  beat  of  the 
sinus  may  be  shown  by  a  simple 
experiment.  The  ventricle  is  con- 
nected with  a  lever  suspended  by 
a  spring  so  as  to  record  its  con- 
tractions on  a  dram.  A  platinum 
loop  connected  with  a  galvanic 
battery  is  put  round  the  heart, 
K  either  round  the  sinus  or  round 
the  ventricle  (Fig.  433).  When 
a  current  is  allowed  to  pass 
through  the  inner  loop,  the 
corresponding  part  of  the  heart 
is  warmed.  When '  the  ventricle 
alone  is  warmed,  the  beats  be- 
come larger,  but  the  rhythm  is 
Fig.  433.  unaltered.     On  lowering  the  loop 

so  as  to  warm  the  sinus,  the 
rhythm  of  the  whole  heart  is  quickened,  but  the  size  of  the  ventricular 
beats  is  unaffected.  The  different  rhythmic  power  of  these  parts  of  the 
heart,  is  apparently  connected  with  the  histological  characters  of  the 
muscle  fibres  at  each  part.  The  lowly  differentiated  sinus  cell  has  well- 
marked  rhythmic  power  and  a  quick  rhythm  of  beat,  but  is  not  able  to 
exert  such  force  in  its  contraction.  The  more  highly  differentiated 
ventricle  cell  has  only  a  slight  rhythmic  power,  but  beats  forcibly  and 
is  a  good  servant  of  the  sinus. 


THE   PROPAGATION   OF   THE   WAVE   OF   CONTRACTION 

The  normal  contraction  started  in  the  sinus  venosus  is  propagated  to  the 
auricles,  thence  to  the  ventricle,  and  thence  to  the  bulbus  aortae.  Between 
the  contractions  of  each  of  these  cavities  there  is  a  slight  pause,  whereas 
the  contraction  spreads  so  rapidly  over  each  cavity  that  all  parts,  say  of  the 
auricles  or  ventricle,  appear  to  contract  simultaneously.  It  is  obvious  that 
the  excitatory  wave  might  be  propagated   through  the   heart   from  one 


THE  CAUSATION   OF  THE  HEART  BEAT 


987 


muscle  cell  to  another,  or  by  means  of  nerve  fibres  which  would  excite  the 
muscular  tissue  of  each  cavity  to  contract. 

The  distinct  pause  which  intervenes  between  the  contractions  of  auricles 
and  ventricle  was  long  regarded  as  evidence  for  the  nervous  character  of  the 
contraction,  and  as  showing  the  operation  of  a  nerve  centre  in  the  co- 
ordination of  the  contractions  of  different  cavities.  A  contraction  wave 
may  however  be  started  at  any  part  of  the  heart  and  may  travel  from  this 
to  all  other  parts.  Thus,  although  the  normal  direction  of  the  contractions 
is  from  sinus  to  ventricle,  it  is  possible,  by  stimulating  the  apex  of  the 
ventricle,  to  excite  contractions  in  the  reverse  order,  viz.  from  ventricle  to 
sinus.     Such  a  fact  is  at  variance  with  all  our  present  knowledge  of  excitation 


1 


Fig.  434.     Heart  of  tortoise  ■p-ith  auricle  slit  up  so  as  to  cause  a  partial 
block.    (Gaskell.) 

of  motor  nerves.  Excitation  of  the  nerve  going  to  the  sartorius,  or  of  any  part 
of  the  nerve,  may  excite  contractions  of  all  the  fibres  of  which  the  muscle 
is  composed.  On  the  other  hand,  excitation  of  a  part  of  the  muscle  which 
is  free  from  nerve  fibres  causes  a  contraction  which  is  limited  to  the  muscle 
fibres  directly  excited  and  does  not  extend  to  the  nerves.  If  motor  nerves 
arose  from  the  hypothetical  motor  ganghon  of  the  heart  and  passed  to  the 
ventricular  muscle,  one  would  not  expect  that  contraction  of  the  ventricular 
muscle  could  excite  these  nerves  and  so  cause  the  propagation  of  a  wave  of 
contraction  in  the  reverse  direction. 

That  the  propagation  cannot  be  due  to  any  nerve  trunks  running  from 
sinus  to  ventricle  is  shown  by  various  experiments  of  Engebnann  and 
Gaskell.  Thus,  if  the  auricle  is  slit  up  by  a  series  of  interdigitating  cuts,  1  he 
contraction  wave  starting  from  the  sinus  travels  along  the  auricular  muscle 
iiound  the  end  of  each  section  and  finally,  on  arrival  at  the  ventricle, 
causes  a  contraction  of  this  cavity.  In  the  heart  of  the  tortoise  the  nerve 
trunks  run,  not  in  the  interauricular  septum,  but  in  a  band  of  tissue  joining 
the  sinus  to  the  ventricle;    this  hand  can  be  exercised  with  all  its  contained 


988'  PHYSIOLOGY 

nerves  without  interfering  in  any  way  with  the  normal  sequence  of  contrac- 
tions. Moreover  the  pause  observed  between  the  contractions  of  auricles 
and  ventricles  has  been  shown  by  Gaskell  to  be  due  to  the  retardation  of  the 
excitatory  wave  which  occurs  in  its  propagation  through  the  muscular 
tissue  in  the  auriculo-ventricular  junction.  A  similar  retardation  of  the 
wave  can  be  produced  at  any  point  either  in  auricles  or  ventricle  by  diminish- 
ing the  conducting  muscular  tissue  to  a  sufficiently  small  extent.  Thus, 
if  the  auricle  of  the  tortoise  be  divided  as  in  the  diagram  (Fig.  434),  it  will 
be  noticed  that  the  sinus  first  contracts,  then  the  auricular  half  As:  a 
distinct  pause  then  occurs  while  the  contractile  process  is  passing  over  the 
'  bridge,'  and  finally  Av  contracts,  followed  by  the 
ventricle.  The  apparent  pause  between  the  contrac- 
tion of  the  auricles  and  ventricle  is  due  therefore  to 
a  partial  '  block '  at  the  auriculo-ventricular  junc- 
tion. If  the  block  be  increased  in  the  experiment 
just  quoted,  as,  for  instance,  by  allowing  the  bridge 
of  tissue  to  dry  or  by  making  it  still  narrower,  it  may 
be  found  that  only  one  out  of  every  two  contractions 
passes  across  the  bridge  (Fig.  435),  and  the  slightest 
Fig.    435.     Contraction     increase  in  the  resistance  to  the  propagation  of  the 

or  auricles  and  ventn-  . 

cle  of  tortoise  hoart.     wave  may  lead  to  the  block  becoming  complete.     On 

The  aimculo-ventricu-     moistening  the  bridge  again  every  contraction  may 
lar   groove    has    been  °  °       D  J  J 

clamped  so  as  to  pro-     be  seen  to  pass. 

fSo^g  V*X  ebv°ej  BY  the  methylene-blue  method  it  is  possible  to 

second  contraction  to     demonstrate  a  close  network  of  non-medullated  fibres 

pass.    (Gaskell.)  surrounding  all  the  muscle  cells  of  the  heart.     It  is 

obvious  that  the  experiment  just  quoted  would  not 

exclude   the   possibility   of   propagation    occurring   through   such   a  nerve 

network.     The  properties  of  the  network  would  have  to  differ  from  those 

of  any  of  the  nerve  tissues  with  which  we  are  acquainted ;  whereas  we  know 

that  under  certain  circumstances  impulses  may  be  transmitted  from  fibre  to 

fibre,  even  in  striated  muscle,  and  such  a  mode  of  propagation  is  the  most 

obvious  explanation  of  the  phenomena  observed  in  the  heart. 

If  the  auricles  be  soaked  for  some  time  in  distilled  water,  they  enter  into 
a  condition  of  what  is  known  as  water-rigor  (Wasserstarre).  In  this  con- 
dition they  are  incapable  of  contracting,  but  can  still  propagate  the  wave  from 
sinus  to  ventricle.  This  experiment  has  been  regarded  as  a  demonstration 
of  the  part  taken  by  nerve  fibres  in  the  propagation  of  the  wave,  but  such 
an  explanation  is  not  necessary,  since  a  similar  condition  of  water-rigor  in  a 
voluntary  muscle  fibre  has  been  shown  to  allow  the  passage  of  an  excitatory 
wave  through  the  affected  part  to  the  normal  portion  of  the  muscle,  which 
then  responds  by  a  contraction. 

A  series  of  interesting  researches  by  Carlson  on  the  mechanism  of  the  heart  beat  in 
tin-  king-crab  Limulus' h&B  been  thought  to  throw  light  on  the  vexed  question  of  the 
automatism  of  the  vertebrate  heart. 

In  Limulus  the  heart  forms  a  segmented  tube  of  ordinary  striated  muscular  fibres. 
In  large  specimens  the  tube  may  be  from  10  to  15  cm.  long  and  2  to  2i  cm.  broad. 


THE  CAUSATION   OF  THE  HEART  BEAT 


08'J 


Like  the  lie-arts  of  most  other  invertebrates  and  of  all  vertebrates,  it  has  a  local  system 
of  ganglion  cells,  but  so  situated  that  they  can  be  cut  away  entirely  from  the  muscular 
portions  of  the  organ.  The  arrangement  of  the  cardiac  nervous  system  in  Limulus  is 
shown  in  Fig.  436. 

The  ganglion  cells  are  collected  chiefly  in  a  dorsal  nerve  ganglion  cord  which  runs 
almost  the  whole  length  of  the  heart.  Prom  this  cord  non-mcdullated  nerve  fibres  pass 
directly  into  the  substance  of  the  heart,  and  also  send  branches  to  two  lateral  nerve 
trunks,  by  which  fibres  are  distributed  to  all  parts  of  the  heart. 

The  heart  normally  contracts  about  forty  times  per  minute.  Each  contraction 
affects  all  parts  practically  simultaneously,  though  in  the  dying  heart  the  posterior 
portions  apparently  contract  slightly  before  the  anterior,  and  may  continue  to  contract 
after  the  anterior  end  has  come  to  a  standstill. 


os  mnc      In  la' 

l-'io.  430.     Heart  of  Limulus  from  dorsal  surface.     (Carlson.) 
mnc,  median  nerve  cord;  In,  lateral  nerve  trunks. 

Division  of  the  muscular  tissue  leaving  the  nerve  strands  intact  does  not  alter  in 
any  way  the  synchronism  of  contraction  of  the  two  ends  of  the  heart.  Division  of  the 
nervous  cord  into  two  parts,  the  section  being  carried  between  the  posterior  third  and 
anterior  two-thirds,  causes  complete  lack  of  co-ordination  between  the  two  ends;  both 
ends  of  the  heart  continue  to  contract,  but  at  different  rhythms.  Extirpation  of  the"' 
nerve  cord  abolishes  spontaneous  contractions.  If  the  anterior  half  of  the  dorsal 
ganglionic  cord  be  excised,  all  parts  of  the  heart  will  continue  to  contract  in  unison. 
If  now  the  lateral  nerve  trunks  be  divided,  the  anterior  half  of  the  heart  ceases  to  con- 
tract, showing  that  it  was  being  excited  by  impulses  arising  in  the  posterior  part  of  the 


Fig.  437.     '  Nerve-muscle  preparation  '  of  heart  of  Limulus  consisting  of  the  muscle 
of  the  two  anterior  segments,  with  the  two  lateral  norves.     (Caklson.) 

ganglionic  cord.  It  is  possible  therefore  to  make  a  nerve-muscle  preparation  of  the 
anterior  part  of  the  heart,  consisting  of  the  muscle  of  the  first  two  segments  with  a 
longer  stretch  of  the  lateral  nerves  (Fig.  437).  Stimulation  of  the  lateral  nerves  with 
a  single  shock  causes  a  single  beat  of  the  anterior  segments ;  tetanising  shocks  cause 
a  continued  contraction  of  the  muscle  preparation. 

There  seems  to  be  no  doubt  that  in  this  animal  the  beat  of  the  heart  is  originated 
and  co-ordinated  by  the  action  of  the  local  ganglionic  centres.  Moreover  Carlson  has 
Shown  that  the  inhibitory  nerve  to  the  heart  acts,  not  by  direct  influence  on  the  muscle- 
fibres,  but  by  an  inhibition  of  the  automatic  activity  of  the  ganglionic  cells,  thus  con- 
tinuing for  this  special  case  the  general  view  of  inhibition  long  ago  put  forward  by 
Morat,  hut  not  now  generally  accepted. 

The  heart  muscle  does  not  show  a  refractory  period,  but  on  din  nutation  with 

repeated  shocks  there  may  bo  a  summation  of  contractions,  which  maj  fuse  to  a  com- 
plete tetanus.     The  question  naturally  arises  how  far  the  heart  of  Limulus  is  to  be 


990  PHYSIOLOGY 

regarded  as  a  special  ca  le,  or  how  far  we  may  transfer  results  gained  from  experience 
on  this  heart  to  those  of  other  hearts  in  which  a  perfect  separation  between  ganglion 
cells  and  muscle  fibres  is  ao1  so  easily  attainable.  Carlson  has  sought  to  show  the 
applicability  of  his  results  to  the  explanation  of  the  cardiac  mechanism  in  vertebrate 
by  a  series  of  observations  on  other  invertebrates'  hearts,  where  the  muscular  ami 
nervous  tissues  are  not  so  ea  ib  di  ociable.  Such  hearts  present  phenomena  verj 
analogous  to  those  of  the  frog's  heart.  According  to  him  the  phenomenon  of  the 
refractory  period,  the  '  all  or  none  '  law  of  contraction,  and  the  absence  of  tetanus  in 
the  heart  of  the  frog  is  due,  not  to  the  peculiar  functions  of  the  muscle  fibres,  hut  to 
the  fact  that  in  all  our  experiments  we  are  affecting  muscular  and  nervous  tissues 
simultaneously. 

In  the  absence  of  more  perfect  knowledge  of  the  properties  of  the  nerve  nets  which 
surround  involuntary  and  cardiac  muscle  fibres,  a  decision  of  the  point  is  not  yet  possible. 
The  muscle  and  nerve  fibres  of  Limulus  show  however  important  differences  from  the 
cardiac  muscle  of  the  frog  in  their  reaction  to  chemical  stimuli.  Acceptation  of  the 
neurogenic  theory  would  necessitate  the  predication  of  a  type  of  nervous  tissue  endowed 
with  properties  for  which  we  have  no  analogy  in  any  of  the  nerve  tissues  which  have 
been  the  subject  of  exact  investigation,  whereas  the  myogenic  theory  ascribes  only  to 
t  he  muscle  cells  of  the  heart  properties  which  are  the  common  attribute  of  all  protoplasm 
or  arc  displayed  in  a  less  marked  degree  by  the  ordinary  skeletal  muscle  fibres.  It 
would,  at  any  rate,  be  premature  to  transfer  unreservedly  all  the  results  obtained  on' 
the  heart  of  the  Limulus,  the  muscle  fibres  of  which  have  the  structure  and  behaviour' 
of  skeletal  muscle  fibres;  to  the  explanation  of  the  phenomena  exhibited  by  the  hearts 
of  vertebrates. 

THE   HEART    BEAT   AS    A   WAVE   OF   CONTRACTION 

If  the  beat  of  the  frog's  ventricle,  or  a  strip  of  mammalian  ventricle,  be 
recorded,  the  curve  obtained  resembles  closely  the  twitch  of  a  voluntary- 
muscle  produced  in  response  to  a  single  excitation.  Whereas  however  a 
single  contraction  with  the  subsequent  relaxation  of  voluntary  muscle  lasts 
only  about  one-tenth  of  a  second,  the  contraction  of  the  mammalian  ventri- 
cular muscle  lasts  three-tenths  of  a  second,  of  the  frog's  ventricle  about 
half  a  second,  and  of  the  tortoise  ventricle  about  two  seconds.1  In  the  heart, 
as  in  a  voluntary  muscle  fibre,  the  contractile  process  originates  at  the 
stimulated  point  and  travels  thence  to  all  other  points. 

The  progress  of  the  excitatory  wave  is  well  seen  if  a  record  be  taken  of  the 
electrical  changes  resulting  in  the  frog's  heart  from  a  single  stimulation.  If 
the  two  ends  of  a  strip  of  ventricular  muscle  be  connected  with  the  two 
terminals  of  a  capillary  electrometer,  stimulation  at  one  end  causes  a  diphasic 
variation,  showing  that  the  excitatory  process  starts  at  the  stimulated  end 
and  travels  to  the  other  end  of  the  heart.  Thus  if  the  acid  of  the  electro- 
meter be  connected  with  the  base  of  the  ventricle  and  the  mercury  of  the 
capillary  be  connected  with  the  apex,  stimulation  at  the  base  causes  a  wave 
passing  from  base  to  apex.  Directly  after  the  stimulation  therefore  the  base 
becomes  negative  and  the  column  of  mercury  moves  towards  the  acid; 
a  moment  later  the  contraction  extends  to  the  apex.  All  parts  of  the 
heart  are  now  in  a  similar  condition  of  excitation  :  there  is  no  difference  of 
potential  between  the  two  terminals,  and  the  mercury  comes  back  quickly 

1  The  duration  of  the  contraction  depends  on  the  temperature.     The  figures  given    j 
are  for  the  mammalian  heart  at  37°  C.  and  for  the  amphibian  heart  at  about  15°  C. 


THE  CAUSATION  OF  THE  HEART  BEAT 


991 


to  the  base  line.  Relaxation,  like  contraction,  starts  first  at  the  base 
and  proceeds  thence  to  the  apex.  There  is  thus  a  small  period  during 
which  the  apex  is  still  contracted  while  the  base  is  relaxed  and  the  apex 
is  therefore  negative  to  the  base.  This  terminal  negativity  of  the  apex 
is  shown  on  the  capillary  electrometer  by  the  excursion  of  the  column 
of  mercury  away  from  the  point  of  the  capillary  (cp.  Fig.  87,  p.  231). 

Analogous  effects  are  obtained  on  leading  off  the  spontaneously 
beating  heart  in  the  frog  or  tortoise  (Fig.  438).  The  conditions  are 
however  rather  more  complex,  and  the  most  usual  variation,  as  Gotch 
has  shown,  is  triphasic.  In  its  most  primitive  form  the  vertebrate  heart 
is  composed  of  a  simple  tube,  in  which  a  contraction  starts  at  the  venous 
end  and    is    propagated    in    a  wave-like    maimer    along  the  tube  to  the 


■ 

■    - 

■    i    i 

t    (1 

"5 

^ 

Auricle' 

HVcntriclt 

mm 

Fig.  43S.     Electrometer  record  of  variation  of  spontaneously  beating  tortoise 
heart.    (Gotch.) 

arterial  end.  In  the  higher  vertebrates  the  heart  at  its  first  appear- 
mie  tubular  form,  but  the  simple  tube  very  rapidly 
becomes  modified,  partly  by  twisting  on  itself,  partly  by  the  outgrowth 
of  the  dorsal  or  the  ventral  wall  of  the  tube  to  form  the  cavities  of  the 
auricle  and  ventricle.  Gotch  suggests  that  the  excitatory  process  follows 
the  course  of  the  original  tube,  and  that  the  typical  form  of  the  curve 
is  due  to  the  base  becoming  excited  twice,  first  at  the  part  in  con- 
tinuity with  the  auricle,  and  secondly  when  the  wave  sweeps  up  to 
the  bulbus  aorta;.  But  it  is  possible  that  in  the  cold-blooded  as  in 
the  mammalian  heart,  there  may  be  a  special  conducting  tissue  which 
leads  the  excitatory  process  to  many  different  parts  of  the  ventricle 
almost  simultaneously. 

There  is  no  doubt  that  the  ventricular  systole  is  comparable  with  a 
simple  muscular  twitch  and  cannot  be  regarded  as  the  summation  of  several 
contractions.     Since  the  excitatory  process  extends  in  the  form  of  a  wave 


992  PHYSIOLOGY 

not  only  to  all  parts  of  the  same  cavity  but  to  all  parts  of  the  heart,  it  is 
evident  that  the  musculature  of  the  heart  is  to  be  compared,  not  with  skeletal 
muscle  composed  of  many  fibres,  but  to  a  single  muscle  fibre  in  which  all 
parts  are  in  functional  continuity. 

THE  BEAT  OF  THE  MAMMALIAN  HEART 

The  mammalian  heart,  like  the  heart  of  cold-blooded  animals,  will  beat 
for  some  time  after  it  has  been  cut  out  of  the  body,  and  a  perfectly  rhythmic 
acl  ivity  may  be  maintained  for  hours  by  feeding  the  heart  from  the  coronary 
arteries  either  with  defibrinated  blood  or  with  oxygenated  Ringer's  solution, 
with  or  without  the  addition  of  glucose. 

Ganglion  cells  are  found  in  the  mammalian  heart  around  the  openings  of  the  great 
veins,  along  the  border  of  the  interauricular  septum,  in  the  groove  between  auricles 
and  ventricles,  and  in  the  basal  parts  of  the  ventricles. 

The  ventricles  of  mammals  are  endowed  with  a  greater  rhythmic  power 
than  the  corresponding  cavities  in  the  frog  and  tortoise.  It  is  possible  to 
sever  or  crush  all  the  nervous  and  muscular  connections  between  auricles  and 
ventricles  without  destroying  their  mechanical  connection  by  means  of  fibrous 
tissue.  Such  a  procedure  does  not,  even  for  a  moment,  stop  the  contractions 
of  the  ventricles,  which  go  on  beating  at  a  rhythm  which  is  independent  of  and 
slower  than  that  of  the  auricles.  Porter  has  shown  that  a  mere  fragment 
of  the  ventricular  wall,  perfectly  free  from  ganglion  cells,  may  maintain 
rhythmic  contractions  for  some  hours  if  fed  by  an  artificial  circulation  through 
a  branch  of  the  coronary  artery.  We  may  therefore  conclude  that  in  the 
mammalian  as  in  the  amphibian  heart,  the  cause  of  the  rhythm  is  to  be 
sought  in  the  properties  of  the  muscle  fibres  themselves,  and  that  every  part 
of  the  heart  muscle  possesses  the  power  of  rhythmic  activity,  the  normal 
sequence  of  the  beats  being  determined  by  the  greater  frequency  of  the 
natural  rhythm  of  the  venous  end  of  the  heart. 

In  the  mammalian  as  in  the  amphibian  heart,  the  excitatory  condition 
started  at  one  point  in  the  muscle  spreads  through  the  muscle  in  all  directions, 
and  the  process  of  conduction  of  excitation  seems  to  be  independent  of  nerve 
fibres.  The  excitatory  process  may  be  conducted  not  only  in  the  ordinary 
direction  from  auricles  to  ventricles,  but  also  from  ventricles  to  auricles. 
If  the  ventricles  be  excited  at  a  rhythm  of  higher  frequency  than  the  natural 
beat  which  is  starting  at  the  venous  end  of  the  heart,  we  may  obtain  a 
reversed  rhythm  in  which  the  order  of  the  beats  is  ventricles — auricles. 
It  is  difficult  to  conceive  of  an  arrangement  of  neurons  which  would  propa- 
gate impulses  impartially  from  auricles  to  ventricles  or  from  ventricles  to 
auricles.  Such  a  condition  would  seem  to  be  in  contradiction  to  the  law 
of  forward  direction  which  obtains  throughout  the  nervous  system.  On  the 
other  hand  the  phenomena  are  easily  explained  on  the  assumption  that  the 
whole  of  the  musculature  of  the  heart  acts  in  many  respects  as  a  single 
muscle  fibre,  along  which  an  excitatory  process  may  be  propagated  in  any 
direction.    But  in  the  adult  mammalian  heart,  on  superficial  dissection, 


THE  CAUSATION  OF  THE  HEART   BEAT 


993 


the  muscle  fibres  both,  of  auricles  and  ventricles  are  seen  to  arise  from  a  fibro- 
cartilaginous ring  surrounding  the  auriculo-ventricular  junction,  leaving 
apparently  no  muscular  continuity  between  the  two  cavities.  On  this 
account  it  was  thought  for  many  years  that  the  propagation  of  the  contrac- 
tion from  auricles  to  ventricles  must 
occur  by  means  of  nerve  fibres,  and 
it  was  only  with  the  discovery  by 
His  of  a  distinct  band  of  modified 
muscle  fibres,  passing  from  the  auri- 
cles to  the  ventricles,  the  '  auriculo- 
ventricular  bundle,'  that  an  anato- 
mical basis  was  furnished  for  the 
physiological  behaviour  of  the  heart. 
The  heart  is  developed  from  a  mus- 
cular tube  in  which  at  the  beginning 
we  must  assume  muscular  continuity 
throughout.  The  primitive  vertebrate 
heart  is  formed  by  a,  modification  of 
this  muscular  tube.  In  this  heart,  as 
Keith  has  shown,  we  may  distinguish 
five  chambers,  namely,  the  sinus 
venosus,  the  auricular  canal,  the 
auricle,  the  ventricle  and  the  bulbus 
(Fig.  439).  The  musculature  of  these 
chambers  is  continuous  throughout. 
In  the  adult  heart,  e.g.  of  man,  the 
anatomical  relations  of  the  different 
cavities  have  become  considerably 
modified  in  the  course  of  develop- 
ment.   The   sinus   venosus,   i.  e.   the 

part  where  in  the  lower  vertebrates  the  contraction  wave  takes  its 
origin,  is  now  represented  merely  by  the  termination  of  the  superior 
vena  cava  and  of  the  coronary  sinus  in  the  right  auricle.  These  two 
veins  are  derived  from  the  right  and  left  ducts  of  Cuvier  in  the  embryo. 
The  sinus  venosus  is  also  represented  by  a  small  amount  of  tissue  under- 
lying the  taenia  terminalis  of  the  right  auricle,  as  well  as  by  the  remains 
of  the  Eustachian  and  venous  valves.  The  auricular  canal  gives  rise 
to  the  auricular  septum  and  to  the  auricular  ring  surrounding  the  auricu- 
lar-ventricular orifice,  and  in  some  hearts  it  is  prolonged  into  the  ventricle 
as  the  intraventricular  or  invaginated  part  of  the  auricular  canal.  In  the 
adult  heart  two  accumulations  of  more  primitive  tissue  are  found  in  the 
region  corresponding  to  the  sinus  venosus  of  the  embryo,  and  these  are  known 
as  the  sino-auricular  node  and  the  auriculo-ventricular  node.  The  sino- 
auricular  node  (Fig.  440)  lies  in  the  groove  between  the  superior  vena  cava 
and  the  right  auricle.  The  auricular-ventricular  node  lies  at  the  base  of 
the  auricular  septum  on  the  right  side,  below  and  to  the  right  of  the  opening 
63 


Fig.  439.     A  generalised  type  of 
vertebrate  heart.     (Keith.) 

o,  sinus  venosus ;  b,  auricular  canal ; 
c,  auricle;  d,  ventricle;  e,  bulbus  cordis; 
/,  aorta;  1-1,  sino-auricular  junction  and 
venous  valves ;  2-2,  canalo-auricular  junc- 
tion; 3—3,  annular  part  of  auricle;  4-4, 
invaginated  part  of  auricle;  5,  bulbo- 
ventricular  junction. 


994 


PHYSIOLOGY 


of  the  coronary  sinus.  From  this  point  a  bundle  of  muscular  fibres  (the 
bundle  of  His  or  the  auriculo-ventricular  or  A.V.  bundle)  runs  along  the  top 
of  the  interventricular  septum  just  below  its  membranous  part  and  then 
divides  into  the  right  and  left  septal  divisions,  which  pass  down  in  each  ven- 
tricle on  the  interventricular  septum  into  the  papillary  muscle  arising  IV 

the  septum.  Each  half  of  the  bundle  gives  off  several  branches  which  break 
up  more  and  more,  finally  forming  a  reticulated  sheet  of  tissue  over  the 
greater  part  of  the  interior  of  the  ventricles  just  below  the  endocardium. 
The  fibres  composing  this  tissue  are  more  primitive  in  character  than  the 
rest  of  the  cardiac  musculature  and  have  long  been  distinguished  as  the 


Superior  I'ena  Cava . 


Srnoaurici/farnodCi 


Sulcus  lirminalis 

Auriculo-  Vent. 

'Biirnllv 

Left  Branch 

Foramen  Ovale. 
Auriculo-  Vent 

~Li0(la 

ComnarySim/s 
Tricuspid Valve 


Aorta 


RtAppendix 


I'k;.  440.  Diagrammatic  representation  of  course  of  A.V.  bundle. 

'  fibres  of  Purkinje.'  In  them  the  fibrillation  is  confined  to  the  periphery  of 
the  muscle  cell.  They  are  distinguished  by  a  high  glycogen  content.  They 
may  be  regarded  as  a  part  of  the  muscular  wall  of  the  heart  specially -differen- 
tiated for  the  rapid  conduction  of  the  excitatory  process  to  all  parts  of  the 
ventricles  (Figs.  441  and  442). 

Numerous  nerve  fibres  and  ganglion  cells  are  found  to  accompany  the  muscle  fibres 
of  the  auriculo-ventricular  bundle.  We  have  however  no  reasons  for  regarding  the 
nervous  structures  as  concerned  in  the.  propagation  of  the  excitatory  wave. 

The  auriculo-ventricular  bundle  forms  the  only  continuous  muscular 
tissue  between  the  auricles  and  ventricles,  and  destruction  of  it  causes  com- 
plete abolition  of  the  normal  sequence  of  beat  between  auricles  and  ventricles. 
By  leading  off  different  parts  of  the  heart  to  the  string  galvanometer,  it  is 
possible  to  determine  the  time  relations  of  the  excitatory  process.  It  is 
then  found  that  the  mass  of  Purkinje  tissue,  known  as  the  sino-auricular 


THE  CAUSATION  OF  THE  HEART  BEAT 


995 


node,  is  the  starting-point  of  the  excitatory  process  concerned  in  each  heart 
beat.  It  is  therefore  spoken  of  as  the  '  pace-maker  '  of  the  heart.  At  each 
beat  a  contraction  starts  at  the  sino-auricular  node,  spreads  a  short  way  up 
the  great  veins,  and  alone;  the  auricular  muscle  in  all  directions.    When  it 


Fig.  441.  Left  ventricle,  laid  open  to  display  the  interventricular  septum,  on 
which  the  course  of  the  left  division  of  the  auriculo-vontricular  bundle  and 
its  ramifications  are  shown  in  black.     (After  Tawara.) 


Fig.  442.     Fibres  of  Purkinje,  from  the  subendocardial  network.     (Tawaka.) 

arrives  at  the  auriculo-ventricular  node,  the  impulse  is  carried  on  to  the 
ventricles  along  the  auriculo-ventricular  bundle,  spreading  along  the  branches 
of  this  bundle  to  almost  all  parts  of  the  ventricular  muscle.  Although 
normally  the  sino-auricular  node  initiates  each  heart  beat,  this  node  can  be 
put  out  of  action  by  injury  or  cooling  without  stopping  the  rhythmic 
sequence  of  the  heart  beat,  the  office  of  pace-maker  being  now  taken  up  by 


996  PHYSIOLOGY 

the  auriculo-ventricular  node.  A  specialisation  of  function  accompanies 
the  differentiation  in  structure  which  we  find  in  the  auriculo-ventricular 
bundle  and  its  branches.  Lewis  has  shown  that  the  conduction  of  the 
excitatory  process  along  the  auriculo-ventricular  bundle  of  the  Purkinje 
tissue  occurs  about  ten  times  as  fast  as  the  conduction  through  the  ordinary 
muscular  tissue  of  the  heart,  the  rates  being  about  5000  mm.  and  500  mm. 
per  second  respectively.  Although  all  parts  of  the  ventricles  receive  the 
impulse  to  contraction  almost  simultaneously,  the  contraction  wave,  as 
judged  by  the  electrical  changes,  is  found  to  commence  slightly  earlier  at  two 
points,  namely,  on  the  anterior  surface  near  the  apex  to  the  right  of  the 
groove  separating  right  and  left  ventricles,  and  at  the  extreme  apex  of  the 
heart  where  the  endocardiac  tissue  comes  very  close  to  the  surface.  On 
the  other  hand,  the  conus  arteriosus  is  the  last  part  of  the  heart  to  begin 
contracting. 

The  limitation  of  the  muscular  continuity  to  a  single  narrow  bundle,  which  is 
endowed  with  greatly  increased  conducting  powers  and  ends  in  a  network  of  tissue 
endowed  with  similar  powers,  is  evidently  designed  (to  use  an  old-fashioned  but 
convenient  word)  to  ensure  that  all  parts  of  the  ventricles  contract  practically 
simultaneously.  If  this  were  not  the  case,  the  sudden  contraction  of  the  muscle  fibres 
near  the  base  of  the  ventricles  would  simply  bulge  out  the  still  uncontracted  portion 
near  the  apex,  and  there  would  be  a  risk  of  injury  or  even  rupture  of  the  uncontracted 
part  of  the  ventricle  under  the  stress  of  the  pressure  produced  by  the  contracting  part. 
On  the  other  hand,  if  all  parts  of  the  heart  were  endowed  with  a  similar  rapid  power  of 
conduction,  any  part  slightly  more  excitable  or  irritated  than  the  rest,  might  serve  as 
a  centre  for  emitting  excitatory  waves,  wliich  would  interfere  with  those  transmitted 
from  the  auricles ;  and  the  tendency  to  heart  delirium  would  be  enormously  increased. 

THE   HUMAN   ELECTROCARDIOGRAM 

The  passage  of  the  excitatory  wave  over  the  different  heart  cavities  is 
associated  with  corresponding  electrical  changes  resulting  in  differences  of 
potential.  If  we  lead  off  any  two  parts  of  the  heart's  surface  to  a  string 
galvanometer  or  capillary  electrometer,  we  obtain  movements  which  are 
caused,  partly  by  changes  occurring  in  the  muscle  just  underlying  the 
electrode,  partly  by  changes  occurring  at  a  distance  and  transmitted  by  the 
intervening  muscle  acting  simply  as  a  moist  conductor.  These  two  kinds  of 
effect  may  be  alluded  to  as  direct  and  indirect.  If  we  lead  off,  not  from  the 
heart  itself,  but  from  neighbouring  tissues  in  contact  with  the  heart,  we 
shall  still  obtain  the  indirect  effect  of  the  electrical  changes  at  each  heart 
beat,  and  these  can  be  obtained,  as  Waller  has  shown,  when  the  intact 
animal  is  led  off  to  the  electrometer  or  galvanometer  by  his  hmbs.  In  an 
animal  such  as  the  dog  the  two  fore  hmbs  may  form  one  lead  and  the  two 
hind  hmbs  the  other.  In  man,  where  the  heart  hes  asymmetrically,  it  is 
usual  to  lead  off  the  right  arm  and  left  arm,  the  right  arm  and  left  leg,  or  the 
left  arm  and  left  leg,  the  hand  or  foot  being  immersed  in  salt  water  con- 
nected to  the  galvanometer  by  a  zinc  electrode  contained  in  a  porous  pot  full 
of  saturated  zinc  sulphate  solution.  By  this  means  an  electrocardiogram 
is  obtained  similar  to  that  shown  in  Fig.  443. 


THE  CAUSATION  OF  THE  HEART  BEAT 


997 


In  view  of  the  mechanism  of  the  propagation  of  the  excitatory  wave 
in  the  ventricle,  we  should  not  expect  the  cardiogram  obtained  in  this 
indirect  fashion  to  be  easy  of  interpretation,  at  any  rate  so  far  as  regards 
the  course  of  the  wave  through  the  ventricular  muscle.     Such  an  electro- 


Fiq.  44o.     Electa 


jlf  frc 


the  two  hands 


,gram  of  man.  obtained  by  leading 

to  a  string  galvanometer. 

c  is  the  carotid  pulse  tracing.     The  different  parts  of  the  curve  are  designated 

by  the  letters  P,  Q,  R,  s,  T,  first  applied  to  them  by  Einthoven. 

cardiogram  however  is  of  considerable  use  clinically,  especially  for  the 
determination  of  the  relation  between  the  auricular  and  the  ventricular  con- 
tractions. The  different  points  in  a  typical  tracing,  such  as  that  contained 
in  the  figure,  are  designated  by  the  letters  p,.  Q,  R,  s,  t,  which  were  first 
applied  to  them  by  Einthoven  and  are  retained  because  they  do  not  involve 
any  theoretical  interpretation  of  the  curves.     Of  these  p  is  certainly  due  to 


Rod. art. 
Fiq.  444.  Simultaneous  tracings  of  the  jugular  venous  pulse  and  the  radial  arterial 
pulse,  from  a  case  in  which  the  A.V.  bundle  was  destroyed  by  disease.  The 
contractions  of  the  auricles  are  marked  by  the  a  waves  on  the  venous  pulse. 
They  are  more  rapid  than  and  quite  independent  of  the  ventricular  contractions. 
(Mackenzie.) 

the  auricular  contraction  and  Q  marks  the  beginning  of  the  ventricular 
contraction.  The  A.V.  interval  is  given  by  the  distance  between  p  and  Q, 
the  total  duration  of  the  excitatory  condition  in  the  ventricle  by  the  distance 
between  q  and  T. 

The  fibres  of  the  auriculo-ventricular  bundle  may  be  destroyed  by  disease-  In 
such  eases  we  get  a  series  of  phenomena  known  under  the  name  of  Stokes-Adams 
disease,  the  main  characteristic  of  which  is  the  slow  contractions  of  the  ventricle,  accom- 
panied by  a  rapid  venous  pulse  at  a  rhythm  entirely  independent  of  the  ventricular 
pulse.     The  automatic  activities  of  auricle  and  ventricle  are  in  fact  dissociated  (Fig.  444) 


998  PHYSIOLOGY 

At  certain  intervals  or  at  certain  stages  of  the  disease,  the  fibres  of  the  bundle  may 
present  only  a  partial  block,  so  that  the  ventricle  responds  once  to  every  second  con- 
traction of  the  auricle.  The  existence  of  this  disease  is  shown  at  once  on  the  electro- 
cardiogram by  the  dissociation  of  the  normal  relation  between  the  auricular  and 
ventricular  variations.     It  may  be  also  shown  by  a  study  of  the  venous  pulse  (Fig-  444). 


THE  PHYSIOLOGICAL   PROPERTIES   OF  THE   CARDIAC   MUSCLE 

THE   RESPONSE   OF   HEART   MUSCLE   TO   DIRECT   EXCITATION 

When  a  skeletal  muscle  is  directly  stimulated  with  induction  shocks  of 
varying  strength,  within  narrow  limits  the  height  of  the  contraction  is 
proportional  to  the  strength  of  the  stimulus.  If  the  frog's  ventricle,  rendered 
motionless  by  a  Stannius  ligature,  be  stimulated  with  a  single  induction 
shock,  if  it  responds  at  all  it  will  respond  with  a  maximal  contraction,  no 
change  in  the  extent  of  the  contraction  being  obtainable,  however  the  stimu- 
lus may  be  increased.  There  is  thus  no  proportionality  in  the  heart  between 
strength  of  stimulus  and  height  of  contraction.  The  heart,  if  it  contracts 
at  all,  always  contracts  to  its  utmost,  the  height  of  the  contraction  being 
dependent,  not  on  the  strength  of  stimulus,  but  on  other  conditions  affecting 
the  muscle  at  the  time  of  its  response. 

Although  much  stress  has  been  laid  on  this  supposed  difference  between 
heart  muscle  and  voluntary  muscle,  a  renewed  investigation  of  the  response 
of  the  latter  to  graded  stimuli  by  Gotch  and  by  Keith  Lucas  tends  to  show 
that  the  distinction  is  not  so  fundamental.  According  to  these  observers  the 
fact,  that  the  response  to  a  minimal  stimulus  in  skeletal  muscle  is  smaller  than 
the  response  to  a  maximal  stimulus,  is  simply  owing  to  the  fact  that  in  the 
former  case  only  a  small  proportion  of  the  muscle  fibres  is  active,  so  that 
increasing  the  strength  of  the  stimulus  merely  increases  the  number  of  fibres 
thrown  into  contraction.  According  to  this  view  therefore  a  maximal  con- 
traction of  skeletal  muscle  would  be  one  involving  all  the  fibres.  In  the 
heart  muscle  all  the  muscle  fibres  are  functionally  continuous,  so  that  a  stimu- 
lus, if  it  excites  at  all,  must  excite  all  the  fibres,  and  every  contraction  must 
be  analogous  to  the  maximal  contraction  of  a  skeletal  muscle.  The  existence 
of  the  '  all  or  none '  law  in  any  contractile  tissue  would  be  therefore 
dependent  on  the  existence  of  functional  continuity  between  all  the  con- 
tractile elements  of  the  tissue. 

Li  the  retractor  penis  of  the  dog  it  is  possible  to  get  graded  contractions 
with  graded  strength  of  stimuli,  and  in  this  case  it  is  easy  to  observe  that 
with  increasing  strength  of  stimulus  a  greater  extent  of  the  muscle  is  thrown 
into  the  contractile  state.  Closely  connected  with  this  maimer  of  response 
is  the  fact  that  in  heart  muscle,  under  normal  circumstances,  it  is  not  possible 
to  get  summation  of  contractions  by  putting  in  a  stimulus,  however  strong, 
before  the  muscle  has  returned  to  rest.  If  however  the  propagation  of  the 
first  contraction  throughout  the  heart  muscle  be  retarded  or  prevented  by  a 
partial  death  of  the  tissue,  or  by  stimulus  of  the  vagus  nerve,  it  is  possible, 
as  Frank  has  shown,  to  obtain  an  apparent  summation  of  two  stimuli,  i.  e. 
a  curve  in  which  the  second  contraction  is  superposed  on  and  rises  higher 


THE  CAUSATION  OF  THE  HEART   BEAT  999 

than  the  first.  Such  a  result,  on  the  explanation  given  above,  would  be  due 
to  a  phenomenon  of  '  block,'  limiting  the  propagation  of  the  first  contractile 
wave  and  yielding  more  to  the  second.  This  however  is  not  the  explana- 
tion given  by  the  original  observer. 

SUMMATION   OF   STIMULI 

If  an  isolated  frog's  ventricle,  which  is  not  beating,  be  stimulated  with 
inadequate  shocks,  it  may  be  found,  on  repeating  these  shocks  at  short 
intervals  of  time,  that  they  become  adequate  and  cause  a  contraction  of  the 
ventricle.  A  stimulus  therefore,  which  is  subminimal, 
may  nevertheless  cause  some  change  in  the  heart 
muscle,  so  that  the  latter  responds  more  readily  to 
subsequent  stimuli. 


A  similar  improving  effect  of  previous  stimulation     Fig.  445.    Group  of  pul- 

.      r  x  .  sations  showing    stair- 

on  the  condition  of  the  heart  muscle  may  be  observed        case  '  character. 
on  the  contractions  themselves.     Thus  in  a  Stannius 

preparation,  if  the  ventricle  be  excited  with  single  induction  shocks,  once 
in  every  ten  seconds,  the  first  four  or  five  contractions  form  an  ascending 
series,  each  contraction  being  rather  higher  than  the  preceding  one.  This 
is  often  spoken  of  as  the  'staircase  phenomenon'  (Fig.  445). 

THE    REFRACTORY    PERIOD 

At  each  contraction  of  the  heart  muscle  there  is  a  sudden  decomposition 
of  contractile  materia!  which,  so  far  at  least  as  concerns  the  incidence  of  an 
external  stimulus,  is  maximal,  i.  e.  complete.  Directly  this  has  occurred,  a 
process  of  assimilation  or  re-formation  of  contractile  material  begins.  This 
lasts  throughout  the  diastolic  period,  and  the  store  of  contractile  material  is  at 
its  maximum  just  before  the  next  contraction.  A  mechanical  analogy  is 
furnished  by  a  bucket  into  which  a  stream  of  water  is  constantly  flowing, 
and  which  tips  up  automatically  and  empties  out  its  contents  as  soon  as  the 
water  reaches  a  certain  height.  It  is  evident  that  the  power  of  the  heart 
muscle  to  contract  in  response  to  a  stimulus  (its  '  irritability  ')  must  be  at  a 
minimum  immediately  after  the  automatic  discharge  or  decomposition  has 
taken  place,  and  will  continually  increase  from  this  point  as  the  store  of  con- 
tractile material  grows,  until  it  arrives  at  such  a  height  that  the  explosive 
discharge  occurs  spontaneously.  Hence  in  each  cardiac  cycle  there  is  a 
period,  known  as  the  refractory  period,  in  which  stimuli  applied  to  the  hearl 
have  no  effect.  This  will  be  followed  by  a  period  in  which  a  stimulus  is 
followed  by  an  extra  contraction,  but  with  a  prolonged  latent  period.  Just 
before  the  next  spontaneous  contraction  the  irritability  is  at  its  height,  and 
the  heart  muscle  responds  with  a  contraction  to  a  minimal  stimulus.  These 
facts  are  well  shown  in  Fig.  446. 

When  a  tracing  is  being  taken  from  part  of  the  heart,  e.g.  the  ventricle, 
which  is  beating  rhythmically  in  consequence  of  a  stimulus  comnuuricated 
to  it  from  some  other  part  such  as  the  sinus  venosus,  an  extra  contraction  is 
followed  by  a '  compensatory  pause,'  and  in  certain  cases  the  first  contraction 


1000 


PHYSIOLOGY 


after  the  pause  is  considerably  augmented.  This  is  due  to  the  fact  that 
one  of  the  impulses  travelling  from  the  sinus  arrives  at  the  ventricle  during 
the  refractory  period  ensuing  on  the  application  of  the  artificial  stimulus; 
hence  it  produces  no  effect  and  the  ventricle  has  to  wait  for  the  arrival  of  the 
next  succeeding  excitatory  wave  from  the  sinus  before  it  gives  its  next  beat. 


Fig.  446.  Tracings  of  spontaneous  contractions  of  frog's  ventricle,  to  show  refractory 
period.  In  each  series  the  surface  of  the  ventricle  was  stimulated  by  an  induction 
shock  at  E,  as  indicated  by  the  tracing  of  the  signal.  In  1,  2  and  3,  this  stimulus 
had  absolutely  no  effect,  since  it  fell  during  the  refractory  period.  In  4,  5,  6,  7 
the  effect  of  the  shock  was  to  interpolate  an  extra  contraction  in  the  series,  the 
latent  period  (shaded  part)  gradually  diminishing  from  4  to  7  (diastolic  rise  of 
irritability).  In  8  the  irritability  of  the  preparation  was  already  considerable, 
and  the  latent  period  inappreciable.  The  '  compensatory  pause  '  after  the 
extra  beat  is  also  well  shown  in  4,  5,  6,  7,  8.     (Makey.) 

Hence  the  compensatory  pause  does  not  occur  when  we  are  testing  the  effects 
of  artificial  stimuli  on  the  sinus  venosus. 

On  account  of  the  refractory  period  which  ensues  on  the  commencement 
of  the  contractile  process  on  heart  muscle,  it  is  impossible  to  throw  the 
muscle  into  a  tetanus,  since  all  the  stimuli  which  fall  during  systole  are 
entirely  ineffective.  By  using  very  strong  stimuli  it  is  possible  to  intercalate 
extra  contractions  before  the  heart  has  returned  to  the  base  line,  i.  e.  before 
diastole  is  complete.  So  that  in  this  way  one  may  obtain  almost  a  continuous 
contraction  (presenting  however  waves  on  its  summit),  which  differs  from 
the  tetanus  of  skeletal  muscle  in  the  fact  that  its  height  is  no  greater  than 
the  height  of  a  single  contraction. 


THE  CAUSATION  OF  THE  HEART   BEAT  1001 

Only  when  the  functional  continuity  of  the  heart  muscle  is  impaired  by 
the  '  block '  effect  of  vagal  stimulation  or  by  the  administration  of  muscarine 
is  it  possible  to  obtain  phenomena  even  superficially  analogous  to  the  sum- 
mation of  contractions  in  skeletal  muscle.1 


FACTORS   MODIFYING   THE   ACTIVITY   OF   CARDIAC   MUSCLE 

INFLUENCE   OF   TENSION   AND   DISTENSION 

When  we  examine  the  behaviour  of  a  heart  isolated  from  the  central 
nervous  system  and  from  the  rest  of  the  body,  as  for  instance  in  the  heart- 
lung  preparation  (vide  p.  955),  we  find  that  it  has  a  marvellous  power  of 
adaptation,  i.  e.  of  regulating  its  activity  according  to  the  mechanical  demands 
which  are  made  upon  it.  Thus  while  we  may  maintain  the  venous  inflow 
constant  so  that  the  heart  is  sending  out  a  litre  of  blood  per  minute,  it  makes 
no  difference  to  the  output  of  the  heart  whether  the  average  arterial  pressure, 
and  therefore  the  resistance  to  the  outflow  of  blood,  be  maintained  at  80  or 
160  mm.  Hg.,  although  in  the  latter  case  the  heart  must  do  exactly  twice  as 
much  work  in  order  to  maintain  the  outflow  at  the  same  level.  Again 
if  we  maintain  the  arterial  pressure  constant  and  alter  the  venous 
inflow,  we  find  that  within  very  wide  limits  the  heart  is  able  to  expel 
against  the  arterial  resistance  the  whole  of  the  blood  which  flows  into  it  from 
the  veins.  In  this  way  we  can  alter  the  output  of  a  small  heart  of  50  gms. 
from  300  to  3000  c.c.  per  niinute.  As  we  should  expect,  this  variation  in 
the  work  done  by  the  heart  is  associated  with  corresponding  variations 
in  the  chemical  changes  which  occur  at  each  heart  beat.  Evans  has  shown 
that  the  respiratory  exchanges  of  the  heart  increase  pari  passu  with  the 
work  it  has  to  do.  Thus  in  an  isolated  dog's  heart,  weighing  70  grms.,  with 
a  constant  inflow  and  output  of  35  litres  per  hour,  raising  the  arterial  pressure 
from  80  mm.  Hg.  to  140  mm.  Hg.  increased  the  oxygen  consumption  from 
228  to  404  c.c.  per  hour.  In  another  experiment  with  a  heart  of  59  grms., 
in  which  the  arterial  pressure  was  maintained  constant  at  80  mm.  Hg., 
increasing  the  output  from  9-3  to  92  litres  per  hour  raised  the  oxygen  con- 
sumption from  155  to  649  c.c.  per  hour.     In  these  experiments  the  maximum 

/      work  done  in  calories      \ 

efficiency  of  the  heart    — — ; ,   ,    .. : ; — —    varied  between  20  and 

Vtotal  metabolism  in  calories/ 

30  per  cent.,  and  was  of  the  same  order  as  that  found  for  voluntary  muscle. 

Careful  investigation  of  the  volume  and  pressure  changes  of  the  heart 

under  varying  conditions  of  arterial  resistance  and  venous  filling  enables 

us  to  throw  some  light  on  the  mechanism  of  this  power  of  adaptation. 

Let  us  take  first  the  changes  in  volume  as  recorded  by  the  cardiometer. 

A  heart  is  contracting  100  times  per  minute  and  forcing  out  at  each  beat 

10  c.c.  of  blood  into  the  aorta  against  an  average  pressure  of  80  mm.  Hg., 

with  systolic  and  diastolic  pressures  respectively  of  100  and  60  nun.  Hg.     In 

order  that  the  left  ventricle  may  force  10  c.c.  of  blood  against  this  resistance, 

1  According  to  Mines  the  effect  of  vagus  excitation  in  enabling  the  production  of 
summation  is  due  to  the  shortening  of  the  refractory  period  which  results  from  vagal 
stimulation. 


1002 


PHYSIOLOGY 


the  pressure  in  its  interior  must  rise  at  each  heart  beat  above  the  maximum 
systolic  pressure  in  the  aorta,  e.g.  to  110  mm.  Hg.  The  aortic  valves  will 
open  as  soon  as  the  pressure  rises  above  60  mm.  Hg.  The  arterial  resistance 
is  now  increased  so  as  to  bring  the  average  pressure  up  to  120  mm.  Hg.  The 
heart  now  may  raise  the  pressure  in  its  interior  to  120  mm.  Hg.    This  will 

be  higher  than  the  diastolic  pressure 
in  the  aorta  and  a  certain  amount 
of  blood  will  escape,  but  the  outflow 
of  blood  will  cease  as  soon  as  the 
pressure  in  the  aorta  is  equal  to 
that  in  the  ventricle.  Diastole  will 
then  occur,  the  ventricle  will  relax 
before  it  has  emptied  out  10  c.c.  of 
blood.  Let  us  assume  it  has  forced 
out  3  c.c.  of  blood — it  will  then 
contain  an  excess  of  7  c.c.  of  blood 
at  the  end  of  diastole.  Meanwhile 
the  venous  inflow  is  proceeding  at 
the  same  rate  as  before,  so  that  at 
the  end  of  diastole  it  has  7  c.c.  more 
blood  than  it  had  at  the  end  of 
the  previous  beat,  i.  e.  its  diastolic 
volume  will  be  increased  and  the 
heart  will  be  dilated.  At  the  in- 
creased beat  we  find  that  the  con- 
traction of  the  ventricle  is  much 
more  forcible.  The  maximum  pres- 
sure now  rises  to  130  mm.  Hg.  and 

8  c.c.  of  blood  are  sent  out  into 
the  aorta.  At  the  end  of  this  beat 
the  heart  will  be  still  fuller  than 
before,      containing     an    excess    of 

9  c.c.  of  blood.  The  third  beat 
is  still  more  forcible,  the  intra- 
ventricular pressure  rising  to  a 
maximum    of    140    mm.    Hg.,    and 

10  c.c.  of  blood  are  expelled.  After  this  the  heart  goes  on  beating  regularly, 
expelling  10  c.c.  of  blood  at  each  beat,  i.  e.  the  same  amount  as  it  receives 
from  the  veins,  and  the  arterial  pressure  is  maintained  constant  at  an  average 
of  120  mm.  Hg.  But  the  heart  remains  more  dilated  than  it  was  previously, 
since  it  contains  an  excess  of  9  c.c.  of  blood.  If  now  the  arterial  resistance 
be  suddenly  reduced  to  its  previous  amount,  the  first  beat  after  the  change 
may  send  out  17  c.c.  of  blood,  the  second  beat  12  c.c.  of  blood  and  the  third 
beat  10  c.c.  as  before.  We  see  therefore  that  the  energy  set  free  at  each 
contraction  of  the  heart  is  increased  by  increasing  the  volume  of  the  heart ; 
but  increased  volume  of  the  heart  means  increased  length  of  the  muscular 


Fig.  447.  Effect  of  increased  arterial  pres- 
sure on  the  volume  changes  of  the  heart, 
with  a  steady  inflow  of  154  c.c.  blood  per 
10  seconds. 

C.  =cardiorueter  curve.  B.P.  =artorial  blood 
pressure.  V.P.  =pressure  in  the  inferior 
vena  cava.  The  hues  100  and  80  show  the 
height  of  the  blood  pressure  in  mm.  Hg. 


THE  CAUSATION  OF  THE   HEART   BEAT 


1003 


fibres  composing  its  wall,  so  we  arrive  at  a  statement  similar  to  that  made 
previously  for  voluntary  muscles,  namely,  that  the  energy  of  contraction  is 
a  function  of  the  length  of  the  muscle  fibres,  i.  e.  to  the  extent  of  active  surface 
involved.  This  reaction  of  the  heart  to  increasing  distension  has  long  been 
known  but  was  ascribed  to  the  excitatory  influence  of  tension  on  the  muscle 
fibres.  It  is  evident  that  in  a  resting  heart  increasing  distension  of  its 
cavities  will  tend  to  stretch  its  muscle   fibres  and    therefore  to  exert   a 


Fia.  448.     Effect  of  alterations  in  venous  supply  on  volume  of  heart.     Heart,  67  gms. 


Arterial 

Venous 

Output  of  heart 

pressure 

pressure 

in  10  sees. 

124 

= 

95 

=          80 

130 

= 

145 

=       140 

124 

= 

55 

=         33 

A  . 
B  . 
C     . 

•  The  curved  lino  at  tho  side  represents  the  value  of  the  cardiomutor  excursions 
in  capacity  of  ventricles  in  c.c. 

tension  on  them.  By  an  accurate  record  of  the  pressure  changes  within 
the  contracting  ventricle  imder  varying  conditions,  it  is  possible  to  exclude 
the  tension  on  the  fibres  as  the  determining  factor.  In  a  heart  bea 
regularly  the  inflow  of  blood  is  proceeding  during  diastole,  during  the  relaxa 
tion  of  the  ventricles,  i.  e.  the  muscles  are  giving  before  the  inflowing  > >1< »< ><  1 
The  latter  is  therefore  able  to  distend  the  heart  without  exercising  more  than 
a  minimum  pressure  on  its  walls,  and  it  is  found  that  the  pressure  in  the  ven- 
tricles may  be  approximately  zero  at  the  end  of  diastole  whether  the  heart 
is  contracting  against  a  resistance  of  80  mm.  Hg.  or  a  resistance  of  120  mm. 
Hg.,  or  whether  it  is  receiving  5  c.c.  or  10  c.c.  during  the  peril  id  of  diastole. 


1004  PHYSIOLOGY 

With  a  larger  outflow  or  a  bigger  resistance  the  energy  of  contraction  is 
increased,  although  the  tension  on  the  heart  wall  at  the  beginning  of  the 
contraction  is  not  altered.  The  only  condition  then,  which  always  changes 
pari  passu  with  the  energy  of  contraction,  is  the  distension  of  the  heart 
cavities,  i.e.  the  length  of  its  muscle  fibres;  and  we  are  therefore  justified 
in  regarding  this  last  factor  as  the  one  which  determines  the  energy  of  the 
response  of  the  muscle  to  excitation.  Naturally  if  the  distension  increased 
beyond  a  certain  extent,  it  would  be  associated  with  increased  tension  on  the 
muscle  fibres.  But  the  changes  of  initial  tension  and  excitatory  response 
are  not  proportional.  It  is  evident  that  the  capacity  of  the  heart  for  adapting 
itself  to  changes  in  mechanical  demands  made  upon  it  will  be  limited  by  the 
inability  of  the  heart  to  dilate  further,  as  is  probably  the  case  in  the  intact 
animal,  where  its  dilatation  is  limited  by  the  pericardium  or  by  the  mechani- 
cal disadvantage  at  which  the  further  dilated  heart  acts.  The  more  the 
heart  attains  a  globular  form,  the  greater  the  mechanical  disadvantage  of 
the  muscle  fibres  in  raising  the  pressure  in  the  interior  of  the  ventricles  (vide 
p.  960),  so  that  by  continually  increasing  the  demands  on  the  heart,  we  shall 
finally  arrive  at  a  stage  at  which  this  organ  is  unable  to  deal  with  the  blood 
applied  to  it  and  rapidly  fails  to  expel  any  of  its  contents. 

The  physiological  condition  of  the  heart  is  measured  by  the  maximum 
pressure  which  it  is  able  to  produce  in  its  cavities  when  it  contracts,  starting 
from  a  certain  initial  size  or  length  of  fibres.  As  the  heart  becomes  fatigued 
this  pressure  falls,  so  that  the  heart  must  dilate  in  order  that  each  contraction 
shall  produce  the  same  maximum  pressure  as  before.  Fatigue  of  the  heart  is 
shown  therefore,  not  by  failure  to  do  its  work,  but  by  the  fact  that  it  can 
do  its  work  only  when  it  is  undergoing  considerable  dilatation.  Dilatation 
is  therefore  a  measure  of  fatigue.  What  is  often  spoken  of  as  the  tonus 
of  the  heart  is  really  synonymous  with  physiological  condition.  A  heart 
in  good  condition  has  a  high  tonus.  It  empties  itself  almost  completely 
at  each  beat,  even  when  receiving  a  considerable  quantity  of  blood  during 
diastole.  A  heart  with  a  low  tonus  is  in  the  condition  of  a  fatigued  heart. 
It  is  widely  dilated  and  when  it  has  finished  contracting  still  contains  a  large 
amount  of  residual  blood. 

This  property  of  the  cardiac  muscle  is  responsible  for  the  power  of 
'  compensation '  possessed  by  a  diseased  heart.  We  may  take  as  an  example 
the  destruction  of  one  aortic  valve,  a  lesion  which  can  be  produced  experi- 
mentally in  a  dog.  In  this  case,  immediately  after  the  lesion  is  established, 
no  additional  resistance  is  offered  to  the  expulsion  of  the  blood,  and  the  ven- 
tricle will  send  the  normal  amount  into  the  aorta.  During  the  succeeding 
diastole  the  blood  at  a  high  pressure  in  the  aorta  will  leak  back  into  the 
ventricle  through  the  damaged  valve.  The  arterial  pressure  therefore  falls 
rapidly,  and  the  ventricle  receives  blood  from  two  sides,  i.  e.  by  regurgitation 
through  the  aortic  valves,  and  in  the  normal  way  from  the  auricles  and  veins. 
At  the  end  of  diastole  the  ventricle  is  therefore  overfilled.  Increased 
stretching  of  its  fibres  however  has  the  effect  of  exciting  an  increased  con- 
traction, and  the  heart  at  its  next  systole  throws  out  not  only  the  normal 


THE  CAUSATION  OF  THE  HEART   BEAT  1005 

quantity  of  blood  but  also  that  which  it  has  received  back  from  the  aorta. 
The  arterial  system  thus  receives  at  each  beat  the  normal  quantity  of  blood 
plus  the  amount  which  leaks  back  into  the  ventricle  after  each  systole ; 
so  that  the  amount  of  blood  remaining  in  the  aorta  and  available  for  passage 
on  to  the  capillaries  is  the  same  as  in  the  normal  animal.  On  this  account, 
after  a  lesion  of  the  aortic  valves  has  been  established,  the  average  of  the 
arterial  pressure  remains  the  same  as  before,  although  the  oscillations  of 
pressure  with  each  heart  beat  are  increased  in  extent.  The  augmented 
output  by  the  ventricles  naturally  involves  increased  work  on  the  part  of  their 
muscular  walls,  which  react  in  the  same  way  as  skeletal  muscle  does  to 
increased  work,  i.  e.  by  hypertrophy.  The  final  effect  therefore  is  a  heart 
bigger  than  normal,  with  hypertrophied  and  thickened  .walls,  but  capable 
of  maintaining  an  adequate  circulation  throughout  all  parts  of  the  body; 
in  other  words,  in  the  healthy  animal  complete  compensation  has  taken 
place. 

4 


Fig.  449.  Tracing  of  contractions  of  a  frog's  heart  (by  Ringer),  showing  effect 
of  adding  a  trace  of  GaCl2  to  the  NaCl  solution  used  previously  for  perfusion. 
The  arrow  marks  the  point  at  which  the  addition  was  made. 


INFLUENCE    OF    TEMPERATURE    ON    THE    HEART   RATE 

The  frequency  of  the  heart  varies  directly  with  the  temperature.  The 
higher  the  temperature  the  greater  the  frequency.  At  40°  C.  the  contraction 
of  the  mammalian  heart  may  be  four  times  as  frequent  as  at  25°  C. 


INFLUENCE    OF    THE   CHEMICAL   COMPOSITION    OF   THE 
SURROUNDING   MEDIUM   ON   THE    HEART   MUSCLE 

The  tissues  of  the  heart,  like  all  other  cells  of  the  body,  require  for  the 
normal  display  of  their  functions  a  definite  osmotic  environment,  i.  e.  a 
certain  molecular  concentration  of  the  fluid  with  which  they  are  bathed. 
This  is  equivalent  to  a  0-65  per  cent,  sodium  chloride  solution  for  the  frog's 
heart,  and  to  a  0-9  per  cent,  solution  for  the  mammalian  heart.  As  Ringer 
first  showed,  the  nature  of  the  neutral  salt  employed  for  making  up  the 
normal  solution  is  all-important  to  the  heart  muscle.  Thus  a  strip  of 
muscle  from  the  apex  of  the  tortoise's  ventricle  as  a  rule  does  not  beat 
spontaneously.  If  it  be  immersed  in  a  0-7  per  cent,  solution  of  sodium 
chloride,  it  begins  to  beat  rhythmically  after  a  short  latent  period.  The 
contractions  soon  reach  a  maximum  and  then  gradually  die  away.  Sodium 
chloride  therefore  acts  as  a  stimulus  to  contraction,  but  is  unable  tq 
maintain  the  beats  for  any  considerable  length  of  time.  The  strip  of 
muscle  ceases  contracting  in  a  condition  of  relaxation.     On  now  adding 


1006  PHYSIOLOGY 

to  the  solution  a  trace  of  calcium  chloride  or  calcium  sulphate,  the  con- 
tractions begin  again  (Fig.  449).  The  relaxations  after  each  contraction 
then  become  more  and  more  incomplete,  until  finally  the  heart  stops  in  a 
tonically  contracted  condition.  If  now  a  trace  of  potassium  chloride  or 
phosphate  be  added,  the  contractions  recommence  and  may  last  for  many 
hours,  although  the  solution  contains  nothing  which  can  furnish  energy 
to  the  contracting  muscle.  It  has  been  suggested  that  the  rhythmic  con- 
tractions of  the  heart  muscle  may  be  the  result  of  the  constant  chemical 
stimulus  of  the  inorganic  salts  present  in  the  blood  plasma,  sodium  acting 
as  a  stimulus  to  contraction,  while  the  calcium  salts  are  necessary  for  the 
maintenance  of  the  systolic  tone,  and  the  potassium  salts  for  the  occurrence 
of  relaxation. 

The  exact  significance  of  these  different  salts  for  the  functions  of  cardiac 
and  other  forms  of  muscular  tissue,  though  they  have  been  the  subject  of 
many  detailed  investigations,  must  be  still  regarded  as  an  open  question. 


Fig.  450.     A  frog's  heart,  poisoned  by  excess  of  calcium  salts,  recovers  its  spontaneous 
rhythm  on  adding  a  trace  of  KC1  to  the  perfusion  fluid.     (Ringer). 

The  fluids,  containing  the  three  salts  mentioned  above  in  slightly  varying 
proportions,  are  commonly  used  to  maintain  the  beat  in  an  excised  heart 
either  of  a  cold-  or  of  a  warm-blooded  animal.  In  the  case  of  the  latter  it 
is  necessary  to  keep  the  fluid  saturated  with  oxygen.  According  to  Locke 
the  addition  of  glucose  to  the  solutions  enables  the  beats  to  go  on  for  a 
longer  period  of  time,  and  will  in  fact  renew  the  rhythm  of  a  heart  which 
has  ceased  beating  while  being  fed  with  pure  saline  solution. 

The  following  represent  the  fluids  most  frequently  used  : 

Ringer's  Fluid 

(for  frog's  heart)  • 

1     per  cent,  sodium  bicarbonate    .  .  .  .1  c.c. 

1  ,,        calcium  chloride  .  •  •  .1  c.c. 

1  „        potassium  chloride     ....     0-75  c.c. 

0-6        „        sodium  chloride  .  .  .to   100  c.c. 

Locke's  Fluid 
(for  mammalian  heart) 
0-015  per  cent,  sodium  bicarbonate, 


0-024 
0-042 
0-92 

,,         calcium  chloride, 
„        potassium  chloride, 
,,         sodium  chloride, 

0-1 

„        glucose, 
in  distilled  water. 

The  influence  of  the  chemical  composition  of  the  medium  on  the  contraction  of  the 
heart  may  be  investigated  in  the  following  ways  : 


THE  CAUSATION   OF  THE  HEART   BEAT 


1007 


One  of  the  simplest  methods  is  that  devised  by  Goteh,  represented  in  the  diagram 
(Fig.  451).  The  apparatus  consists  of  a  small  glass  jar  with  inlet  and  outlet  tubes. 
A  disc  of  cork  is  fixed  on  to  a  brass  rod  so  that  it  can  be  let  down  into  the  fluid.  On 
the  upper  end  of  the  brass  rod  is  poised  a  light  lever  with  a  paper  point.  To  fix  the 
heart  in  the  apparatus,  the  top  of  the  ventricle  is  transfixed  by  a  fine  hook  to  which  is 
attached  a  thread  connected  with  the  lever.  The  heart  is  fastened  to  the  cork  by  a  pin 
through  the  bulbus  aorta?.  The  glass  jar  is  filled  with  the  fluid  whose  action  it  is 
desired  to  investigate.  It  is  usual  to  start  with  Ringer's  fluid  in  order  to  obtain  a 
normal  beat,  and  then  to  try  in  turn  the  various  constituents  of  this  fluid. 


"NT 


Fig.  451.     Gotch's  frog  heart  apparatus. 


Fit;.  452.  Brodie's  perfusion 
apparatus  for  the  mamma- 
lian heart. 


Another  method  of  investigating  the  action  of  the  heart  of  cold-blooded  animals  is 
by  perfusing  the  heart  cavities  with  the  fluid  under  investigation.  Two  forms  of 
perfusion  are  made  use  of.  In  the  method  first  introduced  by  Williams  a  double 
cannula  is  tied  into  the  ventricle,  the  rest  of  the  heart  being  cut  away.  The  tubes 
leading  to  and  away  from  the  perfusion  cannula  are  armed  with  valves  so  as  to  allow 
the  fluid  to  pass  only  in  one  direction.  The  contractions  of  the  ventricle  may  be 
recorded  either  by  connecting  the  outgoing  tube  with  a  manometer,  which  may  bo  a 
mercurial  or  a  membrane  manometer,  or  by  connecting  some  form  of  recording  apparatus 
with  the  vessel  in  which  the  heart  is  contained,  so  as  to  register  changes  in  the  volume 
of  the  ventricle.  A  large  number  of  different  forms  of  apparatus  have  been  devised 
for  these  purposes. 

In  another  method  the  fluid  is  allowed  to  flow  through  the  whole  heart  pa  sing  in 
by  the  sinus  and  out  by  the  aorta.  Here  again  the  activity  of  the  heart  may  be  registered 
either  by  recording  the  pulsations  in  the  arterial  column  of  fluid  or  by  connecting  a 
tambour  or  piston  recorder  with  the  vessel  in  which  the  heart  is  contained. 


1008  PHYSIOLOGY 

The  heart  of  warm-blooded  animals  can  also  be  investigated  by  a  somewhat  similar 
method.  It  was  shown  by  Porter  that  the  mammalian  heart  could  be  kept  alive  by 
transfusing  oxygenated  blood  serum  through  the  coronary  vessels,  and  Locke  found 
that  the  same  results  could  be  obtained  by  using  oxygenated  Ringer's  solution,  modified 
so  as  to  have  the  same  tonicity  as  mammalian  blood.  Brodie's  apparatus  for  this 
purpose  consists  of  a  chamber  a  to  contain  the  heart,  and  of  a  tube  B,  through 
which  the  perfusion  fluid  is  carried  to  the  heart  (Fig.  452).  Both  are  enclosed  in  a 
large  outer  jacket  c,  through  which  is  kept  flowing  a  stream  of  water  at  body  tempera- 
ture. The  chamber  a  is  bell-shaped  and  is  fitted  into  the  jacketing  tube  c  by  a  ground- 
glass  joint  d.  Its  upper  orifice  is  closed  by  a  piece  of  rubber  tubing  of  such  size  that 
the  perfusion  tube  b  slips  through  it  easily.  By  means  of  the  glass  handle  v,  fused  into 
the  tube  about  half-way  down,  B  can  be  drawn  up  or  lowered  into  any  desired  position. 
To  its  lower  end  the  heart  cannula  is  attached  by  a  ground  joint.  Its  upper  end  is 
fitted  by  a  second  ground  joint  with  a  small  bulb  w,  which  has  two  tubes,  E  and  S,  fitted 
into  it.  These  latter  are  connected  by  rubber  tubing  with  aspirators  containing  the 
solutions  to  be  perfused.  The  lower  half  of  the  tube  B  is  nearly  filled  up  with  a  thermo- 
meter L,  the  bulb  of  which  projects  into  the  heart  cannula  T.  The  upper  half  is  almost 
filled  with  a  piece  of  glass  tubing  sealed  at  both  ends,  so  that  the  perfusion  fluid  passes 
in  a  thin  layer  down  the  tube  and  thus  offers  a  large  surface  for  heating  purposes.  Also 
by  filling  the  interior  of  the  tube  in  this  way  its  capacity  is  reduced  to  a  very  small 
amount.  The  large  outer  tube  O  is  kept  supplied  with  warm  water,  entering  through  the 
tube  o  and  overflowing  through  a  side-tube  at  the  top  into  a  wide  T-piece  n.  By  raising 
or  lowering  this  T-piece  the  level  of  the  water  in  the  jacket  is  adjusted.  The  water- 
supply  comes  from  a  cold-water  tap,  but  on  its  passage  to  g  passes  through  a  metal 
spiral  heated  by  a  Bunsen  burner.  By  varying  the  rate  of  flow  and  the  position  of  the 
burner,  the  temperature  of  the  water  can  be  regulated  with  considerable  accuracy. 
The  upper  end  of  the  supply-tube  G  is  provided  with  a  thermometer  so  that  the  tempera- 
ture of  the  inflowing  water  can  be  seen  and  regulated.  In  using  the  apparatus  the 
heart  cannula  is  removed,  and  the  tube  b  is  then  passed  through  e  and  pushed  down 
until  its  lower  end  issues  just  below  the  level  of  the  chamber  A.  The  circulation  of  the 
warmed  water  through  the  jacket  is  thenstarted  and  adjusted  to  the  proper  temperature. 
One  of  the  rubber  tubes,  s,is  next  attached  to  the  reservoir  containing  the  main  perfusion 
fluid,  and  the  tube  b  filled  with  fluid  and  left  to  warm  while  the  heart  is  being  prepared. 
The  heart  having  been  excised  and  washed  well  in  saline  so  as  to  remove  as  much 
blood  as  possible,  the  cannula  is  tied  into  the  aorta.  The  cannula  is  now  held  under 
the  perfusion  tube,  filled  with  the  warm  saline,  and  at  once  attached  in  its  proper 
position  and  the  perfusion  started.  A  bent  pin,  to  which  a  long  thread  is  tied,  is  hooked 
into  the  apex  of  the  heart,  and  the  perfusion  tube  pulled  up  until  the  heart  lies  quite 
within  the  warm  chamber.  When  thus  drawn  up  the  bulb  w  lies  just  below  the  surface 
of  the  water  in  the  outer  jacket.  The  tube  is  held  firmly  in  position  by  a  clamp  which 
fixes  one  arm  of  the  handle  J\  The  heart  cannula  is  provided  with  a  side  opening  v, 
on  to  which  a  long  piece  of  fine  rubber  tubing  is  passed.  This  renders  possible  the 
removal  of  any  gas  bubbles  that  may  collect  in  the  cannula,  or  the  washing  out  of  the 
cannula  with  a  stream  of  fluid  if  necessary.  The  beats  of  the  heart  are  recorded  by 
means  of  a  simple  lever  attached  by  the  thread  previously  fixed  to  the  heart. 

THE  SIGNIFICANCE  OF  THE  REACTION  OF  THE  BLOOD  FOR  THE 
HEART  BEAT.  It  was  long  ago  shown  by  Gaskell  that  the  reaction  of  the 
perfusing  fluid  has  a  marked  influence  on  the  frog's  heart.  When  weak 
acids  are  transfused  through  this  heart,  there  is  a  gradual  diminution  of 
tonus,  the  beats  become  smaller  and  finally  disappear.  A  similar  relaxation 
may  be  obtained  as  the  result  of  the  action  of  carbon  dioxide.  Weak 
alkalies  on  the  other  hand  produce  a  gradual  decrease  of  tonus,  so  that  the 
heart  is  finally  arrested  in  a  contracted  condition.  There  will  thus  be 
some  reaction,  intermediate  between  the  weak  acid  and  the  weak  alkaline 


THE  CAUSATION  OF  THE  HEART   BEAT  1009 

fluids,  which  will  represent  the  optimum  reaction  for  the  beat  of  the  frog's 
heart.  Mines  has  shown  that  this  optimum  reaction  differs  for  the  different 
cavities  of  the  heart,  and  also  for  the  hearts  from  various  animals,  a 
shifting  of  the  reaction  of  the  transfusing  fluid  to  the  acid  side  always 
bringing  about  a  diminished  contraction  and  tonus,  while  the  opposite 
effects  are  produced  by  an  increase  in  the  alkaline  reaction.  In  the 
mammal  under  normal  conditions,  the  chief  factor  affecting  the  reaction  of 
the  blood  is  the  tension  of  carbonic  acid  in  this  fluid ;  and  an  increase  in  the 
carbonic  acid  of  the  blood,  when  sufficiently  pronounced,  always  brings 
about  dilatation  of  the  heart.  The  resistance  of  the  hearts  of  different 
animals  is  however  not  of  the  same  strength.     Thus,  a  dog's  heart  is  much 


I 


rapi'ii'ii'lll  I 


Fig.  453.  Volume  curve  or  ventricles  (cat)  (lower  curve).  The  upper  curve  is  the 
arterial  pressure,  maintained  by  an  adjustable  resistance  at  130  mm.  Hg. 
Between  the  arrows  the  air  used  for  artificial  respiration  was  replaced  by  a 
mixture  containing  20  per  cent.  CO,  and  25  per  cent,  oxygen.  Note  the 
dilatation  with  impaired  contraction,  followed  by  increased  amplitude  of 
contraction. 

more  susceptible  to  the  presence  of  a  small  excess  of  carbonic  acid  in  the 
blood  than  is  the  cat's  heart  (cp.  Fig.  453).  There  is  probably  an  optimum 
tension  of  carbon  dioxide  in  the  blood,  varying  between  5  and  6  per  cent, 
of  an  atmosphere,  at  which  the  physiological  condition  of  the  ventricular 
muscle  is  at  an  optimum,  but  the  tension  may  be  reduced  considerably 
below  this  without  causing  any  marked  change  in  the  action  of  the  heart. 

V  uidell  Henderson  found  that  vigorous  artificial  ventilation  of  the  lungs  brought 
about  a  condition  in  which  the  heart's  contraction  was  very  forcible  and  the  heart's 
cavities  almost  empty.  He  ascribed  this  condition  to  the  hypertonicity  of  the  heart 
muscle  produced  by  washing  the  carbonic  acid  out  of  the  blood.  These  results  were 
however  probably  due  to  the  mechanical  influence  of  the  respiratory  movements 
on  the  venous  filling  of  the  heart;  and  there  seems  no  reason  to  believe  that  the 
condition  of  '  acapnia '  (deficiency  of  carbon  dioxide  in  the  blood)  had  anything  to 
do  with  the  results  observed.  The  improving  effects  of  administration  of  carbon 
dioxide,  described  in  the  first  edition  of  this  work,  have  not  been  confirmed  b\ 
recent  and  accurate  experiments. 


THE   NUTRITION   OF   THE   HEART 

Li  the  frog's  heart  the  muscle  fibres  are  supplied  directly  by  the  blood 
within  the  cavities,  the  spongy  ventricular  wall  permitting  the  access  of 
64 


1010  PHYSIOLOGY 

blood  between  the  fibres.  In  the  mammalian  heart  the  muscular  tissue  is 
nourished  through  the  coronary  arteries,  which  break  up  into  a  mesh-work 
of  capillaries  around  all  the  fibres. 

The  flow  of  blood  through  the  coronary  circulation  may  be  measured,  either  in 
the  whole  animal  or  in  the  heart-lung  preparation,  by  introducing  a  cannula  through  the 
wall  of  the  right  auricle  into  the  coronary  sinus  and  collecting  the  blood  from  the  latter 
outside  the  body.  Another  method  is  to  feed  a  heart  from  the  aorta  through  the 
coronary  arteries  with  blood  and  collect  the  total  outflow  from  the  cut  pulmonary  artery. 
By  a  comparison  of  these  two  methods,  it  is  found  in  the  dog  that  the  blood  flow  through 
the  coronary  sinus  forms  about  three-fifths  of  the  total  blood  passing  through  the 
coronary  arteries.  It  is  therefore  possible  to  measure  the  flow  through  the  coronary 
sinus  in  the  heart-lung  preparation  under  varying  conditions  of  pressure  and  output. 
The  figures  so  obtained  multiplied  by  f:  will  represent  approximately  the  total  flow 
through  the  coronary  circulation. 

Blood  enters  the  coronary  arteries  from  the  aorta  both  during  systole 
and  diastole,  though  it  is  probable  that  the  systole  of  the  ventricles  exercises 
a  direct  effect  in  increasing  the  resistance  to  the  flow  of  blood  through  the 
heart,  and  squeezes  out  the  contained  blood  into  the  coronary  veins.  This 
may  be  one  reason  why  the  flow  of  blood  through  the  coronary  system  is 
greater  in  a  beating  heart  than  in  a  heart  which  is  quiescent.  The  most 
important  factor  in  determining  the  flow  through  the  coronary  vessels  is  the 
arterial  pressure.  The  marked  effect  of  this  factor  is  shown  in  the  following 
Table : 

Heart  weight,  107  gms.     Total  output  per  minute,  1400  c.c. 

Arterial  Coronary  circulation 

pressure  per  minute 

60  50 

100  90 

128  124 

166  208 

190  500 

We  see  from  this  Table  that  the  heart  muscle  is  supplied  with  blood 
in  proportion  to  its  needs,  since  its  work  and  its  respiratory  exchanges 
increase  continuously  with  the  rise  of  arterial  resistance.  Indeed  in  this 
particular  experiment,  under  the  severe  test  of  contracting  against  an  average 
pressure  of  190  mm.  Hg.,  over  one-third  of  the  whole  blood  leaving  the  heart 
was  passing  through  its  muscular  walls,  one  gramme  of  muscular  tissue  being 
irrigated  with  5  c.c.  of  blood  per  minute.  Another  important  factor  in 
determining  the  coronary  flow  is  the  effect  of  the  metabolites  produced 
by  the  contracting  heart  muscle  itself.  This  is  well  shown  when  the  heart 
is  asphyxiated.  Thus  in  one  experiment  while  the  arterial  pressure  was  main- 
tained constant,  the  total  coronary  flow  was  56  c.c.  per  minute.  Artificial 
respiration  was  then  discontinued,  and  during  the  succeeding  minutes  the 
coronary  circulation  was  61,  72,  150,  180.  The  circulation  then  failed.  Car- 
bonic acid  produces  also  an  increase  in  the  flow  through  the  coronary  arteries, 
but  it  is  impossible  with  the  highest  attainable  percentages  of  carbon 
dioxide  in  the  blood  to  effect  such  an  increase  in  the  coronary  flow  as  is 
observed  during  asphyxia.     The  dilatation  of  the  coronary  vessels,  which 


THE   CAUSATION   OF   THE   HEART   BEAT  1011 

occurs  in  the  latter  condition,  must  therefore  be  ascribed  to  non -gaseous 
metabolites  produced  by  the  contracting  muscle.  Thus  the  heart  contains 
in  itself  a  mechanism  for  increasing  the  flow  of  blood  through  its  tissues, 
whenever  this  becomes  inadequate  and  the  muscle  is  suffering  for  lack  of 
oxygen.  Mechanical  and  physiological  factors  thus  co-operate  in  providing 
the  most  important  muscle  in  the  body  with  oxygen  sufficient  for  its  needs. 

If  a  coronary  artery  be  ligatured,  the  heart  very 'often  beats  for  one  or 
two  minutes  with  unimpaired  force,  then  a  beat  is  dropped  occasionally, 
and  very  shortly  afterwards  the  heart  stops  altogether  and  the  blood 
pressure  falls  to  zero.  On  inspection  of  the  heart  immediately  after  the 
blood  pressure  has  fallen,  its  muscular  wall  is  seen  to  be  in  a  state  of  fibrillar 
contractions,  or  '  delirium  cordis.'  All  the  strands  of  muscle  fibres  are 
contracting  more  or  less  rhythmically,  but  the  rhythms  of  no  two  parts 
coincide,  so  that  the  heart  dilates  and  is  incapable  of  carrying  on  the  circula- 
tion It  is  probably  in  this  way  that  sudden  deaths  occur  in  cases  where 
the  coronary  arteries  are  diseased  or  calcified.  In  such  cases  a  man  may 
drop  down  dead,  having  previously  shown  no  symptoms  of  heart  mischief. 

Delirium  cordis  may  be  explained  as  the  result  of  block,  produced  by 
interference  with  the  nutrition  of  a  large  part  of  the  cardiac  wall.  The  con- 
tractile wave  arriving  at  this  part,  in  some  directions  will  not  spread  at  all, 
in  others  will  spread  at  a  lower  rate,  so  that  different  parts  of  the  heart 
receive  the  impulse  to  contract  at  different  times  and  a  state  of  inco- 
ordination results.  The  same  condition  can  be  produced  by  freezing  the 
apex  of  the  ventricle,  so  causing  a  block,  or  by  stimulating  the  surface  of  the 
ventricle  at  a  rate  which  is  greater  than  can  be  taken  up  by  the  ventricle  as 
a  whole,  as,  e.g.,  by  tetanising  currents.  Such  a  condition  in  the  higher 
animals,  as  the  dog  and  man,  is  practically  irrecoverable,  although  in  the 
rabbit,  and  very  rarely  in  the  dog,  it  is  sometimes  possible  to  bring  the  heart 
back  to  a  state  of  rhythmic  contraction  by  kneading  it  rhythmically. 

According  to  Mines  delirium  cordis  is  susceptible  of  a  simpler  explanation.  This 
condition  is  easily  brought  on  in  the  mammalian  heart  by  stimulation  of  its  surface  with 
strong  faradic  currents.  The  effects  on  the  heart  muscle  of  increased  frequency  of  con- 
traction are  to  decrease  the  rate  of  propagation  and  to  decrease  the  length  of  the  wave 
of  excitation.  Ordinarily  in  the  naturally  beating  heart  the  wave  of  excitation  is  so  long 
and  spreads  so  rapidly,  that  it  excites  the  whole  of  the  ventricle  at  a  considerable 
interval  before  it  has  ceased  ill  any  one  part.  When  however  the  muscle  is  stimulated 
more  frequently,  the  wave  becomes  slow  and  short,  so  that  more  than  one  wave  can 
exist  at  one  time  in  a  single  chamber.  The  main  factor  then,  in  the  production  of 
delirium  cordis  after  obstruction  of  the  coronary  artery,  would  probably  be  a  diminished 
rate  of  conduction  through  the  affected  part. 


SECTION  IX 

THE    NERVOUS    REGULATION    OF   THE    HEART 

In  order  that  the  activity  of  the  heart  may  be  adapted  to  the  needs  of  the 
body  as  a  whole,  its  automatic  mechanism  must  be  subject  to  the  centra! 
nervous  system,  which  must  be  able  to  affect  the  heart  in  either  of  two  ways, 
viz.  by  increasing  or  diminishing  its  activity.  This  subjection  to  the 
integrative  action  of  the  central  nervous  system  is  also  necessary  for  the 
sake  of  the  organ  itself;  otherwise  the  peripheral  adaptation  of  the  heart 
muscle  to  change  in  arterial  resistance  might  result  in  its  exhaustion  and 
permanent  damage. 

The  regulation  is  effected  through  the  intermediation  of  afferent  and 
efferent  nerve  fibres  connecting  the  heart  with  the  central  nervous  system. 
The  importance  of  these  nerves  is  shown  by  the  behaviour  of  animals  in 
which  they  have  been  extirpated.  Thus  a  dog,  in  whom  all  the  nerves  of  the 
heart  had  been  divided,  survived  the  operation  for  eight  months,  the  pulse 
reading  during  the  time  not  having  appreciably  altered  and  the  animal  being 
in  a  fair  condition  of  health.  Although  he  regained  his  normal  weight  after 
the  operation,  he  was  found  incapable  of  carrying'  out  even  a  moderate 
amount  of  work,  such  as  that  represented  by  running,  since  the  mechanism 
for  increasing  the  action  of  the  heart  in  response  to  the  needs  of  the  muscles 
had  been  lost. 

THE  EFFERENT  CARDIAC  NERVES 

The  heart  in  vertebrates  is  supplied  with  nerve  fibres  from  two  sources : 
from  the  medulla  oblongata  along  the  vagus  nerve,  and  from  the  upper 
dorsal  region  of  the  spinal  cord  through  the  mediation  of  the  sympathetic 
system. 

The  fibres,  which  run  through  the  sympathetic  system,  take  a  somewhat 
different  course  in  the  animals  on  which  the  regulation  of  the  heart's  activity 
has  been  chiefly  studied,  viz.  the  frog  and  the  mammal.  In  the  frog 
(Fig.  454)  the  sympathetic  fibres  leave  the  spinal  cord  by  the  anterior  root 
of  the  third  spinal  nerve ;  they  then  pass  through  the  ramus  communicans 
to  the  corresponding  sympathetic  ganglion,  whence  they  run  up  through 
the  second  ganglion  and  the  annulus  of  Vieussens  to  the  first  ganglion; 
they  then  pass  into  the  cervical  sympathetic  strand  to  the  ganglion  trunci 
vagi ;  here  they  join  the  vagus  and  pass  down  with  the  true  vagus  fibres 
to  the  heart. 

In  the  dog  (Fig.  455)  the  sympathetic  fibres  leave  the  spinal  cord 
by  the  anterior  roots  of  the  second  and  third  dorsal    nerves,  run    in  the 


THE  NERVOUS  REGULATION  OF  THE  HEART   1013 


white  rami  communicantes  to  the  stellate  ganglion,  and  thence  by  the 
Hamulus  of  Vieussens  to  the  inferior  cervical  ganglion.  Cardiac  branches 
convey  the  sympathetic  fibres  to  the  heart  and  are  given  off  from  the 
stellate  ganglion,  the  inferior  cervical  ganglion,  and  from  the  trunk  of 
the  vagus. 

By   the   nicotine   method   it  is   possible   to   trace   out   the   cell   connections   of 
these  fibres.     As  they  leave  the  cord  they  are  medullated  nerve  fibres,  similar  to  the 


.^Juq.  Gancjl.  Vagus 


Vago-symparhft 


Vert.  I. 
Aorta 


FIG.  4f>4.  Sympathetic  chain  of  frog  (right  side)  to  show  connection  with  vagus 
nerve.  The  sympathetic  ganglia  with  their  branches  are  black.  Of  the 
peripheral  branches  only  the  splanchnic  nerve  is  represented.  (Modified 
from  E( 

other  fibres  making  up  the  visceral  outflow  throughout  the  dorsal  region;  the  white 
Sbrea  pass  along  the  ramus  communicans  to  the  stellate  ganglion,  where  they  end. 
forming  synapses  with  the  cells  of  the  ganglion.  Here  fresh  relays  of  fibres,  winch 
are  non-medullated,  start  and  carry  the  impulses  to  the  heart  along  the  various  cardiac 
nerves  just  mentioned.  In  the  heart  these  fibres  are  distributed  to  the  muscle  fibres 
without  the  intervention  of  any  other  ganglion  cells.  On  the  other  hand  the  fibres, 
which  leave  the  sragus  to  pass  to  the  heart,  make  connection  with  the  cells  of  Bemak's 
ganglion,  and  probably  with  all  the  other  intrinsic  cardiac  ganglia  described  above, 
whence  mm  medullated  fibres  carry  their  impulses  to  the  heart  muscle. 


ACTION    OF    THE    VAGUS 

The  action  (if  the  vagus  fibres  on  the  heart  is  almost  identical  in  frog  and 
mammal.     If  in  the  dog  the  peripheral  end  of  the  cut  vagus  he  stimulated, 


11)1 1 


PHYSIOLOGY 


while  the  arterial  blood  pressure  is  being  recorded  by  means  of  a  mercurial 
manometer,  the  pulse  is  seen  to  become  slower,  or  with  a  stronger  stimulus 
to  cease  altogether,  and  the  blood  pressure  falls  towards  zero.  On  discon- 
tinuing the  stimulus,  the  heart  begins  to  beat  again  and  the  pressure  rises 
after  a  few  beats  to  normal  (Fig.  456). 

If  the  stimulation  of  the  vagus  be  prolonged,  the  blood  pressure,  on  dis- 


X  r.Sp.  \c. 


Fig.  455.     Diagram  of  cardiac  inhibitory  and  accelerator  fibres  in 
the  dog.     (From  Fostek.) 

r.Vg,  roots  of  the  vagus ;  r.Sp.Ac,  roots  of  the  spinal  accessory ;  G.J,  ganglion 
jugulare;  G.h.V,  ganglion  trunci  vagi;  Vg,  trunk  of  vagus  nerve;  C.Sy,  cervical 
sympathetic;  G.C,  inferior  cervical  ganglion;  A.V,  annulus  of  Vieussens;  A.sb,  sub- 
clavian artery ;  n.c,  cardiac  nerves ;  G.St,  ganglion  stellatum ;  D2,  D3,  D4,  D5, 
second,  third,  fourth,  and  fifth  dorsal  spinal  roots;  G.Th,  ganglia  of  the  thoracic 
chain. 


continuance  of  the  stimulus,  may  rise  above  normal  owing  to  the  asphyxia 
of  the  vaso-motor  centres  produced  by  the  prolonged  cessation  of  the 
circulation.  Even  during  the  application  of  the  stimulus  the  heart  often 
begins  to  beat  again  with  a  slow  rhythm.  In  this  case  we  speak  of  an 
'  escape  '  of  the  heart  from  the  vagus  influence.  This  escape  is  generally 
confined  to  the  ventricles,  and  the  heart  beats  are  found  on  opening  the  chest 
to  be  purely  ventricular,  the  auricles  and  great  veins  remaining  in  a  state  of 


THE  NERVOUS  REGULATION   OF  THE  HEART         1015 

diastole.  Vagus  escape  is  favoured  by  distension  of  the  heart  cavities,  and 
is  often  synchronous  with  the  respiratory  efforts,  which  supervene  after  a 
certain  duration  of  inhibition  as  a  result  of  the  asphyxia  of  the  respiratory 
centre. 

When  the  arterial  system  is  dilated,  so  that  the  mean  systemic  pressure, 
and  consequently  the  venous  pressure  during  cardiac  inhibition,  are  low,  or 
when  the  asphyxial  gasps  of  the  animal  are  prevented  by  anaesthesia  or  by  a 
section  of  the  spinal  cord,  the  heart  may  fail  to  recover  from  the  inhibition 
produced  even  by  a  transitory  stimulation  of  the  vagus.  In  such  cases  it  is 
necessary  to  knead  the  heart  in  order  to  reatore  its  rhythmic  action. 

To  study  the  influence  of  the  vagus  on  the  auricles  and  ventricles 
respectively,  it  is  necessary  to  work  with  the  chest  opened  and  to  record 
separately  the  contractions  of  the  different  segments  of  the  heart .    It  is  then 


Fig.  456.     Blood  pressure  tracing  from  carotid  of  dog  (taken  with  Hiirthle's 
manometer),   showing  effect  of  excitation  of  vagus  (between  the  arrows). 
o,  abscissa  line  of  no  pressure. 

found  that  the  vagus  may  affect  the  heart  in  one  of  several  ways.  Its  most 
marked  action  is  on  that  part  of  the  heart  where  it  enters,  viz.  the  venous 
end.  It  may  affect  that  part  of  the  auricle  corresponding  to  the  primitive 
sinus  venosus,  where  the  rhythm  of  the  whole  heart  is  determined.  In  this 
case  the  sole  effect  of  the  vagus  on  the  auricles  and  ventricles  will  consist  in 
an  alteration  of  rhythm.  They  may  cease  to  beat  altogether  or  they  may 
give  beats  of  normal  strength  but  at  a  slower  rhythm  than  before.  Often 
indeed  under  these  conditions  the  beats  of  the  ventricles  may  be  increased 
in  size,  since  the  strength  and  extent  of  their  contractions  are  determined, 
not  by  the  strength  of  the  stimulus  arriving  from  the  auricles,  but  by 
the  length  of  their  fibres,  and  this  will  be  greater  with  any  prolongation 
of  the  diastolic  period,  and  consequent  increased  diastolic  filling  of  the 
ventricle. 

If  the  vagus  acts  on  the  auricles  without  affecting  the  sinus  part  of  the 
auricles  (sino-auricular  node),  the  rhythm  will  be  unaltered,  but  the  response 
of  the  auricles  to  the  impulses  received  by  them  will  be  diminished,  and  the 
amplitude  of  the  excursions  of  the  lever  attached  to  them  will  therefore  be 
considerably  reduced.  Indeed  the  auricular  contractions  may  be  reduced 
to  such  an  extent  that  they  cause  no  movement  of  the  lever.  It  is  only 
by  observing  their  surface  that  one  may  perceive  a,  slight  contraction  of 


L016  PHYSIOLOGY 

their  fibres.  Under  such  circumstances  the  rhythm  of  the  ventricles  will  be 
unchanged. 

Generally  the  vagus  absolutely  stops  the  action  of  all  parts  of  the  auricles  ; 
in  such  cases  the  ventricles  also  cease  beating.  Very  often  after  a  short 
pause  the  ventricles  commence  to  beat  at  a  slow  rhythm,  and  it  is  then  seen 
that  they  are  contracting  independently  of  the  auricles  and  sinus.  That 
the  ventricle  is  really  inaugurating  the  beat  is  shown  by  the  fact  that  occa- 
sionally one  may  observe  a  reversed  beat,  i.  e.  a  contraction  of  the  auricle 
following  instead  of  preceding  each  ventricular  contraction.  Whether  the 
vagus  has  a  direct  action  on  the  mammalian  ventricle  is  still  doubtful;  its 
effect  is  at  any  rate  very  slight  as  compared  with  that  on  the  venous  end 
of  the  heart.  The  fact  that  stimulation  of  the  vagus  causes  as  a  rule 
temporary  cessation  of  the  ventricular  beat,  while  functional  separation  of 
the  ventricles  from  the  auricles  causes  no  such  temporary  stoppage,  would 
seem  to  indicate  that  this  nerve  has  a  direct,  though  slight,  action  on  the 
ventricles. 

Finally  the  vagus  may  affect  the  tissue  which  conducts  the  excitatory 
process  from  one  cavity  to  another.  Under  vagus  stimulation  the  auricles 
may-  beat  at  a  greater  rhythm  than  the  ventricles,  a  block  having  been 
produced  in  the  tissue  passing  from  auricles  to  ventricles,  viz.  the  auriculo- 
ventricular  bundle. 

Engelmann  has  described  these  effects  of  vagus  excitation  as  negatively  chronotropic 
(diminution  of  rhythm),  negatively  inotropic  (diminished  strength  of  contraction), 
and  negatively  dromotropic  (diminished  conductivity),  and  has  distinguished  a  fourth 
action,  viz.  one  on  the  irritability  of  the  muscle  to  direct  stimuli,  which  he  calls  nega- 
tively batltmotropic.  He.  ascribes  these  four  actions  to  four  different  sets  of  nerve  fibres, 
but  it  is  evident  that  they  are  due  not  so  much  to  a  difference  in  the  nature  of  the 
impulse  as  to  a  difference  in  the  place  of  incidence  of  the  impulse. 

Thus,  if  the,  vagus  fibres  which  are  distributed  to  the  remains  of  the  sinus  are 
specially  active,  we  shall  get  alterations  of  rhythm  affecting  the  whole  heart.  If  those 
which  supply  the  A. V.  bundle  are  excited,  the  most  pronounced  effect  will  be  on  the 
propagation  of  the  excitatory  process  from  auricles  to  ventricles. 

Practically  the  same  description  will  apply  to  the  action  of  the  vagus 
on  the  frog's  heart.  Since  it  is  easy  in  this  animal  to  register  the  contrac- 
tions of  the  empty  heart,  it  is  possible  to  show  that  the  vagus  has  a  direct 
inhibitory  action  on  the  ventricles,  diminishing  the  strength  of  its  contrac- 
tion in  response  to  the  stimuli  transmitted  to  it  from  the  venous  end.  This 
action  of  the  vagus  on  the  ventricle  is  not  however  universal,  and  in  the 
tortoise  it  is  impossible  to  show  any  such  action.  In  both  these  animals 
the  auricles  show  the  same  effects  as  in  the  mammal,  viz.  an  influence 
limited  to  the  rhythm  when  only  the  sinus  is  affected,  or  a  diminution  of  the 
strength  of  contraction  wrhen  the  sinus  is  unaffected  and  the  chief  action  of 
the  vagus  is  on  the  auricular  muscle. 

Ever  since  the  discovery  in  1845  by  the  brothers  E.  H.  and  E.  F.  Weber 
of  the  action  of  the  vagus  on  the  heart,  much  work  has  been  expended  with 
a  view  to  determining  the  intimate  nature  of  the  inhibitory  process.  In 
the  former  neurogenic  theory  it  was  supposed  that  the  vagus  altered  the 


THE  NERVOUS  REGULATION  OF  THE  HEART  1017 

activity,  perhaps  by  a  process  of  '  interference,'  of  the  ganglion  cells  respon- 
sible for  the  origination  of  the  rhythm.  Many  facts  however  point  to  the 
inhibitory  impulses  as  being  continued  to  the  heart  muscle  itself.  Thus 
tetanisation  of  any  portion  of  the  frog's  ventricle,  especially  if  it  be  filled 
with  blood,  causes  an  evident  relaxation  of  the  part  between  the  electrodes. 
Application  of  nicotine  to  the  heart  prevents  stimulation  of  the  trunk  of  the 
vagus  from  having  any  influence  on  the  heart,  presumably  from  paralysis 
of  the  cells  of  Remak's  ganglion,  which  he  at  the  termination  of  the  vagus 
fibres,  or  of  the  synapses  between  the  vagus  fibres  and  the  ganglion  cells. 
It  is  still  possible  to  inhibit  the  heart  by  direct  stimulation  either  of  the 
fibres  leaving  this  ganglion  in  the  sino-auricular  junction,  or  of  the  nerve 
trunks  which  run  in  the  inter-auricular  septum.  We  must  conclude  therefore 
that  the  inhibition  of  the  heart  muscle  is  peripheral  and  depends  on  the 
direct  action  of  the  nerve  fibres  on  the  muscle  cells  themselves.  These  nerve 
fibres  are  paralysed  by  atropine,  after  administration  of  which  no  inhibitory- 
effects  can  be  produced  by  stimulation  of  nerve  or  muscle  or  any  part  of  the 
heart.  On  the  other  hand,  muscarine  apparently  stimulates  the  inhibitory 
nerve-endings,  and  when  applied  to  the  isolated  auricle  or  ventricle  causes 
weakening  of  the  beat  and  finally  complete  inhibition,  an  effect  which  can 
be  removed  by  its  antagonist  atropine. 

Two  views  have  been  held  as  to  the  essential,  nature  of  the  inhibitory 
process.  According  to  that  put  forward  by  Claude  Bernard,  the  natural 
tendency  of  any  tissue  during  rest  is  towards  anabolism.  Activity  involves 
disintegration  or  breaking  down  of  the  living  material,  and  this  disintegra- 
tion must  be  succeeded  by  a  process  of  building  up  or  anabolism,  which 
restores  the  tissue  to  its  previous  functional  condition.  On  this  view  the 
state  of  inhibition  would  merely  prolong  the  period  of  rest  intervening 
between  two  periods  of  activity,  so  allowing  a  greater  time  for  restitution  to 
take  place,  with  a  corresponding  improvement  in  the  functional  capacity  of 
the  tissue.  According  to  Hering  and  Gaskell  a  state  of  anabolism  can  be 
induced  in  a  tissue  comparable  to  the  state  of  sudden  disintegration  which 
is  associated  with  activity.  Excitation  of  the  vagus  nerve  does  not  merely 
allow  the  normal  process  of  building  up,  which  goes  on  during  rest,  to  take 
place,  but  actually  hastens  this  process,  just  as  the  excitation  of  a  motor 
nerve  to  a  skeletal  muscle  induces  an  active  breakdown  of  the  contractile 
tissue,  or  the  excitation  of  the  augmentor  nerve  to  the  heart  induces  an 
increased  rate  of  beat  and  therefore  increased  functional  activity. 

If  stimulation  of  an  inhibitory  nerve  induces  the  opposite  chemical 
change  to  that  occurring  during  activity,  one  would  expect  to  find  that, 
just  as  an  active  part  of  a  tissue  is  negative  to  an  inactive  part,  so  a  part  of 
the  tissue  which  is  under  the  influence  of  an  inhibitory  stimulus  should  be 
electro-posi/uc  to  any  part  which  is  not  being  so  stimulated.  According  to 
GaskeD  this  condition  is  realised  in  the  heart  of  the  tortoise.  The  auricles 
are  brought  to  a  standstill  by  separating  them  from  the  sinus  venosus.  The 
apex  of  one  auricle  is  then  injured  by  heat,  and  the  injured  point  and 
uninjured  base  are  led  off  to  a  galvanometer.    The  usual  demarcation  current, 


1018  PHYSIOLOOxY 

dependent  on  the  difference  of  potential  between  the  injured  and  uninjured 
portion,  is  thus  observed.  If  the  vagus  be  now  stimulated,  the  auricles 
remain  at  rest  but  the  demarcation  current  is  increased,  i.  e.  a  positive 
variation  is  produced — an  electrical  condition  opposed  in  sign  to  that  which 
would  take  place  when  the  auricles  contract.  Doubt  still  exists  however  as 
to  the  exact  interpretation  to  be  put  on  this  experiment- 
It  was  mentioned  above  that  potassium  salts  promote  relaxation  of  the  ventricle, 
so  acting  as  antagonists  to  calcium  salts.  If  potassium  salts  be  present  in  a  sufficient 
concentration  in  the  circulating  fluid,  the  heart  is  brought  to  a  standstill  in  a  condition 
of  diastole,  as  if  the  vagus  mechanism  were  in  action.  On  removal  of  the  excess  of  K 
ions,  the  heart  at  once  starts  beating  again.  Howell  has  shown  that  during  stimula- 
tion of  the  vagus  the  amount  of  potassium  in  a  diffusible  form  in  the  heart  muscle  is 
increased.  He  has  therefore  suggested  that  the  action  of  the  vagus  in  stopping  the 
heart  is  due  to  the  liberation  of  potassium  salts.  Potassium  normally  exists  in  a 
large  percentage  in  the  heart  muscle,  but  in  a  combined  form;  and  Howell  assumes 
that  stimulation  of  the  vagus  effects  a  dissociation  of  this  combined  potassium,  so  that 
the  liberated  ions  arc  able  to  exert  their  inhibitory  influence  on  the  heart. 


THE   TONIC   ACTION   OF   THE   VAGUS 

If  both  vagi  of  a  mammal  be  divided,  the  heart  as  a  rule  beats  more 
frequently,  showing  that  under  normal  circumstances  tonic  impulses  are 
constantly  descending  the  vagi  and  holding  the  heart's  action  in  check. 
The  extent  of  the  quickening,  which  is  produced  by  section  of  the  vagi,  varies 
in  different  animals  and  is  apparently  associated  with  the  conditions  of  life 
of  the  animal  and  its  powers  of  carrying  out  prolonged  muscular  exertions. 
Thus  in  the  dog  or  horse  the  pulse,  which  is  normally  slow,  may  be  doubled 
in  frequency  by  section  of  the  vagi.  In  the  rabbit,  which  has  a  frequent 
pulse  and  is  able  to  run  only  for  a  short  distance,  division  of  both  vagi 
causes  very  little  alteration  in  the  pulse  rate.  It  is  stated  that  the  tonic 
action  of  the  vagi  is  much  greater  in  the  hare  than  in  the  rabbit. 

This  tonic  action  may  be  increased  by  various  conditions  of  the  blood, 
e.g.  the  presence  of  drugs  such  as  morphia. 

ACTION   OF   THE   SYMPATHETIC   CARDIAC   NERVES 

Stimulation  of  the  sympathetic  cardiac  nerves  at  any  part  of  their  course 
has  an  effect  on  the  heart  the  exact  reverse  of  that  produced  by  stimulating 
the  vagi.  In  most  cases  the  pulse  frequency  is  increased  in  consequence 
of  the  action  of  these  nerves  on  that  part  of  the  heart  from  which  the  rhythm 
starts.  The  frequency,  which  is  attained  by  maximal  stimulation  of  the 
accelerator  nerves,  is  independent  of  the  previous  rate  of  the  heart  beat.  The 
increase  in  rate  involves  a  shortening  of  the  time  of  the.  cardiac  cycle,  which 
chiefly  affects  the  diastolic  period.  The  size  of  the  auricular  and  ventricular 
contractions  may  be  increased  at  the  same  time  as  their  rate.  In  fact, 
like  the  vagus  nerves,  the  sympathetic  fibres  of  the  heart  can  influence 
rhythm,  strength  of  contraction,  or  conduction  from  auricle  to  ventricle, 
according  to  the  part  of  the  heart  muscle  which  is  affected. 


THE  NERVOUS  REGULATION  OF  THE  HEART 


1019 


The  augmentor  effect  on  the  strength  of  the  ventricular  beats  is  often 
very  marked.  The  sympathetic  fibres  are  much  less  easily  tired  than  the 
vagus  fibres,  and  have  a  longer  latent  period.  Whereas  the  latent  period 
of  the  vagus  in  the  mammal  is  considerably  less  than  one  second,  that  of 
the  accelerator  nerves  may  amount  to  ten  or  even  twenty  seconds  (Fig.  457). 


mmtrmfmmnmi^^ 


Fig.   457.     Tracings  of  ventricular  (upper  curve)  and  auricular 

contractions  (lower  curve). 
From  x  to  y  the  accelerator  nerves  stimulated.     Lowest  line  —  seconds. 


Flo.  458.  Tracing  to  show  effect  of  stimulation  of  the  vago-sympathetic  nerve  on  the 
frog's  heart.  The  rhythm  is  unaltered,  but  the  beats  of  auricle  and  ventricle 
are  much  decreased  in  size.     On  ceasing  the  stimulation  the  beats  become  augmented. 

((  I  \SKEIX.) 


Fig.  459.     A  tracing  similar  to  Fig.  458.     In  this  case  however,  the  stimulation  caused 
complete  stoppage  (inhibition)  of  both  auricular  and  ventricular  beats.     (Gaskell.) 

Hence  if  the  vago-sympathetic  of  the  frog  be  stimulated,  the  first  effect  is 
inhibition  due  to  vagus  action.  The  vagus  nerve-endings  then  become 
fatigued,  and  the  influence  of  the  accelerator  fibres  makes  itself  apparent; 
the  heart  commences  to  beat,  and  the  beats  become  more  rapid  and  forcible 
than  before  (Figs.  458,  459). 

Like  the  vagus,  the  sympathetic  nerve  fibres  appear  to  exercise  a  tonic 
influence  on  the  heart  so  that,  after  extirpation  of  the  stellate  ganglion  on 
each  side,  the  pulse  frequently  becomes  permanently  slowed. 


1020 


PHYSIOLOGY 


THE   ACTION   OF   ADRENALINE    ON   THE   HEART 

The  medullary  part  of  the  suprarenal  glands  forms  and  secretes  into  the 
blood  stream  a  substance,  adrenaline,  which  has  a  marked  action  both  on  the 
heart  and  blood  vessels  and  plays  therefore  an  important  part  in  the  regula- 
tion of  the  circulation.  Whether  this  secretion  is  a  constant  one  has  not  yet 
been  fully  ascertained,  but  there  is  no  question  that  under  certain  specified 
conditions  there  may  be  a  marked  influx  of  this  substance  into  the  blood 
stream.  The  action  of  adrenaline  on  any  part  of  the  body  is  practically 
identical  with  that  of  excitation  of  the  sympathetic  nerve  supply  to  the  same 
part.     Its  isolated  action  on  the  heart  is  best  studied  on  the  perfused  heart  or 


- 

150 

100 

a 

50 

Fig.  400. 
Intraventricular  pressure  tracings  (left  ventricle)  from  dog's  heart  (heart-lung 
preparation).     (To  be  read  from  right  to  left.)     The  scale  shows  pressure 
in  mm.  Hg. 

a.  Under  influence  of  adrenaline. 

b.  Under  simultaneous  influence  of  adrenaline  and  C02  (15  per  cent.)     (Patterson). 


in  the  heart-lung  preparation.  On  adding  j1,,  mgm.  of  this  substance  to  the 
500  c.c.  of  blood  circulating  through  the  heart-lung  preparation,  a  maximum 
effect  is  at  once  produced  and  this  lasts  for  15  to  20  minutes.  The  action  is, 
like  that  of  the  sympathetic  nerve,  accelerator  and  augmentor.  Through 
its  influence  on  the  sinus  or  the  sino-auricular  node,  the  rhythm  of  the  heart 
is  markedly  increased,  in  the  dog  to  about  240  per  minute.  At  the  same  time 
the  energy  of  each  contraction  is  augmented.  This  is  especially  shown  in  a 
heart  which  is  beginning  to  fail  and  is  therefore  undergoing  a  certain  degree 
of  dilatation.  Directly  the  adrenaline  reaches  the  heart,  the  contractions 
become  extremely  energetic  so  that  the  heart  rapidly  diminishes  in  volume, 
the  venous  pressure  falls,  and  the  blood  flowing  into  it  at  each  diastole  is 
thrown  out  with  violence  into  the  aorta.  The  more  powerful  beat  enables 
the  output  of  the  heart  at  each  beat  to  be  maintained  or  even  increased,  in 
spite  of  the  shorter  duration  of  the  systole.  With  each  beat  the  maximum 
pressure  in  the  ventricle  therefore  rises  to  a  marked  extent  (see  Fig.  460). 


THE  NERVOUS  REGULATION  OF  THE  HEART    1021 

The  strain  oil  the  ventricular  wall  of  this  sudden  contraction,  which  is 
necessary  to  empty  the  heart  during  the  period  of  systole,  is  often  so  great 
that  small  haemorrhages  are  produced  throughout  the  substance  of  the 
muscle.  The  stimulation  effect  of  adrenaline  is  shown  moreover  by  the 
considerable  rise  in  the  respiratory  exchanges  of  the  heart  under  the  influence 
of  this  substance,  the  oxygen  intake  being  increased  two  or  three  times  above 
that  which  obtained  before  the  administration  of  the  adrenaline.  The  action 
of  adrenaliue  therefore  is  in  general  to  enable  the  heart  to  cope  with  a  bigger 
strain,  either  in  the  shape  of  arterial  resistance  or  increased  venous  inflow, 
than  it  could  do  without  the  stimulus  of  this  substance. 

The  wonderful  adaptation  of  the  heart  to  its  functions  is  illustrated 
moreover  by  the  fact  that  adrenaline,  which  increases  the  metabolism  of 
the  heart  to  such  an  extent,  exercises  at  the  same  time  a  dilator  effect  on 
the  coronary  vessels,  so  that  apart  from  the  high  arterial  pressure  and  the 
metabolites  produced  by  the  contracting  heart  muscle,  the  vessels  are 
dilated  by  the  action  of  the  same  hormone  which  evokes  the  need  for  an 
increased  flow  of  blood  through  the  working  muscle. 

There  is  thus  a  marked  antagonism  in  the  influence  of  the  two  common 
hormones  on  the  heart,  both  of  them  being  produced  during  general  muscular 
activity.  Carbonic  acid  in  excess  causes  dilatation  of  the  heart,  diminished 
functional  activity,  slowing  of  rhythm.  Adrenaline  causes  increased  func- 
tional activity,  diminution  of  cardiac  volume,  and  increased  rhythm.  The 
action  of  adrenaline  is  so  pronounced  that  it  is  possible  to  administer  20  or 
30  per  cent,  carbonic  acid  to  a  heart-lung  preparation  without  altering 
its  output,  if  adrenaline  be  administered  at  the  same  time.  The  heart  is 
slowed  by  the  carbonic  acid,  but  the  beat  is  maintained  and  contraction  is 
effective  in  emptying  the  heart  of  its  content. 

THE   HEART   REFLEXES 

The  part  of  the  nervous  system  chiefly  concerned  in  the  central  co- 
ordination of  the  various  afferent  impulses  which  act  on  the  heart  is  the 
medulla  oblongata.  It  is  in  this  situation  that  we  find  the  nerve  cells  giving 
origin  to  the  efferent  fibres  of  the  vagus  nerves,  and  also  the  collection  of 
grey  matter  in  which  the  afferent  fibres  of  the  vagus  terminate.  Direct 
stimulation  of  the  vagus  ceutre  may  cause  slowing  and  stoppage  of  the 
'  heart.  The  tonic  influence  of  the  vagi  can  be  abolished  by  destruction  of  this 
centre.  In  this  region  we  also  find  the  vaso-motor  centre,  so  that  the 
activity  of  one  can  affect  that  of  the  other.  This  cardiac  centre  may  be 
played  upon  by  impulses  arriving  at  it  through  various  afferent  nerves  or 
from  the  higher  parts  of  the  brain  and  uivimj;  rise  to  the  changes  of  the  pulse 
rate  associated  with  the  emotional  conditions,  or  it  may  be  directly  affected 
by  the  composition  of  the  blood  circulating  through  its  capillaries. 

The  nerve  cells,  which  give  off  the  accelerator  or  augmentor  fibres,  are 
situated  in  the  interrnedio-lateral  tract  of  the  spinal  cord,  near  the  point  of 
origin  of  these  fibres.     We  might  therefore  speak  of  an  augmentor  centre  in 


1022 


PHYSIOLOGY 


this  region;  but  it  seems  probable  that  the  activity  of  these  cells  is  sub- 
ordinate to  impulses  arriving  at  them  from  the  common  meeting-place 
of  visceral  impulses,  viz.  the  medulla. 

The  most  important  of  the  afferent  nerves,  which  affect  refiexly  the 
action  of  the  heart,  are  the  nerves  coming  from  the  heart  itself  and  the  aorta. 
In  the  mammalian  ventricle,  nerve  fibres  can  be  seen  running  over  the 
surface  of  the  ventricle  which  are  entirely  afferent,  stimulation  of  their 
peripheral  ends  causing  no  effect  on  the  heart  beat.  Stimulation  of  their 
central  ends  may  cause  one  of  four  conditions  : 

(a)  Slowing  of  the  heart. 

(b)  Kise  of  blood  pressure  from  constriction  of  the  splanchnic  area. 

(c)  Fall  of  blood  pressure  by  dilatation  of  the  arterioles  of  the  body. 


Sup-,  lar.  n.    . 


Depressor 


I 


sec. 


Vagus- 


Sup-,  lar.  n.-j 


y 


-S 


ymp. 


-Vagus 


y--  Sup-.  Cerv.  Gang. 
--Depressor 
-Cerv.  symp.  n. 


— Vago.  symp. 


RABBIT 


DOG 


Fig.  461.  Diagrams  of  the  connections  of  the  depressor  nerve  in  the  rabhit  and  dog, 
according  to  Cyon.  It  will  bo  noticed  that  in  the  latter  animal  the  depressor  nerve 
runs  in  the  vagus  trunk,  together  with  the  sympathetic  nerve,  for  the  greater  part 
of  its  course. 

(d)  Reflex  movements.  The  heart  does  not  seem  to  be  provided  with  the 
nerves  of  ordinary  or  tactile  sensibility.  There  is  no  doubt  however  that 
under  abnormal  circumstances  impulses  arising  in  the  heart  can  give  rise  to 
sensations  of  pain,  which  are  referred  not  so  much  to  the  heart  as  to  the 
surface  of  the  body  over  the  left  side  of  the  chest  and  left  arm,  in  the  region 
of  the  distribution  of  the  cutaneous  branches  of  the  second  and  third  dorsal 
roots. 

An  important  afferent  nerve  coming  from  the  heart,  or  rather  from  the 
beginning  of  the  aorta,  is  the  depressor  nerve.  In  the  rabbit  this  rises  by 
two  roots,  one  from  the  trunk  and  the  other  from  the  superior  laryngeal 
branch  of  the  vagus,  and  runs  parallel  with  the  vagus  to  the  cardiac  plexus 
(Fig.  461).  It  is  purely  afferent,  stimulation  of  its  peripheral  end  causing  no 
effect.  On  stimulating  its  central  end,  fall  of  blood  pressure  (Fig.  462)  and 
reflex  slowing  of  the  heart  are  produced,  the  latter  effect  being  abolished  by 
section  of  both  vagi.    It  has  been  shown  by  Bayliss  that  the  depressor  effect 


THE  NERVOUS  REGULATION  OF  THE  HEART    1023 

is  due  to  universal  dilatation  of  the  blood  vessels  of  the  body,  the  greater 
part  however  being  played  by  the  splanchnic  area.  This  nerve  is  probably 
brought  into  action  whenever  the  pressure  in  the  aorta  is  so  high  as  to  con- 
stitute a  serious  check  to  the  expulsive  action  of  the  heart.  It  is  stated  that 
under  these  conditions  a  current  of  action  may  be  detected  in  the  trunk  of 
the  depressor  nerve  and  that,  if  both  depressor  nerves  be  cut  when  the  aortic 
pressure  is  high,  the  blood  pressure  rises  still  higher.  It  presents  a  means  by 
which  the  heart  can  be  relieved  of  a  load  too  great  for  its  powers,  and  there- 
fore dangerous  to  its  future  welfare.  In  many  animals  the  depressor  fibres 
are  bound  up  with  the  trunk  of  the  vagus  and  cannot  be  excited  separately. 


Via.  462.     Blood -pressure  curve  from  rabbit,  showing  effect  of  excitation  of  central 
end  of  depressor  nerve  (mercurial  manometer).     (Bayliss.) 

Stimulation  of  the  central  end  of  the  vagus  generally  causes  reflex  slowing 
of  the  heart  through  the  cardiac  centre  and  the  other  vagus.  Inflation  of 
the  lungs  causes  acceleration  of  the  heart — whether  due  to  diminution  of 
the  tonic  action  of  the  vagi,  or  to  reflex  excitation  of  the  accelerator  nerves, 
is  not  known.  Most  sensory  nerves  of  the  body  when  stimulated  give  either 
a  slowing  or  a  quickening  of  the  heart.  Stimulation  of  the  fifth  nerve,  as 
in  the  nasal  mucous  membrane,  always  causes  reflex  inhibition. 

There  are  two  very  important  reflex  mechanisms  associated  with  the 
heart  itself.  II  the  arterial  pressure  be  raised,  either  by  stimulation  of  the 
splanchnic  nerves  or  by  obstruction  of  the  aorta,  the  heart  is  slowed.  In 
this  slowing,  which  is  effected  through  the  vagus,  two  factors  are  concerned. 
In  the  first  place  any  rise  of  arterial  pressure  within  the  skull  raises  the  intra- 
cranial pressure  and  excites  the  vagus  centre  directly.  In  the  second  place 
impulses  starting  in  the  root  of  the  aorta  and  in  the  left  ventricle  travel  to 
the  central  nervous  system  chiefly  by  way  of  the  depressor  fibres  and  cause 
a  reflex  slowiug  of  the  heart.     According  to  '  Marey's  law '  the  pulse  rate 


1024  PHYSIOLOGY 

varies  inversely  as  the  blood  pleasure.  This  relation,  though  general,  is  not 
universal.  Thus  the  rise  in  blood  pressure  and  the  increased  filling  of  the 
heart  associated  with  muscular  exercise  are  attended  by  an  increased  pulse 
rate.  In  the  quickening  of  the  heart,  which  accompanies  bodily  exercise, 
another  reflex  mechanism  comes  into  play,  to  which  attention  has  been 
called  by  Bain  bridge.  Any  distension  of  the  right  auricle  evokes  a  reflex 
quickening  of  the  pulse  rate,  chiefly  by  diminishing  the  vagus  tone  but 
also  probably  to  a  less  extent  by  reflex  stimulation  of  the  reflex  accelerator 
nerves.  It  thus  seems  that  the  heart  is  connected  with  the  heart  centre 
in  the  medulla,  governing  its  rate  of  beat,  by  two  sets  of  afferent  nerves, 
which  are  stimulated  by  a  rise  of  pressure  within  the  cavities  to  which  they 
are  distributed.  Stimulation  of  the  one  set  coming  from  the  arterial  end — 
e.  g.  the  left  ventricle,  causes  a  reflex  slowing  of  the  heart.  Stimulation  of 
the  other  set,  which  are  distributed  to  the  venous  end  of  the  heart,  evokes 
increased  frequency  of  the  heart  beat.  Both  these  sets  of  impulses  are  of 
great  importance  in  correlating  the  activity  of  the  heart  and  the  amplitude 
of  the  circulation  with  the  metabolic  needs  of  the  body  as  a  whole. 

THE   PULSE    RATE   IN   MAN 

The  normal  pulse  rate  in  man  is  about  72  per  minute.  It  is  largely 
influenced  by  bodily  movements.  It  varies  considerably  with  age.  The 
following  Table  represents  the  average  pulse  rate  in  man  at  different  ages  : 

Age  in  years  Pulse  rate  per  minute 

0  .  .  •  136 

5  .  .  88 

10-15  .  .  78 

1.5-60  .  .  68-72 

It  must  be  remembered  that  marked  differences  in  the  pulse  rate  may  be 
found  in  different  individuals  without  having  any  pathological  significance. 
Thus  pulse  rates  of  30  per  minute  and  120  per  minute  have  been  observed  in 
men  who  were  otherwise  perfectly  healthy.  The  pulse  rate  is  raised  by 
warmth  and  diminished  by  cold  apphed  to  the  surface  of  the  skin.  It  is 
also  increased  somewhat  by  the  taking  of  food.  The  act  of  swallowing  causes 
a  reflex  quickening  of  the  rate  by  inhibition  of  the  tonic  vagus  action. 


SECTION  X 

THE    NERVOUS    CONTROL    OF   THE    BLOOD  VESSELS 

During  muscular  activity  the  metabolism  of  the  body  as  a  whole,  judged 
by  its  gaseous  interchanges,  may  be  increased  six  or  eight  fold.  This 
increase  is  due  almost  exclusively  to  the  additional  metabolic  changes 
consequent  on  muscular  activity.  The  muscles  therefore  during  activity 
require  a  greater  supply  of  blood  in  order  to  obtain  from  it  the  oxygen 
necessary  for  their  contraction,  and  to  get  rid  of  the  carbon  dioxide,  which 
is  the  end-result  of  their  activity.  In  the  same  way  every  organ  of  the 
body  requires  an  increased  blood  supply  during  activity.  Blood  must  be 
diverted  from  the  inactive  to  the  active  tissues.  All  parts  of  the  body  must 
co-operate  in  subordination  to  the  activity  of  that  tissue  whose  function 
for  the  time  being  is  of  the  greatest  importance  to  the  organism.  This 
subordination  of  the  part  to  the  whole,  i.  e.  of  every  part  to  the  organ  whose 
activity  is  specially  evoked  by  the  needs  of  the  whole  organism,  is  chiefly 
effected  through  the  central  nervous  system,  though  local  and  chemical 
mechanisms  also  play  some  part  in  the  process. 

Our  knowledge  of  the  nervous  control  of  the  blood  vessels  dates  from  the 
discovery  by  Claude  Bernard  that  nerve  fibres  run  in  the  cervical  sympa- 
thetic to  the  blood  vessels  of  the  head  and  neck,  and  maintain  them  in  a 
state  of  tonic  constriction.  Bernard  showed  that  if  in  the  rabbit  the  cervical 
sympathetic  on  one  side  be  divided,  the  vessels  in  the  corresponding  ear 
dilate.  Vessels  come  into  prominence  which  were  previously  invisible,  and 
on  account  of  the  greater  flow  of  blood  thus  produced,  the  ear  on  the  side 
of  the  section  becomes  warmer  than  the  normal  ear.  If  the  head  end  of  the 
divided  sympathetic  nerve  be  stimulated,  all  the  vessels  of  the  ear  contract, 
and  the  ear  becomes  colder  than  that  of  the  other  side.  The  fact,  that  the 
dilatation  of  the  vessels  is  produced  by  section  of  the  cervical  sympathetic 
and  lasts  for  a  considerable  time  after  any  irritant  effect  of  the  section 
must  have  passed  off,  shows  that  the  ear  vessels  are  continually  under  the 
influence  of  tonic  constrictor  impulses  proceeding  to  them  along  the  nerve 
fibres  of  the  cervical  sympathetic. 

It  can  be  easily  shown  that  these  impulses  take  their  origin  in  the  central 
nervous  system.  The  paralysis  of  the  ear  vessels,  though  lessening  the  resist- 
ance to  the  flow  of  blood  there,  affects  too  small  a  vascular  area  to  have 
any  marked  influence  on  the  total  resistance  of  the  circulation  and  therefore 
on  the  arterial  blood  pressure.  If  the  spinal  cord  be  divided  on  a  level 
with  the  origin  of  the  first  dorsal  nerve,  the  blood  pressure  sinks  considerably. 
65  1025 


1026  PHYSIOLOGY 

In  the  dog  it  may  fall  from  120  mm.  Hg.  to  40  or  50  mm.  Hg.  The  heart 
after  the  section  beats  more  rapidly  than  before,  so  that  the  fall  of  pressure 
must  be  ascribed  to  a  change  affecting  the  blood  vessels  and  lowering  the 
resistance  to  the  flow  of  blood.  Since  a  maximal  effect  on  the  blood  pressure 
is  produced  by  section  of  the  cord  at  this  level,  one  may  conclude  that  the 
tonic  constrictor  impulses  to  all  the  vessels  of  the  body  pass  through  this 
segment  of  the  cord  before  leaving  it  to  be  distributed  to  the  arterial  walls. 
The  source  of  these  impulses  may  be  made  out  by  studying  the  effect  of 
sections  through  different  levels  of  the  nervous  system.  Division  of  the 
cord  at  about  the  first  or  second  lumbar  nerve  causes  no  effect  on  the  blood 
pressure.  On  making  a  section  at  the  sixth  dorsal  root  a  considerable  fall 
of  pressure  is  produced,  almost  but  not  quite  as  great  as  that  observed  after 
section  at  the  first  dorsal  segment ;  stimulation  of  the  lower  end  of  the  cut 
cord  causes  almost  universal  vascular  constriction  and  a  large  rise  of  blood 
pressure.  On  the  other  hand,  the  fall  of  pressure  is  maximal  when  the 
section  is  carried  through  the  first  dorsal  segment  or  through  any  part  of  the 
cervical  cord.  Section  of  the  crura  cerebri,  or  of  the  brain  stem  at  the  upper 
border  of  the  fourth  ventricle,  leaves  the  blood  pressure  unaffected.  Destruc- 
tion of  a  small  region  of  the  medulla  situated  on  each  side  of  the  middle  line 
in  the  neighbourhood  of  the  facial  nucleus,  i.  e.  in  the  forward  prolongation 
of  the  lateral  columns  after  they  have  given  off  their  fibres  to  the  decussating 
pyramids,  causes  an  immediate  and  maximal  lowering  of  the  blood 
pressure. 

We  must  therefore  conclude  that  all  the  vessels  in  the  body. are  kept 
in  a  state  of  tonic  contraction  by  impulses  arising  in  this  portion  of  the 
medulla  oblongata,  travelling  down  the  cord  as  far  as  the  dorsal  region,  and 
then  passing  out  of  the  cord  by  the  dorsal  and  upper  lumbar  nerves.  This 
conclusion  is  confirmed  by  the  fact  that,  whereas  stimulation  of  the  anterior 
roots  of  the  cervical  and  lower  lumbar  and  sacral  nerves  has  no  influence  on 
the  blood  pressure,  a  rise  of  arterial  pressure  can  be  obtained  by  stimulating 
any  of  the  anterior  roots  from  the  first  or  second  dorsal  to  the  second  or 
third  lumbar.  The  same  effect  is  produced  by  stimulation  of  the  white 
rami  communicantes  from  these  roots  to  the  sympathetic  system,  or  by 
excitation  of  the  sympathetic  system  itself. 

The  portion  of  the  medulla  concerned  with  the  sending  out  of  the  tonic 
vaso-constrictor  impulses  is  spoken  of  as  the  vaso-motor  centre.  In  this 
region  it  is  exposed  to  and  played  upon  by  afferent  impulses  from  all  portions 
of  the  body,  from  the  higher  centres  of  the  brain  and  the  cortex  cerebri,  and 
especially  by  afferent  impulses  travelling  by  the  vagi  from  the  viscera  of 
the  chest  and  abdomen.  Whether  in  the  absence  of  all  afferent  stimuli  the 
centre  would  be  active  is  doubtful;  all  we  know  is  that  the  sum  of  the 
stimuli  arriving  at  the  centre  produces  a  state  of  average  continued  activity, 
which  is  responsible  for  the  maintenance  of  arterial  tone  and  for  the  regulation 
of  the  arterial  blood  pressure. 

The  centre  may  also  be  affected  directly  by  changes  in  its  blood  supply, 
or  in  the  composition  of  the  blood  flowing  through  it.     Thus  anything  which 


THE  NERVOUS  CONTROL  OF  THE    BLOOD    VESSELS     1027 

interferes  with  tire  gaseous  exchanges  of  the  centre,  whether  obstruction  to 
respiration,  absence  of  oxygen  in  the  air  breathed,  or  a  failure  of  the  blood 
supply  as  by  ligature  of  the  cerebral  arteries,  calls  forth  an  increased  state 
of  activity  of  the  centre.  This  can  be  best  studied  by  observing  the  changes 
in  the  blood  pressure  produced  in  a  curarised  animal  by  the  cessation  of 
artificial  respiration. 

These  changes  depend  partly  on  the  stimulation  of  the  vaso-motor  and 
vagus  centres  by  the  venous  blood,  and  partly  on  the  affection  of  the  heart 
itself.  We  will  first  consider  them  with  both  vagi  cut,  in  order  to  shut 
out  the  action  of  the  vagus  centre.  The  blood  pressure  is  registered  by 
means  of  a  mercurial  manometer  in  connection  with  the  carotid  artery. 
On  leaving  off  the  artificial  respiration,  the  blood  pressure  may  remain 
at  the  same  height  for  some  seconds,  the  only  change  noticed  being  the 
absence  of  the  respiratory  oscillations.  Sooner  or  later  the  blood  pressure 
suddenly  rises  rapidly  (Fig.  463,  a),  and  in  another  ten  seconds  may 
reach  a  height  twice  as  great  as  it  was  previously.  The  heart  beats  a  little 
more  forcibly  in  consequence  of  the  increased  cardiac  tension,  but  its  fre- 
quency is  almost  unaltered.  The  blood  pressure  remains  at  this  height 
for  about  a  minute  and  then  gradually  falls,  the  heart  beats  becoming 
smaller  and  smaller  until  the  pressure  has  sunk  to  a  point  very  little  above 
the  abscissa  line  (level  of  no  pressure).  This  fall  in  pressure  is  due  to  the 
fii  Hi,  re  of  the  heart.  The  heart,  badly  supplied  with  oxygen,  cannot  overcome 
the  high  resistance  presented  by  the  contracted  arterioles;  it  gets  overfilled, 
and  gradually  loses  the  power  of  expelling  any  of  its  contents.  If,  when  the 
blood  pressure  has  sunk  to  its  lowest  point,  the  heart  be  rapidly  cut  out  of  the 
bodj  it  will  begin  to  beat  fairly  forcibly,  being  relieved  of  the  excessive 
internal  tension.  The  vessels  however  remain  constricted  until  the  death 
of  the  animal.  This  is  shown  by  two  facts.  If,  while  the  pressure  is  sinking, 
artificial  respiration  be  recommenced,  the  heart  supplied  with  oxygen  at  once 
begins  to  beat  more  forcibly,  and  the  blood  pressure  may  rise  to  an  e  in 
er  height  than  immediately  after  the  commencement  of  the  asphyxia. 
Agahij  if  the  volume  of  the  kidney  be  recorded  by  means  of  the  oncometer, 
the  rise  of  general  blood  pressure  produced  by  asphyxia  is  seen  to  be  accom- 
panied by  a  .marked  shrinking  of  the  kidney,  and  this  shrinking  endures  until 
the  animal  dies,  showing  that  the  fall  of  blood  pressure  following  the  rise 
is  due,  not  to  a  giving  way  of  the  arterial  resistance,  but  to  failure  of  the 
heart. 

Similar  results  are  obtained  when  the  vessels  to  the  brain  are  ligatured, 
or  when  the  animal  has  to  respire  an  indifferent  gas  free  from  oxygen,  such 
as  nitrogen  (Fig.  463,  b)  or  hydrogen.  In  the  imcurarised  animal  the  rise 
of  blood  pressure  is  associated  with  increased  respiratory  movements  and 
finally  with  convulsive  spasms  which  may  involve  practically  every  muscle 
of  the  body. 

We  have  spoken  above  of  the  phenomena  of  asphyxia  as  being  due  to 
the  circulation  of  venous  blood.  There  are  however  two  factors  which  may 
be  concerned  and  which  may  influence  the  medullary  cent  res  and  the  heart. 


I  (US 


PHYSIOLOGY 


When  the  renewal  of  the  lung  ventilation  is  stopped   by  ligature  of  the 

trachea  or  by  cessation  of  the  respiratory  movements,  the  increasing  venosity 
of  the  blood  involves  a  diminished  percentage  of  oxygen  and  an  increased 
percentage  of  carbon  dioxide;  and  when  asphyxia  is  excited  by  cessation 
of  the  circulation  through  the  medullary  centres,  these  centres  may  suffer 
at  the  same  time  from  lack  of  oxygen  and  from  the  accumulation  of  carbon 
dioxide.  The  question  arises  whether  one  or  both  of  these  factors  are  con- 
cerned. It  is  easy  to  investigate  the  action  of  each  separately.  A  pure 
oxygen  lack  may  be  brought  about  by  allowing  an  animal  to  breathe  some 
inert  gas,  such  as  nitrogen  or  hydrogen,  or  in  the  curarised  animal  one  of  thesa 
gases  may  be  administered  by  the  pump  used  for  artificial  respiration.  The 
effects  of  accumulation  of  carbon  dioxide  in  the  blood  and  tissues  may  be 


A 

200     * 

wmmmmtt     \ 

r 

A 

/ 

-150  on 

ml 

r 

t 

1 1 

Resp.  off 
MM   I 

-100 

M   M  J 

Fig.  463.     Blood-pressure  changes  in  a  cat.     A,  after  cessation  of  respiratory  move- 
ments.    B,  as  a  result  of  artificial  respiration  with  nitrogen.     (Mathison.) 

produced  by  the  administration  of  gaseous  mixtures  containing  excess  of 
oxygen,  i.  e.  30  to  40  per  cent.,  with  varying  percentages  of  carbon  dioxide. 
In  the  first  case,  the  tension  of  the  carbon  dioxide  in  the  blood  will  be  kept 
below  normal;  in  the  second  case,  the  tension  of  oxygen  in  the  blood  will 
be  kept  above  normal.  In  order  to  obtain  results  uncomplicated  by  the 
influence  of  anaesthetics,  the  experiments  may  be  carried  out  in  animals 
which  have  been  deprived  of  consciousness  by  destruction  of  the  brain  above 
the  superior  corpora  quadrigemina.  At  different  times  physiologists  have 
been  inclined  to  ascribe  the  excitatory  phenomenon  of  asphyxia  either  to 
absence  of  oxygen  or  to  excess  of  carbon  dioxide.  Mathison  has  shown  that 
both  conditions  may  concur  in  the  production  of  the  rise  of  blood  pressure 
in  asphyxia.  In  Figs.  463  and  464  the  rise  of  arterial  pressure  produced  by 
a  short  period  of  asphyxia  is  compared  with  that  produced  by  oxygen  lack, 
by  a  surplus  of  carbon  dioxide,  and  by  the  injection  of  lactic  acid  into  the 
circulation.     There  are  certain  minor  details  in  these  curves  which  are  of 


THE  NERVOUS  CONTROL  OF  THE   BLOOD   VESSELS    1029 

interest.  When  the  oxygen  of  the  lungs  is  rapidly  washed  out  with  a  neutral 
gas,  the  asphyxial  rise  conies  on  about  half  a  minute  later  than  it  would 
with  pure  asphyxia.  In  the  latter  case  it  seems  that  the  first  rise  is  due 
to  the  accumulation  of  carbon  dioxide.  The  rise  however  under  nitrogen, 
when  it  occurs,  is  extremely  abrupt,  and  the  subsequent  fall  of  blood  pressure, 
i.  e.  the  heart  failure,  is  earlier  in  onset  and  more  rapid  than  with  ordinary 
asphyxia.  When  excess  of  carbon  dioxide  is  administered,  i.  e.  5  to  10 
per  cent.,  a  marked  rise  of  pressure  occurs  which,  like  that  produced  by 
oxygen  lack,  is  almost  entirely  conditioned  by  stimulation  of  the  vaso-motor 
centres  and  resulting  constriction  of  the  peripheral  arterioles.  If  a  loop  of 
intestine  be  placed  in  a  plethysmograph,  it  will  be  seen  that  the  rise  of 


A 

220- 

/A. 

-/ 

i 

hoo- 

on 

I'l    1    1    1 

C02  12-  4 per  cent 
02  30  per  cent 

i  i  }  n  n  n  i 

-220 

V 


Lactic 


2c.c.M 


15 

i    i    i    I    I 


Fig.   404.     Asphyxial  blood-pressure  changes  in  cuiarised  cat.     A,  inhalation  of 
C08.     B,  injection  of  lactic  acid.     (Mathison.) 


pressure  coincides  with  a  shrinkage  in  volume  of  the  intestine,  pointing  to 
a  vascular  constriction  (Fig.  465).  The  rise  of  blood  pressure  due  to  the 
vascular  constriction  may  be  maintained  for  a  considerable  period,  e.  g.  ten 
to  fifteen  minutes,  and  we  do  not  get  the  rapid  fall  of  pressure  due  to  failure 
of  the  heart  that  is  observed  in  an  ordinary  asphyxia  tracing.  If  partial 
oxygen  lack  or  abnormally  increased  tension  of  carbon  dioxide  be  continued 
for  some  time,  a  state  of  narcosis  or  paralysis  finally  ensues  which  affects 
not.  only  the  higher  centres  but  also  those  of  the  medulla,  so  that  death  may 
result  without  convulsions  or  excessive  rise  of  blood  pressure. 

Is  there  any  common  factor  in  the  two  conditions  of  oxygen  lack  and 
carbon  dioxide  excess,  which  may  account  for  the  similarity  in  their  effects  ? 
It  has  been  shown  that,  whenever  there  is  a  deficiency  of  oxygen,  the  metabo- 
lism of  the  tissues  undergoes  alteration,  so  that  as  a  result  of  activity,  e.  g.  in 
muscles,  lactic  acid  is  formed  instead  of  carbon  dioxide.     Lactic  acid  can 


1030 


IMIYSloUXiY 


Jnf.  Vol. 


i  off 

*^«*,V'"*%/    VV     -100 


B.P. 


C02   7% 


therefore  be  detected  in  the  blood  whenever  violent  exercise  is  taken  sufficient 
to  produce  dyspnoea,  or  when  the  access  of  oxygen  is  diminished  by  poisoning 
with  carbon  monoxide,  or  by  reducing  the  tension  of  this  gas  in  the  air 
breathed.     Oxygen  lack  can  bo  regarded  therefore  as  synonymous  with  the 

production  of  lactic  acid.  Lactic  acid 
introduced  into  the  blood  stream,  as 
is  shown  in  the  curve  in  Fig.  464,  B, 
is  equally  efficacious  with  oxygen  lack 
or  with  carbon  dioxide  excess  in  the 
production  of  a  rise  of  blood  pressure 
indistinguishable  from  the  asphyxia! 
rise.  It  seems  therefore  that  the 
common  factor  in  asphyxia  is  the 
increased  acidity  or  H'  ion  concen- 
tration of  the  blood.  We  shall  have 
occasion  to  return  to  this  question  in 
dealing  with  the  regulation  of  the 
respiratory  movements. 

If  in  the  dog,  and  to  a  less  extent 
in  other  animals,  the  vagi  be  left 
intact,  the  blood  pressure  tracing 
during  asphyxia  has  quite  another 
appearance.  At  the  point  of  the 
tracing,  corresponding  to  the  rapid 
rise  in  the  previous  experiment,  there 
is  in  this  case  only  a  slight  rise  of 
pressure,  but  the  heart  begins  to  beat 
very  slowly.  At  each  beat  it  neces- 
sarily sends  out  a  greater  volume  of 
blood  than  when  it  is  beating  more 
frequently,  and  hence  the  oscillations  on  the  blood  pressure  curve  caused  by 
the  heart  beats  become  very  large.  This  slow  beat  is  due  to  the  action  of  the 
vagus  centre,  and  is  at  once  abolished  by  section  of  the  two  vagi.  The  sparing 
of  the  heart  by  means  of  this  vagus  action  enables  it  to  last  longer,  and 
the  final  fatal  fall  of  blood  pressure  due  to  heart  failure  comes  on  rather 
later  than  when  the  vagi  are  divided.  In  the  increased  vagus  action,  which 
occurs  during  asphyxia,  two  factors  are  probably  involved.  The  cardio- 
inhibitory  centre  in  the  medulla  probably  partakes  of  the  general  excita- 
tion of  the  medullary  centres  due  in  the  first  place  to  carbon  dioxide  excess, 
in  the  second  to  oxygen  lack.  More  important  is  the  direct  action  of  the 
rise  of  blood  pressure  on  the  medullary  centre.  The  rise  of  arterial  pressure 
causes  increased  mtracranial  tension,  and  any  increase  of  the  latter  excites 
the  vagus  centre  and  produces  slowing  of  the  pulse.  The  vagus  slowing 
is  therefore  absent  in  asphyxia  if  the  arterial  blood  be  allowed  to  escape 
through  a  mercury  valve  so  as  to  prevent  any  rise  of  pressure  in  the  brain 
cavity. 


on 


Fio.  465.  Tracing  of  arterial  blood 
pressure  and  of  intestinal  volume, 
to  show  the  influence  of  a  moder- 
ate increase  in  the  C02  tension  of 

'     the  blood.     (Mathison.) 


THE  NERVOUS  CONTROL  OF  THE   BLOOD   VESSELS    1031 

During  the  period  of  increased  pressure,  waves  are  often  observed  on  the 
blood-pressure  curve.  These  are  of  two  kinds.  In  completely  curarised  animals 
we  may  observe  oscillations  of  blood  pressure,  corresponding  with  the  respira- 
tory rhythm  before  the  administration  of  curare,  or  if  the  vagi  are  cut,  presenting  a 
rhythm  similar  to  that  usual  in  animals  with  divided  vagi.  They  are  certainly  due  to 
irradiation  of  impulses  from  the  excited  respiratory  centre  to  the  vaso-motor  centre  in 
the  medulla.  In  fact  if  the  curarisation  is  not  complete,  a  slight  twitch  of  the  diaphragm, 
insufficient  by  itself  to  have  any  mechanical  influence  on  the  circulation,  may  be  observed 
to  accompany  each  rise  on  the  blood-pressure  curve.  Besides  these  curves  others  are 
occasionally  seen  which  must  arise  in  a  slow  rhythmic  variation  of  the  constrictor 
impulses  sent  out  from  the  vaso-motor  centre.  These  waves  are  known  as  the  Traube 
curves  and  are  not  to  be  confused  with  the  waves  on  an  ordinary  pressure  curve  due  to 
respiration,  being  much  slower  in  their  rhythm  than  the  latter.     They  are  observed  not 


Fig.  406.     Blood-pressure  tracings  showing  Traube  curves 


only  dining  asphyxia,  but  may  occur  in  blood-pressure  tracings  from  normal  dogs,  and 
are  frequent  in  dogs  poisoned  with  morphia.  Fig.  466  represents  tracings  obtained  from 
under  I  In'  influence  of  morphia  and  curare.  The  upper  curve,  taken  while  artificial 
ation  was  being  carried  en,  shows  the  three  forms  of  curves — the  oscillations  due 
to  the  heart  beat  next  in  size  those  due  to  the  respiratory  movements,  which  in  their 
t  in  ii  arc  superposed  on  the  slow  prolonged  curves.  The  lower  curve  is  taken  immediately 
alter  cessation  of  the  artificial  respiration  and  shows  only  the  heart  beats  and  the 
Traube  curves.  The  presence  of  these  waves  may  generally  be  ascribed  to  a  state  of 
abnormal  excitation  of  the  vaso-motor  centre.  This  excitation  may  arise  in  various 
ways.  A  very  frequent  cause  is  the  one  just  described,  viz.  increased  venosity  of  the 
blood  supplied  to  the  centre.  Well-marked  Traube  curves  are  often  observed  in  cases 
of  hemorrhage.  In  spite  of  the  loss  of  blood,  the  vaso-motor  centres  maintain  a  normal 
arterial  blood  pressure  by  means  of  vascular  constriction.  As  the  bleeding  continues. 
this  means  becomes  inadequate,  and  at  this  point  the  '  efforts  '  of  the  centres  take  on  a 
rhythmic  character,  giving  well-marked  Traube  curves,  just  as  the  arm  of  a  man  holding 
up  a  weight  begins  to  shake  before  he  is  obliged  to  give  way  through  fatigue.  If  the 
bleeding  still  continues,  the  pressure  sinks  steadily  and  the  curves  disappear.  The 
ourves  may  also  be  often  observed  during  operations  involving  exposure  of  the  cord, 
and  may  possibly  be  ascribed  in  this  case  to  abnormal  irritations  ascend  im;  the  posterior 
columns. 

The  vaso-motor  centre  may  also  be  directly  affected  by  drugs  such  a.s  digitalis  or 
Btrophanthus,  both  of  which  cause  a  rise  in  general  blood  pressure  from  stimulation 
of  the  centre. 


1032 


PHYSIOLOGY 


SPINAL    CENTRES 

The  great  fall  of  blood  pressure  observed  after  section  of  the  cord  in  the 
lower  cervical  region  is  not  permanent.  After  one  or  two  hours  the  pressure 
begins  to  rise,  and  if  the  animal  be  kept  alive  may  attain  a  height  only  a 
little  inferior  to  that  found  in  normal  animals. 

If  the  spinal  cord  of  such  an  animal  be  destroyed,  the  blood  pressure 
sinks  practically  to  zero  and  the  circulation  comes  to  an  end,  because  the 
animal  lias  been,  so  to  speak,  bled  to  death  into  its  own  dilated  blood  vessels. 
In  addition  to  the  chief  vaso-motor  centre  in  the  medulla  there  is  a  series 
of  subsidiary  centres  in  the  spinal  cord,  centres  which  we  may  probably 
locate  in  the  portions  of  grey  matter  situated  in  the  lateral  horns  of  the 
cord  and  giving  origin  to  the  fibres  which  go  to  make  up  the  white  rami 


iosecs 


Fig.  407.  Blood-pressure  tracing  taken  by  a  mercurial  manometer  from  carotid 
artery  of  a  dog,  three  hours  after  section  of  the  cord,  just  below  the  medulla 
oblongata.  At  o  the  artificial  respiration  was  discontinued.  A  general  spasm 
of  the  skeletal  muscles  occurred  between  x  and  x.  The  muscles  then  relaxed, 
and  were  flaccid  during  the  rest  of  the  rise  of  blood  pressure. 

communicantes.  By  means  of  these  spinal  centres  a  certain  degree  of 
adaptation  is  possible  between  the  blood  supply  of  the  various  parts  of  the 
trunk.  The  important  co-ordination  between  the  state  of  the  blood  vessels 
and  the  condition  of  the  central  pump,  the  heart,  is  however  wanting, 
since  the  blood  vessels  are  now  cut  off  from  the  cardiac  centres  and  from 
the  part  of  the  central  nervous  system  which  receives  the  afferent  impulses 
carried  by  the  vagi. 

The  spinal  centres,  like  the  chief  vaso-motor  centre,  are  susceptible  to 
changes  in  the  composition  of  the  blood  supplied  to  them.  If  an  animal  be 
kept  alive  by  means  of  artificial  respiration  for  a  little  time  after  division 
of  the  cord  just  below  the  medulla,  the  blood  pressure  slowly  rises  as  the 
spinal  centres  begin  to  take  on  their  automatic  f mictions.  If  artificial 
respiration  be  now  discontinued  the  asphyxia  excites  the  centres  of  the  cord. 
The  motor  discharge  to  the  skeletal  muscles  reveals  itself  in  a  single  prolonged 
spasm,  since  the  respiratory  centre  is  unable  to  take  any  part  in  directing  the 
motor  discharges.  Simultaneously  with  the  spasm  of  the  skeletal  muscles 
general  constriction  of  the  blood  vessels  occurs  which  outlasts  the  muscular 
spasms  and  causes  a  considerable  rise  of  blood  pressure  (Fig.  467). 


THE  NERVOUS  CONTROL  OF  THE   BLOOD   VESSELS    1033 

In  this  rise  of  pressure  the  main  factor  is  lack  of  oxygen,  and  precisely 
similar  curves  are  obtained  whether  the  asphyxia  be  produced  by  cessation 
of  artificial  respiration  or  by  administration  of  nitrogen.  The  same  effect 
may  be  produced  by  a  very  large  excess  of  carbon  dioxide,  or  by  the  injection 
of  acids  into  the  circulation.  There  is  a  striking  difference  between  the 
sensibility  of  the  spinal  centres  to  these  substances  as  compared  with  the 
medullary  centres.  Thus  the  medullary  vaso-motor  centre  is  readily 
i'xi  ited  by  ventilation  with  5  per  cent,  carbon  dioxide,  whereas  a  rise  of 
blood  pressure  is  obtained  from  the  spinal  animal  only  when  mixtures  con- 
taining 25  per  cent,  and  upwards  of  carbon  dioxide  are  employed.  The 
excitation  of  the  medullary  centre  comes  on  about  thirty  seconds  after  the 
administration  of  nitrogen  has  commenced,  in  contrast  to  that  of  the  spinal 
centres  which  does  not  occur  until  two  minutes  or  more  have  elapsed.  In 
the  intact  animal  a  maximal  stimulation  of  the  vaso-motor  centre  is  pro- 
duced in  the  cat  by  the  injection  of  2  c.c.  N/20  lactic  acid,  whereas  5  c.c. 
of  X  2  acid  are  required  to  excite  spinal  cord  centres.  Here  therefore,  as  in 
the  medulla,  the  common  factor  is  probably  increased  H  ion  concentration, 
the  excitation  threshold  for  the  medullary  centres  being  only  about  one- 
fifth  that  of  the  spinal  centres. 

The  local  spinal  centres  are  connected  with  the  medullary  vaso-motor 
centre  on  each  side  by  tracts  of  nerve  fibres  which  descend  in  the  lateral 
columns  of  the  cord. 

THE    PERIPHERAL    TONE    OF    THE    BLOOD    VESSELS 

Division  of  the  sciatic  nerve  causes  an  immediate  dilatation  of  the 
vessels  of  the  lower  limbs  in  consequence  of  their  severance  from  the  tonic 
activity  of  the  vaso-motor  centres.  This  dilatation  passes  off  in  a  day  or 
two  and  the  vessels  acquire  a  tone,  i.  e.  remain  in  a  state  of  average  constric- 
t  ion  which  can  be  increased  or  diminished  by  local  conditions.  This  recovery 
of  tone  has  been  ascribed  by  many  physiologists  to  the  existence  of  a  third 
set  of  nerve  centres  in  the  walls  of  the  arteries.  In  the  absence  of  any 
direct  histological  evidence  of  the  existence  of  such  centres,  it  seems  more 
rational  to  ascribe  the  tonus  to  the  automatic  activity  of  the  muscular  fibres 
themselves. 

THE    COURSE    AND    DISTRIBUTION    OF   THE   VASO-MOTOR    NERVES 

Since  the  blood  vessels,  like  the  heart,  are  the  seat  of  an  automatic 
activity,  complete  nervous  control  of  these  tubes  can  be  secured  only  by  the 
provision  of  two  sets  of  nerves  :  one  set — augmentor  or  motor — which  will 
increase  the  state  of  constriction  of  the  vessels;  another  set — inhibitor  or 
dilator — which  will  diminish  the  tone  of  the  arteriole  muscle  and  cause 
vascular  dilatation.  Our  knowledge  of  the  existence  of  this  second  class 
of  nerve  fibres  to  the  vessels  we  owe  also  to  Claude  Bernard,  who  observed 
that  stimulation  of  the  chorda  tympani  nerve  not  only  evoked  secretion 
from  the  submaxillary  gland  but  also  increased  the  blood  flow  through  its 
vessels  five  or  six  fold.     Subsequent  researches  have  revealed  the  fact  that 


1031 


PHYSIOLOGY 


nearly  all  the  vessels  of  the  body  receive  vaso-constrictor  fibres,  and  that 
many  receive  also  vaso-dilator  fibres.  In  order  to  determine  the  course 
and  distribution  of  the  vascular  nerves,  it  is  necessary  to  have  means  at  our 
disposal  for  investigating  the  condition  of  the  blood  flow  through  different 

parts  and  organs  of  the  body. 
Let  us  see  what  effects  will 
ensue  on  the  local  circulation 
by  constriction  or  dilatation 
of  the  arterioles  with  which 
it  is  supplied.  If  the  arte- 
rioles a  in  the  organ  b 
dilate  (Fig.  468),  the  first 
effect  is  a  diminution  of  the 
resistance  to  the  flow  of 
blood  into  the  capillaries 
beyond.  Supposing  that  the 
arterial  pressure  in  the  trunk 
c  remains  constant,  a  local 
diminution  of  resistance  in 
A  will  at  once  determine  an  increased  flow  of  blood  through  the  arterioles, 
and  the  fall  of  pressure  from  A  to  the  capillaries  will  be  less  than  when 
the  arteriole  was  constricted.  If  the  organ  is  distensible  and  elastic,  the 
increased  pressure  in  the  arterioles  and  capillaries  will  cause  dilatation  of 
these  vessels,  and  a  consequent  dilatation  of  the  whole  organ.  The  same 
effect  on  intraeapillary  pressure,  and  therefore  on  the  volume  of  the  part, 
may  be  caused  by  obstruction  to  the  flow  of  blood  from  the  veins. 
Provided  that  there  is  no  obstruction  to  the  flow  of  blood  through  the  vein,  and 
that  the  general  blood  pressure  in  c  remains  constant,  dilatation  of  an 
organ  may  be  taken  as  an  expression  of  vaso-dilatation  in  the  arteries 
with  which  it  is  supplied.  The  diminution  of  the  resistance  in  A  may  also 
increase  the  velocity  of  the  flow  through  the  part,  since  the  amount  of  blood 
flowing  in  a  given  period  of  time  through  any  vessel  varies  directly  as  the 
difference  of  pressure,  and  inversely  as  the  resistance  in  the  vessel. 

We  can  therefore  use  the  following  criteria  for  the  occurrence  of  a  vaso- 
dilatation in  the  arterial  supply  to  any  part  or  organ  : 

(1)  If  the  surface  of  the  part  is  translucent,  the  increased  filling  of  the 
blood  vessels  will  cause  redness  or  blushing. 

(2)  The  increased  size  of  the  vessels  will  cause  an  increase  in  the  volume 
of  the  organ  concerned. 

(3)  An  increased  velocity  of  blood  flow  will,  if  the  part  be  normally 
below  the  temperature  obtaining  in  the  central  organs  of  the  body,  raise  its 
temperature,  and  vaso-dilatation  can  thus  be  detected  by  the  application  of 
the  hand  or  of  a  thermometer. 

(4)  Any  of  the  methods  mentioned  in  a  previous  chapter  may  be  used 
to  determine  the  velocity  in  the  arteries  going  to  the  part,  and  an  increased 
velocity  may  be  interpreted  as  due  to  vaso-dilatation. 

(5)  The  increased  flow  through  the  part  may  be  detected  by  cutting 


THE  NERVOUS  CONTROL   OF  THE   BLOOD   VESSELS    1035 


the  main  efferent  vein  and  measuring  the  total  volume  of  blood  which  flows 
from  it-  in  a  given  time. 

Of  these  methods  the  two  most  used  are  those  based  on  determination 
either  of  the  volume  of  the  part,  or  of  the  venous  outflow  from  the  part. 
A  fallacy  may  however  arise,  unless  means  be  taken  to  ensure  that  the 
general  arterial  pressure  remain  constant  during  the  experiment.  A  rise 
of  geseral  blood  pressure  will  cause  an  expansion  of  the  vessels  and  of  the 
part  supplied,  and  also  increased  velocity  of  blood  flow  through  the  part. 
In  all  cases  therefore  where  it  is  desired  to  investigate  the  conditions  of  the 
local  circulation,  it  is  necessary  to  combine  a  determination  of  the  general 
blood  pressure  with  some  means  of  estimating  changes  in  the  local  conditions. 
We  may  take  as  an  instance  an  experiment  on  the  blood  supply  to  the 
kidney. 


to  oncometer 


Fio.  469,     Diagram  of  oncometer. 


Fig.  470.     Diagram  of  oncograph. 


For  this  purpose  we  may  use  a  kidney  plethysmograph  or  oncometer.  The  structure 
of  Roy's  oncometer  is  shown  in  Fig.  469.  The  oncometer  is  a  metal  capsule,  the  two 
halves  of  which  an-  hinged  together  and  come  in  contact  at  the  whole  of  their  circum- 
ference except  at  h,  where  a  small  depression  is  left  in  each  half  for  the  passage  of  the 
kidney  vessels  and  ureter.  A  piece  of  peritoneal  membrane  is  attached  to  the  rim  of 
each  half  of  the  oncometer,  the  space  between  this  and  the  brass  capsule  being  filled 
with  warm  oil.  The  kidney  rests  in  the  oncometer  on  tliis  bed  of  warm  oil,  from  which 
it  is  separated  by  a  membrane.  A  tube  leads  from  the  cavity  between  the  brass  capsule 
and  membrane  to  a  registering  apparatus,  or  oncograph  (Fig.  470),  which  is  a  piston 
recorder  containing  oil.  Any  swelling  of  the  kidney  will  drive  oil  out  of  the  oncometer 
into  the  cylinder  of  the  oncograph  and  so  raise  the  piston,  the  excursions  of  which  are 
recorded  by  a  lever  writing  on  a  blackened  surface. 

Schafer's  plethysmograph  (Fig.  471).  which  can  be  adapted  to  almost  any  organ  of 
the  body,  is  made,  of  vulcanite1  previously  moulded  to  the.  size  of  the  organ  whose 
volume  is  the  object  of  investigation.  In  one  side  of  the  box  a  depression  is  left  sufficient 
to  accommodate  easily  the  vessels,  nerves,  or  ureter  going  to  the  organ.  The  oncometer 
i  red  «illi  a  jlass  lid  which  is  made  air-tight  by  means  of  vaseline,  the  space 
between  the  lid  and  the  vessels  being  also  packed  with  cotton- wool  and  vaseline.     A 

ulass  tube  is  fixed  into i  corner  of  the  plethysmograph  and  leads  to  a  piston  recorder 

"i  tambour.  Every  variation  in  the  volume  of  the  organ  causes  a  movement  of  air  into 
or  out  of  the  oncometer  and  thus  gives  rise  to  a  corresponding  movement  of  the  recording 
lever. 


1  A  very  good  material  for  this  purpose  is  'Stent's  composition,'  used   by  dentists 
for  taking  a  mould  of  the  jaw  in  fitting  artificial  teeth. 


1036 


PHYSIOLOGY 


The  kidney  being  placed  in  some  such  apparatus,  a  cannula  is  inserted 
in  the  carotid  artery  and  connected  with  a  mercurial  manometer,  so  that 
two  tracings  are  obtained  at  the  same  time  on  the  moving  blackened  surface. 


Fig.  471.     Diagram  of  Schafer's  air  plethysmograph. 

In  the  Figure  given  (Fig.  472),  the  upper  curve  represents  the  carotid  blood 
pressure,  while  the  lower  is  the  tracing  of  the  oncograph  lever.  At  the 
beginning  of  the  experiment  the  lower  dorsal  nerve  roots  had  been  dissected 
out  and  prepared  for  stimulation.     The  peripheral  end  of  the  anterior  root 


Blood  pressure 


Kidney  volume 


Fig.  472.  Simultaneous  tracings  of- carotid  blood  pressure  and  volume  of  kidney. 
Between  X  and  X  the  peripheral  end  of  the  divided  tenth  dorsal  nerve  was 
stimulated.     Time-marking  =  seconds.     (Bradford.) 

of  the  tenth  dorsal  nerve  was  excited  by  means  of  an  interrupted  current 
at  the  point  marked  with  a  cross  on  the  tracing.  This  stimulation  was 
followed  by  a  rise  of  blood  pressure  together  with  a  diminution  in  the  kidney 
volume.  The  increased  blood  pressure  would  by  itself  tend  to  force  more 
blood  into  the  kidney  and  so  increase  its  volume.  The  fact  that  the  kidney 
volume  diminished  shows  that  there  must  have  been  active  contraction  of 


THE  NERVOUS  CONTROL  OF  THE   BLOOD   VESSELS    1037 

the  arterioles  of  the  kidney,  emptying  this  organ  of  blood  and  so  causing  it 
to  decrease  in  size.  This  contraction  of  the  vessels  would  tend  to  cause  a 
rise  in  general  blood  pressure  and  must  have  taken  some  part  at  any  rate 
in  the  rise  actually  observed.  If  the  oncometer  in  this  experiment  had 
been  used  alone,  it  would  have  been  impossible  to  determine  whether  the 
shrinkage  of  the  kidney  might  not  be  due  to  a  lowering  of  general  blood 
pressure,  in  consequence  of  vaso-dilatation  occurring  elsewhere,  or  in  con- 
sequence of  the  failure  of  the  heart's  activity.  On  the  other  hand,  without 
the  oncometer  it  would  have  been  possible  to  determine  only  that  there 
was  increased  peripheral  resistance  somewhere  or  other  in  the  body. 

Instead  of  taking  the  volume  of  the  kidney,  we  might  have  determined  the  blood 
flow  through  its  vessels  either  directly  by  means  of  a  cannula  in  the  renal  vein,  or  by 
the  indirect  method  of  Brodie.  This  method  depends  on  the  fact  that  under  normal 
conditions  the  amount  of  blood  leaving  an  organ  is  equal  to  that  entering  it  during  any 
short  space  of  time.  If  the  efferent  vein  be  clamped  for  five  or  ten  seconds,  the  blood 
entering  the  organ  during  this  time  cannot  escape,  and  therefore  accumulates  in  the 
organ  and  increases  its  volume.  If  the  organ  be  in  a  plethysmograph,  the  increase  of 
volume  during  this  period  may  be  measured  and  is  exactly  equal  to  the  volume  of  blood 
passing  through  the  artery  into  the  organ  during  the  five  or  ten  seconds  of  the  closure. 
The  vein  must  not  be  obstructed  too  long,  otherwise  the  increasing  distension  of  the 
organ  will  appreciably  increase  the  resistance  to  the  entry  of  blood,  and  so  diminish  the 
velocity  of  the  blood  in  the  artery. 

The  direct  determination  of  the  venous  outflow  is  not  well  a'dapted  to  large  organs 
on  account  of  the  very  rapid  loss  of  blood  which  occurs  through  the  open  vein.  The 
method  is  however  of  great  value  in  dealing  with  the  circulation  through  small  organs 
such  as  the  submaxillary  glands.  In  such  a  case  it  is  usual  to  hinder  or  prevent  the 
clotting  of  the  blood  by  the  preliminary  injection  of  leech  extract,  and  then,  after 
placing  a  cannula  in  the  efferent  veins  of  the  organ,  to  allow  blood  from  the  cannula 
to  drop  on  to  a  mica  disc  attached  to  a  Marey  tambour.  This  tambour  is  connected 
by  a  tube  with  a  registering  tambour,  every  drop  on  the -disc  giving  rise  to  a  small 
elevation  of  the  lever  of  the  second  tambour. 


COURSE   OF   THE   VASO-CONSTRICTOR   FIBRES 

In  investigating  the  course  of  the  vaso-constrictor  fibres  we  have  to 
detennine  : 

(1)  The  origin  of  the  fibres  from  the  central  nervous  system; 

(2)  The  course  of  the  fibres  on  their  way  to  their  peripheral  distribution 
in  the  blood  vessels; 

(3)  Their  connections  with  nerve  cells. 

The  two  first  details  can  be  found  by  stimulating  various  nerves  and 
nerve  roots  in  different  parts  of  their  course  and  observing  the  effects  pro- 
duced on  the  local  and  general  circulation.  The  importance  of  the  third 
heading  is  due  to  the  fact  that  the  vascular  nerves,  like  the  visceral  nerves 
generally,  do  not  have  their  last  cell  station  in  the  spinal  cord.  The  fibres 
carrying  vaso-constrictor  impulses,  on- leaving  the  cord,  do  not  pass  direct 
to  the  blood  vessels,  but  come  to  an  end  in  a  collection  of  ganglion  cells, 
which  may  belong  to  the  main  chain  of  the  sympathetic,  or  be  situated  more 
peripherally  and  belong  to  the  group  of  collateral  or  peripheral  ganglia. 


1038  PHYSIOLOGY 

These  fibres,  as  they  leave  the  central  nervous  system,  are  small  medullated 
nerves.  They  end  in  the  ganglion  by  arborising  round  ganglion  cells, 
whence  a  fresh  relay  of  fibres  starts  and  carries  the  impulses  on  to  the 
muscle  fibres  of  the  blood  vessels.  The  post-ganghonic  fibres  differ  from 
the  pre-ganglionic  fibres  in  being  non-medullated. 

The  discovery  of  the  ganglia,  with  which  any  given  set  of  nerve  fibres 
is  connected,  is  rendered  easy  by  the  fact  that  in  many  animals  the  sympa,- 
thetic  ganglion  cells  are  paralysed  by  nicotine  (Langley).  The  nicotine 
may  be  painted  on  the  ganglion  or  may  be  injected  into  the  blood  stream. 
The  first  effect  of  the  drug  is.  a  powerful  stimulation  of  the  ganglion  cells, 
so  that,  if  the  drug  be  injected,  there  is  an  enormous  rise  of  blood  pressure 
owing  to  the  universal  vaso-constriction  that  is  produced.  The  stimulation 
gives  place  to  a  condition  of  paralysis;  the  blood  pressure  falls  below 
normal,  owing  to  the  cutting  off  of  the  peripheral  vascular  nerves  from  the 
vaso-motor  centre.  Stimulation  of  the  pre-ganglionic  fibres  is  now  without 
effect,  although  the  normal  results  follow  stimulation  of  the  post-ganghonic 
non-medullated  fibres. 

By  these  methods  it  has  been  determined  that  all  the  vaso-constrictor 
nerves  of  the  body  leave  the  spinal  cord  by  the  anterior  roots  of  the  spinal 
nerves  from  the  first  dorsal  to  the  third  or  fourth  lumbar  inclusive.  From 
the  roots  they  pass  by  the  white  rami  communicantes  to  the  ganglia  of  the 
sympathetic  chain  lying  along  the  front  of  the  vertebral  column.  Here 
they  take  different  courses  according  to  their  destination. 

The  fibres  to  the  head  and  neck  leave  by  the  first  four  thoracic  nerves, 
pass  into  the  sympathetic  chain  through  the  ganglion  stellatum  and  ansa 
Vieussenii  to  the  inferior  cervical  ganglion,  and  up  the  cervical  sympathetic 
trunk  to  the  superior  cervical  ganglion.  Here  they  end,  and  the  impulses 
are  carried  by  a  fresh  relay  of  fibres,  which  start  from  cells  in  this  ganglion 
and  travel  as  non-medullated  fibres  on  the  walls  of  the  carotid  artery  and 
its  branches. 

The  constrictors  to  the  fore  limb  in  the  dog  leave  the  cord  by  the  white 
rami  of  the  fourth  to  the  tenth  thoracic  nerves.  The  fibres  run  up  the 
sympathetic  chain  to  the  stellate  ganglion,  where  they  all  end  in  synapses 
round  the  cells  of  this  ganglion.  The  impulses  are  carried  on  by  non- 
medullated  fibres  along  the  grey  rami  of  the  sympathetic  to  the  cervical 
nerves  which  make  up  the  brachial  plexus,  and  run  down  in  the  branches  of 
this  plexus  to  be  distributed  to  the  vessels  of  the  fore  limb. 

The  constrictor  impulses  to  the  hind  limb  in  the  dog  arise  from  the 
nerve  roots  between  the  eleventh  dorsal  and  third  lumbar  roots.  All 
the  fibres  end  in  connection  with  cells  in  the  sixth  and  seventh  lumbar 
and  first  and  second  sacral  gangha  of  the  sympathetic  chain,  whence 
the  impulses  are  carried  by  grey  rami  to  the  nerves  making  up  the  sacral 
plexus. 

The  most  important  vaso-motor  nerve  of  the  body  is  the  sjjlanchnic 
nerve.  This  nerve  receives  most  of  the  fibres  forming  "the  white  rami  from 
the  lower  seven  dorsal  and  upper  two  or  three  lumbar  roots,  the  latter  fibres 


THE  NERVOUS  CONTROL  OF  THE   BLOOD   VESSELS     1039 

often  taking  a  separate  course  as  the  lesser  splanchnics.  The  fibres  can  be 
seen  to  pass  through  the  sympathetic  chain  of  the  thorax  without  inter- 
ruption, and  for  the  most  part  have  their  cell  station  in  the  large  ganglia, 
especially  the  semilunar  ganglia,  of  the  solar  plexus,  whence  a  thick  mesh- 
work  of  non-medullated  fibres  is  distributed  along  all  the  vessels  of  the 
abdominal  viscera.  The  area  of  the  vessels  innervated  by  this  nerve  is  so 
large  that  section  of  this  nerve  on  each  side  causes  a  considerable  fall  in  the 
general  blood  pressure.  This  fall  is  more  marked  in  animals  such  as  the 
rabbit  and  other  herbivora,  in  which  the  alimentary  canal  is  proportionately 
very  much  developed  and  has  a  correspondingly  large  blood  supply. 


VASO-DILATOR   NERVES 

(Since  the  arteries  are  in  a  constant  condition  of  moderate  contraction, 
a  dilatation  might  be  brought  about  by  a  relaxation  of  this  tone  by  an 
inhibition  of  the  normal  constrictor  impulses  proceeding  to  the  vessels  from 
the  vaso-motor  centre.  We  find  however  in  many  parts  of  the  body 
evidence  of  the  existence  of  a  nerve  supply  to  blood  vessels  antagonistic 
in  its  function  to  the  vaso-constrictors.  Thus,  if  the  chorda  tympani  nerve 
going  to  the  submaxillary  gland  be  cut,  no  change  is  evident  in  the  blood 
vessels  of  the  gland.  But  if  its  peripheral  end  be  stimulated,  there  is  instantly 
free  secretion  of  saliva  from  the  gland,  and  all  the  blood  vessels  are  largely 
dilated.  In  consequence  of  this  dilatation  the  blood  rushes  through  the 
capillaries  so  quickly  that  it  has  no  time  to  lose  much  of  its  oxygen;  the 
blood  flowing  from  the  vein  is  therefore  bright  arterial  in  colour,  and  is 
increased  to  six  or  eight  times  the  previous  amount.  If  atropine  be  injected 
into  the  animal,  the  action  of  the  chorda  tympani  on  the  blood  vessels  is 
unaffected,  although  the  secretion  on  stimulation  is  abolished.  The  chorda 
tympani  is  therefore  said  to  contain  vaso-dilator  fibres  for  the  vessels  of  the 
submaxillary  gland.  Other  examples  of  vaso-dilator  (or  dilatator)  nerves 
are  the  small  'petrosal  nerve  to  the  parotid  gland,  the  lingual  nerve  to  the 
blood  vessels  of  the  tongue,  and  the  nervi  erigentes  or  pelvic  visceral  nerves 
to  those  of  the  penis. 

The  course  of  these  typical  dilator  nerves  differs  widely  from  that  of  the 
constrictors.  Whereas  the  latter  leave  the  central  nervous  system  over  a 
limited  area  of  the  cord,  the  vaso-dilators  take  their  origin  together  with 
any  of  the  cerebro-spinal  nerves.  Thus  the  chorda  tympani  fibres,  and 
probably  those  contained  in  the  petrosal  nerve,  arise  from  the  nervus  inter- 
medius  between  the  seventh  and  eighth  cranial  nerves.  The  nervi  erigentes 
leave  the  lower  end  of  the  cord  by  the  anterior  roots  of  the  second  and  third 
sacral  nerves.  All  of  them,  like  the  vaso-constrictors  and  probably  all 
visceral  nerve  fibres,  are  interrupted  by  ganglion  cells  before  reaching  to 
their  destination.  These  cells  however  he,  not  in  the  lateral  chain  of  the 
sympathetic,  with  which  the  nerves  have  no  connection  at  all,  but  peri- 
pherally, and  are  generally  embedded  in  the  organs  to  which  the  nerves  are 
distributed.    Thus  the  chorda  tympani  fibres  to  the  submaxillary  glands  are 


1010 


PHYSIOLOGY 


interrupted  by  cells  embedded  in  the  gland  itself.  The  nervi  erigentes  pass 
to  ganglion  cells  in  the  hypogastric  plexus  lying  on  the  neck  of  the  bladder. 
Whether  any  large  numbers  of  the  fibres  making  up  the  sympathetic 
system  of  nerves  are  vaso-dilator  in  function  is  still  uncertain.  In  the  dog 
dilatation  f>f  the  vessels  of  the  soft  palate  and  gums  can  be  produced  by 
stimulation  of  the  cervical  sympathetic  of  the  same  side,  or  of  the  stellate 
ganglion  or  its  rami  communicant  es.  The  effect  has  not  yet  been  observed 
in  any  other  animals.  It  is  probable  that  the  splanchnic  nerves  convey  vaso- 
dilator fibres  to  the  vessels  of  the  abdomen,  since  stimulation  of  these  nerves 
may  cause  a  fall  of  blood  pressure,  provided  that  the  constrictor  fibres,  which 
predominate,  have  been  paralysed  by  the  previous  administration  of  large 
doses  of  ereotoxin,  derived  from  ergot. 


K 

/ 

Nerve  freshly  divided. 
Constriction. 


Nerve  four  days  degenerated. 
Dilatation. 


Fig.  473.  Plethysmographic  tracing  of  hind  limbs,  shewing  effect  of  stimulating 
the  sciatic  nerve  on  the  volume  of  the  limb.  A,  immediately  after  section  of  the 
nerve;  B,  four  days  after  section.  The  nerve  was  stimulated  betweeen  the  two 
vertical  lines.     Curves  to  be  read  from  right  In  left.     (Bowditch  and  Warren.) 

The  presence  of  vaso-dilator  fibres  in  the  nerves  going  to  the  limbs  has 
been  the  subject  of  much  debate.  Since  these  nerves  contaiu  also  con- 
strictor fibres,  the  effect  of  the  constriction  overpowers  any  effects  due  to 
simultaneous  stimulation  of  possible  dilator  fibres.  Moreover  the  dilators 
apparently  do  not  conduct  any  tonic  influences  to  the  blood  vessels,  so  that 
the  only  effect  of  section  of  a  mixed  nerve  is  that  due  to  the  removal  of  the 
tonic  constrictor  influences,  and  the  vessels  in  the  area  of  distribution  of 
the  nerves  are  dilated. 

Various  methods  have  been  employed  to  show  the  presence  of  dilator 
fibres  in  such  a  mixed  nerve  trunk.  Of  these  the  chief  two  are  those  depend- 
ing on  the  unequal  time  taken  for  the  two  sets  of  fibres  to  degenerate  and 
on  the  varying  excitability  of  the  two  sets  of  fibres  to  different  kinds  of 
stimulation.  Thus,  if  the  sciatic  nerve  be  cut,  a  primary  dilatation  of  the 
vessels  of  the  leg  and  foot  is  produced  which  however  passes  off  after  two 
or  three  days.  If  now  the  peripheral  end  of  the  divided  nerve  be  stimulated, 
dilatation  of  the  vessels  is  brought  about  (Fig.  473).  Apparently  the  con- 
strictor fibres  degenerate  before  the  dilator  fibres  so  that,  at  a  certain  period 
after  the  nerve  section,  only  the  latter  respond  to  stimulation.  On  the 
other  hand,  it  is  often  possible  in  the  freshly  cut  nerve  to  obtain  dilatation 
by  stimulating  its  peripheral  end  with  induction  shocks  repeated  at  slow 
intervals — one  to  four  per  second.  The  effects  of  different  rates  of  stimula- 
tion on  the  limb  nerves  of  the  cat  are  shown  in  Fig.  Hi. 


THE  NERVOUS  CONTROL  OF  THE   BLOOD    VESSELS     1041 

When  we  endeavour  to  trace  these  limb  dilator  fibres  back  to  the  cord, 
we  find  no  trace  of  their  passage  through  the  sympathetic  system.  It  was 
shown  by  Strieker  and  Morat  that  dilatation  of  the  vessels  of  the  hind  limb 
can  be  produced  by  stimulating  the  posterior  roots  of  the  nerves  going  to  the 
limb,  i.  e.  far  below  the  point  of  origin  from  the  cord  of  the  constrictor  fibres 
to  the  same  part  of  the  body.  Since  it  has  been  definitely  shown  by  embryo- 
logists  and  histologists  that  in  higher  mammals  all  the  fibres  making  up  the 
posterior  roots  have  their  origin  in  the  cells  of  the  posterior  root  ganglion, 
this  observation  was  widely  discredited,  until  it  was  confirmed  by  Bayliss 


Flo.  474.  Effect  on  the  volume  of  the  hind  limbs  of  the  eat  of  stimulating  the  sciatic 
nerve  with  induction  shocks  at  different  rates.  It  will  be  noticed  that  with  one 
shock  per  second  there  is  hardly  any  constriction,  but  considerable  dilatation, 
whereas  with  <>4  shocks  per  second  the  only  effect  produced  is  vaso-eonstriction. 
Curves  to  be  read  from  right  to  left.     (Bowditcii  and  Waiiren.) 

for  all  manner  of  stimuli.  Stimulation  of  the  posterior  roots,  either  before 
in  after  they  have  passed  through  the  ganglia,  causes  dilatation  of  the  vessels 
in  the  area  of  the  supply  qf  the  roots,  whatever  be  the  nature  of  the  stimulus 
employed,  whether  electrical,  chemical,  or  mechanical  (Fig.  175).  This  effect 
is  not  destroyed  by  previous  section  of  the  posterior  roots  on  the  proximal 
Bide  of  the  ganglia,  showing  that  the  fibres  by  means  of  which  the  dilatation 
is  produced  have  the  same  origin  and  course  as  the  ordinary  sensory  nerves 
to  the  limbs.  Since  the  vaso-dilator  impulses  pass  along  these  nerves  in  a 
direction  opposite  to  that  taken  by  the  normal  sensory  impulses,  Bayliss 
lias  designated  them  as  antidromic  impulses.  So  far  this  phenomenon  of 
a  nerve  fibre  functioning  (not  merely  conducting)  in  both  directions  is 
almost  without  analogy  in  our  knowledge  of  the  other  nerve  functions  of 
(ifj 


1042 


PHYSIOLOGY 


the  body.    There  is  do  doubt  however  that  similar  antidromic  impulses  are 
involved  in  the  production  of  the  so-called  trophic  changes,  such  as  localised 


Fig.  475.     Effect  of  excitation  of  peripheral  end  of  the  seventh  lumbar  posterior 
root  in  the  dog.     (Bayliss.) 
Uppermost  curve,  volume  of  left  hind  limb;    next  below,  arterial  blood 
pressure;  the  third  line  marks  the  period  of  stimulation;  bottom  line,  time- 
marking  in  seconds. 

erythema  or  the  formation  of  vesicles  (as  in  herpes  zoster),  which  may  occur 
in  the  course  of  distribution  of  a  sensory  nerve,  and  is  always  found  to  be 
associated  with  changes,  inflammatory  or  otherwise,  in  the  corresponding 
sup.  nerve  p/ex. 


Fig.  476.     Diagram  to  illustrate  the  production  of  vasodilatation  in  the  area 
of  distribution  of  a  sensory  nerve. 
prg,  posterior  root  ganglion;  sens.nf,  sensory  nerve  fibre,  branching  to  supply 
dilator  fibres  to  the  skin  arteries,  and  sensory  fibres  to  the  skin. 

posterior  root  ganglion.  Moreover  evidence  has  been  brought  forward  that 
these  fibres  may  take  part  in  ordinary  vascular  reflexes  of  the  body,  that 
in  fact  they  are  normally  traversed  by  impulses  in  either  direction. 

Some  observations  by  Hans  Meyer  and  Bruce  tend  to  indicate  that  in 
the  antidromic  vaso-dilatation,  as  well  as  in  the  reddening  and  inflammatory 
changes  ensuing  on  local  excitation,  we  are  dealing  with  axon  reflexes,  perhaps 


THE  NERVOUS  CONTROL  OF  THE   BLOOD   VESSELS    1043 

the  only  remains  of  the  local  reflexes  of  a  primitive  peripheral  subcutaneous 
nervous  system.  If  croton  oil  or  mustard  oil  be  applied  to  the  skin  or  to  the 
conjunctiva,  redness,  swelling,  and  all  the  signs  of  a  local  inflammation  are 
produced.  The  course  of  events  is  not  altered  by  destruction  of  the  central 
nervous  system  or  by  section  of  the  sensory  nerve  roots  (posterior  spinal 
root  or  trigeminus)  on  the  central  side  of  the  ganglion.  If  however  they 
be  divided  peripherally  of  the  ganglion,  and  time  be  allowed  for  complete 
degeneration  of  the  nerve  fibres  to  their  peripheral  terminations,  the  applica- 
tion of  croton  or  mustard  oil,  even  to  the  delicate  conjunctiva,  is  without 
effect.  The  same  results  may  be  produced  if  the  peripheral  terminations  of 
the  nerves  be  paralysed  by  the  subcutaneous  injection  of  local  anaesthetics. 
We  must  assume  that  the  axons  of  the  peripheral  sensory  nerves  branch, 
some  branches  going  to  the  surface,  others  to  the  muscle  cells  of  the  cutaneous 
arterioles,  as  indicated  in  the"diagram  (Fig.  476). 


^wjtmi^ 


^»*^lM*^ta»Mta, 


FlG.   477.     Blood-pressure  curve  from   carotid  of  dog.     Between  the  arrows   the 
central  end  of  a  sensory  nervt  was  stimulated.     (Hurtkle's  manometer.) 

Gaskell  has  drawn  an  analogy  between  the  nerves  distributed  to  the 
blood  vessels  and  those  going  to  the  heart,  which  is  indeed  only  a  specialised 
part  of  the  general  blood  tubes  of  the  body.  These  nerves,  according  to 
their  action  on  the  metabolic  activity  of  the.  tissues  supplied,  are  divided  by 
Gaskell  into  anabolic  and  catabolic  nerves.  The  anabolic  nerves,  as  indicated 
bv  their  name,  cause  a  building  up  or  regeneration  of  the  contractile  tissue. 
They  therefore  act  as  inhibitory  nerves.  This  class  would  include  the  vagus 
and  the  vasodilator  fibres.  The  catabolic  nerves  cause  an  increased  activity 
of  the  contractile  tissue,  and  active  contraction  is  associated  with  and 
derives  its  energy  from  disintegration  or  catabolism  of  the  muscular 
substance.  An  ordinary  motor  nerve  to  a  muscle  is  therefore  a  catabolic 
nerve.  This  class  would  include  the  accelerator  nerves  to  the  heart,  and 
the  vaso-constrictors.  The  course  of  these  two  sets  of  nerves  bears  out  this 
comparison,  the  path  taken  by  the  accelerator  nerves  being  identical  at 
first  with  that  of  the  vaso-constrictor  fibres  to  the  head  and  neck. 


VASO-MOTOR   REFLEXES 

The  vasomotor  centre  with  its  efferent  tracts  is  constantly  played  upon 
by  impulses  arriving  at  it  from  the  vascular  system,  including  both  heart 
and  blood  vessels,  from  the  viscera,  from  the  muscles,  and  from  the  surface 
of  the  body.     The  reflex  effects  produced  by  stimulation  of  the  various 


1014 


PHYSIOLOGY 


afferent  nerves  may  be  classified,  according  as  they  affect  the  general  blood 
pressure  or  the  circulation  through  restricted  areas  of  the  body,  as  general 
and  local. 

The  afferent  impulses  affecting  the  general  blood  pressure  are  distin- 
guished as  pressor  and  depressor,  and  these  names  are  sometimes  applied 
to  the  nerves  which  carry  the  impulses.  A  pressor  reflex  is  one  which 
induces  a  rise  of  general  blood  pressure  by  constriction  of  the  blood  vessels, 
especially  in  the  splanchnic  area  (Fig.  477).  Effects  of  this  kind  are  pro- 
duced by  stimulation  of  nearly 
all  the  sensory  nerves  of  the 
Bp  skin.  Practically  all  impulses, 
which  if  consciousness  were 
present  would  be  attended  with 
pain,  cause  also  a  rise  of  general 
blood  pressure.  A  rise  of  pres- 
sure may  be  produced  by  the 
stimulation  of  such  nerves  as  the 
Spleen  fifth,  the  central  end  of  the 
splanchnic  nerves,  or  of  the 
nerves  distributed  to  the  surface 
of  the  body.  This  rise  occurs 
in  all  animals  under  morphia 
and  curare.  In  the  rabbit,  when 
anaesthesia  is  induced  by  means 
of  chloral  or  chloroform,  stimu- 
lation of  sensory  nerves  may 
cause  a  fall  of  blood  pressure. 
The  chief  example  of  a  depressor  nerve  we  have  already  studied  in 
dealing  with  the  reflexes  from  the  heart.  The  fall  of  pressure  produced  by 
stimulation  of  this  nerve  is  effected  chiefly  by  dilatation  of  the  splanchnic 
area  (Fig.  478),  though,  as  Bayliss  has  shown,  practically  all  the  vessels  of 
the  body  partake  in  the  relaxation.  The  lowering  of  blood  pressure  produced 
by  stimulation  of  this  nerve  differs  from  that  obtained  on  stimulating  the 
sensory  nerves  of  the  rabbit  under  chloral,  in  that  its  effect  lasts  as  long  as 
the  stimulation  is  continued,  whereas  in  the  latter  case  the  effect  shows  signs 
of  fatigue  and  disappears  before  the  excitation  is  shut  off. 

So  far  as  the  general  blood  pressure  is  concerned,  the  most  important 
impulses  arriving  at  the  centre  are  those  from  the  vascular  system,  especially 
from  the  heart  itself,  and  those  from  the  higher  parts  of  the  brain.  Whatever 
the  condition  of  the  heart,  the  brain  always  demands  a  normal  arterial 
pressure,  since  on  this  depends  the  supply  of  a  proper  quantum  of  blood  to 
the  master  tissues  of  the  body.  A  failing  heart  therefore  evokes  indirectly 
constriction  of  the  blood  vessels,  a  fact  which  may  lead  to  a  vicious  circle  in  I 
cases  where  the  heart  is  unable  to  perform  its  normal  functions  and  to 
empty  itself  against  the  resistance  of  the  blood  vessels.  In  this  case  the 
heart  dilates  more  and  more,  until  the  slightest  increase  in  the  demands  upon 
it,  as  by  a  slight  muscular  exertion,  may  suffice  to  stop  its  action  altogether. 


FlG.  478.  Simultaneous  tracing  of  arterial 
blood  pressure  and  splenic  volume  from 
a  rabbit,  showing  the  marked  swelling  of 
the  spleen  associated  with  fall  of  general 
blood  pressure  on  stimulation  of  the  cen- 
tral end  of  the  depressor  nerve.  The  nerve 
was  excited  between  a  and  b.     (Bayliss.) 


THE  NERVOUS  CONTROL  OF  THE   BLOOD   VESSELS    1045 

Under  normal  circumstances  every  part  of  the  body  receives  just  so 
much  blood  as  it  needs  for  its  metabolic  requirements.  Hence  activity  must 
be  associated  with  an  increased  flow  of  blood  through  the  part.  Two 
mechanisms  are  involved  in  the  production  of  this  adaptation.  In  the  first 
place,  stimuli  arising  in  any  part  of  the  body  may  affect  the  vascular  system 
in  two  directions,  causing  reflexly  dilatation  of  blood  vessels  in  the  part 
which  is  the  origin  of  the  impulses  and  constriction  of  the  blood  vessels  in 
the  rest  of  the  body,  so  that  a  normal  or  raised  blood  pressure  is  available 
for  driving  an  increased  supply  of  blood  through  the  dilated  vessels  of  the 
part.  Thus,  if  both  hind  limbs  of  an  animal  be  placed  in  a  plethysmograph, 
it  will  be  seen  that  stimulation  of  the  anterior  crural  or  peroneal  nerve  in 
t  he  left  leg  causes  dilatation  of  this  leg  and  constriction  of  the  leg  of  the  other 
side.  At  rest  the  organs  of  the  chest  and  abdomen  contain  more  than  half 
of  the  total  quantity  of  blood  in  the  body,  so  that  very  little  change  in  the 
rapacity  of  these  organs  suffices  to  furnish  the  extra  supply  of  blood  needed 
by  any  part  during  a  state  of  increased  activity. 

THE   CHEMICAL   REGULATION   OF   THE    BLOOD   VESSELS 

Another  factor,  which  is  possibly  involved  in  the  production  of  the 
increased  blood  flow  through  active  organs,  is  a  chemical  stimulation  of  the 
vessels  themselves,  by  means  of  substances  (metabolites)  produced  as  a 
result  of  the  chemical  changes  accompanying  activity.  The  great  increase 
in  the  flow  through  the  muscles  which  accompanies  muscular  exercise  is 
probably  brought  about  largely  by  this  means.  It  has  been  shown  that  the 
passage  of  blood  containing  lactic  acid  or  carbon  dioxide  (both  results  of 
muscular  metabolism)  causes  a  marked  dilatation  of  the  blood  vessels  of  a 
limb.  The  Table  given  below  shows  the  influence  of  activity  on  the 
blood  flow  through  various  organs. 

We  thus  see  that  carbon  dioxide,  which  is  the-  universal  hormone  set 
free  in  the  circulation  when  the  activity  of  the  body  as  a  whole  is  increased, 
has  a  double  effect  on  the  blood  vessels — a  central  effect  through  the 
vaso-motor  centres,  medulla  and  spinal  cord,  causing  contraction  of  the 
blood  vessels,  and  a  local  peripheral  effect  causing  dilatation  of  the  blood 
vessels.  The  general  result  therefore  will  be  to  cause  dilatation  of  the 
blood  vessels  of  the  part  where  the  carbon  dioxide  is  produced  and  where  it 
is  present  in  greatest  concentration,  and  vascular  constriction  elsewhere 
under  the  influence  of  the  sensitive  nervous  centres. 

Flow  in  Cubic  Centimetres  fer  Minute  per  100  Grm.  Tissue 


Levator  labii  superioris  (of  the  horse) 
Kidney      ..... 
Hind  limb  .... 

Hind  limb  (after  section  of  nerves) 
Thyroid  gland   .... 
Rabbit's  brain  .... 
Heart        ..... 


17-5 

85 

— 

140 

3-4 

— 

9-9 

, — 

5900 

— 

1360 

— 

1010 


PHYSIOLOGY 


ACTION  OF  ADRENALINE.  This  substance,  produced  by  the  supra- 
renal glands,  has  a  marked  influence  on  the  calibre  of  the  blood  vessels. 
If  1  c.c.  of  a  1  in  10,000  solution  of  this  substance  be  injected  into  the  jugular 
vein,  there  is  at  once  a  universal  constriction  of  the  arterioles  with  the 
exception  of  those  of  the  brain.  If  the  vagi  are  cut,  we  obtain  a  simultaneous 
augmentor  action  of  this  drug  on  the  heart  and  constrictor  effect  on  the 
blood  vessels,  so  that  the  arterial  pressure  rises  to  an  enormous  extent,  up 
to  300  mm.  Hg.  or  more.    The  same  result  occurs  after  section  of  the  vaso- 


Fio.  479.  Curve  Bhowing  the  effect  of  a  sudden  rise  in  the  arterial  resistance  on 
the  output  and  volume  of  the  ventricles.  Systole  causes  a  downward  movement 
of  the  lever. 

n,  heart  volume;  bp,  arterial  blood  pressure;  s,  signal  Bhowing  duration  of 
stimulation  of  splanchnic  nerve ;  T,  time  marker,  10  sees. 

motor  nerves  or  after  destruction  of  the  brain  and  spinal  cord,  so  that  there 
is  no  doubt  that  adrenaline  acts  directly  on  the  blood-vessel  wall.  The 
action  of  this  drug  as  a  whole  is  therefore  largely  to  augment  the  energy  of 
the  circulation.  The  arterial  pressure  rises,  and  the  blood  will  be  therefore 
travelling  at  a  much  greater  pace  through  any  part  of  the  body  where  the 
vessels  are  maintained  in  a  dilated  condition,  e.  g,  in  an  active  muscle,  or 
where  there  are  no  vaso-motor  nerves,  as  in  the  vessels  of  the  brain.  It  is 
therefore  not  surprising  that  we  have  evidence  of  the  secretion  of  adrenaline 
in  increased  quantities  into  the  blood  during  any  condition  of  stress.  When- 
ever the  splanchnic  nerve  is  stimulated,  there  is  an  increased  production  of 
adrenaline.  On  this  account  the  rise  of  pressure  produced  under  these 
circumstances  shows  a  stepped  curve,  the  first  rise  being  due  to  the  direct 
action  of  the  vaso-motor  nerves  of  the  blood  vessels,  the  second  being 


THE  NERVOUS  CONTROL  OF  THE   BLOOD   VESSELS    1047 

brought  about  by  the.  stimulation  of  the  suprarenals  and  the  discharge  of 
adrenaline  into  the  general  circulation.  Simultaneously  with  this  second 
rise  of  blood  pressure,  we  notice  in  the  curve  given  in  Fig.  479  a  diminished 
volume  of  the  heart  due  to  more  effective  contraction  of  this  organ. 

This  diminished  volume  of  the  heart  is  often  associated  with  a  marked 
quickening  of  the  heart  rate,  both  effect*  being  due  to  the  action  of  adrenaline 
on  the  heart.  During  asphyxia  the  rise  of  arterial  pressure  is  largely  brought 
about  through  the  intermediation  of  the  splanchnic  nerves  and  is  therefore 
also  associated  with  the  discharge  of  adrenaline.    It  is  on  this  account  that 


Fig.  480.     Effect  of  excitation  of  splanchnic  nerves  on  tho  blood  pressure  and 
on  the  volume  of  the  denervated  hind  limb  of  the  cat.     (Bayliss.) 

in  the  whole  animal,  provided  that  sufficient  oxygen  is  supplied,  very  large 
percentages  of  carbon  dioxide  may  be  inhaled  without  causing  fatal  dilata- 
tion of  the  heart,  the  effect  of  the  adrenaline  discharged  into  the  blood  stream 
serving  to  counteract  the  injurious  influence  of  carbon  dioxide  on  the  heart 
muscle.  These  two  chemical  influences,  the  local  production  of  carbon- 
dioxide  and  the  discharge  of  adrenaline  into  the  general  circulation,  must 
always  be  kept  in  mind  in  trying  to  account  for  the  behaviour  of  the  blood 
vessels  under  the  most  various  conditions.  Thus  in  Fig.  480  is  shown  the 
effect  of  temporary  stimulation  of  the  splanchnic  nerve  on  the  blood  pressure 
and  on  the  volume  of  the  hind  limb  of  the  cat.  It  will  be  noticed  that  the 
volume  of  the  hind  limb  increases  passively  with  the  rise  of  pressure  and  then 
diminishes  much  below  its  previous  amount.  This  diminution  is  due  to  the 
discharge  of  adrenaline  into  the  blood  stream  as  the  result  of  ■stimulation  of 
the  splanchnic  nerve,  and  is  absent  if  the  suprarenals  have  been  previously 
destroyed.  The  curve  shown  in  Fig.  481,  which  with  the  foregoing  one  was 
taken  by  Bayliss  to  indicate  a  local  adaptation  of  the  blood  vessels  to  their 
internal  pressure,  is  probably  brought  about  by  the  local  production  of  carbon 
dioxide  (von  An  rep).     Temporary  occlusion  of  the  abdominal  aorta  is  here 


1018  PHYSIOLOGY 

shown  to  cause  first  a  diminution  of  the  volume  of  the  hind  limb,  followed 
by  a  marked  increase.  During  the  period  of  obstruction  the  circulation  of 
the  hind  limb  was  interrupted,  and  there  was  thus  accumulation  of  carbon 
dioxide  in  the  tissues  and  around  the  blood  vessels.  This  caused  a  relaxa- 
tion of  the  blood-vessel  walls  and  a  corresponding  increased  volume  of  the 
limb  when  the  blood  was  allowed  once  more  to  flow  by  release  of  the  aortic 
obstruction. 


Signal 

Time  10  sees. 

Fig.  -181.  Effect  o£  temporary  compression  of  the  abdominal  aorta  on  the  volume  of 
the  denervated  hind  limb.  Two  compressions,  the  second  not  marked  by  the 
signal.  Blood  pressure  taken  in  the  femoral  artery  of  one  hind  limb,  the  other 
hind  limb  being  in  the  plethysmograph.     (Baymss.) 


THE   REGULATION    OF    THE    BLOOD    FLOW   THROUGH    THE 
CAPILLARIES 

Up  to  the  present  we  have  emphasised  only  two  factors  as  regulating 
the  blood  flow  through  the  peripheral  parts  of  the  body,  viz.  the  general 
blood  pressure,  and  the  state  of  contraction  or  tone  of  the  arterioles  supplying 
those  parts.  We  have  regarded  the  capillaries  as  a  close  meshwork  of  canals, 
the  calibre  of  which  depends  entirely  on  the  extent  to  which  they  were 
distended  by  the  pressure  of  blood  within  them.  There  is  no  doubt  how- 
ever that  both  the  calibre  of  and  the  resistance  to  the  flow  of  blood 
through  the  capillaries  are  intimately  dependent  on  the  nutritive  condition 
of  the  cells  composing  their  walls.  Certain  observers  have  described  spon- 
taneous   changes   taking   place   in    the   diameter    of    the    capillaries,   and 


THE   NERVOUS  CONTROL   OF  THE   BLOOD   VESSELS     1049 

have  ascribed  them  to  active  contraction  or  change  of  form  of  the  endo- 
thelial cells,  which  was  apparently  independent  of  concomitant  arterial 
alteration.  In  a  subsequent  chapter  we  shall  have  occasion  to  study 
in  the  capillary  circulation  the  impressive  changes  following  slight  injury, 
chemical,  thermal  or  mechanical,  which  give  the  salient  features  to  the 
picture  of  inflammation.  But  it  is  certain  that  nutritive  changes  of  less 
degree,  falling  within  normal  physiological  events,  also  influence  consider- 
ably the  flow  through  the  capillaries,  either  by  increasing  their  lumen  or  by 
altering  the  resistance  to  the  passage  of  blood  through  them.  Thus  during 
activity  the  total  capacity  of  the  capillaries  of  muscle  may  be  increased  from 
0'02  per  cent,  to  15  per  cent,  of  the  total  volume  of  the  muscle  (Krogh).  The 
phenomena  of  dropsy  show  us  that  the  capillary  wall  is  very  sensitive  to  the 
continued  absence  of  oxygen,  oxygen  starvation  rapidly  increasing  its 
permeability;  and  it  seems  that  the  presence  of  oxygen  is  an  essential  con- 
dition of  any  reactivity  to  moderate  nutritional  changes  on  the  part  of 
the  capillaries.  The  dilator  effect  we  have  already  studied  of  carbonic  acid 
and  other  weak  acids  on  the  arterioles  seems  to  be  shared  by  the  capillaries. 
In  such  a  case  it  is  difficult  to  dissociate  the  effects  of  arterial  dilatation 
from  those  of  capillary  dilatation.  At  least  one,  chemical  substance  is  known 
however,  which  has  diametrically  opposite  effects  on  the  two  sets  of  vessels. 
Histamine,  the  amine  produced  by  the  decarboxylation  of  histidine.  has  been 
3howri  by  Dale  to  have  a  constrictor  effect  on  the  arterioles  and  a  dilator 
effect  on  the  capillaries.  It  has  been  suggested  that  the  production  of 
histamine  or  of  other  substances  with  a  similar  action  plays  an  important 
part  in  giving  rise  to  the  symptoms  of  surgical  shock.  In  this  condition, 
which  is  found  notably  after  widespread  laceration,  especially  of  the 
muscles,  and  consequent  destruction  of  the  tissues,  there  is  a  continually 
increasing  depression  of  the  blood  pressure  due  to  the  ever  lessening  volume 
of  blood  in  circulation.  Since  this  lowering  of  blood  pressure  does  not 
depend  on  any  direct  action  of  the  heart  nor  is  it  associated  with  vaso-motor 
paralysis,  it  lias  been  concluded  that  the  prime  factor  at  work  is  a  general 
dilatation  of  the  capillaries,  leading  to  stagnation  of  the  blood  in  these  vessels 
and  an  increased  exudation  into  the  tissues,  thus  causing  a  constant  leak  of 
Mood  fluid  from  the  general  circulation. 

No  evidence  has  yet  been  brought  forward  for  a  direct  action  of  the 
central  nervous  system  on  the  capillaries.  Certain  facts  however  point  to 
a  connection  between  nerve  lesions  and  the  calibre  of  the  capillaries  supplied 
by  the  nerves.  Thus  if  in  the  cat  the  sciatic  nerve  be  cut  on  the  right  side. 
Eor  t  he  next  few  hours  the  pad  of  the  foot  on  that  side  is  flushed  and  warmer 
than  the  left  foot.  The  next  day  the  flush  has  disappeared,  in  fact  the  pad 
of  the  right  loot  may  be  paler  than  that  of  the  left  foot.  The  right  foot  is 
however   still  a  degree  or  two  warmer  than  the  left   foot.     This  condition 

may  1 xplained  on  the  assumption  that    the  immediate  effect   of  cutting 

the  sciatic  nerve  is  to  cause  dilatation  both  of  the  arterioles  and  of  the 
capillaries.  The  capillary  dilatation  passes  oil',  so  that  on  the  day  alter  the 
seciion.  although  the  arterioles  are  still  dilated  and  there  is  a  more  rapid 


L050  PHYSIOLOGY 

flow  of  blood  through  the  pad  and  a  correspondingly  higher  temperature 
than  on  the  sound  side,  the  capillaries  are  contracted  so  that  the  pad  contains 
less  blood  and  is  paler  than  on  the  opposite  side.  These  observations 
suggest  a  question  whether  the  whole  of  the  antidromic  effects,  observed  by 
Bayliss  to  follow  stimulation  of  sensory  nerves,  may  not  really  be  confined 
to,  or  have  their  chief  seat  in,  the  capillaries.  It  is  indeed  certain  that  the 
closely  allied  phenomena  of  herpes  zoster  and  the  erythematous  eruptions 
along  the  course  of  a  nerve,  and  having  their  origin  in  morbid  conditions  of 
tlic  nerve  or  of  the  posterior  root  ganglion,  are  due  to  changes  in  the  capil- 
laries or  in  the  tissues  immediately  around  them.  This  question  must 
however  be  left  for  further  investigation. 


SECTION  XI 

THE    CIRCULATORY    CHANGES    DURING    MUSCULAR 
EXERCISE 

In  the  preceeding  sections  we  have  studied  separately  a  number  of 
mechanisms  by  which  the  heart  or  the  vessels  react  to  this  or  that  con- 
dition, in  order  to  bring  about  an  appropriate  modification  of  the  circulation. 
In  so  doing  we  have  analysed  somewhat  artificially  the  factors  which  are 
normally  involved  simultaneously  in  the  adaptation  of  the  circulation  to 
the  necessities  of  the  body,  as  determined  by  the  exigencies  of  its 
environment.  This  adaptation  is  in  fact  a  necessary  condition  of  the 
survival  of  the  individual  in  the  struggle  for  existence.  Our  view  of  the 
working  of  the  circulation  as  a  whole  is  imperfect  until  we  can  effect  a 
synthesis  of  these  isolated  mechanisms,  and  trace  out  the  chain  of  events 
Concerned  in  that  intimate  co-operation  of  all  parts  of  the  circulation  with 
all  other  systems  and  organs  of  the  body  which  must  be  involved  in  every 
act  of  life.  For  this  purpose  we  cannot  do  better  than  take  as  an  example 
the  complex  of  adaptations  which  are  involved  in  muscular  exericse.  Though 
for  purposes  of  experiment  the  exercise  may  be  that  involved  in  working  a 
stationary  bicycle,  we  must  remember  that  it  is  the  same  series  of  processes 
as  are  brought  into  play  in  the  supreme  struggle  for  life  against  an  enemy 
or  rival,  or  in  the  chase  for  food  which  is  necessary  to  avoid  death  by 
hunger.  For  the  analysis  of  the  different  events  in  the  circulation,  we  have 
hitherto  had  large  recourse  to  animal  experiments ;  but  with  the  facts  thus 
gained  at  our  disposal,  we  can  proceed  to  investigate  the  subject  in  man 
himself,  with  the  added  advantages  of  his  voluntary  co-operation  and  of 
the  absence  of  abnormal  conditions  such  as  anaesthetics,  etc. 

On  initiating  such  experiments  in  man  we  meet  at  once  with  a  new  fact 
— viz.  that  under  normal  circumstances  a  reflex  and  automatic  adaptation 
of  the  heart  and  vessels  is  preceded  and  reinforced  by  the  active  intervention 
of  impulses  proceeding  from  the  brain.  Thus  the  willed  effort,  or  the  emotion 
of  fear  or  anger  which  normally  initiates  extensive  muscular  movements, 
gives  rise  at  the  same  time  to  impulses  starting  in  the  brain  centres,  which 
excite  changes  in  the  circulatory  and  respiratory  systems  of  the  same  character 
as  those  which  will  be  later  excited  reflexly  or  automatically  as  a  result  of 
the  exerciseJ.'jThus  during  muscular  movements  we  find  the  respiratory 
exchanges  aha  the  ventilation  of  the  lungs  increased,  the  blood  pressure 
raised,  and  the  pulse  quickened.  With  a  man  seated  on  a  stationary  bicycle 
the  mere  question  "  Are  you  ready  ?  "  evokes  increase  of  muscular  tone  in  the 
act  of  attention,  increased  pulmonary  ventilation,  and  a  rise  of  pulse  rate 

1051 


1052 


PHYSIOLOGY 


and  of  blood  pressure.  And  these  changes  are  increased  as  soon  as  the  word 
"  go  "  is  given  and  the  man  starts  to  pedal,  i.e.  before  the  increased  metabolic 
changes  in  the  muscles  can  have  had  time  to  affect  the  medullary  centres, 
or  the  muscular  contractions  the  vigour  of  the  circulation.  The  reinforcing 
impulses  from  the  cortex,  which  stimulate  the  medullary  centres  and  put 
these  various  mechanisms  into  action,  are  effective  especially  at  the  beginning 
of  muscular  work.  In  any  steady  work  produced  without  particular  effort 
or  attention,  the  subsequent  adaptations  of  the  different  organs  of  the  body 
are  probably  chiefly  automatic,  the  central  reinforcing  impulses  being  of 
especial  importance  when,  under  emotional  stress  of  any  description,  the 
animal  has  to  put  forth  its  maximum  effort. 


Fig.  482.  Chart  showing  the  effect  of  increasing  amounts 
of  muscular  work  on  the  total  ventilation  of  the  lungs  V, 
on  the  blood  flow  BF,  and  on  the  oxygen  absorption  02. 
(From  Means  and  Newbttrgh  ) 


Increased  work  means  increased  metabolism.  We  have  seen  that  the 
oxygen  intake  and  the  C02  output  may  undergo  a  ten  or  twelve  fold  augmenta- 
tion during  violent  muscular  effort  carried  out  for  a  short  time,  and  a  five  fold 
increase  is  not  uncommon  and  may  last  for  many  hours.  The  muscles  of  a 
warm-blooded  animal  become  rapidly  fatigued  on  being  deprived  of  an 
adequate  amount  of  oxygen.  A  necessary  condition  then  of  all  muscular 
exercise  is  that  the  muscles  shall  be  supplied  with  oxygen  in  proportion  to 
their  requirements.  Since  the  arterial  blood  is  under  normal  conditions  90  to 
95  per  cent,  saturated  with  oxygen,  no  appreciable  further  amount  can  be 
provided  by  increasing  the  saturation  of  the  haemoglobin  in  the  blood ;  so 
that  an  eight  to  twelve  fold  increase  in  the  oxygen  usage  by  the  muscles  must 


CIRCULATORY  CHANGES  DURING  MUSCULAR  EXERCISE  1053 

imply  a  corresponding  increase  in  the  blood  supplied  to  these  organs.  This 
increased  blood  flow  to  the  muscles  involves  in  its  turn  an  increase  in  the 
blood  flow  through  the  lungs  and  in  the  ventilation  of  the  lungs.  Li  the  next 
chapter  we  shall  have  occasion  to  study  the  method  by  which  the  respiratory 
centre  is  enabled  to  adjust  its  activity,  and  therewith  the  rate  at  which  the 
air  in  the  pulmonary  alveoli  is  renewed,  in  exact  proportion  to  the  needs  of  the 
body  for  oxygen.  We  are  concerned  here  chiefly  with  the  mechanism  l>v 
which  the  circulation  through  the  lungs  and  muscles  can  be  and  is  increased 
in  like  proportion.  The  measurement  of  the  circulation  through  the  lungs  is 
identical  with  the  measurement  of  the  output  of  the  right  ventricle.  This 
has  been  investigated  by  Krogh  and  Lindhard  and  by  Means  and  Newburgh 
in  the  healthy  man  during  rest  and  during  exercise.  In  Fig.  482  are  shown 
results  obtained  by  the  two  last-named  observers.  It  will  be  seen  that  the 
blood  flow  through  the  luDgs,  or  the  output  of  the  right  ventricle  per  minute, 
increases  in  a  manner  almost  absolutely  proportional  to  the  consumption  of 
oxygen,  and  that  both  increase  pari  passu  with  the  work  done  per  minute. 
How  is  this  admirable  adjustment  of  the  activity  of  the  heart  and  circulation 
to  the  oxygen  needs  of  the  muscles  effected  ?  The  output  of  the  heart  depends 
on  the  inflow  into  this  organ,  so  that  our  problem  is  to  determine  the 
factors  which  increase  the  inflow  into  the  heart  in  proportion  to  the  needs  of 
the  muscles.  At  or  before  the  onset  of  muscular  exercise,  unless  this  is  quite 
moderate,  there  is  contraction  of  the  splanchnic  vessels,  so  that  the  blood  is 
diverted  from  the  viscera  to  the  muscles  and  later  on  also  to  the  skin.  Every 
muscle  as  we  have  seen  acts  as  an  accessory  heart,  the  muscular  contractions 
emptying  the  capillaries  into  the  veins,  and  in  the  latter  driving  on  the  fluid 
towards  the  heart  in  virtue  of  the  valves  present  in  these  vessels.  The  more 
active  the  muscles  therefore,  the  more  rapidly  the  blood  which  enters  them 
is  passed  on  with  force,  tow  aids  the  big  veins  and  the  heart.  The  circulation 
through  the  big  veins  of  the  abdomen  and  chest  is  aided  by  the  respiratory 
movements,  which  are  also  augmented  in  proportion  to  muscular  activity, 
each  inspiration  driving  the  blood  out  of  the  big  veins  in  the  abdomen  and 
aspiring  it  mto  the  veins  and  heart  cavities  within  the  thorax.  The  blood 
flow  into  the  heart  is  thus  increased  in  proportion  to  the  activity  of  the 
muscles.  Under  resting  conditions  it  seems  probable  that  the  filling  of  the 
heart  is  what  Krogh  has  described  as  '  inadequate  ' — i.  e.  the  amount  of  blood 
entering  the  heart  during  each  diastole  is  not  sufficient  to  fill  this  organ  up  to 
the  limits  set  by  the  fibrous  and  inextensible  pericardium.  The  first  effect  of 
muscular  exercise  will  be  to  increase  the  filling  of  the  heart  and  therefore 
the  output  at  each  beat,  and  this  will  go  on  until  the  tilling  (luring  each 
diastole  has  become  '  adequate.'  The  heart  therefore,  at  the  beginning  of 
muscular  exercise,  automatically  reacts  by  increasing  the  output  per  beat. 
Whether  diastolic  tilling  of  the  heart  be  adequate  or  inadequate,  the  pressure 
in  its  cavities  just  before  systole  will  !»■  approximately  zero.  If  now  the 
inflow  be  Mill  further  increased,  the  diastolic  pressure  within  the  heart  and 
in  the  big  veins  will  begin  to  rise,  since  the  heart  cannot  lint  her  increase 
appreciably   its   output    per   beat.     Now   comes   in   the   reflex   mechanism 


1054 


PHYSIOLOGY 


described  by  Bainbridge.  The  increasing  tension  on  the  venous  side  of  the 
heart  evokes  reflexly  a  quickening  of  the  heart  rhythm,  chiefly  by  inhibition 
of  the  vagus  tone,  possibly  also  by  reflex  stimulation  of  the  sympathetic 
accelerator  nerves.  Further  increase  in  the  inflow  into  the  heart  is  met  by 
corresponding  quickening  of  the  heart  rhythm.  Distension  of  the  big  veins 
is  thus  prevented,  and  the  output  of  each  ventricle  per  minute  is  increased 
seven,  ten  or  even  twelve  times.    The  part  played  by  increase  of  output  per 

beat  and  by  increase  of  pulse 
rate  respectively  in  augmenting 
the  total  output  of  the  heart  is 
shown  in  Fig.  483.  In  this 
figure  the  first  rise  in  pulse 
rate  from  sixty-eight  to  ninety- 
eight  and  the  corresponding 
increase  in  output  per  beat 
can  be  regarded  as  associated 
with  the  initial  changes  origi- 
nated by  the  act  of  attention 
and  volition.  It  will  be  seen 
that  between  270  to  600  kilo- 
grammetres'  work  per  minute 
the  pulse  rate  remains  prac- 
tically unchanged,  while  the 
output  per  beat  increases 
steadily  with  the  work.  After 
this  point  there  is  very  little 
further  increase  in  the  output 
per  beat,  which  towards  the 
end  begins  to  diminish,  while  there  is  a  steady  increase  in  the  pulse  rate. 

By  this  means  the  blood  is  driven  through  the  lungs  at  a  rate  correspond- 
ing to  the  increased  needs  of  the  muscles  for  oxygen.  The  passage  of  this 
blood  through  the  muscles  is  provided  for  by  two  mechanisms.  In  the  first 
place  we  have  the  contraction  of  the  splanchnic  vessels,  so  that  the  blood 
pressure  is  raised  and  all  the  available  blood  can  be  driven  through  the 
working  tissues.  In  the  second  place  the  muscles  in  their  activity  produce 
lactic  acid,  C02,  and  possibly  other  metabolites,  whioh  cause  dilatation  of 
the  arterioles  and  capillaries  in  the  muscles  themselves.  During  rest  it  is 
probable  that  the  majority  of  the  capillaries  are  closed ;  during  activity 
these  dilate  and  are  filled  with  blood,  so  that  the  capillary  bed  in  the  muscles 
ma}r  be  increased  many  times  in  area,  and  each  element  of  the  muscle  is 
brought  into  close  relation  with  a  dilated  capillary  through  which  is  flowing 
a  rapid  stream  of  oxygenated  blood.  Krogh  has  shown  that  the  number  of 
blood-containing  capillaries  in  each  square  millimetre  cross-section  of  the 
muscle  may  be  increased  40  to  100  times  during  maximal  activity  of  the 
muscle.  As  a  result  the  oxygen  tension  in  the  muscle  fibres  becomes  ahnost 
equal  to  that  in  the  capillaries  themselves. 


Fig.  483  Chart  showing  the  effect  of  increasing 
amounts  of  muscular  work  on  the  pulse  rato  P, 
shown  by  dots  ;  on  the  heart  output  per  beat, 
VpB,  and  on  the  co-efficient  of  oxygen  utilisa- 
tion in  the  blood,  (J.     (From  Means  and  New- 

BOTtGH.) 


CIRCULATORY  CHANGES  DURING  MUSCULAR  EXERCISE      1055 


This  production  of  acid  products  in  the  muscles  aids  also  dissociation  of 
the  oxyhemoglobin  passing  through  the  capillaries  and  therefore  sets  free 
oxygen  for  the  use  of  the  muscles.  On  this  account  we  find  almost  invariably 
that  the  utilisation  of  the  oxygen  taken  in  from  the  lungs  is  more  complete 
during  exercise.  The  oxygen  utilisation  per  litre  of  blood  as  it  flows  round 
the  circulation  is  known  as  the  '  co-efficient  of  utilisation.'     Thus  if  328  c.c. 

of  oxygen  were  used  per  minute  and  the  blood  flow  were  4-5  litres  per  minute, 
090 
—  =73  c.c.  oxygen  would  be  utilised  per  litre  of  blood.     If  the  oxygen 
t'.j 

capacity  of  the  blood  were  193  c.c.  per  litre,  the  co-efficient  of  utilisation 

73 
would  be  —  =  38  per  cent.    In  Fig.  -183  the  co-efficient  of  the  oxygen 

utilisation  is  given  by  the  curve  0. 

It  has  been  shown  by  Cannon 
that  every  state  of  excitement,  and 
especially  fear  and  anger,  is  attended 
with  increased  secretion  of  adrena- 
line into  the  blood  stream.  During 
the  violent  exercise  associated  or 
caused  by  emotional  stress,  there 
will  be  an  excess  of  adrenaline 
circulating  in  the  blood,  which  will 
reinforce  the  activity  of  the  circu- 
lation. Thus  it  will  increase  the 
constriction  of  the  splanchnic  area 
already  excited  by  the  central 
effects  of  the  increased  CO.,  or 
lactic  acid  in  the.  blood.  In  the 
heart  the  adrenaline  will  increase 
fli.'  contractile  power  and  also  the 
rate  of  beat,  while  by  its  dilator 
action  on  the  coronary  vessels  it 
will  aid  the  supply  of  oxygen  to 
the  heart  muscle.  At  the  same 
time,  as  we  have  seen  (p.  844), 
adrenaline  will  cause  a  rapid  con- 
version of  the  glycogen  of  the  liver  into  sugar,  so  that  the  contracting 
muscles  may  be  rapidly  supplied  with  the  food  which  they  can  utilise  with  the 
greatest  ease  and  readiness.  It  is  doubtful  whether  these  adjuvant  effects 
-of  adrenaline  are  to  be  reckoned  with  except  in  cases  of  severe  emotional 
stress. 

Training.  The  muscular  efficiency  of  a  man  is  measured  by  the  extent 
to  which  he  can  call  upon  his  body  for  increased  efforts,  i.e.  by  his  margin 
of  response.  This  margin  in  normal  individuals  may  lie  600  per  cent., 
i.  c.  over  a  moderate  period  of  time  the  individual  may  increase  his  muscular 
wink,  his  respiratory  exchanges,  and  the  rate  of  his  circulation  six  times 


K9.M*t*fS   105 

Work   per  M.nute 

Fin.  4:84.  ( 'halt  showing  tho  effects  of  mus- 
cular work  on  the  blood  flow  and  oxygen 
consumption  in  a  subject  with  aortic 
disease,  as  compared  with  a  normal  indi- 
vidual (shown  in  lighter  lines).  (From 
Means  and  New-burgh.) 
(For  oxygen  consumption  omit  the  decimal 
point  and  read  in  c.c.s.) 


um 


PHYSIOLOGY 


above  that  obtaining  during  rest.  This  margin  in  a  normal  individual  can 
be  increased  by  training,  the  essential  features  in  which  are  graduated 
exercise  and  healthy  diet,  so  that  the  muscle  grows  and  becomes  free  from 
interstitial  fat,  while  the  fluid  parts  of  the  body  and  of  the  blood  are 
diminished  so  that  a  larger  amount  of  oxygen  can  be  carried  per  unit 
volume  of  blood.  The  well-trained  individual  may  have  a  margin  of  as 
much  as  120  per  cent.  Disease  is  marked  by  a  diminution  of  the  margin. 
In  Fig.  484  is  given  diagrammatically  the  response  of  the  circulation  and 
respiration  of  a  man  with  heart  disease 
affecting  the  aortic  and  mitral  valves.  This 
man  had  no  discomfort  and  was  able  to  do 
ordinary  work  without  ill  effects.  On  testing 
him  on  measured  muscular  tasks,  it  will 
be  seen  that,  although  at  first  he  reacts  like 
the  normal  individual,  his  margin  is  dimin- 
ished, and  when  doing  only  315  kilogram- 
metres  of  work  per  minute,  the  rise  in  the 
oxygen  intake  and  in -the  heart  output  fails 
to  keep  pace  with  the  increase  in  the  work 
and  loses  also  the  parallelism  which  is  so 
marked  a  feature  in  normal  individuals. 
With  increasing  disease  the  time  would  finally 
come  when  the  margin  was  reduced  to  50 
per  cent,  or  100  per  cent.,  so  that  even  the 
act  of  changing  from  a  recumbent  to  an 
erect  position  might  be  too  much  for  the 
enfeebled  adaptive  mechanisms  of  the  body 
and  the  patient  would  have  to  keep  his  bed . 
There  is  thus  no  definite  dividing  fine 
between  health  and  disease,  the  change  from 
one  to  the  other  being  but  a  progressive 
Fig.  485.     Curved  showing  the  in-  diminution  of  margin  or  extent  of  adaptation. 

flnenee  of  exercise  on  the  civcula-  1Ir       ,  .,     .      .,  ,       ..,      •      , 

tion.     The  exercise  was  a  six-mile  We    have    seen     that     tne     physiological 

run.  Ordinates  =  mm.  Hg.  pes-  condition  of  the  heart  is  measured  by 
the  degree  of  dilatation  of  its  cavities,  i.  e. 
the  length  of  its  muscle  fibres,  required 
in  order  that  in  its  beat  it  may  set  up  a  contractile  stress  adequate 
to  expel  its  contents  against  the  arterial  resistance.  Thus  a  degree  of 
filling  of  the  heart,  which  in  a  well-trained  man  may  be  adequate  to  excite  a 
contraction  sufficient  entirely  to  empty  its  cavities,  in  a  weaker  heart  would 
be  inadequate,  so  that  blood  would  accumulate  at  each  diastole  until  the 
stretching  of  the  fibres  was  sufficient  to  ensure  that  the  amount  entering 
during  diastole  was  expelled  at  each  systole.  The  trained  man — i.  e.  with 
a  heart  in  good  condition- — will  therefore  have,  a  considerable  range  over 
which  the  output  per  beat  can  be  increased  with  increasing  inflow  without 
alteration  of  rhythm.     In  the  untrained  man  this  margin  will  be  smaller. 


sure  and  rate  per  minute. 
LOWSLEY.) 


(O.  s. 


CIRCULATORY  CHANGES  DURING  MUSCULAR  EXERCISE      1057 

so  that  the  second  mechanism  of  adaptation,  viz.  quickening  of  the  heart 
beat,  will  be  sooner  brought  into  action  to  cope  with  the  increased  inflow 
associated  with  muscular  exercise.  Thus  one  finds  a  considerable  difference 
in  the  effect  of  exercise  on  the  pulse  rate  m  trained  and  untrained  individuals 
respectively,  and  this  is  specially  shown  in  the  rate  of  recovery  in  the  pulse 
when  the  exercise  comes  to  an  end,  the  effects  lasting  much  longer  in  the 
untrained.  In  all  cases  exercise  not  carried  to  exhaustion  tends  to  be  fol- 
lowed by  a  prolonged  diminution  both  in  pulse  rate  and  in  blood  pressure 
(cf.  Fig.' 485). 


67 


SECTION  XII 

THE   INFLUENCE  ON  THE;  CIRCULATION  OF  VARIA- 
TIONS   IN    THE    TOTAL    QUANTITY    OF    BLOOD 

PLETHORA   AND   HYDREMIC   PLETHORA 

The  effects  of  increasing  the  total  volume  of  circulating  fluid  may  be  studied 
by  injecting  several  hundred  cubic  centimetres  of  defibrinated  blood  or 
normal  saline  fluid  into  a  vein.     In  the  latter  case,  since  the  blood  is  rendered 


0  30GOSZC  I     I     I     '     |     '     |     '     I'     I     "     I     '     I     '     I     '     I     '     I     '     I     '     I 1" 

Imin2      3  44      5      6      7      8      9      10     II      12      13     14     15     IS     17      18        21 
Fig.  486.     Effects  of  hydremic  plethora  on  the  pressures  in  the  carotid  artery  (thick 
line),  portal  vein  (thin  line),  and  inferior  vena  cava  (dotted  line).     (Bayliss  and 
Starling.) 

The  arterial  pressure  is  in  mm.  Hg. ;  the  venous  pressures  in  mm.  H20. 

more  dilute,  the  condition  is  called  hydrseinic  plethora  (Fig.  486).  On  the 
arterial  pressure  the  result  of  such  an  injection  is  not  very  marked.  There  is 
a  slight  initial  increase  in  the  pressure,  but  the  increase  is  by  no  means 
proportional  to  the  amount  of  fluid  injected,  showing  that  the  fluid  is  not 
to  any  large  extent  contained  in  the  arterial  system.  On  examining  the 
pressure  in  the  veins  however,  we  find  a  very  great  relative  rise  of  pressure, 
and  on  opening  the  abdomen  it  is  seen  that  all  the  veins  are  distended  and 
that  the  liver  is  swollen.    The  effect  of  increasing  the  volume  of  circulating 

1058 


VARIATIONS  IN  TOTAL^QUANTITY  OF  BLOOD 


1059 


fluid  would  be  to  increase  the  mean  systemic  pressure,  and  therefore  oue 
would  expect  to  find  a  large  increase  both  in  arterial  and  venous  systems. 
But  the  organism  prevents  the  rise  on  the  arterial  side  by  relaxing  the 
whole  system  of  arterioles,  so  that  the  distribution  of  pressures  is  altered, 
and  the  venous  approximates  more  closely  to  the  arterial  pressure.  This 
arterial  dilatation  augments  the  velocity  of  the  blood  :  it  has  been  found  that 
the  velocity  may  be  accelerated  to  six  or  eight  times  the  normal  rate  by 


Diastole 


Fig.  487.  Cardiometer  tracing  from  dog's  heart  to  show  effect  of  increasing  the 
volume  of  circulating  blood  (hydraeraic  plethora)  on  the  total  output  and  the 
volume  of  the  heart.  Between  the  parts  a  and  b  30  c.c.  of  warm  normal  salt 
solution  were  injected  intravenously,  and  between  B  and  c  20  c.c.  more.  It  will 
bo  noticed  that  both  the  systolic  and  the  diastolic  volume  are  increased,  i.  e. 
the  heart  is  moro  distended  during  diastole,  and  does  not  contract  to  its 
normal  size  in  systole.  The  contraction  volume,  and  therefore  the  output, 
is  very  largely  increased.     (Roy.) 

injecting  an  amount  of  salt  solution  equivalent  to  50  per  cent,  of  the  total 
blood. 

The  high  venous  pressure  causes  increased  diastolic  filling  of  the  ventricles, 
and  therefore  augments  the  strength  of  the  beat.  The'frequency  is  also 
generally  raised  if  the  vagi  are  intact  in  consequence  of  the  greater 
distension  of  the  auricles.  Thus  the  work  of  the  heart  is  increased  in  three 
ways,  viz.  by 

(1)  Rise  of  arterial  pressure. 

(2)  Greater  frequency  of  beat. 

(3)  Increased  output  at  each  beat  (Fig.  487). 

These  series  of  changes  result  in  the  relief  of  the  vascular  system.    The 


1060  PHYSIOLOGY 

heightened  pressure  in  the  abdominal  veins  and  capillaries  causes  a  great 
leakage  of  fluid  in  the  form  of  lymph  from  the  capillaries  of  the  intestines  and 
liver,  while  the  increased  pressure  and  velocity  of  the  blood  in  the  glomeruli  of 
the  kidney  induce  a  copious  secretion  of  urine,  so  that  within  a  couple  of  hours 
after  the  injection  of  salt  solution  the  volume  of  the  circulating  fluid  may 
have  returned  to  normal. 

This  recovery  is  effected  with  greater  difficulty  if  the  plethora  has  been 
brought  about  by  the  injection  of  defibrinated  blood,  since  this  fluid  cannot 
escape  rapidly  from  the  capillaries,  nor  can  i  t  be  excreted  unchanged  by  the 
kidneys.  Hence  it  is  easy  to  kill  an  animal  by  wearing  out  its  heart,  if  too 
large  quantities  of  defibrinated  blood  be  injected.  The  ultimate  fate  of  the 
injected  blood  is  to'  be  used  as  food  by  the  tissues,  and  to  be  eliminated  by 
the  ordinary  channels. 

It  must  be  remembered  that  the  blood  serum  of  one  animal  is  often  poisonous  for 
the  corpuscles  of  another.  Thus  a  few  cubic  centimetres  of  dog's  serum  injected  into 
the  peritoneal  cavity  of  a  rabbit  will  cause  death.  This  poisonous  action  is  also  shown 
by  mixing  dog's  serum  with  defibrinated  rabbit's  blood,  in  which  case  the  red  corpuscles 
of  the  latter  are  broken  up,  setting  free  haemoglobin  (hemolysis). 

THE   EFFECTS   OF   HEMORRHAGE.     ANEMIA 

Any  diminution  of  the  total  volume  of  the  blood,  as  by  bleeding,  would 
tend  to  lower  the  pressure  on  both  sides  of  the  system.  The  vaso-motor 
centre  however  strives  to  maintain  the  normal  arterial  pressure,  and  so  the 
circulation  through  the  brain,  unaltered.  This  object  is  attained  by  a 
general  vascular  constriction,  which  diminishes  the  total  capacity  of  the 
system  and  alters  the  distribution  of  pressures  throughout  the  system,  so 
as  to  keep  the  blood  as  much  as  possible  on  the  arterial  side.  Thus  a  slight 
loss  of  blood  has  no  influence  on  the  arterial  blood  pressure,  but  causes  a  fall 
of  pressure  in  the  veins,  blanching  of  the  abdominal  organs,  and  diminished 
flow  of  urine.  The  heart  beats  more  frequently,  and  so  aids  in  emptying  the 
venous  into  the  arterial  system. 

The  deficiency  of  circulating  fluid  caused  by  bleeding  is  soon  remedied  by 
a  transfer  of  fluid  from  the  tissues  to  the  blood.  This  transfer  is  independent 
of  the  flow  of  lymph  from  the  thoracic  duct  into  the  blood,  and  is  the  direct 
consequence  of  the  universal  fall  of  capillary  pressure  which  results  from 
the  bleeding.  The  abstraction  of  fluid  from  the  tissues  is  responsible  for 
the  extreme  thirst  which  is  the  result  of  haemorrhage,  and  which  directs  the 
animal  to  take  up  by  the  alimentary  canal  the  fluid  which  is  wanting  to  the 
body.  The  transfer  of  fluid  from  tissues  to  blood  is  extremely  rapid ;  even 
during  the  course  of  a  bleeding  it  is  found  that  the  later  samples  of  blood  are 
more  dilute  than  those  obtained  at  the  beginning.  This  mechanism  suffices 
only  to  make  up  the  supply  of  circulating  fluid.  After  a  bleeding  however, 
an  animal  has  lost  proteins  and  blood  corpuscles,  and  these  constituents  of 
the  blood  are  but  slowly  restored,  the  former  directly  from  the  food,  the  latter 
by  an  increased  activity  of  the  blood-forming  cells  in  the  red  marrow. 


CHAPTER  XIV 

LYMPH    AND    TISSUE    FLUIDS 

In  no  part  of  the  body  does  the  blood  come  in  actual  contact  with  the  living 
cells  of  the  tissue.  In  all  parts  the  blood  flows  in  capillaries  with  definite 
walls  consisting  of  a  single  layer  of  cells,  and  is  thus  separated  from  the 
tissue-elements  by  these  walls  and  by  a  varying  thickness  of  tissue.  In  some 
organs,  such  as  the  liver  and  lung,  every  cell  is  in  contact  with  the  outer 
surface  of  some  capillary ;  while  in  others,  such  as  cartilage  (which  is  quite 
avascular),  a  considerable  thickness  of  tissue  may  separate  any  given  cell 
from  the  nearest  capillary.  A  middleman  is  thus  needed  between  the  blood 
and  the  tissues,  and  this  middleman  is  the  tissue  fluid  or  lymph  which  fills 
spaces  between  all  the  tissue  elements,  so  that  any  tissue  can  be  regarded  as 
a  sponge  soaked  with  lymph. 

Throughout  these  spaces  we  find  a  close  network  of  vessels,  lined  and 
separated  from  the  tissue  spaces  by  a  layer  of  extremely  thin  endothelial 
cells,  and  this  plexus  communicates  with  definite  channels — lymphatics, 
by  which  any  excess  of  fluid  in  the  part  is  drained  off.  The  lymphatics 
all  run  towards  the  chest,  where  those  of  the  hind  limbs  join  a  large  vessel 
(the  receptaculum  chyli),  which  receives  the  lymph  from  the  alimentary  canal, 
to  form  the  thoracic  duct.  This  runs  up  on  the  left  side  of  the  oesophagus, 
and  after  receiving  the  lymphatic  trunks  from  the  left  fore  lirhb  and  the  left 
side  of  the  neck,  opens  into  the  venous  system  at  the  junction  of  the  left 
internal  jugular  with  the  subclavian  vein.  A  small  vessel  on  the  right  side 
drains  the  lymph  from  the  right  fore  limb  and  right  side  of  the  chest  and 
neck. 

The  lymph  may  be  looked  upon  as  a  part  of  the  plasma  which  exudes 
through  the  capillary  wall,  bathos  all  the  tissue  elements,  passes  between 
the  endothelial  cells  into  the  peripheral  lymphatic  network,  whence  it  is 
laivied  liy  lymphatic  trunks  into  the  thoracic  duct,  by  which  it  is  returned 
again  to  the  blood. 

It  is  easy  to  obtain  lymph  for  examination  by  putting  a  cannula  (a  small 
tube  of  glass  or  metal)  into  the  thoracic  duct,  and  collecting  the  fluid  that 
drops  from  it  in  a  glass  vessel. 

We  ma}*  also  tap  in  a  similar  way  one  of  the  large  lymphatic  trunks  of  the 
limbs ;  but  in  the  latter  case  we  have  to  use  artificial  means  to  induce  a  flow 
of  l\  mph,  since  little  or  none  can  be  obtained  from  a  limb  at  rest,  the  only 
pari  of  the  body  where  there  is  normally  a  constant,  flow  of  lymph  being  the 

1001 


10C2  PHYSIOLOGY 

alimentary  canal.  And  thus  we  cannot  regard  the  flow  of  lymph  from  a 
part  as  any  index  of  the  chemical  changes  going  on  at  that  part.  In  a  limb 
at  rest  foodstuffs  are  being  taken  up  from  the  blood  and  burnt  up  by  the 
muscles  with  the  production  of  C02.  although  we  may  not  be  able  to  obtain 
a  drop  of  lymph  from  a  cannula  in  one  of  the  lymphatics.  The  lymph 
is  thus  truly  a  middleman ;  as  any  substance,  oxygen  or  foodstuff,  is  taken 
up  by  a  tissue  cell  from  the  lymph  surrounding  it,  this  latter  recoups  itself 
at  once  at  the  expense  of  the  blood.  Thus  there  would  seem  to  be  no  need 
for  lymphatics  to  drain  the  limb,  were  it  not  that  under  many  conditions 
which  we  shall  study  directly,  the  exudation  of  lymph  from  the  blood  vessels 
is  so  excessive  that,  if  it  were  not  carried  off  at  once  and  restored  to  the  blood, 
it  would  accumulate  in  the  tissue  spaces,  give  rise  to  dropsy,  and  by  pressure 
on  the  cells  and  blood  vessels  affect  them  injuriously. 


PROPERTIES   OF   LYMPH 

Lymph  obtained  from  the  thoracic  duct  of  an  animal  varies  in  compo- 
sition and  appearance  according  to  the  condition  of  the  animal,  whether 
recently  fed  or  fasting.  From  a  fasting  animal  the  lymph  is  a  transparent 
liquid,  generally  slightly  yellowish,  and  sometimes  reddish  from  admixture 
of  blood  corpuscles.  When  obtained  from  an  animal  shortly  after  a  meal, 
it  is  milky  from  the  presence  of  minute  particles  of  fat  that  have  been 
absorbed  from  the  alimentary  canal.  In  the  latter  case,  if  the  intestines  be 
exposed,  the  small  lymphatics  are  to  be  seen  as  white  lines  running  from  the 
intestine  to  the  attached  part  of  the  mesentery.  It  is  owing  to  this  fact 
that  these  lymphatics  have  received  the  special  name  lacteals,  the  lymph 
in  them  being  called  the  chyle.  The  fatty  particles  form  the  molecular  basis 
of  the  chyle. 

On  microscopic  examination  the  transparent  lymph  of  fasting  animals 
presents  colourless  corpuscles  similar  to  those  of  blood,  or  perhaps  we  ought 
to  say  identical,  since  the  leucocytes  of  the  blood  are  partly  derived  from  the 
corpuscles  that  have  entered  with  the  lymph  through  the  thoracic  duct. 

All  the  lymphatics  pass  at  some  point  of  their  course  through  lymphatic 
glands,  which  we  may  look  upon  as  factories  of  leucocytes,  since  these  are 
much  more  numerous  in  the  lymph  after  it  has  traversed  the  gland  than 
before.  Leucocytes  are  also  formed  in  all  the  numerous  localities  where 
we  find  adenoid  tissues,  such  as  the  tonsils,  air  passages,  alimentary  canal 
(Peyer's  patches  and  solitary  follicles),  Malpighian  bodies  of  the  spleen,  and 
thymus. 

The  lymph  from  the  thoracic  duct  is  alkaline,  has  a  specific  gravity  of 
about  1015,  and  clots  at  a  variable  time  after  it  has  left  the  vessels,  forming 
a  colourless  clot  of  fibrin,  just  like  blood  plasma.  It  contains  about  6  per 
cent,  of  solid  matters,  the  proteins  consisting  of  fibrinogen,  paraglobulin,  and 
serum  albumen.  The  salts  are  similar  to  those  of  the  liquor  sanguinis,  and 
are  present  in  the  same  proportions. 


LYMPH  AND  TISSUE  FLUIDS  1063 


THE   PRODUCTION   OF   LYMPH 

Many  physiologists  have  thought  that,  in  the  transudation  of  the  fluid 
which  forms  the  lymph,  there  is  an  active  intervention  on  the  part  of  the 
endothelial  cells  forming  the  capillary  wall,  and  that  lymph  is  therefore 
to  be  regarded  as  a  true  secretion.  A  careful  investigation  of  the  known 
experimental  facts  has  failed  to  show  that  the  endothelial  cells  act  otherwise 
than  passively,  as  filtering  membranes  of  variable  permeability.  The  factors 
which  are  responsible  for  the  transudation  of  lymph  may  be  divided  into 
two  classes — mechanical  and  chemical,  the  former  depending  largely  on  the 
pressure  of  the  blood  in  the  vessels,  and  the  latter  chiefly  on  the  metabolism 
of  the  ceUs  outside  the  vessels. 

According  to  the  views  here  laid  down,  the  formation  of  lymph  may  be 
compared  to  a  process  of  filtration.  If  this  be  correct  the  amount  of  lymph 
formed  in  any  given  capillary  area  must  be  dependent  on  the  difference 
of  pressure  between  the  blood  in  the  vessels  and  the  fluid  in  the  extravascular 
tissue  spaces.  This  latter  pressure  is  normally  extremely  low,  so  that  in 
attempting  to  test  the  truth  of  this  view  we  must  try  the  effects  of  altering 
the  pressure  inside  the  vessels,  in  the  expectation  of  finding  that  the  lymph 
production  will  rise  and  fall  as  the  capillary  pressure  is  increased  or  dimin- 
ished. On  attempting  to  carry  out  such  experiments  in  different  parts  of 
the  body,  we  have  to  recognise  another  factor  besides  the  capillary  pressure, 
viz.  the  permeability  of  the  vessel  wall.  Whereas  the  capillary  walls  in  the 
limbs  and  connective  tissues  generally  present  a  very  considerable  resistance 
to  the  filtration  of  lymph  through  them,  and  keep  back  the  larger  portion  of 
the  proteins  of  the  blood  plasma,  the  intestinal  capillaries  are  much  more 
permeable,  giving  at  moderate  capillary  pressures  a  continual  flow  of  lymph 
and  separating  off  only  a  small  proportion  of  the  proteins.  It  is  in  the 
iiver  however  that  we  find  the  greatest  permeability.  Here  a  very  small 
pressure  sufficies  to  produce  a  great  transudation  of  lymph,  containing 
practically  the  same  amount  of  protein  as  the  blood  plasma  from  which  it  is 
formed. 

The  ease  with  which  fluid  passes  out  from  the  capillaries  of  the  liver  is  probably  due 
to  the  fact  that  these  vessels,  unlike  most  other  capillaries  of  the  body,  have  not  a  com- 
plete endothelial  lining.  Thus  it  is  impossible  to  display  a  continuous  endothelial  lining 
by  means  of  silver  nitrate.  The  cells  surrounding  the  capillaries  are  large  and  branched, 
and  possess  marked  phagocytic  powers,  so  that  after  an  injection  of  carmine  granules 
or  bacteria  into  the  blood  stream,  these  bodies  are  found  in  quantity  within  the  cells. 
Owing  to  the  incompleteness  of  this  investment  the  liver  cells  in  many  places  abut 
on  the  lumen  of  the  capillary.  On  injecting  the  blood  system  of  the  liver  the  injection 
is  found  to  run  with  ease  into  channels  situated  within  the  cells  themselves,  and  it  is 
reasonable  to  conclude  that  the  blood  plasma  takes  the  same  course  through  these 
intracellular  channels,  by  which  it  passes  into  the  lymphatics  which  lie  at  the  periphery 
of  the  lobules. 

Li  experiments  on  the  lymph  production  in  the  limbs,  alterations  of 
capillary  pressure  have  but  slight  effect.  The  lymph  flow  from  a  limb 
lymphatic  is  practically  unaltered  by  changes  in  its  arterial  supply,  although 


1064  PHYSIOLOGY 

a  definite  increase  may  be  obtained  by  ligaturing  all  the  veins  of  the  limb 
so  as  to  cause  a  very  great  rise  of  capillary  pressure.  The  lymph  flow  from 
the  intestines  can  be  measured  by  collecting  the  lymph  from  the  thoracic 
duct.  If  the  lymphatics  which  leave  the  liver  in  the  portal  fissure  be 
previously  ligatured,  the  whole  of  the  thoracic  duct  lymph  in  an  animal  at 
rest  is  derived  from  the  intestines.  It  will  be  found  that  lowering  of  the 
capillary  pressure  in  these  organs  by  obstructing  the  thoracic  aorta  stops 
the  flow  of  lymph  absolutely,  whereas  a  rise  of  capillary  pressure,  such  as  that 
produced  by  ligature  of  the  portal  vein,  causes  a  four  or  five  fold  increase 
of  the  lymph. 

The  effect  of  rise  of  capillary  pressure  on  the  lymph  flow  is  still  more 
striking  in  the  case  of  the  liver.  If  the  inferior  vena  cava  be  obstructed 
just  above  the  opening  of  the  hepatic  veins,  there  is  a  great  fall  of  arterial 
pressure  but,  owing  to  the  damming  back  of  the  blood,  a  rise  of  pressure 
in  the  liver  capillaries  to  three  or  four  times  the  normal  height.  This  rise 
causes  a  large  increase  in  the  lymph  flow  from  the  thoracic  duct.  The 
lymph  may  be  increased  eight  to  ten  times  in  amount,  and  it  contains  more 
protein  than  before.  If  the  portal  lymphatics  be  previously  ligatured, 
obstruction  of  the  inferior  vena  cava  has  no  effect  on  the  lymph  flow, 
showing  that  the  whole  of  this  increase  is  derived  from  the  one  region  of  the 
body  where  the  capillary  pressure  is  increased,  viz.  the  fiver. 

We  must  conclude  that,  in  those  regions  of  the  body  where  the  capillaries 
are  fairly  permeable,  the  most  important  factor  in  lymph  production  is  the 
intracapillary  pressure. 

In  the  case  of  the  limbs  and  connective  tissues  generally,  the  pressure 
factor  is  probably  under  normal  conditions  of  less  importance,  so  that  the 
second  factor,  the  chemical,  comes  here  more  into  prominence.  The 
capillary  wall  not  only  permits  of  filtration  under  certain  pressures  but  also 
allows  the  passage  of  water  and  dissolved  substances  by  diffusion  and 
osmosis.  These  osmotic  interchanges  between  blood  and  cell  through  the 
intermediation  of  the  lymph  are  constantly  going  on  in  the  normal  life  of  the 
tissue,  and  are  quite  independent  of  the  amount  of  lymph  produced.  Thus  a 
gland  cell  may  use  up  oxygen,  calcium,  or  sugar,  and  create  a  vacuum  of 
these  substances  in  the  layer  of  lymph  immediately  surrounding  the  cell. 
There  is  at  once  a  disturbance  of  the  equilibrium,  and  a  flow  of  these  sub- 
stances from  blood  to  lymph  is  set  up.  In  consequence  of  the  wonderful 
arrangements  in  the  tissues  for  ensuring  the  intimate  contact  of  blood  and 
lymph  without  intermingling,  these  changes  can  occur  with  great  rapidity. 
We  find,  for  instance,  that  if  a  very  large  amount  (40  grm.)  of  dextrose  be 
injected  into  the  circulation,  osmotic  equilibrium  between  blood  and  lymph 
is  established  within  half  a  minute  of  the  termination  of  the  injection.  In 
this  case  the  rise  of  osmotic  pressure  caused  by  the  injection  of  the  sugar 
attracts  water  from  the  tissue  fluid,  and  this  in  its  turn  from  the  tissue  cells, 
until  the  osmotic  pressure  inside  and  outside  the  vessels  is  the  same.  By 
this  means  the  volume  of  the  circulating  blood  is  increased  at  the  expense  of 
the  tissues.    A  process  of  this  character  may  however  work  under  normal 


LYMPH  AND  TISSUE  FLUIDS  1065 

circumstances  in  the  reverse  direction,  and  lead  to  a  passage  of  fluid  from 
blood  to  tissues  and  tissue  spaces.  Every  active  contraction  of  a  muscle,  for 
instance,  is  attended  by  the  breaking  down  of  a  few  large  molecules  into  a 
number  of  smaller  ones,  and  this  increase  in  the  number  of  molecules  causes 
a  rise  of  osmotic  pressure  in  the  muscle  fibre  and  surrounding  lymph,  and 
therefore  a  passage  of  fluid  from  blood  to  lymph.  In  the  same  way  a  cell 
of  the  submaxillary  gland,  when  stimulated  by  means  of  its  nerve,  pours  out 
a  quantity  of  fluid  into  the  gland  duct,  and  so  into  the  mouth.  This  fluid 
comes  in  the  first  instance  from  the  cell  itself,  but  the  cell  recoups  itself  from 
the  surrounding  lymph,  raising  the  concentration  of  this  fluid,  and  the 
difference  in  concentration  thus  caused  at  once  induces  a  passage  of  water 
from  blood  to  lymph.  Hence  salivary  secretion  is  associated  with  a  large 
flow  of  fluid  through  the  capillary  walls  of  the  gland.  In  this  passage  the 
endothelial  cells  of  the  capillaries  play  no  part,  the  whole  process  being  con- 
ditioned by  changes  in  the  extravascular  gland  cell.  We  have  only  to 
paralyse  the  gland  cell  by  means  of  atropine  in  order  to  see  that  the  active 
flushing  of  the  gland,  which  accompanies  activity,  produces  merely  a  minimal 
increase  in  the  lymph  flow  from  the  gland. 

The  influence  of  tissue  activity  in  the  production  of  lymph  is  still  better 
shown  in  the  case  of  a  large  gland,  such  as  the  liver.  Stimulation  of  this 
organ  by  the  injection  of  bile  salts  into  the  blood  stream  causes  a  large 
increase  in  the  lymph  flow  from  the  organ,  and  therefore  in  the  lymph  flow 
from  the  thoracic  duct. 

It  is  important  to  remember  that  the  relative  insusceptibility  of  the 
limb  capillaries  to  pressure  holds  only  for  the  absolutely  normal  capillary. 
Any  factor  which  leads  to  impaired  nutrition  of  the  vascular  wall,  such 
as  deficiency  of  supply  of  blood  or  oxygen,  the  presence  of  poisons  in  the 
blood  or  in  the  surrounding  tissues,  scalding  or  freezing,  increases  at  the 
same  time  its  permeability.  Under  such  conditions  the  limb  capillary 
reacts  to  changes  of  pressure  like  a  liver  capillary,  the  slightest  increase 
of  pressure  causing  an  appreciable  increase  in  the  lymph  production.  This 
increased  lymph  production  may  be  too  great  to  be  carried  off  by  the 
lymphatic  channels,  so  that  the  exuded  fluid  stays  in  the  tissue  spaces, 
distending  them  and  causing  the  condition  known  as  oedema  or  dropsy. 

LYMPHAGOGUES-  Among  the  substances  which  have  a  direct  action 
on  the  vessel  wall  are  a  number  of  bodies  which  were  described  by  Heiden- 
hain  as  lymphagogues  of  the  first  class.  As  their  name  implies,  these  bodies 
on  injection  into  the  blood  stream  cause,  an  increased  flow  of  lymph  from 
the  thoracic  duct  (Fig.  488).  They  may  be  extracted  from  the  dried  tissues 
of  crayfish,  mussels,  or  leeches  by  simple  boiling  with  water.  Commercial  pep- 
tone has  a  similar  effect.  Heidenhain  regarded  these  bodies  as  direct  excitants 
of  the  secretory  activities  of  the  endothelial  cells.  They  are  however  general 
poisons,  having  a  special  action  on  the  vascular  system,  and  their  effect  on 
lymph  production  is  probably  due  simply  to  their  deleterious  action  on  the 
capillary  wall.  Although  these  bodies  act  chiefly  on  the  liver  capillaries,  so 
that  the  main  increase  in  the  thoracic  duct  lymph  is  derived  from  the  fiver, 


1066 


PHYSIOLOGY 


they  can  be  shown  also  to  have  some  effect  in  the  same  direction  on  the 
intestinal  and  skin  capillaries.  In  fact  the  injection  or  ingestion  of  these 
bodies  often  gives  rise  to  a  copious  eruption  of  nettle-rash,  i.  e.  swellings  of 
the  skin  due  to  an  increased  exudation  of  lymph  into  the  meshes  of  the 
cutis. 

An  increased  lymph  flow  from  the  thoracic  duct  may  be  produced  also 
by  the  injection  of  large  amounts  (10  to  40  grm.)  of  innocuous  crystalloids, 
such  as  dextrose,  urea,  or  sodium  chloride,  into  the  circulation.  In  this 
case  the  lymph  becomes  much  more  dilute.  The  explanation  of  the  action 
of  these  bodies  is  very  simple.  We  have  already  seen  that  injection  of 
large  amounts  of  dextrose  into  the  circulating  blood  raises  the  osmotic  pres- 
sure of  this  fluid.     The  blood  therefore  imbibes  water  from  the  tissues  and 


O  I  2  345678  9  10 
Inj  of  mussel  extract 

Fig.   488.     Changes  in  lymph  flow  in  portal,  inferior  cava,  and  arterial  pressures, 

resulting  from  injection  of  a  member  of  the  first  class  of  lymphagogues  (extract 

of  mussels).     (Stabling.) 

swells  up,  i.  e.  a  condition  of  hydraemic  plethora  is  brought  about  as  surely  as 
if  several  hundred  cubic  centimetres  of  normal  salt  solution  were  injected 
into  the  circulation.  This  increase  in  the  total  volume  of  the  blood  causes 
a  rise  of  pressure  throughout  the  vascular  system — arteries,  capillaries, 
and  veins — and  the  increased  capillary  pressure,  combined  with  the  watery 
condition  of  the  blood,  induces  a  great  transudation  of  lymph,  especially 
in  the  abdominal  organs  (Fig.  489).  The  lymph  is  more  watery  because  the 
blood  also  is  diluted.  That  the  action  of  these  bodies  is  purely  mechanical 
is  shown  by  the  fact  that,  if  the  rise  of  capillary  pressure  be  prevented  by 
bleeding  the  animal  immediately  before  the  injection,  the  increase  in  the 
lymph  flow  is  also  prevented  (Fig.  489,  b),  although  the  concentration  of  the 
sugar  or  salt  in  the  blood  is  still  greater  than  in  the  experiments  in  which 
bleeding  was  not  performed. 


MOVEMENT   OF    LYMPH 


In  the  frog  the  circulation  of  lymph  is  maintained  by  rhythmically  con- 
tracting muscular  sacs,  which  are  placed  in  the  course  of  the  main  lymph 


LYMPH  AND   TISSUE  FLUIDS 


1067 


channels  and  pump  the  lymph  into  the  veins.  In  the  higher  animals  and  in 
man  the  onward  flow  of  lymph  is  effected  partly  by  the  pressure  at  which  it 
is  secreted  from  the  capillaries  into  the  interstices  of  the  tissues,  but  also  to 
a  large  extent  by  the  contractions  of  the  skeletal  muscles.  In  the  smaller 
lymph  radicles  the  pressure  of  lymph  may  attain  8  to  10  mm.  soda  solution. 


H--h^ir-t--~<-+-i-!-!-!-i-+-t--f+4-i--H-t--i-n  - 

3±j±^L±l±Il:t:!l+h±±tEt^^^Tri^R"tj 


78910 

r  dextrose 


ti+FR 


'Kl'Hl'TT-Frl  Tii"Hj^%^j-J-Tt-i-r 
3*S#3~'"Ili"u  '"LP"1" 


01  2345678910 
eied  to  240  ccm       Inj  , 

Fig.  489.     Effect  on  lymph  flow  and  on  arterial  and  venous  pressures  of  injection 
of  concentrated  solution  of  glucose. 
In  B  the  animal  was  bled  to  240  c.c.  before  the  injection.     The  double  line 
=  lymph  flow  in  c.c.  per  ten  minutes ;  thin  line  =  portal  vein ;  thick  line  = 
carotid  arteiy ;  dotted  line  =  inferior  vena  cava. 

Iii  the  thoracic  duct,  at  the  point  where  it  opens  into  the  great  veins  of  the 
neck,  the  pressure  is  obviously  the  same  as  in  these  veins,  that  is  to  say, 
from  —  4  to  0  mm.  Hg.,  the  negative  pressure  being  occasioned  by  the  aspira- 
tion of  the  thorax.  This  difference  of  pressure  is  sufficient  to  cause  a  certain, 
amount  of  flow.  It  must  be  remembered  however  that  under  normal 
circumstances  no  lymph  at  all  flows  from  a  resting  limb.  The  only  part  of 
the  body  which  gives  a  continuous  stream  of  lymph  during  rest  is  the  alimen- 
tary canal,  the  lymph  in  which  is  poured  out  into  the  lacteals,  and  thence 


1068  PHYSIOLOGY 

makes  it  way  through  the  thoracic  duct.  Movement,  active  or  passive, 
of  the  limbs  at  once  causes  a  flow  of  lymph  from  them.  Since  the  lymphatics 
are  all  provided  with  valves  (Fig.  490),  the  effect  of  external  pressure  on  them 
is  to  cause  the  lymph  to  flow  in  one  direction  only,  i.  e.  towards  the  thoracic 
duct  and  great  veins.  Hence  we  may  look  upon  muscular  exercise  as  the 
greatest  factor  in  the  circulation  of  lymph.  The  flow  of  lymph  from  the 
commencement  of  the  thoracic  duct  in  the  abdominal  cavity  to  the  main 
part  of  it  in  the  thoracic  cavity  is  materially  aided  by  the  respiratory  move- 
ments ;  since,  with  every  inspiration,  the  lacteals  and  abdominal  part  of  the 
duct  are  subjected  to  a  positive  pressure,  and  the  intrathoracic  part  of  the 
duct  to  a  negative  pressure,  so  that  lymph  is  continually  being  sucked  into 
Hie  thorax. 


R.B*LBW 

FlO.  400.     A  lymphatic  vessel  laid  open  to  show  arrangement  of 
the  valves.     (Testut.) 


THE   ABSORPTION    OF   LYMPH   AND   TISSUE   FLUIDS 

On  injecting  a  coloured  solution  or  suspension  into  the  connective  tissues 
of  "any  part  of  the  body,  and  gently  kneading  the  part,  it  is  found  that 
the  fluid  fills  all  the  lymphatic  channels  running  from  the  part ;  and  we  can 
in  this  way  inject  the  lymphatics  of  the  limb  and  trace  their  course  on  to 
the  thoracic  duct.  The  same  path  is  taken  by  micro-organisms  as  they 
spread  in  the  tissues,  or  by  particles  of  carmine  or  Indian  ink  which  have  been 
introduced  in  tattooing.  It  is  on  account  of  these  facts  that  the  lymphatics 
are  often  spoken  of  as  the  '  absorbent  system.' 

This  process  of  lymphatic  absorption,  except  in  the  case  of  the  pleural 
and  peritoneal  cavities,  is  however  a  slow  one  unless  aided  to  a  large  extent 
by  passive  or  active  movements  of  the  surrounding  parts,  and  cannot  therefore 
account  for  the  rapid  symptoms  of  poisoning  which  supervene  within  two  or 
three  minutes  after  the  hypodermic  injection  of  a  solution  of  strychnine  or 
other  poison.  That  this  absorption  is  not  dependent  on  the  lymphatics  is 
shown  by  the  fact  that  the  symptoms  occur  almost  as  quickly  when  all  the 
tissues  of  the  limb  have  been  severed,  with  the  exception  of  the  mam  artery 
and  vein.  In  the  same  way,  after  injecting  methylene  blue  or  indigo  carmine 
into  the  pleural  cavity  or  subcutaneous  tissues,  the  dyestuff  appears  in  the 
urine  long  before  any  trace  of  colour  can  be  perceived  in  the  lymph  flowing 
from  the  thoracic  duct.  The  absorption  in  these  cases  is  by  the  blood  vessels, 
and  consists  in  an  interchange  between  blood  and  extra  vascular  fluids, 
apparently  dependent  entirely  upon  processes  of  diffusion  between  these 
two  fluids.  So  long  as  any  difference  in  composition  exists  between  the 
intra-  and  extravascular  fluids,  so  long  will  diffusion  currents  be  set  up, 
tending  to  equalise  this  difference. 


LYMPH  AND  TISSUE  FLUIDS  1069 

More  difficulty  is  presented  by  the  question  of  the  mechanism  of  absorp- 
tion by  the  blood  vessels  of  the  normal  tissue  fluids — such  an  absorption  as 
we  have  seen  to  occur  after  loss  of  blood  by  haemorrhage.  It  seems  probable 
that  this  absorption  depends  on  the  small  proportion  of  protein  contained  in 
the  tissue  fluid  as  compared  with  the  blood  plasma,  and  is  due  to  the  osmotic 
pressure  of  the  protein.  If  blood  serum  be  placed  in  a  bell-shaped  vessel 
(the  mouth  of  which  is  closed  by  a  gelatinous  membrane  which  does  not 
permit  the  passage  of  protein),  and  suspended  in  normal  salt  solution,  it  is 
found  that  the  serum  absorbs  the  salt  solution  until  the  manometer  attached 
to  the  bell-jar  indicates  a  pressure  of  25-30  nun.  Hg.  Thus  we  may  con- 
ceive that  there  is  normally  a  balance  in  the  capillaries  between  the  processes 
of  exudation  and  of  absorption,  the  former  being  conditioned  by  the  capillary 
blood  pressure  and  the  latter  by  the  difference  in  protein  content,  and  there- 
fore of  osmotic  pressure  between  the  blood  plasma  and  tissue  lymph.  A  rise 
of  capillary  pressure  will  upset  this  balance  in  favour  of  transudation  and 
t  he  blood  will  become  more  concentrated,  whereas  a  fall  of  pressure  will  turn 
the  scale  in  favour  of  absorption  and  the  volume  of  blood  will  be  increased 
at  the  expense  of  the  tissue  fluids. 

THE   PART   PLAYED   BY  THE   LYMPH   IN   THE   NUTRITION 
OF   THE   TISSUES 

The  fact  that  the  tissue  cells  are  separated  by  the  lymph  and  the  capillary 
wall  from  the  blood  shows  that,  in  all  interchanges  between  the  blood  and 
tissues,  the  lymph  must  act  as  the  medium  of  communication.  The  lymph 
flow  plays  very  little  part  in  this  process.  The  muscles  of  a  resting  limb 
are  taking  up  nourishment  as  well  as  oxygen  from  the  blood  and  giving  off 
their  waste  products — carbonic  acid  and  ammonia,  though  not  a  drop  of 
lymph  may  flow  from  a  cannula  placed  in  a  lymphatic  trunk  of  the  limb.  In 
fact  the  interchange  of  material  between  tissue  cell  and  blood  through  the 
mediation  of  the  lymph  is  carried  out  in  the  same  way  as  are  the  gaseous 
interchanges,  viz.  by  a  process  of  diffusion.  This  explanation  however  holds 
good  only  for  the  diffusible  constituents  of  the  blood  and  will  not  account 
for  the  supply  of  the  indiffusible  protein  molecules  to  the  cell.  Apparently 
the  only  way  in  which  the  tissues  can  obtain  their  supply  of  protein  is  from 
the  small  proportion  of  this  substance  which  has  filtered  through  the  vessel 
wall  into  the  lymph.  The  increased  exudation  of  concentrated  lymph  to 
1  he  1  issues,  which  occurs  in  inflammatory  conditions  or  as  the  result  of  injury, 
is  therefore  of  advantage,  since  it  furnishes  an  abundant  supply  of  protein 
food  to  be  used  up  in  the  regeneration  of  the  damaged  cells. 


CHAPTER  XV 

THE    DEFENCE    OF   THE   ORGANISM 
AGAINST   INFECTION 

SECTION  I 

THE    CELLULAR   MECHANISMS    OF    DEFENCE 

One  of  the  main  distinctions,  perhaps  the  most  important,  between  the 
animal  and  vegetable  kingdoms  lies  in  the  inability  of  animals  to  build 
up  their  tissues  at  the  expense  of  inorganic  salts,  and  especially  to  synthetise 
the  various  groups  necessary  for  the  formation  of  the  protein  molecule. 
They  are  thus  rendered  dependent  on  the  assimilative  powers  of  the  vegetable 
kingdom,  and  have  to  supply  their  needs  by  using  the  members  of  this  king- 
dom as  food.  The  protozoa,  for  example,  subsist  largely  on  bacteria.  To 
obtain  a  pure  culture  of  any  form  of  amoeba  it  is  necessary  to  cultivate  this 
along  with  some  form  of  bacteria.  The  power  of  the  unicellular  animals  to 
digest  bacteria  meets  with  a  response  on  the  part  of  the  latter,  many  of  them 
developing,  by  way  of  self-defence,  the  habit  of  forming  and  excreting  poisons 
which  will  deter  the  amoeba  from  taking  them  up  or  will  injure  it  after 
it  has  ingested  them.  There  is  thus  a  continuous  struggle  among  the  various 
grades  of  unicellular  organisms  in  which  sometimes  one,  sometimes  another 
type  survives.  An  amoeba  placed  in  contact  with  most  kinds  of  bacteria, 
living  or  dead,  will  rapidly  englobe  and  digest  them.  There  is  however  a 
small  organism  known  as  microsphera  which  is  taken  up  by  the  amoeba,  but 
is  not  thereby  destroyed.  Retaining  its  vitality,  it  reproduces  itself  rapidly 
in  the  body  of  its  host  and  finally  leads  to  disintegration  of  the  latter.  In  the 
same  way  the  flagellate  protozoa  are  often  infected  by  a  species  of  fungus 
known  as  chytridium,  and  die  in  consequence. 

The  liability  of  organisms  to  infection,  by  others  endeavouring  to  five  a 
parasitic  existence  at  their  expense,  extends  throughout  the  whole  of  the 
animal  and  vegetable  kingdoms.  In  some  cases  the  host  and  the 
parasite  arrive  at  a  compromise  in  which  each  benefits  the  other.  This 
condition  is  known  as  symbiosis.  We  have  examples  of  it  in  the  union  of 
fungi  and  algae  which  occurs  in  lichens;  in  the  association  of  nitrogen- 
fixing  bacteria  with  many  plants,  especially  those  belonging  to  the  natural 
order  Leguminosae.  In  herbivorous  animals  the  presence  of  specific  bacteria 
in  the  paunch  or  caecum  causes  the  breakdown  of  the  cellulose  walls  of  the 
food  and  may  indeed  lead  to  a  building  up  of  protein  from  amino-acids  or 

1070 


THE  CELLULAR  MECHANISMS    OF  DEFENCE 


1071 


even  from  salts  of  ammonia.  It  is  probable  that  in  these  cases  the  animal  is 
decidedly  benefited  from  the  presence  of  these  bacteria  in  its  alimentary 
canal,  so  that  here  also  we  may  speak  of  a  symbiosis.  Lr  most  cases  invasion 
of  a  higher  animal  or  plant  by  some  lower  organism  is  fraught  with  danger  to 
the  host,  so  that  special  mechanisms  have  to  be  provided  for  the  protection 
of  the  tissues  from  infection.  The  most  primitive  means  of  defence,  and 
one  which  is  foimd  throughout  the  whole  animal  kingdom,  is  exactly  ana- 
logous to  the  process  by  which  the  amoeba  destroys  and  utilises  any  bacteria 
present  in  its  environment.  The  prevention  of  infection  is  of  course  the 
function  of  the  external  layers  of  the  organism,  i.e.  the  epithelial  covering, 
either  of  the  skin  or  of  the  surface  of  the  gut.  Protection  here  may  be 
of  a  physical  or  chemical  character.  The  cells  may  secrete  a  horny  or 
chitinous  layer  which  presents  a  mechanical  obstruction  to  the  entry  of 


FlO.   401.     a,  amoeba,  infected  by  Microsphtera  :  a,  early  stage. 

amoeba,  full  of  parasitic  Mkrosphczrw.     (Metchmkoit. 

bacteria.  They  may  secrete  mucin,  which  entangles  and  hinders  the  move- 
ments of  invading  micro-organisms,  or  they  may  secrete  substances  which 
actually  destroy  the  life  of  such  organisms.  When  however  a  micro- 
organism has  obtained  entrance  to  the  interior  of  the  body,  e.  g.  through  a 
wound  of  the  surface  epithelium,  the  task  of  dealing  with  the  invader 
becomes  the  office  of  a  special  type  of  cells  belonging  to  the 'meso blast. 
These  cells  are  similar  in  character  to  the  amoeba.  They  have  the  power 
of  extruding  pseudopodia,  of  wandering  from  place  to  place,  and  of  englobing 
and  digesting  particles  of  food  or  bacteria  with  which  they  come  in  contact. 
On  account  of  these  latter  properties  they  have  been  called  by  MetchnikofE 
phagocytes,  and  the  whole  process  by  which  foreign  material  or  the  animal's 
own  dead  tissues  are  got  rid  of  is  spoken  of  as  phagocijtosis.  The  process  can 
be  well  studied,  as  has  been  shown  by  MetchnikofE,  in  the  sponge  or  in  the 
larva  of  the  echinoderm.  At  one  stage  in  the  development  of  the  latter  the 
larva  consists  of  a  sac  which  is  involuted   at  one  extremity  to  form  the 


L072 


PHYSIOLOGY 


alimentary  cavity,  while  the  mesoblast  is  represented  by  amoeboid  cells 
suspended  in  a  semi-liquid  substance  filling  the  body  cavity.  If  a  particle 
of  foreign  substance  be  introduced  into  the  body  cavity,  the  wandering 
mesoderm  cells  collect  round  the  particle  and  fuse  into  plasmodial  masses, 
thus  forming  a  wall,  as  it  were,  around  it.  If  bacteria  be  introduced,  the 
phagocytes  may  be  seen  to  adhere  to  and  ingest  the  still  living  bacteria, 
which  are  then  rapidly  digested  and  destroyed.  A  similar  process  may  be 
observed  in  the  transparent  crustacean  known  as  the  water-flea  (Daphnia), 
and  here  it  may  be  noted  that  the  process  of  phagocytosis  is  not  always 
successful  in  maintaining  the  health  or  life  of  the  host.  Thus  if  the  spores 
of  a  yeast-like  organism,  the  Monospora,  be  introduced  into  the  body  cavity 
of  Daphnia,  the  leucocytes  may,  if  the  spores  be  few  in  number,  lay  hold  of 


Fro.  402.  1,  gastrula  stage  of  starfish  embryo,  with  a  foreign  substance,  jH,  in  its 
body  cavity ;  end,  endoderni ;  ect,  ectoderm ;  vies,  wandering  mcsoblastie 
celts.  2,  the  foreign  body  of  1,  surrounded  by  a  Plasmodium  of  phagocytes 
(highly  magnified).     (After  Metciinikoff.) 

the  latter  and  digest  them.  If  the  spores  be  in  excess,  the  phagocytes  may 
fail  to  ingest  them  or  may  indeed  be  destroyed  as  soon  as  they  approach 
them.  In  this  case  the  spores  germinate,  fill  up  the  body  cavity,  and 
finally  lead  to  the  death  of  the  host.  The  same  process  of  phagocytosis  may 
be  studied  in  its  simple  form  by  injuring  or  infecting  some  tissue  which 
is  free  from  blood  vessels.  Thus  the  tail  fin  of  an  embryonic  axolotl  may 
be  cauterised  with  silver  nitrate,  or  a  small  quantity  of  fluid  containing 
carmine  granules  may  be  introduced  by  means  of  a  hypodermic  syringe.  In 
either  way  a  certain  number  of  cells  are  destroyed  and  the  dead  tissue  there- 
upon acts  as  a  foreign  body.  As  a  result  the  wandering  mesoderm  cells  or 
leucocytes  move  from  the  surrounding  tissues  towards  the  seat  of  the  injury, 
and  the  day  after  the  injury  has  been  inflicted  a  collection  of  leucocytes 
can  be  seen,  many  of  which  contain  particles  of  carmine  or  debris  of  the 
destroyed  tissue  which  they  have  taken  up.  The  cells  finally  wander  away 
from  the  part,  and  the  destruction  is  made  good  by  the  proliferation  of  the 
connective  tissue  cells  and  of  the  epithelium  immediately  adjoining  the 
injury.     In  the  lowest  types  of   metazoa  it  is  impossible  to  speak  of  more 


THE  CELLULAR  MECHANISMS  OF  DEFENCE  1073 

than  one  type  of  wandering  mesoderm  cell.  It  is  probable  indeed  that  the 
same  type  of  cell  may  at  one  time  act  as  a  scavenger  and  at  another  as  the 
chief  agent  in  the  formation  of  connective  tissues.  Even  in  Daphnia, 
according  to  Hardy,  only  one  form  of  leucocyte  is  present,  whereas  in  the 
much  more  highly  organised  crayfish,  belonging  however  to  the  same 
family,  three  different  types  of  leucocyte  may  be  distinguished.  These 
leucocytes  may  be  present  free  in  the  body  cavity  or  they  may  form  an 
element  of  the  connective  tissues.  With  the  formation  of  a  closed  vascular 
system  many  of  the  wandering  mesoderm  cells  became  attached  to  this 
system,  so  that  we  may  distinguish  a  group  of  blood  leucocytes  or  phagocytes 
and  a  group  of  connective  tissue  or  body -cavity  leucocytes.  Moreover  by 
the  formation  of  a  blood  vascular  system,  all  the  tissues  of  the  body  are 
brought  into  material  relationship  with  one  another,  so  that  many  distant 
parts  may  be  drawn  upon  to  supply  the  needs  of  any  one  part.  It  is  evident 
that  injury  of  a  tissue  in  a  higher  animal  containing  blood  vessels  will  involve 
more  complex  consequences  than  a  similar  injury  or  infection  of  the  avascular 
tissue  of  an  invertebrate,  and  that  the  accumulation  of  cells  for  the  defence  of 
the  organism  against  invading  microbes  will  be  much  more  effective  if  the 
blood  vessels  participate  in  the  process  so  that,  by  their  means,  the  phago- 
cytic resources  of  all  parts  of  the  body  can  be  drawn  upon  to  ward  off  a 
localised  attack.  The  process  of  phagocytosis  thus  in  the  higher  animals 
becomes  merged  into  the  more  complex  series  of  "phenomena  to  which  the 
term  '  inflammation  '  has  been  applied.  This  process  can  be  studied  by 
observing  the  effects  of  slight  injury  to  some  transparent  part  of  the  body, 
e.  g.  the  frog's  tongue  or  mesentery  or  the  web  of  the  frog's  foot.  For  this 
purpose  a  small  piece  of  the  skin  of  the  frog's  web  is  snipped  off  with  fine 
curved  scissors,  the  section  being  sufficiently  deep  to  remove  the  skin  with- 
out causing  haemorrhage.  The  first  effect  noticed  in  the  immediate  neigh- 
bourhood of  the  injury  is  a  dilatation  of  the  vessels,  especially  of  the  venules, 
with  acceleration  of  the  blood  flow.  In  the  course  of  an  hour  the  capill  iries 
also  become  dilated,  and  many  capillary  channels,  previously  invisible,  are 
now  occupied  with  blood.  Through  the  dilated  capillaries  there  is  a  rapid 
blood  stream,  the  corpuscles  occupying  the  axis  of  the  vessel,  so  that  there 
is  a  periaxial  layer  of  plasma.  A  little  later  this  acceleration  gives  place 
to  a  slowing  of  the  blood  stream,  and  simultaneously  the  leucocytes  of  the 
blood  are  seen  to  be  adherent  to  the  capillary  wall.  Apparently  the  latter 
becomes  what  we  may  call  '  sticky,'  the  effect  of  the  stickiness  being  to 
increase  the  resistance  to  the  passage  of  the  blood  through  the  vessel  and 
also  to  cause  the  adhesion  of  the  leucocytes  to  the  wall.  As  the  current 
becomes  still  slower,  the  distinction  between  axial  and  peripheral  streams 
disappears.  The  corpuscles  are  closely  packed  together,  the  white  cor- 
puscles being  predominant  at  the  margins  of  the  capillary,  where  they  form 
a  lining  to  the  vessel  (Fig.  493).  The  next  stage  is  the  emigration  of  the 
leucocytes.  These  may  be  observed  to  thrust  a  process  through  the  vessel- 
wall  (according  to  Arnold  this  process  of  emigration  always  occurs  through 
the  stigmata,  i.  e.  the  points  where  the  endothelial  cells  come  in  contact — 


1074 


1MIYS10LOGY 


Fig.  494).  The  prolongation  enlarges  on  the  onter  side  of  the  vessel,  while 
the  portion  of  the  leucocyte  within  the  vessel  becomes  smaller,  so  that  finally 
the  whole  leucocyte  passes  through  and  lies  in  the  lymph  spaces  outside 
the  capillary.  In  the  course  of  five  or  six  hours  all  the  capillaries  and  small 
veins  in  the  neighbourhood  of  the  injury  may  show  a  crowd  of  leucocytes 


„ 


Fig.  493.  Inflamed  mesentery  of  frog,  to  show  marginatum  of  leucocytes  in  the 
inflamed  capillaries,  a  ;  migration  of  leucocytes,  6  ;  escape  of  red  corpuscles,  c  : 
accumulation  of  leucocytes  outside  the  capillaries,  d.  (From  Adami  after 
RlBBERT.)  * 

along  their  outer  surfaces.  The  use  of  this  emigration  seems  to  be  to 
remove  the  tissue  injured  by  the  primary  lesion.  As  soon  as  this  is  effected, 
regeneration  of  the  injured  tissue  occurs  by  a  proliferation  of  the  connective 
tissue  corpuscles  and  the  epithelium,  while  the  leucocytes  move  away  and 
disappear.  The  essential  phagocytic  character  of  the  inflammatory  process 
may  be  shown  if  the  primary  lesion  be  attended  with  infection.  Thus  if  a 
small  quantity  of  the  staphylococcus  be  injected  into  the  subcutaneous  tissue 


Fig.  494.     Emigration  of  leucocytes  through  capillary  wall.     (Arnold.) 

of  the  rabbit,  the  vessels  surrounding  the  point  of  injection  may  within  four 
hours  be  found  densely  filled  with  corpuscles.  In  ten  hours'  time  the  leuco- 
cytes are  present  in  large  numbers  outside  the  vessels,  while  the  injected 
cocci  have  spread  for  some  distance  along  the  lymphatic  spaces  and,  while 
partly  free,  have  been  to  a  large  extent  ingested  by  the  leucocytes.  In 
twenty  hours'  time  the  connective  tissue  fibrils  at  the  point  of  injection  are 
found  to  be  widely  separated  by  the  aggregation  of  leucocytes.  In  forty- 
eight  hours'  time  a  well-defined  abscess  is  produced.  At  the  centre  all 
traces  of  previous  connective  tissue  have  disappeared  and  its  place  has 
been  taken  by  a  dense  mass  of  leucocytes,  many  in  a  state  of  degeneration, 


THE  CELLULAR  MECHANISMS  OE  DEFENCE  1075 

mingled  with  staphylococci,  partly  within,  partly  outside  the  cells.  The 
margin  of  the  abscess  is  formed  by  connective  tissue  infiltrated  with  living 
leucocytes.  A  certain  number  of  cocci  are  to  be  seen  free  in  the  tissue  out- 
side this  layer,  but  in  the  course  of  a  day  or  two  these  free  cocci  disappear, 
and  there  is  thus  a  continuous  layer  of  phagocytes  surrounding  the  abscess 
cavity  and  preventing  any  further  invasion  of  the  body  as  a  whole  from  the 
seat  of  infection.  The  abscess  subsequently  discharges  on  to  the  exterior 
by  a  process  of  necrosis  of  the  superjacent  skin,  and  regeneration  of  tissue 
takes  place  in  the  same  manner  as  in  the  more  trivial  injury.  Inflamma- 
tion in  warm-blooded  animals  thus,  gives  rise  to  dilatation  of  vessels  and 
increased  vascularity  of  the  part,  to  alteration  of  the  vessel  wall  and 
therefore  to  increased  effusion  of  fluid.  There  are  warmth  and  redness  of 
the  part  from  the  vascular  dilatation,  swelling  from  the  effusion  of  lymph, 
and  very  often,  as  a  result  of  the  injury  or  the  swelling  and  the  conse- 
quent involvement  of  sensory  nerves,  pain.  The  four  cardinal  symptoms 
of  inflammation,  namely,  rubor,  color,  turgor,  and  dolor,  which  have 
been  described  for  generations  as  typical  of  this  condition,  leave  out  of 
account  altogether  the  phenomenon  which  Waller's  and  Cohnheim's  obser- 
vations, in  the  light  of  the  comparative  studies  of  MetchnikoS,  have  shown 
us  to  be  the  essential  feature  of  the  process.  This  is  phagocytosis,  the 
accumulation  of  wandering  mesoderm  cells  round  the  seat  of  injury  with 
the  objects  of  removing  injured  tissue,  of  destroying  micro-organisms,  of 
protecting  the  body  from  general  infection,  and  of  preparing  the  way  for 
reintegration  of  tissue. 

Prior  to  the  work  of  Metchnikoff,  the  changes  in  the  blood  vessels  fettered 
the  attention  of  physiologists,  and  the  accumulation  of  leucocytes  was 
regarded  as  secondary  to  these  changes.  Though  the  alteration  of  the 
capillary  wall,  by  permitting  the  adhesion  of  the  leucocytes,  must  no  doubt 
favour  their  emigration  and  their  passage  from  all  parts  of  the  body  into  the 
inflamed  part,  we  know  that  the  same  accumulation  of  leucocytes  occurs 
in  the  entire  absence  of  a  vascular  system.  The  movement  of  the  corpuscles 
towards  dead  or  injured  tissue  must  therefore  have  some  other  explanation. 
We  have  abundant  evidence  to  show  that  the  essential  factor  in  this  aggrega- 
tion of  leucocytes  is  their  chemical  sensibility,  and  that  the  phenomenon 
is  simply  one  of  chemiotaxis.  A  capillary  glass  tube  containing  a  suspension 
of  dead  micrococci,  or  peptone,  or  broth  extracted  from  dead  tissue,  if 
introduced  into  the  anterior  chamber  of  the  eye  or  into  the  subcutaneous 
tissue,  is  found  after  a  short  time  to  be  full  of  leucocytes.  We  must  assume 
that  the  chemical  products  diffusing  out  of  the  ends  of  the  capillary  tube  have 
acini  like  the  malic  acid  discharged  by  the  cells  forming  the  female  organ,  the 
archegonium,  of  ferns.  Just  as  the  latter  causes  a  movement  of  the  anthero- 
zoids.  the  male  cells,  towards  the  ovule,  so  the  chemical  substances  diffusing 
from  the  capillary  tube  have  occasioned  a  positive  chemiotaxis  on  the  part 
of  the  leucocytes.  It  is  worthy  of  note  that  the  positive  chemiotactic 
influence  exerted  by  any  given  species  of  pathogenic  bacterium  is  roughly 
inversely  proportional  to  its  virulence.    A  culture  lacking  in  virulence  may 


1076  J'llYSIOLOUY 

cause  ;i  very  pronounced  aggregation  of  leucocytes  which  speedily  ingest  and 
destroy  the  micro-organism,  whereas  if  a  culture  of  a  more  virulent  variety 
of  the  same  microbe  be  injected,  there  may  be  all  the  signs  of  inflammation, 
swelling,  and  large  effusion  of  fluid,  but  the  tissues  may  contain  very  few 
leucocytes.  Under  these  circumstances  the  micro-organism  rapidly  pro- 
liferates and  spreads  from  the  seat  of  the  lesion,  giving  rise  finally  to  general 
infection. 

So  far  we  have  spoken  merely  of  leucocytes  or  phagocytes,  and  have 
nut  attempted  to  distinguish  between  the  parts  played  by  the  various  types 
of  leucocyte  which  are  found  in  the  blood  and  connective  tissues.  In  the 
higher  animals  there  are  however  very  many  varieties  of  leucocytes  belong- 
ing partly  to  the  blood',  partly  to  the  connective  tissues.  The  following 
Table,  modified  from  Adami,  enumerates  the  leucocytes  which  may  be 
concerned  with  inflammation  in  a  mammal  or  man  : 

Polymorphonuclear  (polynuclear,  finely  Originating  in  adult  mammals  from  the 
granular  oxyphile,  neutrophile,  or  bone  marrow,  and  migrating  from  the 
amphophile    cell).  blood  into  the  inflammatory  area. 

Eosinophile   (coarsely   granular   oxyphile, 
macroxycyte). 

Lymphocyte  (  ?  of  two  types).  Originating  from  lymphoid  tissue  and  from 

Plasma  cell  (  ?  histogenous).  vascular  and   other  endothelia  respec- 

Endotheloid  leucocyte  (mononuclear  leuco-  tively;  present  in  inflamed  area  either 

cyte,  hyaline  cell  (in  part),  '  epithelioid  by  migration  from  blood  or  as  result  of 

cell '  (in  part).  local  proliferation. 

Connective  tissue  wandering  cell  (includ-  Originating  locally  as  result  of  tissue 
ing  clasmatocyte).  proliferation. 

The  part  played  by  each  of  these  forms  is  still  to  a  large  extent  the 
subject  of  discussion.  There  is  no  doubt  that,  in  all  active  inflammations, 
the  polymorphonuclear  leucocyte  is  the  form  which  is  attracted  first  and 
in  largest  numbers  to  the  seat  of  injury.  It  is  the  characteristic  cell  from 
which  pus  is  formed,  and  is  actively  phagocytic.  It  has  nothing  to  do  with 
the  regeneration  of  the  destroyed  tissue.  The  eosinophile  corpuscle  is  also 
present  at  an  early  stage  arovmd  the  inflammatory  focus,  but  is  never  present 
in  numbers  at  all  comparable  with  those  of  the  polymorphonuclear  leucocyte. 
It  is  especially  abundant  in  chronic  inflammations  of  certain  tissues,  such  as 
the  skin.  According  to  Kanthack  and  Hardy,  these  cells  discharge  their 
granules  into  the  surrounding  fluid,  rendering  this  fluid  toxic  for  bacteria. 
Although  later  observations  have  failed  to  confirm  these  views,  no  other 
satisfactory  explanation  has  been  given  as  to  the  part  played  by  these  cells. 
They  are  rarely  seen  to  ingest  bacteria  and  therefore  cannot  be  spoken  of  as 
phagocytic.  The  lymphocyte  predominates  in  certain  chronic  inflammations, 
especially  in  those  caused  by  the  tubercle  bacillus.  They  do  not  ingest 
bacteria.  The  histogenous  wandering  cells  appear  in  the  inflammatory 
area  at  a  later  period  than  the  polymorphonuclear  and  eosinophile  cells. 
They  are  actively  phagocytic  and  are  motile.  As  a  rule  their  phagocytic 
properties  are  exerted,  not  on  bacteria,  but  on  other  cells  and  cell  debris. 


THE  CELLULAR  MECHANISMS   OF  DEFENCE  1077 

After  an  acute  inflammation  their  chief  office  is  to  clear  away  the  remains 
of  the  polymorphonuclear  leucocytes  and  dead  tissues  so  as  to  prepare 
the  way  for  subsequent  regeneration.  It  is  possible  that  these  cells  may 
take  a  part  in  the  formation  of  new  connective  tissue.  They  are  indis- 
tinguishable from  the  immature  form  of  connective  tissue  cells.  It  is 
therefore  difficult  to  be  certain  whether  the  wandering  and  the  fixed  con- 
nective tissue  corpuscles  are  of  identical  or  of  different  origin.  Metchnikoff 
speaks  of  these  cells  as  macrophages,  to  distinguish  them  from  the  poljr- 
morphonuclear  type,  which  he  terms  microphages. 

We  thus  see  that  several  types  of  the  wandering  cells  of  mesoblastic 
origin,  which  take  part  in  inflammation,  do  not  exert  active  phagocytic 
properties  and  cannot  therefore  destroy  bacteria  or  other  invading  organisms 
by  the  process  of  ingestion  and  digestion.  Yet  we  have  evidence  that  the 
part  played  by  such  cells  in  the  defence  of  the  organism  is  no  less  important 
than  that  of  the  actively  phagocytic  cells.  In  the  alimentation  of  the  more 
primitive  invertebrata,  the  cells  fining  tfie  digestive  cavity  take  up  the 
particles  of  food  directly,  and  the  processes  of  digestion  are  carried  out  in 
vacuoles  within  the  cells  themselves.  In  the  higher  animals  this  process  of 
intracellular  digestion  has  almost  disappeared,  and  the  cells  fining  the 
alimentary  tract  have  become  differentiated  into  those  which  secrete 
digestive  ferments  and  those  which  absorb  the  products  of  the  action  of  the 
ferments  on  the  foodstuffs.  Digestion  has  thus  become  extracellular.  It 
seems  that  a  similar  modification  has  taken  place  to  some  extent  in  the 
means  adopted  by  the  organism  for  its  defence  from  infection,  and  that  the 
leucocytes  destroy  bacteria,  not  only  by  the  process  of  intracellular  digestion 
but  also  by  the  excretion  into  the  surrounding  body  fluids  of  substances 
which  have  a  deleterious  influence  on  bacteria.  Thus  normal  blood  serum 
is  found  to  have  a  strong  destructive  influence  on  most  species  of  bacteria, 
whether  pathogenic  or  not.  Since  this  property  is  not  shared  to  anything 
like  the  same  extent  by  the  blood  plasma,  it  may  be  ascribed  to  the  breaking 
down  of  leucocytes  in  the  process  of  clotting  and  the  consequent  liberation 
of  bactericidal  substances.  Extracts  made  from  any  collection  of  leuco- 
cytes have  a  similar  bactericidal  effect,  and  it  has  been  shown  by  Wright 
that  the  ingestion  of  bacteria  by  normal  leucocytes  goes  on  much  more 
rapidly  in  the  presence  of  blood  serum  or  if  the  bacteria  have  been  previously 
subjected  to  the  action  of  blood  serum.  This  adjuvant  action  of  blood 
serum  on  phagocytes  is  destroyed  if  the  serum  be  heated  to  55°  C,  so  that  it 
must  be  due  to  the  presence  in  the  serum  of  some  chemical  substance,  which 
is  unstable  and  destroyed  by  heat  at  a  temperature  far  below  the  coagula- 
tion point  of  the  serum  proteins.  Moreover  there  are  many  species  of 
pathogenic  bacteria  which  cannot  infect  the  animal  as  a  whole.  These 
nevertheless  may  multiply  on  the  surface  of  the  body  or  in  an  abscess  cavity, 
and  lead  to  the  death  of  the  host,  in  consequence  of  the  production  by 
the  bacteria  of  soluble  toxins  which  are  absorbed  into  the  blood  stream. 
Examples  of  such  micro-organisms  are  those  which  are  associated  with 
tetanus  and  diphtheria.    The  process  of  intracellular  digestion  is  obviously 


1078  PHYSIOLOGY 

inadequate  to  deal  with  such  cases  and,  since  we  have  the  power  of  resisting 
and  recovering  from  these  diseases,  there  must  be  other  mechanisms  at  the 
disposal  of  the  body  for  the  neutralisation  of  these »toxins.  The  protec- 
tion of  the  body  against  destruction  by  bacterial  toxins  involves  in  fact 
a  whole  series  of  chemical  mechanisms,  which  we  must  regard  as  of  equal 
importance  and  as  co-operating  with  the  phagocytic  mechanism. 


SECTION  II 

THE    CHEMICAL   MECHANISMS    OF    DEFENCE 

IMMUNITY.  All  infectious  diseases  are  caused  by  the  agency  of  micro- 
organisms. The  greater  number  of  these,  the  bacteria,  belong  to  the  class 
of  fungi  or  schizomycetes ;  a  certain  number  must  be  classed  with  the 
yeasts,  while  others  are  protozoal  in  character.  It  is  especially  in  the  first 
class  of  diseases,  namely,  those  due  to  bacteria,  that  the  organism  has 
developed  chemical  mechanisms  of  defence.  In  the  protozoal  diseases  the 
micro-organisms  occur  for  the  greater  part  as  intracellular  parasites.  One 
attack  of  the  disease  does  not  as  a  rule  confer  immunity,  and  the  treatment 
has  to  be  sought  along  the  lines  of  medication  by  drugs  rather  than  by  the 
development  of  methods  of  protection  normally  displayed  or  developed  by 
the  animal  which  is  the  subject  of  the  infection.  The  diseases  due  to  bacteria 
include  diphtheria,  tetanus,  tubercle,  anthrax,  pyeemia,  and  many  others. 
In  these  diseases  we  have  to  deal  with  a  number  of  phenomena  more  or  less 
common  to  all.  The  infection  in  each  case  is  due  to  the  actual  transference 
of  the  specific  organism  from  one  animal  to  another.  After  the  micro- 
organism has  attained  entrance  into  the  system  there  is  a  period  of  incuba- 
tion before  the  disease  actually  breaks  out.  When  this  occurs,  the  specific 
microbe  is  to  be  found  in  large  quantities  either  in  the  blood  or  in  the  tissues 
of  the  body.  The  disease  is  generally  characterised  by  fever  and  often  by 
local  lesions,  such  as  the  intestinal  ulcers  of  typhoid,  or  the  glandular 
swellings  of  bubonic  plague.  The  micro-organisms  may  develop  in  the 
animal  until  its  death,  or  the  disease  may  terminate  in  recovery  and  the 
total  disappearance  of  the  microbes  from  the  body.  After  recovery  it  is 
found  that  the  patient  is  protected  from  reinfection  by  the  bacterium  which 
was  the  cause  of  the  disease,  and  this  condition  of  immunity  may  last  as 
[ong  as  the  patient  lives.  The  incidence  of  these  bacterial  diseases  is  not 
the  same  for  all  animals,  so  that  in  the  case  of  many  diseases  we  can  speak 
of. a  natural  immunity  of  certain  animals  for  the  diseases  in  question. 

The  pathogenic  micro-organisms  can,  in  a  number  of  cases,  be  culti- 
vated on  artificial  media  outside  the  body,  ft  is  then  found  that  they  may 
be  divided  into  two  classes.  One  class,  of  which  the  diphtheria  and  tetaivus 
bacilli  are  examples,  secrete  in  the  surrounding  culture-fluid  substances 
which  act  as  virulent  poisons  when  injected  into  animals.  Other  bacteria 
do  not  form  such  extracellular  toxins,  but  in  their  case  it  is  found  that,  if 
the  bodies  of  the  bacilli  be  broken  up,  the  injection  of  the  contents  of  the 
bacteria   is  attended  with  poisonous  effects.    The  bacteria  may  be  thus 

107(1 


1080  PHYSIOLOGY 

classified  according  as  they  produce  extracellular  or  intracellular  toxins. 
We  may  deal  first  with  the  manner  in  which  the  body  reacts  to  the  toxins 
excreted  by  the  first  class.     If  a  culture  of  diphtheria  or  tetanus  bacilli  be 
filtered,  the  clear  filtrate  free  from  bacilli  is  found  to  exercise  as  poisonous 
results  as  if  the  culture  itself  of  the  living  bacilli  had  been  employed.     The 
toxins  contained  in  these  fluids  are  extremely  potent.     Thus  five-millionths 
of  a  gramme  of  tetanus  toxin  is  a  fatal  dose  for  a  mouse,  and  -00023  grm. 
would  kill  a  man.     These  weights  apply  to  the  mixture  obtained  by  the 
evaporation  of  the  solution  of  toxin,  so  that  the  pure  toxin  must  be  even 
more  powerful  than  is  represented  in  these  figures.     We  have  at  present  no 
means  of  preparing  a  toxin  in  a  pure  condition,  nor  we  do  know  to  what  class 
of  compounds  it  should  be  assigned.     The  toxin  is  an  unstable  body  and  is 
destroyed   by   heating  to   65°   C.     Similar  toxins   are   widely   distributed 
throughout   the   vegetable   and   animal   kingdoms.     Thus   they  form   the 
active  constituent  of  snake  venom  and  of  the  poison  of  scorpions  and  spiders. 
They  also  occur  in  the  seeds  of  castor  oil  and  of  jequirity,  the  toxins  of 
which  seem  to  be  of  protein  character  and  are  known  as  ricin  and  abrin. 
There  is  a  great  variability  in  the  reaction  of  different  animals  to  these 
toxins.     Thus  to  the  poison  of  tetanus  the  rabbit  is  weight  for  weight  two 
thousand  times  and   the  hen  twenty  thousand  times  more  resistant   than 
the  guinea-pig.     As  in  the  case  of  infection  by  bacteria  themselves,  a  certain 
incubation  time  is  necessary  after  the  introduction  of  the  toxin  before  its 
effects  are  displayed.     There  is  a  striking  difference  in  this  respect  between 
the  action  of  these  complex  bodies  and  the  action  of  drugs,  such  as  strychnine 
or  morphine.     Thus  by  increasing  the  dose  of  strychnine  it  is  possible  to  kill 
an  animal  within  half  a  minute.     The  period  of  survival  after  the  injection 
of  a  dose  of  toxin  cannot  be  reduced  beyond  a  certain  limit,  however  much 
toxin  be  injected.     Thus  a  lethal  dose  of  diphtheria  toxin  kills  a  guinea- 
pig  in  fifteen  hours.     If  ninety  thousand  such  doses  be  injected  into  a 
guinea-pig,  it  is  not  possible  to  reduce  the  time  of  survival  below  twelve 
hours.     Another  characteristic  of  these  toxins  .is  the  specificity  of  their 
action.     One  kind  of  toxin  may  act  chiefly  on  the  central  nervous  system, 
another  on  the  peripheral  nerves,  another  on  the  red    blood  corpuscles. 
In  this  respect  of  course  they  resemble  ordinary  drugs.     Associated  with, 
and  apparently  a  necessary  condition  of,  this  specific  action  is  the  actual 
combination  which  occurs  between  the  toxin  and  the  organ  on  which  it 
exerts  its  effect.     Thus  tetanus  toxin  has  a  specific  affinity  for  the  central 
nervous  system,  and  may  be  removed  from  a  solution  by  shaking  the  latter 
up  with  an  emulsion  of  brain.     In  spite  of  the  excessively  fatal  character  of 
these  toxins  it  is  possible  to  render  an  animal  immune  to  their  action.     If 
a  dose  of  diphtheria  or  tetanus  toxin  which  is  smaller  than  the  fatal  dose 
be  injected  into  an  animal,  the  latter  may  show  signs  of  injury  from  which 
it  recovers.     When  recovery  is  complete,  it  is  found  that  three  or  four  times 
the  fatal  dose  may  be  injected  without  producing  any  evil  effects ;  and  this 
process  of  injection  of  toxin  may  be  repeated  in  continually  increasing  doses 
until  the  animal  is  able  to  withstand  a  dose  one  hundred  thousand  times 


THE  CHEMICAL  MECHANISMS   OF  DEFENCE  1081 

as  large  as  that  which  would  have  been  fatal  to  it  in  the  firso  instance. 
When  a  condition  of  immunity  has  been  produced  in  this  way,  it  is  found 
that  the  blood  serum  of  the  animal  has  the  power  of  neutralising  the  toxin. 
Thus  if  the  blood  serum  from  a  horse,  which  has  been  treated  with  large 
doses  of  diphtheria  toxin,  be  mixed  with  an  equal  quantity  of  the  toxin  itself, 
the  mixture  may  be  injected  into  susceptible  animals  without  the  produc- 
tion of  any  effect.  It  is  possible  in  this  way  to  get  a  serum,  1  c.c.  of  which 
will  neutralise  many  fatal  doses  of  the  toxin  ;  and  this  antitoxic  serum  may 
be  injected  into  a  susceptible  animal  and  used  to  confer  an  artificial  immunity 
on  the  latter,  or  it  may  be  injected  into  a  diseased  animal  and  used  thus  as  a 
curative  agent.  Antitoxin  thus  plays  a  great  part  in  modern  therapeutics, 
especially  of  diphtheria.  In  the  case  of  tetanus  the  toxin  has  a  specific 
affinity  for  the  nervous  system  and  apparently  travels  up  the  axis  cylinders 
of  the  nerves  to  the  central  nervous  system.  By  the  time  that  it  has  arrived 
at  the  central  nervous  system,  and  the  spasms  typical  of  tetanus  have  broken 
out,  the  toxin  is  already  so  firmly  bound  to  the  reacting  tissue  that  the 
injection  of  antitoxin  into  the  blood  stream  has  little  or  no  effect  on  the 
course  of  the  disorder.  The  use  of  the  tetanus  antitoxin  is  therefore  chiefly 
as  a  prophylactic  agent. 

The  question  of  the  manner  in  which  the  antitoxin  is  able  to  combine 
with  and  neutralise  the  toxin  is  one  of  considerable  practical  importance. 
In  this  process  we  have  relations  presenting  marked  analogies  with  the 
neutralisation  of  acids  by  bases.  If  we  define  a  unit  of  toxin  as  that  amount 
which  possesses  a  certain  power,  i.  e.  which  will  kill  a  guinea-pig  in  so  many 
days,  or  will  cause  the  complete  haemolysis  of  1  c.c.  of  blood  in  two  and  a 
half  hours,  we  can  find  the.  amount  of  anti-body  which  is  just  sufficient  to 
neutralise  this  effect,  and  this  amount  of  anti-body  can  be  regarded  also  as 
one  unit.  If  instead  of  one  unit  of  each  we  take  100  units,  the  neutralisation 
is  effected  in  the  same  way.  The  process  is  found  however  to  be  more 
complex  when  we  take  100  units  of  toxin  or  lysin  and  attempt  to  neu- 
tralise them  by  the  fractional  addition  of  antitoxin.  In  the  case  of  a  strong 
acid  and  strong  alkali  we  know  that,  if  100  c.c.  of  alkali  are  just  sufficient  to 
neutralise  100  c.c.  of  acid,  the  addition  of  50  c.c.  of  alkali  will  leave  half  the 
acid  unneutralised.  If  however  we  try  the  same  experiment  in  the  case  of 
mixtures  of  toxin  and  antitoxin,  it  will  be  found  that  the  addition  of  50  units 
of  antitoxin  will  neutralise  much  more  than  half  of  the  toxin,  and  the  same 
applies  to  other  bodies  of  this  class.  Ehrlich  attempted  to  explain  this 
result  by  assuming  that  in  any  toxin  there  is  a  mixture  of  substances,  some 
having  a  strong  affinity  for  the  antitoxin,  and  others,  which  he  calls  toxones, 
possessing  only  a  slight  affinity.  In  the  50  units  of  toxin  first  added,  the 
toxins  would  satisfy  all  their  combining  powers,  whereas  the  toxones  would 
not  begin  to  combine  until  they  were  present  in  large  excess.  Arrheniu.s 
and  Madsen  have  drawn  an  analogy  between  the  neutralisation  of  toxin  by 
antitoxin  and  the  neutralisation  of  a  weak  acid,  such  as  boracic  acid,  by  a 
weak  base,  such  as  ammonia.  They  show  that  in  this  case  the  general 
course  of  events  would  be  similar  to  that  observed  by  Ehrlich.     At  no  time 


1082  PHYSIOLOGY 

would  there  be  complete  neutralisation,  owing  to  the  fact  that  hydrolysis 
constantly  occurs,  so  that  when  equivalent  quantities  of  each  substance  had 
been  added,  the  fluid  would  still  contain  a  certain  amount  of  free  base 
alongside  of  free  acid,  in  addition  to  the  salt  produced  by  the  combination 
of  the  two.  It  is  impossible  however  to  account  in  tins  simple  manner 
for  all  the  phenomena  presented  in  the  neutralisation  of  toxin  by  antitoxin. 
Thus  seventeen  parts  of  ammonia  would  neutralise  exactly  an  equivalent 
quantity  of  boracic  acid,  whether  these  substances  were  dissolved  in  10  c.c. 
or  in  100  c.c.  of  water.  If  however  it  be  found  that  1  c.c.  of  antilysin 
exactly  neutralises  1  c.c.  of  lysin,  these  two  substances  will  no  longer  be  in 
equilibrium  when  the  whole  is  diluted  up  to  10  c.c.  with  water.  If  a  neutral 
mixture  of  lysin  and  antilysin  be  taken  and  filtered  under  pressure  through 
a  gelatin  filter,  no  lysin  or  antilysin  passes  through  the  filter,  so  that  the 
residue  on  the  filter  becomes  concentrated.  On  examining  this  residue  it  is 
found  that  it  has  a  strong  hsemolytic  action,  and  the  same  is  true  of  the 
substance  which  may  be  obtained  by  melting  the  gelatin  out  of  the  pores  of 
the  filter.  It  is  evident  that,  even  in  a  neutralised  mixture,  both  free  lysin 
and  free  antilysin,  or  free  toxin  and  free  antitoxin,  are  present,  and  it  needs 
only  the  alteration  of  the  physical  condition  of  the  mixture  in  order  to 
display  the  action  of  one  or  other  of  these  bodies.  How  then  are  we  to 
regard  this  combination  of  toxin  with  antitoxin  ?  Craw  has  pointed  out 
that  the  combination  is  in  all  respects  comparable  to  that  which  occurs 
between  absorbing  surfaces  and  many  dyestuffs.  If  we  place  some  filter 
paper  in  a  solution  of  fuchsin  or  Congo  red,  the  filter  paper  will  take  up  the 
dye  substance.  The  amount  taken  up  by  the  paper  will  increase  with 
increase  in  concentration  of  the  solution.  There  will  however  be  a  ten- 
dency to  the  formation  of  false  equilibrium  points,  as  in  the  case  of  the 
reaction  of  toxin  and  antitoxin.  Thus  if  two  solutions  of  fuchsin  be  made 
and  to  each  a  sheet  of  filter  paper  be  added,  but  in  one  case  it  be  added  at 
once,  and  in  the  other  case  in  three  parts  at  intervals  of  twelve  hours,  at 
the  end  of  thirty-six  hours  the  paper  which  has  been  added  in  parts  will 
have  removed  more  dyestuff  from  the  solution  than  is  the  case  where  the 
whole  amount  of  paper  was  added  at  once.  In  the  same  way,  when  treating 
a  suspension  of  bacilli  with  an  agglutinating  serum,  it  is  found  that  the 
successive  addition  of  the  bacillary  suspension  to  the  serum  removes  more 
agglutinin  from  the  solution  than  when  the  addition  is  made  at  one 
time. 

The  interactions  therefore  between  these  bodies  must  be  looked  upon  as 
special  examples  of  the  group  of  phenomena  known  as  adsorption,  such  as 
the  adsorption  of  iodine  from  solutions  by  charcoal,  of  iodine  from  water  by 
starch,  or  of  ammonia  by  charcoal.  The  exact  adsorption  which  takes  place 
must  be  a  function  of  the  chemical  configuration  of  the  substance  forming  the 
surface,  since  otherwise  it  would  be  impossible  to  account  for  the  extremely 
specific  character  of  the  interaction  between  toxins  and  their  corresponding 
antitoxins.  The  interaction  must  therefore  be  assigned  to  that  special 
class,  in  which  we  have  already  placed  the  action  of  ferments,  which  is  not 


THE  CHEMICAL  MECHANISMS  OF  DEFENCE  1083 

entirely  chemical  nor  entirely  physical,  but  depends  for  its  existence  on  a 
co-operation  of  both  chemical  and  physical  factors. 

How  are  we  to  account  for  the  production  of  the  antitoxin  as  a  result 
of  the  injection  of  toxins  into  the  body,  a  production  which  is  proportional 
to,  but  far  transcending  in  amount,  the  toxin  injected  ?  In  all  the  specula- 
tions on  the  mode  of  production  and  action  of  antitoxins,  an  important 
part  has  been  played  by  a  conception  put  forward  by  Ehrlich  in  1885  of  the 
nature  of  the  living  protoplasmic  molecule.  According  to  this  conception, 
which  is  spoken  of  as  the  '  side  chain  theory,'  each  unit  of  living  matter 
consists  of  a  centrally  placed  protein  group  with  a  number  of  side-chains 
attached  to  it,  on  the  analogy  of  the  hypothetical  configuration  of  the 
benzene  ring,  to  each  comer  of  which  may  be  attached  an  aliphatic  chain. 
To  explain  the  phenomena  of  nutrition  and  oxidation,  Ehrlich  regarded  some 
of  these  side-chains  as  corresponding  to  unoxidised  food  substances,  while 
(it hers  of  the  side-chains  had  a  strong  affinity  for  oxygen  and  might  be 
regarded,  when  fully  saturated  with  this  substance,  as  peroxide  in  character. 
Activity  in  such  a  unit  would  be  associated  with  interaction  between  these 
two  sets  of  side-chains.  As  a  result  the  food  chain  would  be  converted  to 
carbon  dioxide  and  an  affinity  left  unsaturated  until  it  could  take  up  another 
food  molecule.  In  the  same  way  the  oxygen  side-chain,  having  lost  the 
greater  part  of  its  oxygen,  would  have  a  strong  affinity  for  this  element  and 
would  re-saturate  itself  at  the  expense  of  the  oxygen  brought  to  it  by  the 
blood.  Ehrlich  regards  the  toxins  as  partaking  essentially  of  the  same 
character  as  the  protoplasmic  molecule,  as  being  in  fact  protoplasmic 
fragments  differing  only  from  the  protoplasm  of  the  cell  in  the  greater 
simplicity  of  arrangement  of  their  side-chains.  According  to  him  the  central 
group,  or  nucleus,  of  the  toxin  possesses  two  side-chains,  one  of  which  by  its 
stereomeric  configuration  is  peculiarly  adapted  to  fit  on  to  the  organ  or  cell 
of  thr  body  which  the  toxin  or  active  body  attacks,  and  is  known  as  the 
haptophore  group;  and  another  side-chain,  the  toxophore  group,  which  is 
responsible,  when  the  toxin  is  once  anchored,  for  the  destructive  changes 
wrought  by  the  toxin  on  the  cell  of  the  body.  The  antitoxins  or  antilysins 
are  thus  supposed  to  act  in  virtue  of  their  adaptation  to  the  haptophore 
group,  so  us  to  combine  with  the  toxin  or  lysin  and  prevent  these  from 
exercising  their  injurious  effects  on  the  body.  Ehrlich  has  shown  that,  in 
many  toxins,  the  toxophore  can  undergo  weakening  or  destruction  without 
any  alteration  of  the  haptophore  group;  such  modifications  he  designates 
as  '  toxoids.'1  They  have  the  same  combining  power  for  antitoxins  as  is 
possessed  by  the  ordinary  toxins,  but  are  cither  without  physiological  effect, 
or  their  poisonous  characters  are  only  a  fraction  of  that  possessed  by  ordinary 
toxin. 

The  formation  of  antitoxins  is  accounted  for  (01  rather  described)  on  this 
hypothesis  in  the  following  manner.  When  a  receptor  side-chain  of  the  cell 
is  occupied  by  becoming  attached  to  the  haptophore  group  of  the  toxin, 
this  side-chain  is,  so  to  speak,  shut  out  from  the  normal  activities  of  the  cell. 
A  defect  is  thus  produced  in  the  cell,  to  which  the  latter  endeavours  to  adapt 


1084 


1MIYKIOLOGY 


itself  by  the  product  ion  of  other  side-chains  of  the  same  character.  It 
may  be  regarded  as  a  general  rule  in  living  tissues  that  a  reaction  tends  to 
be  an  over-reaction,  so  that  the  compensation  by  the  cell  should  more  than 
make  good  'the  defect  produced  by  the  attachment  of  the  toxin.  We  thus 
get,  not  one,  but  a  number  of  side-chains  produced  of  the  same  character 
as  that  occupied  by  the  toxin  molecule,  and  therefore  able  also  to  act  as 
receptors  for  the  haptophore  group  of  the  toxin.  These  new  receptor  side- 
chains,  being  produced  in  excess,  are  supposed  by  Ehrlich  to  be  thrown  off 


Fig.  495.  Schematic  representation  of  formation  of  antitoxin  as  side-chains  of  pro- 
toplasmic molecule.  The  black  bodies  are  the  toxin  molecules  which  fit  by 
their  haptophore  end  en  to  the  side-chains  of  the  cell.     (Ehelich.) 

from  the  cell  and  to  circulate  in  the  body  fluids  (Fig.  495,  4).  A  number 
of  protoplasmic  fragments  are  thus  set  free  which  have  a  specific  power  of 
uniting  with  the  toxin,  and  it  is  this  excess  of  side-chains  thrown  off  from 
the  cell  which  represents  the  antitoxin  molecules  found  circulating  in  the 
blood  after  the  injection  of  toxins.  It  will  be  noted  that  this  theory,  though 
chemical  in  form,  is  really  purely  biological.  It  does  not  explain  the 
phenomena  by  reference  to  the  known  laws  of  chemistry,  but  is  a  manner  of 
viewing  the  biological  phenomena,  which  facilitates  their  description  and 
discussion  and  enables  us  to  classify  the  very  complex  phenomena  of 
immunity  in  a  more  or  less  imperfect  fashion. 

The  property  of  giving  rise  to  anti-bodies  on  injection  into  an  animal 
is  not  confined  to  toxins,  a  large  number  of  substances,  e.g.  egg  albumin, 


THE  CHEMICAL  MECHANISMS   OF  DEFENCE  1085 

serum,  proteins,  ferments,  albumoses,  partaking  of  the  same  property.  All 
snch  •  substances  are  classed  together  as  antigens.  Thus  human  serum 
injected  into  a  rabbit  produces  in  the  rabbit's  serum  some  body  which  will 
give  a  precipitate  when  mixed  with  human  serum  even  in  minute  traces. 
This  precipitin  formation  is  specific,  so  that  it  may  be  used  as  a  test  for  the 
origin  of  any  unknown  specimen  of  serum.  In  the  same  way  rennet  fer- 
ment when  injected  gives  rise  to  the  production  of  an  anti-rennin  which  will 
neutralise  the  action  of  this  ferment  on  milk.  Antigens  are  all  colloidal  in 
character  and  probably  optically  active.  Ordinary  drugs  do  not  give  rise 
to  the  formation  of  anti-bodies,  a  necessary  condition  being  apparently 
some  similarity  in  the  molecular  structure  of  the  antigen  to  the  proto- 
plasm of  the  animal  on  which  it  acts  and  to  which  it  becomes  finked  by 
its  haptophore  group. 

CYTOLYSINS.  The  bacteria  of  tetanus  and  diphtheria  cannot  exist  in 
the  body,  infection  by  them  being  limited  to  a  surface  or  abscess  cavity. 
When  a  disease  involves  infection  of  the  tissues  themselves  by  living  micro- 
organisms, somewhat  more  complicated  mechanisms  are  brought  into  play 
for  the  defence  of  the  organism.  We  have  already  seen  that  normal  blood 
serum  may  exert  a  paralytic  or  destructive  action  on  bacteria.  Light  has 
been  thrown  on  the  factors  involved  in  this  destruction  by  a  study  of  the 
phenomenon  of  liwmolysis,  i.  e.  the  destruction  of  red  blood  corpuscles. 
Normal  goat's  serum  may  be  mixed  with  the  red  blood  corpuscles  of  the 
sheep  without  any  injury  to  the  latter.  If  however  sheep's  corpuscles, 
previously  washed  in  normal  saline,  be  injected  at  intervals  of  a  few  days 
into  a  goat,  the  goat's  serum  is  found  to  have  accpiired  the  power  of  rapidly 
dissolving  the  red  blood  corpuscles.  This  hemolytic  power  can  be 
proved  by  mixing  the  serum  and  the  w-ashed  blood  corpuscles  together 
and  allowing  the  mixture  to  stand  in  a  narrow  tube.  The  corpuscles 
rapidly  sink  to  the  bottom,  leaving  the  colourless  serum  above,  unless 
haemolysis  has  occurred,  in  which  case  the  serum  will  be  of  a  transparent 
red  colour.  If  the  hsemolytic  serum  be  heated  to  55°  C.  it  is  found  to  have 
lost  its  power  of  dissolving  sheep's  corpuscles.  This  power  is  at  once  restored 
if  to  the  heated  serum  be  added  any  normal  blood  serum,  even  of  the  sheep 
itself.  It  seems  therefore  that  two  substances  are  involved  in  the  haemolysis, 
namely,  (a)  a  substance  present  in  most  normal  sera  which  is  destroyed  at 
i  temperature  of  60°  C.  and  has  been  called  the  complement,  and  (b)  a 
substance  present  in  the  serum  only  as  a  result  of  the  previous  injection  of 
some  species  of  red  blood  corpuscle,  which  is  resistant  to  the  action  of  heat 
and  is  called  the  amboceptor.  The  reason  for  these  names  will  be  at  once 
apparent  from  the  following  experiment.  Hsemolytic  goat's  serum  is 
mixed  with  sheep's  red  blood  corpuscles  and  the  whole  mixture  kept  at  0°  O, 
at  which  temperature  hsernolysis  is  indefinitely  delayed.  After  some  time 
the  corpuscles  are  separated  by  means  of  the  centrifuge.  On  testing  the 
supernatant  fluid  it  is  found  to  have  no  action  on  sheep's  corpuscles,  though 
it  still  possesses  the  power  of  activating  another  specimen  of  serum  which 
has  been  heated.     The  serum  separated  from  the  corpuscles  has  thus  lost  the 


1086  PHYSIOLOGY 

amboceptor,  but  retained  the  complement.  The  amboceptor  is  found  to  have 
attached  itself  to  the  red  blood  corpuscles.  If  these  be  washed  and  then 
added  to  normal  sheep's  serum,  i.  e.  serum  containing  the  complement,  they 
are  rapidly  dissolved.  When  solution  has  taken  place,  both  complement  and 
amboceptor  are  found  to  have  disappeared.  The  function  of  the  amboceptor 
thus  seems  to  be  to  enable  the  complement  already  present  in  normal  serum 
to  act  upon  the  red  blood  corpuscles.  We  may  regard  the  amboceptor 
therefore  as  having  two  haptophore  groups,  one  of  which  anchors  on  to  the 
red  blood  corpuscle,  while  the  other  attaches  itself  to  the  complement 
(Fig.  496,  7).  The  amboceptor  plus  the  complement  thus  comes  to  resemble 
the  toxin  molecule,  having  a  free  haptophore  group  at  one  end  and  a  toxo- 
phore  group  (the  complement)  at  the  other  end.  The  reaction  to  the  injec- 
tion of  the  red  blood  corpuscles  consists  in  the  formation  of  the  amboceptor, 
which  is  essentially  the  anti-body  of  the  red  blood  corpuscle  (Fig.  496,  8). 


Fia.  496.     Diagram  to  show  the  relation  of  amboceptor  and  complement 
to  the  animal  cell  (7)  and  to  red  corpuscles  (8).     (Ehklich.) 

Similar  specific  anti-bodies  effecting  the  dissolution  of  cells  or  organisms 
may  be  produced  by  the  injection  of  various  species  of  bacterium  or  of 
animal  cells,  such  as  leucocytes,  spermatozoa,  liver  cells,  etc.,  and  there  can 
be  no  doubt  that  bacteriolytic  substances  play  a  considerable  part  in  acquired 
immunity. 

OPSONINS.  In  some  cases  the  anti-bodies  produced  by  the  injection 
of  living  or  dead  micro-organisms  do  not  bring  about  actual  destruction  of 
the  bacteria,  but  alter  them  in  such  a  way  as  to  make  them  more  susceptible 
to  the  action  of  the  phagocytes.  If  washed  white  blood  corpuscles  be  mixed 
with  micrococci,  such  as  those  found  in  an  ordinary  boil,  they  are  found  to 
take  up  the  micro-organisms  in  considerable  numbers.  The  numbers  taken 
up  are  much  increased  in  the  presence  of  serum  derived  from  an  individual 
who  has  received  repeated  minute  injections  of  the  dead  micrococci  in  ques- 
tion. To  the  substances  in  the  serum,  which  thus  prepares  the  micrococci 
for  ingestion  by  the  phagocytes,  Wright  has  given  the  name  of  opsonins. 
The  opsonic  index  of  the  leucocytes  of  any  individual,  in  reference  to  a  given 
species  of  microbe,  is  determined  by  observing  the  number  of  the  microbes 


THE  CHEMICAL  MECHANISMS  OF  DEFENCE  1087 

taken  up  by  the  leucocytes  after  treatment  with  the  serum  of  the  individual, 
and  then  comparing  it  with  the  number  taken  up  by  the  same  leucocytes  when 
the  bacteria  have  been  treated  with  the  serum  of  an  average  individual. 

We  thus  see  that  immunity,  whether  innate  or  acquired,  is  extremely 
complex  in  character  and  may  depend  on  one  or  more  of  many  factors. 
The  immunity  of  an  animal  to  any  given  infection  may  be  determined  by 
the  absence  of  receptor  groups  in  his  body  for  the  toxin  excreted  by  the 
microbe  responsible  for  the  infection,  or  by  the  fact  that  the  receptor  groups 
an-  present  but  are  confined  to  tissues  on  which  the  toxophore  group  can 
have  no  influence.  Thus  e.g.  an  attachment  of  the  tetanus  toxin  to  a 
connective  tissue  cell  would  be  without  effect  on  the  health  of  the  bod)-. 
Again,  immunity  may  be  due  to  the  efficacy  of  the  phagocytes,  either  of  the 
fluids  or  the  connective  tissues,  in  ingesting  and  destroying  the  micro- 
organisms, and  this,  as  we  have  seen,  may  again  be  dependent  on  the  presence 
or  absence  in  the  body  fluids  of  substances  which,  while  not  destroying  the 
micro-organisms,  render  them  more  accessible  to  the  action  of  the  phago- 
cytes. In  those  cases  where  the  infecting  organism  secretes  a  specific  toxin, 
the  mam  line  of  defence  and  the  main  factor  in  the  production  of  immunity 
is  the  formation  of  specific  antitoxins  to  the  poison  in  question.  Finally 
there  may  be  produced  as  a  result  of  the  excess  of  micro-organisms  substances 
such  as  the  amboceptors,  which  render  the  micro-organisms  susceptible  to 
destruction  by  the  complements  or  cytases  normally  present  in  the  circu- 
lating fluids  and  possibly  themselves  derived  from  the  activity  or  destruction 
of  the  leucocytes  and  other  phagocytes  of  the  body. 

fn  this  short  description  we  have  been  able  to  touch  only  upon  the  most 
salient  features  of  the  immunity  problem.  The  question  enters  strictly  into 
physiology  since,  as  we  have  seen,  it  involves  adaptations  on  the  part  of 
the  organism  to  change  in  itself  or  its  environment.  For  the  practical 
application  of  these  facts,  as  well  as  the  consideration  of  the  minuter  details 
and  exceptions,  we  must  refer  the  student  to  works  especially  dealing  with 
the  subjects  of  infectious  diseases  and  immunity. 


CHAPTER  XVI 

RESPIRATION 

SECTION  I 

THE  MECHANICS  OF  THE  RESPIRATORY  MOVEMENTS 

In  unicellular  animals  the  interchange  of  gases,  %.  e.  the  intake  of  oxygen  and 
the  output  of  carbon  dioxide,  is  as  a  rule  carried  out  by  processes  of  diffusion 
occurring  at  the  surface  of  the  cell.  With  increased  size  of  the  organism 
the  surface  becomes  insufficient  for  this  purpose,  and  special  organs  make 
their  appearance  for  presenting  a  large  extent  of  surface  to  the  surrounding 
medium.  In  the  multicellular  animals  the  actual  process  of  tissue  respira- 
tion is  carried  out  between  the  internal  medium,  lymph,  blood,  etc.  and 
the  individual  cells;  and  the  use  of  the  special  organ  of  respiration  is  to 
bring  the  circulating  internal  medium  in  intimate  relation  over  a  large  area 
with  the  surrounding  fluid,  whether  air  or  water.  In  insects  we  find  a  large 
branched  svstem  of  tubes,  the  trachea?,  which  contain  air  and  are  distributed 
to  the  finest  tissues,  renewal  of  the  air  in  the  tubes  being  provided  for  by 
special  respiratory  movements.  In  most  water  animals  the  respiratory 
organ  is  known  as  the  gills,  and  presents  a  large  surface  well  supplied  with 
circulating  blood  over  which  a  continual  stream  of  the  surrounding  water 
is  kept  up.  In  all  these  animals  therefore  we  can  distinguish  two  processes, 
viz.  (1)  the  interchange  of  gases  between  the  tissue  cells  and  the  surrounding 
lymph,  '  internal  respiration  ' ;  (2)  the  interchange  of  gases  between  the 
circulating  fluid  and  the  external  medium,  '  external  respiration.'  In  all 
air-breathing  vertebrates  the  organs  of  external  respiration,  the  lungs, 
arise  as  paired  diverticula  of  the  anterior  part  of  the  alimentary  canal. 
The  renewal  of  the  air  in  the  air  sacs  formed  from  these  diverticula  is 
effected  by  alternate  increase  and  diminution  in  their  size  caused  by  the 
movements  of  respiration,  while  a  rapid  circulation  of  blood  is  carried  out 
through  a  fine  meshwork  of  capillaries  just  underneath  the  surface  of 
the  sacs. 

In  man  the  organs  of  external  respiration,  the  lungs,  are  built  up  in  the  following 
way :  The  trachea  or  windpipe,  a  wide  tube  about  44  inches  long,  divides  below  into 
two  main  branches — bronchi  ;  and  these  subdivide  again  and  again,  becoming  gradually 
smaller.  The  terminal  ramifications  or  bronchioles  open  into  rather  wider  parts — the 
iiifumlibuki,  the  walls  of  which  are  beset  with  a  number  of  minute  cavities,  the  alveoli. 
The  larger  tubes  are  kept  patent  by  rings  or  plates  of  cartilage  in  their  walls.     The 

1088 


MECHANIC'S  OF  THE  RESPIRATORY  MOVEMENTS 


1089 


smaller  tubes  have  no  cartilage,  their  walls  being  composed  of  fibrous  and  elastic  tissue 
and  a  coating  of  unstriated  muscular  fibres,  which  are  able  by  their  contraction  to 
occlude  the  passage.  The  whole  system  of  tubes  is  lined  with  a  layer  of  epithelium — 
ciliated  columnar  in  the  trachea,  bronchi,  and  bronchioles,  and  cubical  over  the  parts 
of  the  infundibulum  not  occupied  by  air  cells.  The  alveoli  are  the  special  respiratory 
parts  of  the  lung.  Their  walls  are  composed  of  connective  tissue  containing  a  large 
number  of  elastic  fibres,  and  are  covered  internally  by  a  single  layer  of  extremely  thin 
large  flattened  cells.  The  alveoli  are  closely  packed 
together,  so  that  in  a  section  of  the  lung  an  alveolus  is 
seen  to  be  in  contact  with  others  on  all  sides.  Imme- 
diately below  the  squamous  epithelium  ramify  blood- 
capillaries  derived  from  the  pulmonary  artery.  These 
form  a  close  network,  and  the  blood  in  them  is  in 
proximity  to  air  on  two  sides,  being  separated  from 
the  air  in  the  alveoli  only  by  the  thin  endothelial  cells 
of  the  capillary  wall  and  the  flattened  cells  fining  the 
alveoli. 

The  lungs  in  their  development  grow  out  from  the 
fore  part  of  the  alimentary  canal  into  the  front  part 
of  the  body  cavity  on  each  side — the  pleural  cavity.  The 
surrounding  body  walls  become  strengthened  by  the 
formation  of  the  ribs,  so  that  the  lungs  are  suspended 
in  a  bony  cage-work,  the  thorax.  Their  outer  surface 
is  covered  with  a  special  membrane,  the  pleura,  which 
is  reflected  on  to  the  wall  of  the  thorax  from  the  roots 
of  the  lungs,  and  completely  lines  the  cavity  in  which 
they  lie.  The  surface  of  the  pleura  facing  the  pleural 
cavity  is  lined  with  a  continuous  layer  of  flattened 
endothelial  cells,  and  is  kept  moist  by  the  secretion  of 
lymph  into  the  cavity.  Thus,  being  attached  to  the 
thorax  only  where  the  bronchi  and  great  vessels  enter, 
the  lungs  are  able  to  glide  easily  over  the  inner  surface 
of  the  thorax,  with  which  under  normal  circumstances  they  are  in  intimate  contact. 


Vi: 


■■■■m 


Fig.  497.  Diagrammatic  re- 
presentation of  the  struc- 
ture of  the  lungs.  The 
trachea  branches  into  two 
bronchi,  which  subdivide 
again  and  again  before 
ending  in  the  infundibula. 
(From  Yeo.) 


A  constant  renewal  of  the  air  in  the  lungs  is  secured  by  movements  of 
the  thorax,  which  constitute  normal  breathing.  With  inspiration  the  cavity 
of  the  thorax  is  enlarged,  and  the  lungs  swell  up  to  fill  the  increased  space. 
The  capacity  of  the  air  passages  of  the  lungs  being  thus  increased,  air  is 
sucked  in  through  the  trachea.  The  movement  of  inspiration  is  followed 
by  that  of  expiration,  which  causes  diminution  of  the  capacity  of  the  thorax 
and  expulsion  of  air.  At  the  end  of  expiration  there  is  normally  a  slight 
pause.  The  number  of  respirations  in  the  adult  is  about  17  or  18  a  minute. 
This  is  however  much  influenced  by  various  conditions  of  the  body,  and 
also  by  the  age  of  the  individual.  Thus  a  newborn  child  breathes  about  14 
times  a  minute,  a  child  of  five  about  26  times,  a  man  of  twenty-five  about  16, 
and  of  fifty  about  18.  The  frequency  is  increased  by  any  muscular  effort, 
so  that  even  standing  up  increases  the  number  of  respirations.  These 
movements  arc  much  affected  by  psychical  activity;  they  are  to  a  certain 
extent  under  the  control  of  the  will,  although  they  can  occur  in  an  animal 
deprived  of  its  brain,  and  are  normally  carried  out  without  any  special  act 
of  volition.  We  can  breathe  fast  or  slow  at  pleasure,  and  can  even  cease 
breathing  for  a  time.  It  is  impossible  however  to  prolong  this  respiratory 
69 


1090  PHYSIOLOGY 

standstill  for  more  than  a  minute ;  the  need  of  breathing  becomes  imperative, 
and  against,  our  will  we  are  forced  to  breathe. 

With  every  inspiration  the  cavity  of  the  thorax  is  enlarged  in  all  dimen- 
sions, from  above  downwards  by  the  contraction  of  the  diaphragm,  and 
in  its  transverse  diameters  by  the  movements  of  the  ribs.1 

The  diaphragm  is  a  sheet  separating  the  cavity  of  the  chest  from  that 

of  the  abdomen.    It  consists  of  a  central  tendon  which  forms  an  arched 

double  cupola,  to  the  circumference  of  which  are  attached  muscle  fibres. 

The  diaphragmatic  muscles  present  two  main  divisions,  namely,  (1)  the 

spinal  or  crural  part,  the  fibres  of  which  arise  from  the  upper  three  or  four 

lumbar  vertebrae  and  from  the  arcuate  ligaments  and  are  inserted  into  the 

posterior  margin  of  the  central  tendon ;  and  (2)  the 

sterno-costal   part,    which   arises    by    a    series    of 

digitations  from  the  cartilages  and  adjoining  bony 

parts  of  the  lower  six  ribs  and  from  the  back  of  the 

ensiform  process.    These  latter  fibres  pass  backwards 

as  they  ascend.    In  the  cavity  of  the  larger  dome  on 

the  right  side  lies  the  liver,  while  the  smaller  dome 

on   the  left   side  is  occupied  by  the   spleen   and 

stomach.      These  viscera  in  the  normal  condition 

are    pressed    against    the    under-surface    of    the 

diaphragm  by  the  elasticity  of  the  abdominal  walls. 

FtgZo^r^Z:    The  central  part  of  the  diaphragm  is  thus  pressed 

pliragm  in  respiration.       up  into  the  chest,  partly  by  the  intra-abdominal 

i  i,  inspiratory  position;    pressure  and  partly  bv  the  elastic  traction  of  the 

e    e,    expiratory    position.       -,.,,-,,  „'  .  .  ,,  ,      , 

(Yeo.)  distended  lungs,     ihe  upper  surface  of  the  central 

tendon  is  united  to  the  pericardium.  This  part, 
during  expiration,  is  the  deepest  part  of  the  middle  portion  of  the  diaphragm. 
Towards  the  back  of  the  pericardial  attachment  the  central  tendon  is  pierced 
for  the  passage  of  the  inferior  vena  cava.  In  expiration  the  lateral  muscular 
zone  of  the  diaphragm  lies  in  contact  with  the  lower  part  of  the  thoracic 
wall.  During  inspiration  the  muscle  fibres  contract  and  draw  the  central 
tendon  downwards,  so  that  the  lower  surface  of  the  lungs  descends.  The 
enlargement  of  the  lungs  at  the  lower  part  of  the  thorax  is  aided  by  the 
abduction  of  the  floating  ribs,  produced  by  the  contraction  of  the  quadralus 
lumhorum  and  deep  costal  muscles.  In  this  contraction  the  diaphragm 
presses  on  the  contents  of  the  abdomen,  so  that  the  abdomen  swells  up 
with  each  inspiratory  movement.  The  middle  of  the  central  tendon,  where 
the  heart  lies,  moves  less  than  the  two  domes,  and  the  part  where  the  vena 
cava  passes  through  the  tendon  is  practically  stationary  during  normal 
respiration.  In  deep  inspiration  however  both  this  part  as  well  as  the  rest 
of  the  pericardial  attachment  is  forcibly  depressed  towards  the  abdomen. 
In  quiet  breathing,  when  observed  by  the  Rontgen  rays,  the  mean  descent 

1  The  student  is  advised  to  consult  the  article  by  Keith  on  the  "  Mechanism  of 
Respiration  in  Man  "  for  a  fuller  account  of  this  subject  (L.  Hill's  "  Further  Advances 
in  Physiology,"  1909). 


MECHANICS  OF  THE  RESPIRATORY  MOVEMENTS        1091 

of  the  right  dome  m  inspiration  has  been  found  to  be  about  12-5  mm.,  and 
of  the  left  dome  12  mm.  We  may  say,  roughly,  that  the  average  descent 
of  the  diaphragm  during  normal  respiration  is  about  half  an  inch.  The 
viscera  and  the  intra-abdominal  pressure  play  an  important  part  in 
determining  the  movement  of  the  diaphragm,  and  especially  in  preserving 
the  abduction  of  the  lower  ribs  and  so  furnishing  a  fixed  point  for  the 
muscular  fibres  of  the  diaphragm.  If  the  contents  of  the  abdomen  are 
removed  from  a  living  animal  the  ribs  are  drawn  inwards  every  time  the 
diaphragm  contracts.  In  children  with  weak  chest  walls  and  with  respira- 
tory obstruction  we  may  often  see  a  depression  round  the  lower  part  of  the 
chest  corresponding  to  the  lower  border  of  the  lungs.  It  corresponds  to 
the  hue  at  which  the  diaphragm  leaves  the  chest  wall,  so  that  the  distending 
force  of  the  abdominal  pressure  on  the  bony  walls  of  the  thorax  abruptly 
gives  place  to  the  pull  of  the  distended  lung.  The  contraction  of  the 
diaphragm  lasts  four  to  eight  times  longer  than  a  simple  contraction  or 
muscle  twitch.    It  may  be  regarded  therefore  as  a  short  tetanus. 

The  enlargement  in  the  other  diameters  is  effected  by  an  elevation  of  the 
ribs.  Each  pair  of  corresponding  ribs,  which  are  articulated  behind  with 
the  spinal  column  and  in  front  with  the  sternum,  forms  a  ring  directed 
obliquely  from  behind  downwards  and  forwards.  With  each  inspiratory 
movement  the  ribs  are  raised,  the  obliquity  becomes  less,  and  the  horizontal 
distance  between  sternum  and  spinal  column  is  therefore  increased.  More- 
over the  ribs  from  the  first  to  the  seventh  increase  in  length  from  above 
downwards,  so  that  when  they  are  raised,  the  sixth  rib,  for  instance,  occupies 
the  situation  previously  taken  by  the  fifth,  and  the  transverse  diameters  of 
the  thorax  at  this  height  are  increased.  With  each  inspiration  there  is  a 
rotation  of  the  ribs.  In  the  expiratory  condition  they  are  so  situated  that 
their  outer  surfaces  are  directed  not  only  outwards  but  also  downwards. 
As  they  are  raised  by  the  inspiratory  movements,  they  rotate  on  an  axis 
directed  through  the  fore  and  hind  ends  of  the  rib,  so  that  their  outer 
surfaces  are  turned  directly  outwards.  In  this  way  a  certain  enlargement 
of  the  thorax  cavity  is  produced.  As  the  thorax  is  raised  there  is  always 
some  stretching  of  the  rib  cartilages. 

In  expiration  the  processes  are  reversed,  and  the  cavity  of  the  thorax 
is  diminished  in  all  three  dimensions. 

The  movements  of  the  thorax  are  effected  by  means  of  muscles.  Inspira- 
tion is  performed  by  the  following  muscles  : 

The  diaphragm,  which  is  the  most  important,  and  almost  suffices  alone 
to  carry  out  quiet  respiration. 

The  external  intercostal  muscles,  which  shorten  and  so  raise  the  ribs. 

The  serratus  posticus  superior. 

It  is  probable  that  an  important  part  is  played  even  under  normal 
eircumstances  in  the  respiratory  movements  by  the  extension  of  the  spinal 
Column.  This  movement,  which  is  specially  marked  at  the  upper  part  of 
the  thorax,  causes  an  increase  on  all  three  diameters  of  this  cavity.  The 
leoatores  costarum,  which  are  often  included  in  the  inspiratory  muscles,  arc 


1092  PHYSIOLOGY 

so  inserted  into  the  ribs  as  to  be  unable  to  influence  their  movements. 
They  are  concerned,  not  in  respiration,  but  in  lateral  movements  of  the 
spine. 

These  muscles  are  the  only  ones  normally  engaged  in  carrying  out  in- 
spiration. When,  in  consequence  of  muscular  exertions  or  from  any  other 
cause,  the  inspiratory  efforts  become  more  forcible,  a  large  number  of 
accessory  muscles  are  brought  into  play.    These  are  : 

The  scaleni, 

Sterno-mastoid, 

Trapezius, 

Pectoral  muscles, 

Rhomboids,  and 

The  serratus  anticus. 

Normal  expiration  is  chiefly  effected  passively.  When  the  inspiratory 
muscles  cease  to  contract,  the  lungs,  which  were  stretched  by  the  previous 
inspiration,  contract  by  virtue  of  the  elastic  tissue  they  contain,  and  the 
thorax  itself  sinks  by  its  own  weight,  and  by  the  elastic  reaction  of  the 
stretched  costal  cartilages. 

It  must  be  remembered  however  that  in  a  position  of  rest  the  elasticity 
of  the  thorax  is  opposed  to  the  elasticity  of  the  lungs.  Elasticity  of  the 
chest  wall  would  therefore  tend  to  produce  inspiration.  This  factor  would 
tend  to  make  inspiration  easier  at  its  onset,  but  would  also  present  an 
impediment  to  the  carrying  out  of  expiration,  so  that  towards  the  end  of  this 
act  there  is  need  for  the  active  co-operation  of  muscular  contractions.  It 
seems  possible  that  more  or  less  muscular  activity  of  the  expiratory  muscles 
is  alternated  with  that  of  the  inspiratory  muscles.  In  fact  Sherrington's 
results  on  the  co-ordination  of  muscular  movements  would  tend  to  make  us 
assume  inhibition  of  the  tone,  e.  g.  of  the  abdominal  muscles,  during  inspira- 
tion, and  active  augmentation  of  their  tone  during  expiration.  Where  the 
tone  of  the  muscles  is  entirely  lost,  e.g.  in  the  condition  of  viscero-ptosis, 
it  has  been  observed  that  the  diaphragm  is  thrown  out  of  action,  breathing 
being  chiefly  carried  out  by  an  elevation  of  the  upper  part  of  the  thorax. 
Probably  under  normal  circumstances  the  internal  intercostal  muscles  also 
contract  with  each  expiration. 

Although  the  action  of  the  intercostal  muscles  has  been  a  subject  of  debate,  physio- 
logical experiments  serve  on  the  whole  to  confirm  the  view  first  put  forward  by  Hani- 
ber^er  and  based  on  a  consideration  of  the  direction  of  the  fibres.  The  external  inter- 
eostals  pass  from  one  rib  to  the  next  below  downwards  and  forwards.  Hence  if  a  pair  of 
ribs  be  isolated  from  the  rest  of  the  chest  wall,  leaving  the  vertebral  and  costal  attach- 
ments intact,  contraction  of  these  muscles  will  cause  a  rise  of  both  ribs.  This  result  will 
be  evident  from  a  consideration  of  Fig.  499,  where  ab  is  a  fibre  of  the  external  intercostal 
muscles,  passing  from  the  rib  vs  to  be  attached  to  the  rib  v's'  at  b.  When  ab  contracts, 
the  tension  it  exerts  on  its  two  attachments  can  be  resolved  into  two  components  ac  acting 
downwards  and  bd  acting  upwards,  bd  however  acts  at  the  end  of  the  long  lever  bv', 
whereas  ac  acts  at  the  end  of  the  short  lever  av.  Hence  the  raising  effect  will  overcome 
the  depressing  effect,  and  both  ribs  will  rise, 

The  fibres  of  the  internal  intercostals  run  in  the  opposite  direction  to  the  external 


MECHANICS  OF  THE  RESPIRATORY  MOVEMENTS 


1093 


muscles,  and  from  a  consideration  of  Fig.  500  it  is  evident  that  their  effect  will  be  to 
depress  any  pair  of  ribs,  thus  acting  as  expiratory  muscles. 

Owing  to  the  fact  that  the  costal  cartilages  make  an  angle  with  the  bony  ribs,  the 
fibres  of  prolongation  of  the  internal  intercostals,  musculi  intercartilaginei,  have  the 
same  relation  to  their  attachments  that  the  external  intercostals  have  to  the  bony  ribs. 
Their  action  therefore  must  be  to  raise  the  cartilages  and  flatten  out  the  angle  between 
the  cartilaginous  and  bony  ribs  so  that  they  must  act  with  the  external  intercostals  as 
inspiratory  muscles. 

In  forced  expiration  a  large  number  of  muscles  may  take  part — such 
as  the  serratus  posticus  inferior  and  the  muscles  forming  the  wall  of  the 
abdomen,  i.  e.  the  rectus,  obliquus,  and  transversus  abdominis  muscles. 

As  the  lungs  are  distended  with  each  inspiration  their  position  changes 
in  relation  to  the  thoracic  wall.  All  parts  are  not  equally  distensible  in  the 
normal  position  of  the  lungs.  There  are  three  areas  which  are  in  contact 
with  the  nearly  stationary  parts  of  the  thoracic  wall  and  cannot  therefore 
be  directly  expanded.     These  are  (1)  the  mediastinal  surface  in  contact  with 


Fro.  499. 


the  pericardium  and  structures  of  the  mediastinum ;  (2)  the  dorsal  surface  in 
contact  with  the  spinal  column  and  with  the  spinal  segments  of  the  ribs; 
(3)  the  apical  surface  lying  in  contact  with  the  deep  cervical  fascia  at  the 
root  of  the  neck.  The  roots  of  the  lungs  move  with  inspiration  somewhat 
forwards  and  downwards.  The  front  parts  of  the  lungs  move  downwards 
and  inwards,  so  that  their  inner  borders  in  front  approach  one  another. 
The  extent  and  boundaries  of  the  lungs  can  be  easily  ascertained  in  the 
living' subject  by  means  of  percussion.  On  tapping  the  finger  laid  on  the 
chest  a  sound  is  emitted  which  varies  with  the  nature  of  the  subjacent  tissues. 
If  this  is  lung  tissue  filled  with  air,  a  clear  resonant  tone  is  obtained;  where 
it  is  solid  tissue,  such  as  the  heart,  or  a  lung  consolidated  with  inflammatory 
products,  or  the  liver,  a  dull  sound  is  obtained.  It  is  easy  to  show  that  the 
resonant  area  of  the  chest  increases  with  each  inspiration.  The  apices  of 
the  lungs  extend  about  one  inch  above  the  clavicle  anteriorly  and  behind 
reach  as  high  as  the  seventh  spinous  process.  During  moderate  expiration 
the  lower  margin  of  the  lungs  extends  in  front  from  the  upper  border  of  the 
sixth  rib  at  its  insertion  to  the  sternum,  and  runs  obliquely  downwards  to 
the  level  of  the  tenth  rib  at  the  back  of  the  chest.  During  the  deepest 
inspiration  the  lungs  descend  in  front  to  the  seventh  intercostal  space 
and  behind  to  the  eleventh  rib,  while  during  deepest  possible  expiration  the 


1094  PHYSIOLOGY 

lower  margins  of  the  lungs  are  elevated  almost  as  much  as  they  descend 
during  inspiration.  In  the  front  of  the  chest  a  triangular  space  can  lie 
always  marked  out  over  the  heart  where  the  note  obtained  on  percussion 
is  dull.  This  space  is  bounded  on  the  right  by  the  left  border  of  the 
sternum  and  extends  out  as  far  as  the  cardiac  apex,  being  bounded  above 
by  the  fourth  costo-sternal  articulation  and  below  by  the  sixth  costal 
cartilage. 

BREATH  SOUNDS.  If  the  ear  be  applied  to  the  chest  wall,  either  directly 
or  through  the  medium  of  a  stethoscope,  each  inspiration  is  found  to  be 
accompanied  by  a  fine  rustling  sound,  the  '  vesicular  murmur.'  It  is 
thought  to  be  caused  by  the  sudden  dilatation  of  the  air  vesicles  during 
inspiration  or  perhaps  by  the  current  of  air  passing  from  the  narrow  terminal 
bronchioles  into  the  wider  infundibula.  It  is  important  to  remember  that 
this  sound  is  heard  only  during  inspiration  and  over  healthy  lungs.  On 
listening  over  the  larger  air  passages,  i.  e.  the  larynx,  trachea,  and  bronchi, 
we  hear  a  much  louder  sound  which  accompanies  both  expiration  and 
inspiration  and  may  be  compared  to  a  sharp  whispered  hah.  This  is  known 
as  the  '  bronchial  murmur.'  It  can  be  heard  also  at  the  back  of  the  chest 
between  the  scapulae  at  the  level  of  the  fourth  dorsal  vertebra,  where  the 
trachea  bifurcates.  In  all  other  parts  of  the  chest  the  healthy  lung  prevents 
the  propagation  of  this  sound  to  the  chest  wall.  If  however  the  lung  is  solid, 
as  occurs  in  pneumonia,  it  conducts  the  sound  easily  from  the  large  air  tubes 
to  the  chest  .wall.  Bronchial  breathing  at  any  part  of  the  chest  other  than 
that  immediately  over  the  air  tubes  is  therefore  a  distinctive  sign  of  con- 
solidation of  the  lung.  Absence  of  breath  sounds  at  any  part  of  the  chest 
implies  either  that  air  is  not  entering  that  part  of  the  lung,  or  that  the  lung 
is  separated  from  the  chest  wall  by  effused  fluid. 

INTRATHORACIC  PRESSURE.  Even  at  the  end  of  expiration  the  lungs 
are  in  a  stretched  condition.  This  is  shown  by  the  fact  that  if  in  an  animal 
or  in  the  corpse  an  opening  be  made  into  the  pleural  cavity,  air  rushes  into  the 
opening  and  the  lungs  collapse,  driving  a  certain  amount  of  air  out  through 
the  trachea.  Since  the  lungs  are  always  tending  to  collapse,  it  is  evident  that 
they  must  exert  a  pull  on  the  thoracic  wall.  This  pull  of  the  lungs  gives  rise 
to  a  negative  'pressure  in  the  pleural  cavity.  If  we  connect  a  mercurial 
manometer  with  the  pleural  cavity,  we  find  that  the  pull  of  the  lungs  amounts 
in  the  corpse  to  6  mm.  of  mercury.  If  the  lungs  are  fully  distended,  as  after 
full  inspiration,  the  elastic  forces  are  more  brought  into  play,  and  the  negative 
pressure  in  the  pleura  may  amount  to  30  mm.  Since  the  lungs  are  always 
tending  to  collapse,  respiration  becomes  impossible  directly  free  openings 
are  made  into  the  pleural  cavities  on  both  sides.  With  each  inspiratory 
movement  air  rushes  in  through  these  openings,  so  that  the  thoracic  move- 
ments can  no  longer  exert  any  influence  on  the  volume  of  the  lungs.  The 
negative  pressure  in  the  thorax  is  diminished  by  any  factor  decreasing  the 
elasticity  of  the  lung  tissue.  Thus  in  an  old  man,  where  the  elastic  tissue  is 
degenerated  and  the  alveoli  are  enlarged,  giving  rise  to  the  condition  known 
as  emfhysema,  the  lungs  may  collapse  only  slightly  or  not  at  all  on  opening 


MECHANICS  OF  THE  RESPIRATORY  MOVEMENTS        1095 

the  chest.  The  lungs  do  not  collapse  on  making  an  opening  in  the  chest 
of  a  new-born  mammal ;  but  this  is  owing  to  the  fact  that  they  completely 
fill  the  thorax  in  the  expiratory  position,  and  it  is  only  later  that,  with  the 
growth  of  the  ribs,  the  thorax  gets,  so  to  speak,  too  large  for  the  lungs  which 
are  therefore  stretched  to  fill  it. 

The  force  exerted  by  the  inspiratory  muscles  is  nearly  all  spent  in  over- 
coming the  elastic  resistance  of  the  lungs  and  costal  cartilages.  A  free  access 
of  air  is  provided  for  by  contractions  of  certain  accessory  muscles  of  respira- 
tion. With  each  inspiration  the  glottis  is  widened  by  abduction  of  the  vocal 
cords.  When  the  glottis  is  observed  by  means  of  the  laryngoscope,  a 
rhythmical  separation  and  approximation  of  the  vocal  cords  are  observed, 
synchronous  respectively  with  inspiration  and  expiration  (Fig.  312,  p.  622). 
When  inspiration  is  laboured,  the  alee  nasi  are  dilated  by  the  action  of  the 
dilator  nasi.  This  movement  of  the  nostril,  which  is  constant  in  many 
animals,  becomes  very  marked  in  children  suffering  from  any  respiratory 
trouble. 

If  a  manometer  be  connected  with  one  of  the  nostrils,  so  as  to  register  the 
pressure  in  the  air  cavities,  it  is  found  that  there  is  a  negative  pressure  of 
—  1  mm.  Hg.  with  inspiration,  and  a  positive  pressure  of  2  or  3  mm.  with 
expiration.  With  forced  inspiration  the  negative  pressure  may  amount 
to  —  57  mm.  Hg.,  and  with  forced  expiration  there  may  be  a  positive  pressure 
of  -f  87  mm. 

PULMONARY  VENTILATION.  Under  no  circumstances  can  we  by  forced 
expiration  empty  the  lungs  of  air.  At  the  end  of  the  most  forcible  exe 
piration,  if  the  pleura  were  perforated,  the  lungs  would  collapse  and  driv- 
more  air  through  the  trachea.  When  breathing  quietly  a  man  takes  in  and 
gives  out  at  each  breath  about  500  c.c.  of  air,  measured  dry  and  at  0°  C.  If 
measured  moist  and  at  the  temperature  of  the  body,  viz.  37°  C,  the 
volume  would  be  about  000  c.c.  This  amount  is  known  as  the  tidal  air. 
By  means  of  a  forcible  inspiratory  effort  it  is  possible  to  take  in  about  1500 
c.c.  more  (complemental  air).  At  the  end  of  a  normal  expiration  a  forcible 
contraction  of  the  expiratory  muscles  will  drive  out  about  1500  c.c.  more 
(supplemental  air).  These  three  amounts  together  constitute  the  '  vital 
capacity  '  of  an  individual.  This  total  may  be  determined  by  means  of  the 
instrument  known  as  the  spirometer,  which  is  merely  a  small  gas-meter  with 
a  gauge  by  which  the  amount  of  air  in  it  can  be  at  once  read  off.  The  person 
to  be  tested  fills  his  lungs  as  full  as  possible,  and  then  expires  to  the  utmost 
into  the  spirometer.  The  air  left  in  the  lungs  after  the  most  vigorous 
expiration  is  known  as  the  residual  air. 

The  residual  air  may  be  determined  by  letting  a  person  expire  to  the  utmost  extent 
and  then  connecting  with  his  mouth  or  nose  a  bag  of  known  capacity  filled  with  hydrogen. 
The  subject  of  the  experiment  then  inspires  and  expires  into  the  bag  two  or  three  times, 
ending  in  the  same  state  of  forced  expiration  as  he  began.  Any  diminution  of  the  total 
volume  of  gas  in  the  bag  will  represent  the  gas  lost  during  the  experiment  by  diffusion 
into  the  blood  vessels.  By  analysis  of  the  gaseous  mixture  in  the  bag,  it  is  possible  to 
determine  the  amount  of  air  in  the  lungs  at  the  beginning  of  the  experiment.  Supposing, 
for  example,  the  bag  held  4000  c.c.  hjdrogen,  after  two  respirations  the  total  volume  is 


1096  PHYSIOLOGY 

unaltered,  but  the  gas  is  found  to  consist  of  3000  c.c.  hydrogen  and  1000  c.c.  oxygen> 
nitrogen,  and  C02,  i.  e.  pulmonary  gases.  Since  the  gas  in  the  lungs  must  have  the  same 
composition  and  1000  c.c.  hydrogen  have  disappeared  from  the  bag,  it  is  evident  that  the 
lungs  will  contain  1000  c.c.  hydrogen  and  '  'T)"°,  i.  e.  330  c.c.  pulmonary  gases.  Thus 
the  total  volume  of  gas  left  in  the  lungs  at  the  end  of  the  forced  expiration  was  1330 
c.c,  which  is  the  residual  volume  for  the  individual. 

The  above  example  is  purely  imaginary.  As  a  result  of  actual  deter- 
minations carried  out,  we  may  assume  the  residual  air  in  the  lungs  as 
something  between  600  and  1200  c.c. 

Of  the  500  c.c.  of  tidal  air  taken  in  at  each  inspiration,  only  a  certain 
part  reaches  the  alveoli,  part  being  required  to  fill  the  air  tubes,  trachea, 
bronchi,  and  bronchioles  which  lead  to  the  air  cells.  The  volume  of  the 
air  tubes  has  been  reckoned  to  amount  to  140  c.c,  so  that  of  the  500  c.c.  about 
360  c.c.  reach  the  alveoli.  For  the  same  reason  the  expired  air  represents 
the  air  from  the  alveoli  (360  c.c.)  diluted  with  140  c.c.  of  air  which  has 
remained  in  the  air  tubes  and  undergone  very  little  change,  other  than  the 
elevation  of  temperature  and  saturation  with  aqueous  vapour.  We  have 
therefore  to  allow  for  this  air  contained  in  the  so-called  '  dead  space  '  of  the 
lungs  when  we  seek  to  arrive  at  the  composition  of  alveolar  air  from  an 
analysis  of  expired  air. 


THE    BRONCHIAL   MUSCULATURE 

Both  the  large  and  smaller  air  tubes  have  a  coating,  consisting  of  un- 
striated  muscle  fibres,  which  in  the  bronchioles  is  complete.  Contraction 
of  these  fibres  must  have  the  following  effects  :  (1)  a  constriction  of  the 
bronchi  and  bronchioles;  (2)  a  diminution  of  the  air  space  of  the  lungs  and 
therefore  of  the  volume  of  the  lung;  (3)  an  increased  resistance  to  the 
passage  of  the  air  into  and  out  of  the  alveoli.  Changes  in  the  condition  of 
contraction  of  these  muscle  fibres  may  be  studied  in  two  ways.  In  the  first 
method  artificial  respiration  is  carried  out,  a  constant  volume  of  air  being 
blown  in  and  sucked  out  at  each  respiration.  Any  diminution  in  the 
calibre  of  the  bronchioles  must  increase  the  resistance  to  the  incoming 
current  of  air  and  so  cause  a  rise  of  pressure  in  the  tracheal  tube.  Einthoven, 
in  investigating  this  subject,  has  made  use  of  an  arrangement  by  means  of 
which  a  mercurial  manometer  is  connected  with  the  trachea  for  a  brief 
space  of  time  during  one  part  of  the  inspiratory  phase.  Any  resistance 
to  the  current  of  air  raises  the  pressure  during  the  whole  inspiration  and 
therefore  at  the  moment  at  which  the  manometer  is  put  into  connection 
with  the  tracheal  tube,  and  a  rise  of  the  mercury  in  the  manometer  is  thus 
produced.  By  this  method  was  obtained  the  tracing  shown  in  Fig.  501. 
By  the  second  method  artificial  respiration  at  a  constant  pressure  is  made 
use  of.  Any  changes  in  the  bronchioles  will  in  this  case  affect  the  volume 
of  air  entering  the  lungs  at  each  stroke  of  the  pump,  and  can  be  measured 
by  recording  either  the  passive  respiratory  movements  of  the  chest  or  the 
changes  in  volume  of  a  lobe  of    the  lung  enclosed  in  a  plethysmograph 


MECHANICS   OF  THE   RESPIRATORY  MOVEMENTS        1097 

(Brodie  and    Dixon).     By  both    these  methods  it    has    been  shown  that 
stimulation  of  the  peripheral  end  of  either  vagus  causes  constriction  of  the 


Fig.  501.  Tracings  of  blood  pressure  (middle  curve)  and  of  intra -tracheal  pressure 
(upper  curve)  taken  by  Einthoven's  differential  manometer.  Between  Q  and  Q' 
the  peripheral  end  of  one  vagus  was  stimulated.     Time  marking  =  seconds. 

bronchioles  (vide  Figs.  502  and  503).  As  a  rule  there  is  little  tonic  action  of 
the  vagi,  section  of  both  vagi  leaving  the  respiratory  pressure  curve  unaltered 
or  lowering  it  slightly  by  2  to  10  mm.  H20.     It  is  very  easy  to  bring  about 


Fig.  502.  Tracings  of  the  volume  changes  of  tho  lung,  with  constant  variations  of' 
tracheal  pressure.  (Bkodie  and  Dixon.)  T.P  t r.i.  h.-al  pressure.  L.V.  Iuiil' 
volume.  B.P.  blood  pressure  (Zero  B.P.  17  mm.  below  time  marker).  Showing 
constriction  of  bronchial  musculature  as  a  result,  of  vagus  excitation. 

a  vagus  tonus  by  allowing  the  animal  to  inhale  air  containing  3  to  4  per 
nut.  carbon  dioxide.  A  peripheral  tonus  may  also  be  produced  by  ad- 
ministration of  muscarine  or  pilocarpine.  In  the  latter  case  Brodie  and 
Dixon   have  shown  that  stimulation  of  the   vagus  may  cause  relaxation 


1098 


PHYSIOLOGY 


of  the  bronchioles,  so  that  this  nerve  appears  to  contain  both  motor  and 
inhibitory  fibres  to  the  bronchioles. 

THE  EFFECTS  OF  BRONCHIAL  CONSTRICTION  :  ASTHMA.  Under 
the  influence  of  vagal  stimulation  or  of  carbon  dioxide,  the  pressure  neces- 
sary to  drive  the  normal  amount  of  air  into  the  lungs  may  be  raised  in  the 
dog  from  125  to  300  mm.  H20.  We  should  therefore  expect  that,  in  cases 
where  bronchial  constriction  is  present,  there  would  be  difficulty  both  in 
inspiration  and  expiration.  There  is  however  a  difference  in  the  mechanical 
conditions  of  the  bronchi  during  the  two  phases  of  a  respiratory  move- 
ment. Normally  the  elastic  structure  of  the  lungs  is  drawing  upon  the 
bronchial  wall,  tending  to  maintain  it  patent,  and  so  opposing  the  action  of 


Tracing  showing  inhibitory  effect  of  vagus  on  the  bronchial  tonus  pro- 
duced by  O'Ol  grm.  pilocarpine. 


the  bronchial  muscle.  During  inspiration  this  expanding  force  is  in- 
creased, so  that  in  the  presence  of  bronchial  constriction  the  access  of  air 
is  rendered  the  easier,  the  more  powerful  the  contraction  of  the  inspiratory 
muscles.  In  expiration  all  parts  of  the  lung  collapse,  drawing  with  them 
the  chest  wall ;  the  pull  of  the  lung  tissue  on  the  bronchial  wall  is  lessened, 
but  is  still  present.  If  however  the  expiratory  muscles  contract  vigorously, 
the  intrapleural  pressure  becomes  positive,  and  the  pull  of  the  lung  tissue 
on  the  bronchial  walls  is  changed  into  a  pressure  tending  to  obliterate  their 
lumen  and  so  impede  the  outflow  of  air. 

It  is  evident  therefore  that,  in  the  presence  of  a  spasmodic  contraction 
of  the  bronchial  muscles,  the  inspiration  will  be  forcible  and  rapid,  but  all 
contractions  of  muscles  must  be  avoided  so  far  as  possible  during  expiration, 
which  must  be  left  to  the  elastic  reaction  of  the  lungs  and  becomes  slow 


MECHANICS  OF  THE  RESPIRATORY  MOVEMENTS        1099 

and  prolonged.  Moreover  it  will  be  of  advantage  to  keep  the  lung  as 
nearly  as  possible  in  the  inspiratory  position,  so  as  to  reinforce  the  elastic 
forces  which  dilate  the  bronchioles  and  aid  expiration.  We  thus  get  the 
typical  breathing  which  occurs  in  man  in  cases  of  spasm  of  the  bronchial 
muscles,  known  as  asthma  nervosum.  This  type  of  breathing  is  often 
described  as  being  marked  by  expiratory  dyspnoea.  This  description  is 
however  erroneous.  It  is  the  inspiratory  muscles,  which  in  these  cases  are 
contracted  to  their  uttermost;  the  expiratory  muscles,  such  as  the 
abdominal,  will  be  found  to  be  quite  flaccid  even  during  expiration. 


SECTION  II 

THE    CHEMISTRY    OF    RESPIRATION 

The  energy  of  the  body  is  derived  almost  entirely  from  the  oxidation  of  the 
carbon  and  hydrogen  of  the  foodstuffs.  An  adult  man  during  the  twenty- 
four  hours  produces  on  the  average  250  c.c.  of  carbon  dioxide  per  kilo,  per 
hour.  A  man  of  70  kilos,  will  therefore  excrete  250  X  70  X  24  =  420,000  c.c. 
carbon  dioxide  in  the  course  of  twenty-four  hours.  During  sleep  the  output 
of  carbon  dioxide  is  lowered  with  the  diminution  in  all  the  metabohc  pro- 
cesses of  the  body  and  amounts, to  only  160  c.c.  per  kilo,  per  hour.  If  we 
assume  that  eight  hours  of  the  twenty-four  are  given  to  sleep,  this  will  leave 
295  c.c.  per  kilo,  per  hour  as  the  average  excretion  of  carbon  dioxide  during 
the  waking  hours.  Since  the  access  of  oxygen  to  the  body  and  the  removal 
of  carbon  dioxide  is  effected  by  the  pulmonary  ventilation,  the  expired  air 
will  differ  from  the  inspired  air  in  containing  more  carbon  dioxide  and  less 
oxygen.  The  oxygen  intake  is  not  however  absolutely  proportional  to 
the  carbon  dioxide  output.  This  is  owing  to  the  fact  that  carbon  is  not 
the  only  element  which  leaves  the.  body  hi  an  oxidised  condition.  Fats,  for 
example,  contain  a  number  of  unoxidised  atoms  of  hydrogen,  which  in  the 
metabohc  processes  of  the  body  are  fully  oxidised,  to  be  excreted  as  water. 
Oxygen  will  also  leave  the  body  in  combination  with  carbon  and  nitrogen 
in  the  urine,  so  that  a  certain  amount  of  oxygen  which  is  taken  in  does  not 
reappear  as  carbon  dioxide  in  expired  air.  There  is  thus  an  absolute 
diminution  in  the  volume  of  expired  air  as  compared  with  that  of  inspired 
air.  This  diminution,  due  to  loss  of  oxygen,  is  greater  in  carnivora  whose 
food  consists  mainly  of  proteins  and  fats,  than  in  herbivora  which  feed 
principally  on  carbohydrates,  and  depends  on  the  respiratory  quotient,  i.  e. 

, ,         , .    CO,  expired. 

the  ratio  — -. — -. 

02  inspired. 

In  man  the  average  respiratory  quotient  can  be  taken  as  0-85.     On  this 

basis  the  amount  of  oxygen  which  will  be  taken  in  during  the  waking  hours 

will  be  347  c.c.  per  kilo,  per  hour.    Taking  round  figures,  we  may  say  that, 

when  awake,  a  man  takes  in  350  c.c.  oxygen  and  gives  out  300  c.c.  carbon 

dioxide  per  kilo,  per  hour.    From  these  figures  we  can  calculate  the  normal 

composition  of  expired  air  when  a  man  is  breathing  quietly.     Under  these 

conditions  the  tidal  air  amounts  to  500  c.c.     If  he  breathes  seventeen  times 

a  minute,  the  total  pulmonary  ventilation  during  the  hour  will  be  500  x  17 

X  60  =  510,000  c.c.  per  hour.     If  the  man  weighs  70  kilos.,  his  expired  air 

1100 


THE  CHEMISTRY  OF  RESPIRATION  1101 

will  contain  300  x  70  c.c.  =  21,000  c.c.  carbon  dioxide.  Hence  the  per- 
centage of  carbon  dioxide  in  the  expired  air  will  be  4-1  per  cent.  In  the 
same  way  we  can  reckon  the  percentage  of  oxygen  in  the  expired  air  at  16-4 
per  cent.  Exact  experiments  have  shown  that  the  volume  of  nitrogen  is 
unchanged  durmg  respiration,  this  gas  taking  no  part  in  the  ordinary 
metabolic  processes  of  the  body.  We  may  therefore  compare  the  ordinary 
composition  of  inspired  and  expired  air  as  follows  : 

Inspired  Air 

Oxygen     .  .  .  .  .  .  .20-96  vols,  per  cent. 

Nitrogen  (including  argon)  .  .  .     79-00       „  „ 

Carbon  dioxide  .....       0-04       „  , 

Expired  Air 

Oxygen     .  .         .         .  ,  .     16-4  vols,  per  cent. 

Nitrogen  .  .  .  .  .  .     79'5       „  „ 

Carbon  dioxide  .  .  .  .  .       4- 1       „  „ 

The  increase  in  the  figure  for  nitrogen  refers  of  course  only  to  the  per- 
centage amount,  shice  the  total  volume  of  air  breathed  is  decreased  by  the 
disappearance  of  a  certain  amount  of  oxygen  without  the  production  of  a 
corresponding  amount  of  carbon  dioxide,  so  that  the  relative  amount  of 
nitrogen  is  slightly  increased.  These  figures  for  the  composition  of  inspired 
and  expired  air  refer  to  dry  air  at  a  temperature  of  0°  C.  and  a  pressure  of 
760  mm.  Under  normal  circumstances  inspired  air  contains  a  variable 
amounij  of  aqueous  vapour  and  has  a  variable  temperature  corresponding 
with,  the  time  of  year.  Expired  air  is  fully  saturated  with  aqueous  vapour 
and  has  the  temperature  of  the  body,  37°  C.  The  aqueous  vapour  at  this 
temperature  is  by  no  means  negligible.  Its  tension  amounts  to  50  mm.  Hg. 
Thus  when  a  man  is  breathing  dry  air  at  a  pressure  of  760  mm.  Hg.,  the 
pressure  of  the  mixture  of  gases  in  the  alveoli  of  his  lungs  will  be  only 
760  —  50,  i.  e.  710  mm.  Hg. 

Only. a  certain  percentage  of  the  500  c.c.  of  tidal  air  reaches  the  alveoli, 
100  to  140  c.c.  being  required  to  fill  the  trachea  and  bronchial  tubes.  Hence 
the  alveolar  air  must  contain  more  carbon  dioxide  and  less  oxygen  than  the 
tracheal  air ;  and  it  is  found  that,  if  we  take  the  air  from  the  alveoli  instead 
of  that  expired  through  the  mouth  or  nose,  the  differences  between  it  and  the 
inspired  air  are  much  more  pronounced. 

A  sample  of  alveolar  air  may  be  obtained  for  analysis  in  the  following  way  (Haldane)  : 
A  piece  of  india-rubber  tubing  is  taken  of  about  1  inch  diameter  and  4  feet  long.  Into 
one  end  (Fig.  501)  is  fitted  a  mouthpiece,  the  other  being  left  open  or  connected  with  a 
spirometer.  About  2  inches  from  the  mouthpiece  is  fixed  a  gas  sampling-bulb,  which  is 
provided  with  three-way  taps  at  the  upper  and  lower  ends.  Before  an  experiment  tin- 
bulb  is  tilled  with  mercury,  if  the  lower  end  is  open,  or  else  it  is  completely  exhausted. 
The  subject  of  the  experiment,  after  breathing  normally  a  few  times,  at  the  end  of  a 
normal  inspiration  puts  his  mouth  to  the  tube,  expires  quickly  and  deeply,  and  closes 
the  mouth-piece  with  his  tongue.  The  tap  of  the  sampling-bulb  is  then  turned,  and  the 
air  last  expelled  from  the  lungs  (wliich  is  therefore  pure  alveolar  air)  rushes  into  the  bulb. 
The  tap  of  the  bulb  is  then  turned  off,  and  the  gas  may  be  removed  for  analysis.     A 


1102  PHYSIOLOGY 

similar  sample  is  then  taken,  in  which  the  subject  expires  deeply  at  the  end  of  a  normal 
expiration.     This  sample  will,  of  course,  contain  more  CO.,  and  less  Oa  than  that  obtained 

at  the  end  of  inspiration.     The  mean  of  the  two  samples  is  taken  as  the  average  >■ 

position  of  alveolar  air. 

The  difference  between  the  composition  of  expired  air  and  alveolar  air 
is  determined  by  the  dilution  of  the  alveolar  air  with  that  contained  in  the 
(had  space.  Hence  with  shallow  breathing  there  will  be  a  large  difference, 
but  this  will  decrease  with  increased  depth  of  respiration.  Thus,  if  the 
alveolar  air  contained  6  per  cent.  C02  and  the  dead  space  amounted  to 
150  ox.,  the  expired  air  would  contain  only  3  per  cent.  C02  when  the  person 
was  taking  in  only  300  c.c.  at  each  respiration.  If  however  he  was  breath- 
ing slowly  and  deeply  so  as  to  raise  the  tidal  air  to  1500  c.c,  only  one-tenth 
of  this  would  be  represented  by  the  dead  space,  and  the  expired  air  would 
contain  nine-tenths  as  much  C02  as  the  alveolar  air,  i.  e.  5- 1  per  cenl . 

Mour/Y-f/£C£. 


Sampung  tube. 


The  changes  in  the  composition  of  alveolar  air  with  respiration  are  by 
no  means  so  marked  as  those  ■  produced  in  the  tidal  air,  since  the  latter 
forms  only  a  small  proportion  of  the  total  air  in  the  lung  alveoli.  Thus 
at  the  end  of  a  normal  expiration  the  alveoli  still  contain  2500  c.c.  of  gases. 
In  inspiration  360  c.c.  atmospheric  air  is  taken  into  this  space  and  mixed 
with  the  2500  c.c.  already  there.  The  '  ventilation  coefficient '  in  quiet 
breathing  is  therefore  only  one-seventh,  and  the  change  in  the  oxygen  and 
carbon  dioxide  content  of  the  alveolar  air  produced  by  this  access  of  360  c.c. 
will  amount  to  less  than  one-half  per  cent.  This  is  illustrated  by  the  follow- 
ing figures  from  Haldane,  giving  the  alveolar  content  in  carbon  dioxide  at 
the  end  of  inspiration  and  at  the  end  of  expiration  respectively. 

Alveolab  CO.,  Tensions 


Alveolar  CO^  at 
inspiration.  (M 
twelve  observations) 


inspiration.  ~  (Mean  of    \  C°2XB£a5on'f 

tiv.lv,.  niK,.rvntim>i.i  expiration 


J.  S.  H.  5-54  5-70  5-62 

J.  G.  P.  6- 17  6-39  6-28 


We  can  thus  speak  of  an  average  jcomposition  of  alveolar  air  which,  in 
spite  of  the  constant  ventilation,  differs  from  the  external  air  in  containing 
an  excess  of  carbon  dioxide  and  a  relative  lack  of  oxygen.  Lavoisier,  who 
was  the  first  to  study  the  chemical  changes  in  respiration  accurately,  regarded 
the  lungs  as  the  seat  of  the  formation  of  carbon  dioxide  and  the  consump- 
tion of  oxygen.    This  view  was  generally  accepted  until  it  was  shown  by 


THE   CHEMISTRY  OF  RESPIRATION 


1103 


Magnus,  in  Heidenkain's  laboratory,  that  the  blood  passing  to  the  lungs 
contained  more  carbonic  acid  gas  and  less  oxygen  than  that  passing  away 
from  the  lungs.  The  effects  of  this  discovery  were  to  transfer  the  chief  seat 
of  oxidation  to  the  tissues  of  the  body,  and  to  show  that  the  blood  acts 
simply  as  a  carrier  of  the  oxygen  from  the  lungs  to  the  tissues,  and  of  the 
carbon  dioxide  from  the  tissues  to  the  lungs.  We  thus  learnt  to  distinguish 
between  external  and  internal  respiratory  processes.    A  consideration  of  the 


^^ 


1'IQ.  5(J5.     Barorofts  modification  of  the  Topler  pump. 

chemical  mechanisms,  involved  in  the  process  of  external  respiration,  in- 
cludes therefore  an  investigation  of  the  manner  in  which  gases  are  held  by 
the  blood  and  of  the  factors  which  are  responsible  for  the  transfer  of  oxygen 
and  carbon  dioxide  from  blood  to  alveolar  air,  and  from  alveolar  air  to  blood. 
If  blood  be  exposed  to  a  Torricellian  vacuum  at  the  ordinary  tem- 
perature, the  whole  of  its  contained  gases  is  given  off.  For  the  purpose  of 
extracting  the  blood  gases,  a  great  variety  of  pumps  have  been  devised.  In 
every  case  a  glass  vessel  is  evacuated  by  means  of  the  mercury  pump,  and 
is  then  put  into  connection  with  a  reservoir  containing  blood  which  has  been 
dehbrinated,  or  has  been  prevented  from  clotting  by  the  addition  of  oxalate 


1104  PHYSIOLOGY 

or  citrate.  In  all  these  pumps  the  main  difficulty  arises  in  the  exclusion  of 
atmospheric  air,  and  it  is  therefore  important  to  dispense  so  far  as  possible 
with  taps.  One  of  the  best  modifications  of  the  Topler  mercury  pump  is 
that  employed  by  Barcroft  (Fig.  505),  which  differs  little  from  the  pump 
devised  by  Bohr. 

The  construction  of  the  pump  is  shown  in  the  diagram.  The  actual  pump  consists 
of  the  parts  a,  b,  c,  d.  The  buJb  b  is  prolonged  below  by  a  wide  tube  dipping  into  the 
mercury  in  the  Woulf  bottle  A.  The  upper  part  of  the  bottle  is  filled  with  water  and 
connected  by  two  taps  at  w  with  the  water-supply  and  with  a  sink.  The  water  being 
turned  on,  mercury  is  forced  up  into  B ;  as  it  rises  into  Y  it  carries  before  it  a  glass  valve 
which  prevents  its  further  passage,  so  that  it  can  escape  only  by  the  tube  C,  driving 
before  it  all  the  air  previously  contained  in  B.  The  water-supply  is  now  turned  off,  and 
the  tap  to  the  sink  turned  on.  The  mercury  runs  back.  Air  cannot  enter  by  c,  since 
this  tube  is  sealed  by  mercury.  The  valve  y  therefore  sinks  and  allows  the  air  in  the 
blood  receivers  G,  g  and  the  rest  of  the  apparatus  to  escape  into  B.  The  process  is  re- 
peated many  times  until  a  high  vacuum  is  produced  in  the  whole  apparatus.  A  measured 
quantity  of  blood  is  now  let  into  the  lower  bulb  G.  F  is  a  condenser  through  which  cold 
water  is  constantly  flowing  (to  prevent  all  the  blood  boiling  away),  while  warm  water 
circulates  round  the  bulbs  G,  G  to  facilitate  the  giving  off  of  the  blood  gases.  The  blood 
boils  in  the  vacuum,  and  the  gases  escape  into  B,  and  may  be  driven  off  and  collected 
over  mercury  in  a  cylinder  D  by  raising  the  mercury  in  B.  The  process  of  exhaustion  is 
repeated  until  no  more  bubbles  rise  into  D  on  filling  the  bulb  B  with  mercury.  E  is  a 
sulphuric  acid  chamber  for  drying  the  gases  as  they  pass  from  the  blood  to  the  bulb  B. 

In  this  way,  from  100  c.c.  of  blood,  about  60  c.c.  of  mixed  gases  may  be 
obtained,  consisting  of  oxygen,  carbon  dioxide,  nitrogen,  and  argon.  Argon 
is  present  only  in  insignificant  quantities,  about  -04  volume  per  cent.  The 
nitrogen  also  forms  only  between  one  and  two  volumes  per  cent,  and  is 
present  in  the  same  proportion  in  both  arterial  and  venous  blood.  The 
amounts  of  oxygen  and  carbon  dioxide  in  these  two  kinds  of  blood  differ 
however  within  wide  limits.  The  following  Table  represents  the  average 
composition  of  the  gases  obtained  from  an  artery  and  a  vein  of  the  dog : 

From  100  vols.  May  be  obtained 


Of  oxygen        Of  carbon  dioxide        Of  nitrogen 
Of  arterial  blood     .  .     20  vols.        .     40  vols.      .      1  to  2  vols. 

Of  venous  blood      .  8  to  12  vols.  .     46     „         .         „         „ 

Measured  at  760  mm.  and  0°  C. 

The  principle  introduced  by  Haldane  (vide  p.  902)  for  the  determination  of  the 
oxygen  combined  in  the  form  of  oxyhemoglobin  may  be  successfully  applied  to  small 
quantities  of  blood,  such  as  1  c.c.  or  even  0"1  c.c,  and  in  the  same  sample  of  blood  the 
carbon  dioxide  may  also  be  determined.  In  this  way  it  becomes  practicable  to  make 
blood-gas  analyses  in  a  patient,  or  in  experiments  on  small  organs  where  it  is  desired 
to  determine  their  gaseous  metabolism  by  comparing  the  arterial  with  the  venous 
blood.     Barcroft's  apparatus  for  dealing  with  1  c.c.  of  blood  is  shown  in  Fig.  506  A. 

The  apparatus  consists  of  two  bottles  of  identical  size  (about  30  c.c.)  attached  to  a 
manometer,  the  tubing  of  which  is  1  mm.  bore.  The  manometer  is  filled  with  clove  oil 
of  known  specific  gravity.  To  fill  it  take  out  the  centre  tube,  pour  in  clove  oil  at  A,  put 
in  the  centre  tube  with  the  glass  tube  B  open  and  some  pressure  on  the  rubber  tube  C. 
The  oil  should  stand  about  half  way  up  each  tube.  Seal  B  in  a  flame.  The  constant 
of  the  apparatus  must  be  determined,  viz.  the  capacity  of  the  bottles  and  with  their 
connections. 


THE  CHEMISTRY    OF  RESPIRATION 


1105 


It  is  determined  by  finding  what  rise  of  pressure  in  the  apparatus  is  produced  by 
the  liberation  of  a  known  volume  of  oxygen  from  hydrogen  peroxide,  which  is  placed  in 
the  bottle,  the  liberation  being  effected  by  the  addition  of  potassium. 

To  determine  the  oxygen  capacity  of  a  sample  of  blood.  Place  2  c.c.  of  ammonia  solution 
(made  by  adding  4  c.c.  of  strong  NH3  to  a  litre  of  water)  in  one  of  the  bottles  and  add 
1  c.c.  of  blood.  Thoroughly  lake  the  blood.  Rub  vaseline  on  the  large  and  small  stoppers. 
Put  0'2  c.c.  of  a  saturated  solution  of  potassium  ferricyanide  in  the  small  tube  in 
the  stopper  of  the  bottle  containing  the  blood  (this  is  best  done  with  a  fine  pipette 
which  goes  down  this  tube).  Insert  the  small  stopper.  Place  the  apparatus  on  the 
side  of  a  large  water  bath  (such  as  a  pail)  with  both  taps  open.  In  about  five  minutes  close 
the  tap  on  the  side  of  the  blood  and  rotate  the  bottle  on  the  stopper  till  the  ferricyanide 
trickles  into  the  laked  blood.  Shake  thoroughly,  replace  in  the  bath,  ancj  repeat  this 
several  times  till  a  constant  difference  of  level  is  obtained.     By  means  of  the  screw  clamp 


Fig.  506.     Barcroft's  blood-gas  apparatus. 
a,  for  1  c.c.;  B,  for  0"!   c.c.   blood. 


bring  the  column  of  oil  on  the  side  of  the  blood  to  its  original  level,  and  then  measure 
the  difference  of  level  between  the  two  sides.  Let  this  difference  of  level  be  y  mm.; 
let  p  be  the  height  of  the  barometer  in  millimetres  of  clove  oil,  and  x  the  volume  of 

oxygen  given  off  in  cubic  millimetres;  then  x  =  y[  -  ).     Except  in  the  most  exact  work 

V 

p  may  be  taken  as  10,000  mm.,  in  which  case  the  expression      may  bu  determined  once 

for  all  and  called  C,  the  constant  of  the  apparatus  :   then  x  =  y  x  C. 

To  determine  the  gaseous  contents  of  a  given  blood.  If  we  wish  to  determine  the  actual 
amount  of  oxygen  as  oxyhsemoglobin  in  the  sample,  the  blood  must  be  carefully  intro- 
duced so  as  to  he  below  the  ammonia  and  not  to  come  in  contact  with  the  air.  The 
stopper  is  then  replaced  in  the  bottle  and  immersed  in  the  bath,  with  both  taps  open 
until  it  has  attained  a  constant  temperature.  The  tap  is  then  closed  and  the  height  of 
the  column  of  oil  noted.  The  blood  is  then  laked  by  rotating  the  apparatus,  and  after 
allowing  five  minutes  for  complete  laking  the  ferricyanide  is  run  in.  The  rest  of  the 
determination  is  carried  out  as  aboVc. 

The  carbon  dioxide  may  be  determined  in  the  same  sample  of  blood  by  adding 
tartaric  acid  in  the  same  way  as  potassium  ferricyanide  was  previously  added.  It  is 
necessary  always  to  determine  the  oxygen  before  the  carbon  dioxide,  since  the  mere 
70  * 


1106 


PHYSIOLOGY 


acidification  of  the  blood  causes  the  evolution  of  a  certain  amount  of  oxygen.  The 
results  obtained  for  carbon  dioxide  are  not  so  accurate  as  those  for  the  oxygen,  owing  to 
the  larger  error  introduced  by  the  increased  solubility  of  this  gas  in  watery  media. 

The  same  apparatus  may  be  used  as  a  differential  blood-gas  manometer,  where  it  is 
desired  to  compare  the  oxygen  contents  of  two  samples  of  blood,  e.  g.  of  arterial  and 
venous  blood.  For  this  purpose  1  c.c.  of  the  arterial  blood  is  introduced  into  one  bottle 
and  1  c.c.  of  the  venous  blood  into  the  other  bottle,  in  each  case  under  1£  c.c.  of  weak 
ammonia.  The  bottles  are  then  placed  on  the  apparatus  and  immersed  in  the  water 
bath  until  no  change  occurs  in  the  height  of  the  column  of  oil.  The  two  taps  are  then 
closed  and  the  apparatus  is  vigorously  shaken.  The  blood  on  each  side  is  laked  and,  in 
contact  with  the  air  in  the  bottles,  becomes  completely  saturated  with  oxygen.  No 
carbon  dioxide  is  given  off,  since  this  combines  with  the  weak  ammonia.  If  the  two  bloods 
contain  the  same  amount  of  oxyhemoglobin,  no  difference  will  be  produced  in  the  level 
of  the  oil  in  the  two  tubes.  If  however  one  be  arterial  and  the  other  venous,  the  venous 
blood  will  absorb  more  oxygen  from  its  bottle  than  the  arterial  blood  from  its  side  of  the 
apparatus,  so  that  the  oil  will  rise  in  the  tube  on  the  side  of  the  venous  blood.  From 
the  degree  of  rise  the  difference  in  the  amount  of  oxygen  taken  up  by  the  blood  on  the 
two  sides  can  be  reckoned,  and  this  figure  will  express  the  relative  saturation  of  the 
luvmoglobin  in  the  two  samples  of  blood. 

For  clinical  purposes  it  is  possible  to  work  with  01  c.c.  of  blood.  Fig.  506  B  represents 
the  form  of  apparatus  devised  by  Barcroft  for  dealing  with  these  minute  quantities. 
The  principle  of  the  apparatus  is  the  same  as  that  of  the  larger  type. 

The  condition  of  the  gases  in  the  blood  can  be  judged  by  the  amount  of 
gas  which  the  blood  will  take  up  when  exposed  to  different  pressures  of  the 
gas.  If  a  gas  is  in  simple  solution  the  amount  of  it  dissolved  varies  directly 
with  the  pressure.  Thus,  if  water  takes  up  a  certain  bulk  of  a  gas  at  a  given 
temperature  and  pressure,  it  will  take  up  twice  as  much  if  the  pressure  of 
the  gas  be  doubled.  Since  the  volume  of  a  gas  varies  inversely  as  the 
pressure,  we  may  say  that  a  fluid  will  dissolve  the  same  volume  of  gas 
whatever  the  pressure.  The  absorption  coefficient  of  a  liquid  for  a  gas  is 
expressed  by  the  number  of  cubic  centimetres  of  gas  which  will  be  taken 
up  at  0°  C.  by  1  c.c.  of  the  liquid  when  the  gas  is  at  a  pressure  of  760  mm. 
Hg.  The  absorption  coefficient  diminishes  with  rise  of  temperature.  The 
following  Table  represents  the  absorption  coefficients  for  oxygen,  carbon 
dioxide,  carbon  monoxide,  and  nitrogen,  in  water  at  various  temperatures 
between  0°  and  40°  C. : 


Temperature 

Oxygen 

Carbon  dioxide 

Carbon  monoxide 

Nitrogen 

0 

0-0489 

1-713 

00354 

00239 

10 

00380 

1194 

0-0282 

0-0196 

20 

00310 

0-878 

0-0232 

00164 

30 

0-0262 

0-665 

00200 

0-0138 

40 

00231 

0-530 

00178 

00118 

From  this  Table  we  see  that  100  c.c.  of  water  at  0°  C.  will  absorb  4-89  c.c. 
oxygen  at  760  mm.  Hg.,  i.  e.  at  one  atmosphere.  If  the  pressure  be  raised 
to  two  atmospheres,  the  volume  of  gas  absorbed  will  be  the  same,  but  if 
these  gases  be  measured  at  the  original  pressure,  i.  e.  at  one  atmosphere, 
the  amount  dissolved  will  be  9-78  volumes.     If  therefore  we  plot  out  the 


THE  CHEMISTRY  OF  RESPIRATION  1107 

absorption  of  the  gas  on  a  curve  of  which  the  ordinates  represent  the  amount 
of  gas  dissolved  and  the  abscissa  the  different  pressures  of  the  gas,  we  shall 
find  that  the  curve  is  a  straight  line.  The  relation  between  the  amount 
absorbed  is  not  altered  by  the  presence  of  other  gases  at  the  same  time. 
The  pressure  of  the  whole  atmosphere  is  760  mm.  Since  the  atmosphere 
consists  roughly  of  four  parts  of  nitrogen  with  one  part  of  oxygen,  the 
atmospheric  pressure  is  due  as  to  one-fifth  to  the  oxygen  and  as  to  four- 
fifths  to  the  nitrogen.  If  we  shake  up  water  at  0°  C.  with  the  atmospheric 
air  at  the  ordinary  pressure,  100  c.c.  of  water  will  absorb  4-89  c.c.  x  *  of 
oxygen,  and  of  nitrogen  2-39  c.c.  x  f.  We  may  therefore  extend  our 
statement  as  to  the  solubility  of  gases  in  fluids  and  say  that  the  amount  of 
gas  dissolved  in  a  fluid  is  proportional  to  the  partial  pressure  of  the  gas. 

When  water  is  shaken  up  with  a  gas  until  it  will  take  up  no  more,  i.  e. 
until  it  is  saturated  for  that  pressure,  a  state  of  equilibrium  exists  between 
the  gas  dissolved  in  the  fluid  and  the  gas  in  contact  with  the  fluid.  In 
this  state  of  equilibrium  the  number  of  molecules  of  the  gas  entering  the 
fluid  is  exactly  equal  to  the  number  of  molecules  of  the  gas  leaving  the 
fluid.  If  we  remove  the  liquid  after  saturation,  say,  at  one  atmosphere,  to  a 
vessel  where  it  is  in  contact  with  gas  at  a  pressure  of  half  au  atmosphere,  the 
liquid  will  give  off  gas  until  the  amount  left  in  solution  is  diminished  to  one- 
half.  The  gas  dissolved  in  a  liquid  thus  has  a  pressure  or  tension  which 
tends  to  make  it  escape  from  the  liquid.  The  Only  way  in  which  we.  can 
measure  this  tension  is  by  finding  what  pressure  of  gas  is  in  exact  equilibrium 
with  the  liquid.  Thus  if  we  take  some  water  containing  carbon  dioxide  in 
solution,  divide  it  into  two  parts,  and  shake  up  one  part-  with  a  gaseous 
mixture  containing  4  per  cent,  of  carbon  dioxide  and  the  other  part  with  a 
mixture  containing  5  per  cent,  of  carbon  dioxide,  and  find  that  the  solution 
loses  gas  to  the  fcrmer  and  takes  up  carbon  dioxide  from  the  latter,  we 
may  conclude  that  the  tension  of  carbon  dioxide  in  the  original  fluid  was 
something-between  4  and  5  per  cent,  of  an  atmosphere.  It  is  by  some  such 
means  that  the  tensions  of  gases  in  the  blood  are  measured,  the  instruments 
for  this  purpose  receiving  the  name  of  aerotonmneters. 

The  solvent  power  of  water  for  gases  is  diminished  if  the  water  contains 
other  solid  substances  in  solution.  Blood  plasma  or  blood  corpuscles  will 
therefore  have  a  smaller  solvent  power  for  gases  than  has  pure  water.  It 
has  been  shown  by  Bohr  that  the  depression  of  solubility  caused  by  the 
presence  of  proteins  or  salts  in  solution  is  the  same  for  all  gases.  The  absorp- 
tion coefficient  of  blood  plasma  for  gases  is  reduced  to  97-5  per  cent,  of  pure 
water,  and  of  blood  to  92  per  cent.,  that  of  the  blood  corpuscles  being  as  low 
as  81  per  cent.  We  may  thus  reckon  the  absorption  coefficient  of  blood 
plasma,  blood,  and  blood  corpuscles  for  oxygen,  nitrogen,  and  carbon 
dioxide. 

From  the  following  Table  we  see  that  100  volumes  of  blood  at  38°  C.  might 
contain  2-2  c.c.  of  oxygen  in  solution  if  the  blood  had  been  exposed  to. 
oxygen  at  a  pressure  of  one  atmosphere.  The  blood  in  the  lungs  is  however 
exposed  to  air  which  contains  only  about  one-sixth  of  its  volume  of  oxygen, 


I  I  OK 


PHYSIOLOGY 


so  that  the  total  amount  of  oxygen  present  in  arterial  blood  in  .solution 
cannot  be  more  than  one-sixth  of  2-2,  i.  e.  about  0-36  c.c.  per  cent.  Since 
arterial  blood,  or  blood  saturated  with  oxygen  by  shaking  with  air,  wdll 
yield  as  much  as  twenty  volumes  per  cent,  of  oxygen  to  a  Torricellian 
vacuum,  the  oxygen  cannot  be  in  simple  solution,  but  must  be  in  some  form 
of  combination  with  some  of  the  constituents  of  the  blood.  Of  this  oxygen 
practically  the  whole  is  contained  in  the  red  blood  corpuscles  in  combina- 
tion with  hsemoglobin,  the  plasma  containing  no  more  than  can  be  accounted 
for  by  simple  solution. 


Blood  plasma  . 

Blood 

Blood  corpuscles   . 

Oxygen 

Nitrogen 

Carbon  dioxide 

15° 

38° 

15° 

38° 

15° 

38° 

0033 
0031 

0-025 

0023 
0-022 
0-019 

0017           0012 
0-016          0011 
0-014          0010 

0-994 
0-937 
0-825 

0-541 
0-511 
0-450 

One  gramme  of  crystallised  ha3moglobin  can  absorb  1-31  c.c.  of  oxygen. 
If  a  solution  of  oxyhemoglobin  be  subjected  in  an  air-pump  to  gradually 
diminishing  pressure  at  the  temperature  of  the  body,  very  little  oxygen 
is  given  off  until  the  partial  pressure  of  the  oxygen  is  diminished  to  about 
30  mm.  Hg.  (Fig.  508).  At  this  point  a  large  evolution  of  gas  begins, 
and  continues  at  falling  pressure  until  at  0  mm.  pressure  all  the  oxy- 
hemoglobin is  dissociated  and  converted  into  haemoglobin.  The  same 
observation  may  be  made  in  a  reverse  direction.  If  a  solution  of  reduced 
hsemoglobin  be  exposed  to  gradually  increasing  pressures  of  oxygen,  it  will 
be  found  that  the  greatest  absorption  takes  place  between  0  and  30  mm.  Hg. 
After  this  point  the  oxygen  is  more  slowly  absorbed  up  to  the  point  of 
complete  saturation. 

Since  there  is  no  direct  proportion  between  the  partial  pressure  of  the 
oxygen  and  the  amount  absorbed,  it  is  evident  that  the  oxygen  combines 
with  hsemoglobin  to  form  an  unstable  chemical  compound,  and  that  this  is 
not  a  mere  question  of  solution.  This  is  further  proved  by  the  fact  that 
we  can  displace  the  oxygen  (02)  from  the  oxyhaemoglobin  by  equivalent 
amounts  of  CO  or  NO.  Haemoglobin  is  also  supposed  to  form  an  unstable 
combination  with  carbon  dioxide,  since  it  takes  up  much  more  of  this  gas 
than  the  corresponding  bulk  of  water  or  salt  solution  would  do.  Although 
carbon  dioxide  combines  with  haemoglobin,  it  does  not  displace  oxygen  from 
the  oxyhemoglobin  molecule.  Thus  we  may  have  haemoglobin  saturated 
at  the  same  time  with  oxygen  and  with  carbon  dioxide.  The  presence  of 
carbon  dioxide  does  however  alter  the  ease  with  which  oxyhaemoglobin 
dissociates. 

The  relation  between  the  partial  pressure  of  oxygen  and  the  amount 
of  oxyhaemoglobin  formed  under  varying  conditions  can  be  investigated  in 
the  following  way  (Barcroft) : 


tup:  chemistry  of  respiration  1109 

A  large  glass  globe  with  a  stop-cook  at  one  or  both  ends  (Fig.  507)  is  filled  with  a 
gaseous  mixture  of  known  composition  containing  oxygen.  Into  it  are  introduced  2  or 
3  c.c.  of  blood  or  of  haemoglobin  solution.  It  is  then  tightly  stoppered  and  immersed  in  a 
horizontal  position  in  a  pail  of  water  kept  at  a  constant  temperature.  In  the  pail  it  is 
suspended  between  its  two  ends,  so  that  it  can  be  slowly  revolved  by  means  of  a  piece  of 
string  passing  round  its  neck.  In  this  way  the  blood  is  continually  spread  in  a  thin  layer 
over  the  sides  of  the  vessel.  At  the  end  of  a  quarter  to  half  an  hour  it  will  have  attained 
equilibrium  with  the  gaseous  mixture.  It  is  then  turned  into  an  erect  position  so  that 
the  fluid  can  run  down  into  the  neck  closed  by  a  stop-cock,  whence  1  c.c.  may  be  drawn 
off  for  analysis  in  a  Barcroft  apparatus.  A  further  portion  of  the  same  blood  may  be 
shaken  up  with  air  so  as  to  saturate  it  completely,  and  the  saturation  of  the  two  samples 
may  be  compared  in  the  differential  gas  apparatus. 


Frc-507.     Barcroft 's  apparatus  for  dotcnnininr;  the  curve  of  absorption  of 
oxygen  by  haemoglobin. 

Barcroft  has  shown  thnt  the  dissociation  curve  of  haemoglobin  is  largely 
altered  by  slight  variations  in  the  fluid  in  which  the  haemoglobin  is  dissolved. 
The  most  important  of  these  conditions  are  (1)  the  saline  content  of  the 
fluid,  (2)  the  reaction  of  the  fluid.  Under  this  latter  heading  must  be  classed 
the  amount  of  carbon  dioxide  present,  since  its  action  on  the  dissociation 
carve  is  similar  to  that  produced  by  the  presence  of  weak  acids  such  as 
lactic  acid.  The  influence  of  dissolved  salts  on  the  dissociation  curve  is 
shown  in  Fig.  508. 

It  is  interesting  to  note  that  the  differences  between  the  dissociation 
curve  of  blood  and  of  haemoglobin  solution,  as  well  as  between  bloods  of 
different  animals,  have  been  shown  by  Barcroft  and  Camis  to  be  dependent 
on  the  saline  content  of  the  solution  in  the  various  cases.  Thus  human 
haemoglobin  solution,  with  a  concentration  of  salts  similar  to  that  of  dogs' 
blood,  gives  the  same  dissociation  curve  as  normal  dogs'  blood. 

More  important  is  the  effect  of  reaction  since,  as  we  shall  see,  it  is  the 
reaction  of  the  blood,  controlled  especially  by  carbon  dioxide  tension,  that 
determines  the  activity  of  the  respiratory  centres.  In  Fig.  509  is  repre- 
sented the  influence  of  varying  tensions  of  carbon  dioxide,  and  in  Fig.  510 
the  effect  of  slight  additions  of  lactic  acid  on  the  dissociation  curve.  It 
will  be  seen  that  the  more  acid  the  blood,  or  the  greater  tension  of  carbon 
dioxide  it  contains,  the  more  readily  does  it  undergo  dissociation.  This  is 
especially  marked  at  the  very  high  tension  of  420  mm.  carbon  dioxide.     It 


1110 


PHYSIOLOGY 


plays  an  important  part  in  the  lower  tensions  such  as  40  and  80  ram.  Hg. 
carbon  dioxide.     It  must  be  remembered  that  40  mm.  carbon  dioxide  repre- 


,,   '      k,u        ^.i-i-i4-r-' — Ht^-iizt." 

•  +  "  —  "B*:              -i  jijjS  1 '*r.'-*1-**rt  'Ti-*— ■"" 

_   , —       ^__,-       j_-^-'"r"^ 

i  -j*      ^'TfT        h 

r]      i,'/ 

Z.A                                  " 

n~  tVw'? 

«t                        -                     •             -           - 

t                              .     it                 _ 

t  f  t^r    ~ 

t-,-^ 

-,   17 

lilt 

It 

-i^U 

lit 

jit 

..lb 

¥j 

X  t- 

j 

Fig.  508.     Dissociation  curve  of  haemoglobin  in  various  solvents. 
I,  in  water;  II,  in  0-7  per  cent.  NaCl;  III,  in  0'9  per  cent.  K.C1. 
(Bahcroft.) 


Sntm  CC  2 

«    -'"                _g  —  :=  =  S-   "^                 J               "'"'*     " 

-'      ^'"  2  "", '""'''•'"''        ^j""" 

* h^/ ^^ /   s''          s^* 

^y%Y^    s                        ^ 

LrZ4/y.^                                    Z? 

jtj-7^^7                      ^ 

U->    /--,     -?£                                          -^ 

Jtl-i  7-  Y                    +' 

^LtZ-t-/                             S 

-ii-4-/   <—   Z                         y 

tit-/-  4            s 

in    7                * 

4jft~/             ^ 

JLTTT,                    y< 

WfL        _,<s 

-J^e-^           -"■"""'"' 

1^ —  zSL 

TO        SO        90        tOO       HO       tZO      130      fW      ISO 
Fia.  509.     Effect  of  varying  tensions  of  COs  on  the  dissociation  curve  of  oxyhemo- 
globin.     The  lowest  curve  is  the  dissociation  at  a  C02  tension  of  420  mm.  Hg.  from 
observations  by  Barcroft.     (Bonn.) 


THE  CHEMISTRY  OF  RESPIRATION 


mi 


sents  approximately  the  normal  carbon  dioxide  tension  in  the  blood.  It  is 
true  that  at  150  ram.  oxygen  pressure  the  blood  is  practically  saturated 
with  oxygen,  whatever  (within  physiological  limits)  the  pressure  of  the  carbon 
dioxide.  At  lower  pressures  of  oxygen  however,  the  pressure  of  carbon 
dioxide  makes  a  considerable  difference.  Thus  at  an  oxygen  pressure  of 
20  nun.  Hg.  the  amount  of  oxyhemoglobin  formed  is  67-5  per  cent,  at  a 
carbon  dioxide  pressure  of  5  mm.,  whereas  at  a  pressure  of  carbon  dioxide 
of  40  mm.  the  amount  of  oxyhemoglobin  is  only  29-5  per  cent.  In  con- 
sequence of  this  fact,  in  the  tissues  where  the  carbon  dioxide  tension  is  high, 


^~"=' 

■*'*'    ^--°'="3 

/      ^^ A**'*" 

7    S ' +' 

/ 

/A<t             A 

"                z 

/A7 

«,  A-          1  J 

^7 

ft 

z 

7  ZZ 

LuZl 

-4    W 

I7Z  _j 

tu     - 

TIT    , 

■t/rX. 

±ir 

.    Jt/ 

j£r            A 

JSL              ^ 

Fig.  510.     Dissociation  curve  of  sheep's  blood. 

1,  normal  blood;  2,  blood  containing  0'04  per  cent,  added  lactic  acid; 

3,  blood  containing  0'08  per  cent,  added  lactic  acid. 

the  oxyhsemoglobin  will  be  dissociated  with  greater  ease,  so  that  oxygen 
will  be  set  free  where  it  is  most  wanted. 

We  are  now  in  a  position  to  understand  how  the  oxygen  is  taken  up 
by  the  blood  as  it  circulates  round  the  pulmonary  alveoli.  Arterial  blood, 
such  as  that  which  fills  the  pulmonary  veins  and  the  systemic  arteries,  is 
very  nearly  (i.  e.  about  90  per  cent.)  saturated  with  oxygen,  and  will  take 
up  only  about  2  volumes  per  cent,  more  on  shaking  it  with  air  at  the  body 
temperature.  Venous  blood  requires  8  to  10  volumes  per  cent,  of  oxygen  to 
saturate  it ;  but  we  have  already  mentioned  that,  at  a  tension  of  30  mm. 
oxygen,  the  blood  becomes  nearly  saturated.  The  tension  of  oxygen  in 
the  alveoli  is  considerably  above  this.  In  the  trachea  the  tension 'of  oxygen 
is  about  \  of  an  atmosphere  (since  the  air  here  contains  16  volumes  per 
cent.),  and  the  tension  in  the  alveoli  will  be  a  little  lower  than  this.  If 
we  take  the  oxygen  tension  in  the  alveoli  at  y  of  an  atmosphere,1  it  will 
still  be  something  over  100  mm.  Hence  the  venous  blood  brought  to  the 
alveoli  by  the  pulmonary  artery  will,  on  there  coming  into  intimate  contact 
with  the  atmosphere,  take  up  oxygen  from  it  to  saturation  or  to  a  point 
not  far  removed  from  it. 

1  The  oxygen  tension  in  the  alveoli  has  been  reckoned  at  about  12'6  per  cent,  to 
13'5  per  cent,  of  an  atmosphere. 


1112  PHYSIOLOGY 

But  in  ordinary  quiet  respiration  many  parts  of  the  lungs  remain  practieally  motion- 
less, so  that  in  some  of  the  alveoli  there  is  little  or  no  renewal  of  the  air.  "Win  1 1 
alveoli  are  cut  out  from  the  respiratory  movements,  there  appears  to  be  a  corresponding 
diminution  in  the  blood  flow  through  the  capillaries  surrounding  them.  A  certain  amount 
of  blood  will  therefore  escape  oxidation  in  traversing  the  lungs,  and  this  will  be 
mingled  with  the  large  mass  of  blood  which  has  undergone  complete  oxidation  in  passing 
round  the  ventilated  alveoli.  Hence  in  the  arterial  blood  of  an  animal  at  rest,  haemo- 
globin is  only  about  90  per  cent,  saturated,  corresponding  to  a  tension  of  about  70 
mm.  Hg.,  which  may  be  looked  upon  as  the  normal  tension  of  oxygen  in  arterial  blood. 
During  muscular  exercise  more  and  more  of  the  alveoli  are  involved  in  the  increased 
respiratory  movements,  so  that  the  percentage  saturation  of  the  haemoglobin  and  the 
tension  of  oxygen  in  the  blood  may  be  actually  increased  during  the  hyperpnoea  which 
accompanies  this  condition. 

The.  blood,  thus  laden  with  oxygen,  travels  to  the  left  side  of  the  heart, 
and  from  there  is  sent  through  the  arteries  to  all  parts  of  the  body.  It 
must  be  remembered  that  neither  in  the  lungs  nor  in  the  tissues'  does  the 
haemoglobin  come  in  actual  contact  with  the  source  of  the  oxygen,  nor 
with  the  cells  which  it  is  to  supply.  In  both  cases  the  interchange  is  effected 
through  the  intermediation  of  the  plasma  and,  in  the  tissues,  of  the  lymph 
as  well.  Since  the  tissue  elements  are  constantly  using  up  oxygen,  they 
absorb  any  oxygen  that  is  present  in  the  surrounding  lymph.  There  is  in 
consequence  a  descending  scale  of  oxygen  tensions  from  red  blood  corpuscle 
through  plasma,  vessel  wall,  lymph,  and  tissue  element.  The  cell  draws 
from  the  lymph,  and  the  lymph  from  the  plasma,  so  that  the  oxygen  tension 
in  the  plasma  sinks.  This  has  the  same  effect  as  if  we  put  the  red  corpuscles 
in  a  mercurial  pump  and  lowered  the  pressure  of  gas.  The  immediate  result 
is  an  evolution  of  oxygen,  which  is  taken  up  by  the  plasma,  to  be  in  turn 
passed  on  to  the  lymph  and  the  tissue  cell. 

The  passage  of  oxygen  out  of  the  capillaries  into  the  tissue  cells  must 
thus  be  proportional  to  the  difference  of  tension  between  the  oxygen  in  the 
capillaries  and  that  in  the  cells.  If  Pb  is  the  oxygen  pressure  in  the  capillary 
blood  and  Pt  that  in  the  tissues,  the  rate  of  flow  of  oxygen  from  capillaries 
to  tissues  must  be  proportional  to  Pb  —  Pt.  If  the  blood  is  to  lose  oxygen 
during  the  whole  of  this  passage  through  the  tissues,  we  may  take  for  Pb 
the  tension  of  the  oxygen  in  the  venous  blood  as  it  leaves  the  tissues.  This 
is  generally  about  30  mm.  Hg.  Pt,  the  tension  of  oxygen  in  the  tissues, 
may  be  determined  in  various  ways.  Verzar's  method  is  based  on  the 
following  argument.  If  the  oxygen  pressure  in  the  tissues  is  nothing,  Pb  —  Pt 
will  equal. 30  —  0  =  30.  In  this  case  any  diminution  in  the  tension  of  the 
oxygen  in  the  blood  will  diminish  the  steepness  of  fall  of  pressure  between 
capillaries  and  tissues,  and  there  must  be  a  corresponding  diminution  in  the 
consumption  of  oxygen  by  the  tissues,  as  determined  by  a  comparison  of 
the  oxygen  contents  in  the  blood  flowing  to  and  away  from  the  tissue 
respectively.  If  however  Pt  is  positive,  e.  g.  20  mm.  Hg.,  Pb  —  Pt  equals 
30  —  20  =  10.  Here  a  drop  in  the  oxygen  tension  of  the  blood  will  give 
rise  to  a  corresponding  drop  in  the  tension  within  the  tissues  :  for  instance, 
if  the  tension  in  the  blood  is  diminished  to  20  mm.  Hg.,  that  in  the  tissues 
will  drop  to  10  mm.  Hg.,  and  the  difference  on  the  two  sides  of  the  capillary 


THE  CHEMISTRY  OF  RESRIRATION 


1113 


wall  will  remain  the  same,  so  that  the  consumption  of  oxygen  by  the  tissues 
will  be  unaltered  by  changes  of  the  oxygen  tension  in  the  blood.  Tested 
by  this  method  Verzar  found  that  the  submaxillary  gland  falls  within  the 
second  case,  and  that  its  oxygen  tension  must  be  but  little  removed  from 
that  of  the  blood  itself.  Altering  the  oxygen  tension  of  the  blood  by  making 
an  animal  breathe  a  mixture  poor  in  oxygen  does  not  affect  in  any  way 
the  oxygen  consumption  in  the  gland.  On  the  other  hand,  in  resting  muscle 
Verzar  found  that  the  oxygen  tension  is  probably  zero,  so  that  its  consump- 
tion could  be  widely  affected  by  diminishing  the  oxygen  tension  in  the  air 
supply  to  the  animal.  Krogh  has  attacked  the  question  in  a  different 
maimer.  In  a  series  of  experiments  he  first  determined  the  rate  of  diffusion 
of  oxygen  through  different  thicknesses  of  various  tissues  (connective  tissue, 
muscle,  etc.)  under  varying  pressures.  Then,  partly  on  the  living  muscle, 
partly  on  injected  specimens,  he  estimated  the  relation  of  the  number  and 
size  of  the  capillaries  to  the  intercapillary  muscular  tissues.  He  found  the 
pressure  differences  necessary  to  supply  the  muscle  fibres  with  oxygen 
extremely  email.  Some  of  his  results  on  the  guinea-pig  are  shown  in  the 
accompanyingJI'able . 


Guinea-pig  muscle 

C. CO- 
per  minute 
per  100  c.c 

tissue 

Capillaries 
per  mm.3 

r>i,      s>         Total  surface 

Capacity  of 

capillaries 

in  100  c.c. 

muscle 

Rest  . 

Massage 
Work 

Maximum  eircula-) 
tion          .          .   1 

0-5 
0-5 
0-5 
0-5 
5 

10 

31 

85 

270 

1400 

2500 

3000 

45 
12 

3 
•04 

1-4 

1-2 

3  cm.2 

8    „ 

32    „ 

200    „ 

390    „ 

750    „ 

002  c.c. 
0-06    .. 
0-3      .. 

2-8      „ 
5-5      „ 

15- 

The  first  thing  that  strikes  us  in  this  Table  is  the  enormous  difference 
between  the  capillary  circulation  of  resting  and  that  of  active  muscle.  In 
the  resting  muscle  the  majority  of  the  capillaries  are  empty  and  collapsed, 
so  that  large  areas  of  muscle  intervene  between  the  few  capillaries  in  which 
the  circulation  of  blood  is  proceeding.  Under  these  conditions  the  pressure 
difference  necessary  to  supply  the  total  oxygen  consumed  by  the  muscle, 
e.  g.  45  mm.  Hg.,  may  fall  below  the  venous  oxygen  tension,  so  that  in  parts 
of  the  muscle  the  oxygen  tension  may  be  zero,  as  maintained  by  Verzar. 
After  massage  a  number  of  capillaries  open,  and  the  number  is  still  further 
increased  by  work,  so  that  there  may  be  a  hundredfold  increase  in  the 
number  of  capillaries  in  every  square  millimetre  of  a  cross-section  of  the 
muscle.  Under  these  conditions  the  passage  of  oxygen  from  the  capillaries 
is  so  facilitated  that  the  oxygen  pressure  in  the  muscle  tissues  becomes 
practically  equal  to  that  of  the  blood.  It  would  appear  that,  so  far  as  the 
supply  of  oxygen  to  the  muscle  is  concerned,  the  increase  in  the  capillary 
area  during  muscular  exercise  is  far  ahead  of  the  actual  needs  of  the  muscle. 


1114 


PHYSIOLOGY 


Krogh  suggests  that  this  enormous  increase  in  the  number  of  patent  capil- 
laries may  be  brought  about  to  meet  requirements  of  the  muscle  other  than 
those  for  oxygen.  These  observations  afford  further  support  for  the  view 
already  put  forward  that  the  capillaries  do  not  play  a  merely  passive  role 
in  the  circulation,  but  by  active  dilatation  or  constriction  are  largely  respon- 
sible for  determining  the  actual  blood  supply  to .  each  tissue  in  accord  with 
its  metabolic  requirements. 

Under  normal  circumstances  a  blood  corpuscle  never  stays  long  enough 
in  the  proximity  of  the  tissues  to  lose  its  whole  store  of  oxygen.  If  however 
the  further  supply  of  oxygen  to  the  blood  be  prevented,  as  in  asphyxia, 
the  last  traces  of  oxygen  disappear  from  the  blood.  The  enormous  avidity 
of  the  tissues  for  oxygen  under  these  circumstances  is  shown  by  the  following 
experiment  (Ehrlich).    If  a  saturated  solution  of  methylene  blue  be  injected 


Fig.  511.  Curves  showing  the  rate  at  which  arterial  blood  is  reduced  on  bubbling 
through  a  gas  free  from  oxygen,  and  the  effect  on  the  rate  of  the  presence  of 
C02  and  of  lactic  acid.  Ordinates  =  percentage  saturation  of  oxyhaemoglobin. 
Abscissae  =  time  in  minutes.     (Mathison.) 

into  the  circulation  of  a  living  animal  and  the  animal  be  killed  ten  minutes 
later,  it  is  found  on  first  opening  the  body  that  most  of  the  organs  present 
their  natural  colour,  although  the  blood  is  a  dark  blue  colour.  On  exposure 
to  the  atmosphere  all  the  organs  acquire  a  vivid  blue  colour.  These  pheno- 
mena are  due  to  the  production  in  the  tissues  of  reducing  bodies,  whose 
avidity  for  oxygen  is  so  great  that  they  are  able  to  decompose  the  methylene- 
blue  molecule,  with  the  formation  of  a  colourless  reduction  product,  which 
on  exposure  to  the  air  undergoes  oxidation  again  and  re-forms  methylene 
blue.  If  the  tissues  are  able  to  effect  the  reduction  of  a  comparatively 
stable  body  like  methylene  blue,  it  is  easy  to  understand  their  power  of 


THE  CHEMISTRY  OF  RESPIRATION  1115 

reducing  oxyhemoglobin,  which  is  so  unstable  that  it  is  decomposed  by 
simple  physical  means  such  as  exposure  to  a  vacuum. 

It  was  long  debated  whether  the  chief  processes  of  oxidation  take  place  in  the 
blood  or  in  the  tissues.  Our  experiences  with  muscle  would  alone  serve  to  convince 
us  that,  in  some  tissues  at  any  rate,  processes  of  oxidation  take  place,  and  the  methylene- 
blue  experiment  shows  that  these  processes  of  oxidation  are  intense  in  all  the  chief  organs 
of  the  body.  It  has  been  found  moreover  that  it  is  possible  to  keep  a  frog  alive  after 
substituting  normal  saline  solution  for  its  blood,  if  it  be  placed  in  absolutely  pure 
oxygen,  and  that  in  this  case  indeed  the  metabolism  of  the  animal  goes'  on  as  actively 
as  before.  As  the  frog  has  no  blood,  it  is  evident  that  its  metabolic  processes,  consisting 
of  the  taking  up  of  oxygen  and  the  giving  out  of  carbon  dioxide,  must  have  their  seat 
in  the  tissues. 

As  a  result  of  the  oxidative  changes  in  the  tissues,  carbon  dioxide  is 
produced,  and  the  tension  of  this  gas  in  the  tissues  therefore  rises.  As 
Barcroft  has  pointed  out,  in  cold-blooded  animals  the  dissociation  of  oxy- 
hemoglobin with  the  setting  free  of  oxygen  must  be  largely  conditioned 
by  the  rise  of  carbon  dioxide  tension  in  the  tissues,  since  at  the  normal 
temperature  of  these  animals  the  evolution  of  oxygen  from  haemoglobin 
is  extremely  slow.  The  alteration  in  reaction  of  the  blood,  caused  by  a  rise 
in  C02  tension  or  by  the  presence  of  small  amounts  of  lactic  acid,  markedly 
quickens  the  rate  at  which  oxyhemoglobin  gives  up  its  oxygen,  as  is  shown 
in  Fig.  511.  The  carbon  dioxide  tension  in  the  tissues  may  be  approximately 
measured  by  taking  the  tension  of  this  gas  in  fluids  such  as  the  bile  or  urine. 
Here  it  may  amount  to  8  or  10  per  cent,  of  an  atmosphere,  and  since  the 
carbon  dioxide  in  venous  blood  is  rarely  above  G  per  cent,  of  an  atmosphere, 
there  is  a  descending  scale  of  tensions  from  tissue  to  blood,  just  as  there  is 
an  ascending  scale  in  the  case  of  oxygen.  This  gas  therefore  passes  from 
the  tissues  through  the  lymph  into  the  blood  by  a  simple  process  of  diffusion. 

The  carbon  dioxide  carried  by  the  blood  is,  like  the  oxygen,  chiefly  in  a 
state  of  chemical  combination.  From  dogs'  venous  blood  we  may  obtain 
by  means  of  the  pump  about  50  c.c.  of  carbon  dioxide  per  100  c.c.  blood. 
Water  at  the  temperature  of  the  body,  if  shaken  up  with  an  atmosphere  of 
carbon  dioxide  at  a  pressure  of  760  mm.  Hg.,  would  take  up  about  50  per 
cent,  of  the  gas,  and  the  plasma  as  a  mere  solvent  would  take  up  slightly 
less.  The  tension  of  carbon  dioxide  in  the  blood  is  however  much  less  than 
1  atmosphere.  Shaken  up  with  pure  carbon  dioxide  at  a  pressure  of  1 
atmosphere,  the  blood  would  take  up  as  much  as  150  per  cent.  If  we 
determine  the  tension  of  the  carbon  dioxide  in  the  blood  by  one  of  the 
methods  to  be  described  later,  we  find  that  in  venous  blood  this  gas  is  at  a 
pressure  of  only  about  5  to  6  per  cent,  of  an  atmosphere  (about  40  nun. 
Hg.).  Taking  the  pressure  of  the  carbon  dioxide  as  .?,-,-  of  an  atmosphere, 
and  knowing  that  at  a  pressure  of  1  atmosphere  the  blood  might  dissolve 
50  volumes  per  cent.,  it  is  evident  that  at  /„-  of  an  atmosphere  the  blood 
would  dissolve  only  ],','  volumes  per  cent.,  i.e.  about  2.V  volumes.  All  the 
rest  of  the  carbon  dioxide  in  the  blood  must  therefore  be  in  combination 
(cp.  Fig.  512). 


1UG 


PHYSIOLOGY 


The  carbon  dioxide  is  contained  chiefly  in  theplasma,  though  a  certain 
amount  is  also  in  combination  in  the  corpuscles.  Part  of  the  carbon  dioxide 
must  be  in  combination  with  some  constituent  common  to  both  plasma 
and  corpuscles.  When  blood  plasma  is  calcined,  the  ash  is  found  to  be 
distinctly  alkaline  and  to  contain  an  amount  of  sodium  greater  than  is 

necessary  to  combine  with 
the  other  acid  radicals,  e.  g. 
CI,  S04,  and  P04,  and  this 
excess  becomes  greater  if  we 
consider  that  a  large  part  of 
the  P04  and  S04  is  derived 
from  the  oxidation  of  the 
sulphur  and  phosphorus  pre- 
sent in  organic  combination 
in  the  plasma.  We  may 
therefore  conclude  that  acon- 
siderable  part  of  the  carbon 
dioxide  exists  in  the  plasma 
as  sodium  bicarbonate. 

The  question  arises 
whether  the  whole  of  the 
combined  carbonic  acid  of 
the  blood  can  be  regarded 
as  existing  in  the  form  of 
sodium  bicarbonate.  Ac- 
cording to  the  analyses  of 
Carl  Schmidt  given  on  page 
909,  the  blood  contains 
4-31  x  Kr2N  sodium.  On 
saturating  blood  with  car- 
bonic acid  and  making 
allowance    for  the    amount 


/ 

s 

+'    *' 

^t     ^ 

/I  y 

/  '  /      ^i' 

/-  ^^     -^ 

/     ~7f           .■' 

/      y' 

~7_7~     / 

Z.      ' 

~1_    ,  ' 

'    ,' 

30         40  50  60  70  80  9< 

Fig.  512.     Curve  of  C02  tension  in  blood. 

(Christiansen,  Douglas  and  Haldane.) 

This  curve  shows  the  influence  of  the   saturation  of 

the  haemoglobin  with  oxygen  on  the  amount  of  C02 

taken  up  by  the  blood  at  various  pressures. 
Upper  curve  =  absorption  of  C02  by  human  blood  in 

presence  of  hydrogen  and  C02. 
Middle  curve  =  absorption  of  C02  by  human  blood  in 

presence  of  air  and  C02. 
Lower  curve  =  absorption  of  C02  in  blood  of  ox  and 

dog  in  presence  of  air. 
The  thick  line  A-B  represents  the  absorption  of  C02  by     0£  this    <rag   jrj   simple  solu- 

human  blood  within  the  body  (supposing  the  blood      .         .    .  °  " 

is  completely  deoxygenated  in  the  tissues).  tlOU,  it  IS  found  that  100  CC 

It  is  evident  that  an  increase  of  15  0.0  .per  cent,  of  C02     of  bjood  ^rj  take  u     about 

ui  the  blood,  as  it  passes  through  the  tissues,  would  ... 

raise    the   tension    of   this  gas   in   the   blood   only     100  CC.  of  carbonic  acid  ill 

22  mm    Hg.  (from  40  to  62).     Under  normal  con-     cnemical  combination.      As- 

ditions   the  rise  of  C02  pressure  in   the  blood  on 

passing  through  the  tissues   is  not  more  than  5-7     suming  this  to  exist  entirely 

in  combination  with  sodium, 
it  would  correspond  to  a  concentration  of  about  4-5  X  10~2N  sodium. 
This  would  be  equivalent  to  0-1035  per  cent,  sodium,  or  to  0*378 
per  cent,  sodium  bicarbonate  in  the  whole  blood.  A  difficulty  in 
assuming  that  all  the  carbonic  acid  is  in  the  form  of  sodium  bicarbonate  is 
presented  by  the  fact  that  the  behaviour  of  blood,  when  exposed  to  varying 
pressures  of  carbon  dioxide,  differs  markedly  from  that  of  a  solution  of 
sodium  bicarbonate.     In  Fig.  513  this  difference  is  represented  graphically. 


THE  CHEMISTRY   OF  RESPIRATION 


1117 


The  upper  curve  gives  the  dissociation  of  a  sodium  bicarbonate  solution, 
and  the  lower  that  of  blood  at  varying  pressures  of  C02,  the  bicarbonate 
being  of  the  strength  which  we  have  assumed  to  exist  in  blood,  viz. 
4-83  X  10~ 2N.  A  solution  of  pure  bicarbonate  has  a  very  small  tendency 
to  dissociate  and  is  completely  stable  at  a  pressure  of  4  —  6  mm.  Hg.  C02. 
If  the  pressure  is  reduced  below  this  the  sodium  bicarbonate  slowly  dis- 
sociates, but  the  dissociation  never  passes  beyond  the  formation  of  sodium 
carbonate,  so  that  in  a  complete  vacuum  sodium  bicarbonate  will  give  off 
only  half  the  total  carbonic  acid  that  it  contains. 


9 

5     BO 

5! 

60 

0 
0 


O     20 


BICARB 

ONATE. 

p 

•&z°° 



p.co2 =► 

FlG.  513.  Dissociation  curve  of  a  4'83  X  10  2N  solution  of  sodium 
bicarbonate  (upper  curve)  compared  with  that  of  human  blood,  at 
,'!7  V.,  at  varying  tensions  of  CO„.     (From  PabsONS.  ) 


Blood  on  the  contrary  at  a  C03  pressure  of  50  mm.  Hg.  is  only  about 
half  saturated  with  C03,  and  to  a  vacuum  gives  off  the  whole  of  its  content 
in  carbonic  acid,  so  that  no  further  evolution  is  attained  on  the  addition 
of  acid.  Are  there  any  conditions  in  the  plasma  or  in  the  whole  blood 
which  may,  so  to  speak,  loosen  this  attachment  of  carbonic  acid  to  sodium 
in  the  bicarbonate,  so  as  to  enable  this  gas  to  be  given  off  more  rapidly  on 
exposure  to  airninishecl  pressure? 

We  may  artificially  make  a  fluid  which  behaves  to  carbon  dioxide  in 
the  same  way  as  blood,  by  mixing  together  sodium  carbonate  and  sodium 
hydrogen  phosphate  Na2HP04.  From  such  a  mixture  the  whole  of  the 
carbon  dioxide  may  be  given  off  when  exposed  to  a  vacuum.  On  the  other 
band,  a.  large  amount  of  carbon  dioxide  will  be  taken  up  with  a  very  small 
difference  in  tension  of  the  gases.  The  behaviour  of  the  mixture  is  due  to 
an  interaction  which  occurs  between  the  acid  radicals  P04  and  C03.     When 


L118  PHYSIOLOGY 

l  lie  mixture  is  exposed  to  a  vacuum,  any  sodium  bicarbonate  present  will 
undergo  dissociation,  carbon  dioxide  being  given  off  and  the  carbonate 
Na2C03  formed.  This  then  reacts  with  the  sodium  phosphate  in  the 
following  way  : 

2NaH2P04  +  Na2C03  =  2Na2HP04  +  C02  +  H20. 

In  this  way  the  whole  of  the  sodium  enters  into  combination  with  the  P04 
and  the  carbon  dioxide  previously  combined  is  given  off.  On  exposing 
the  mixture  to  an  atmosphere  containing  carbon  dioxide,  the  reverse  change 
takes  place,  and  we  get  once  again  sodium  hydrogen  phosphate  and  sodium 
carbonate,  and  finally  sodium  bicarbonate.  It  was  formerly  thought  that 
in  the  blood  plasma  phosphates  were  an  important  factor  in  the  evolution 
of  the  carbon  dioxide.  Blood  plasma  however  contains  the  merest  trace 
of  phosphates,  and  the  role  of  a  weak  acid  competing  with  the  carbon  dioxide 
for  the  sodium  seems  to  be  played  chiefly  by  the  proteins  (including 
haemoglobin)  of  the  corpuscles  and  plasma.  It  may  be  assumed  that  in  a 
complete  vacuum  the  whole  of  the  soda  is  in  combination  with  the  protein 
and  haemoglobin.  On  exposure  of  the  blood  to  increasing  pressure  of  C0„, 
the  sodium  leaves  the  protein  to  combine  with  this  gas  with  the  production 
of  sodium  bicarbonate.  Under  ordinary  circumstances,  with  a  C02  tension 
in  the  blood  of  40  mm.  Hg.,  rather  more  than  half  the  sodium  would  thus 
be  in  combination  with  protein,  and  only  when  the  C02  pressure  exceeds 
100  mm.  Hg.  would  the  whole  of  the  sodium  be  taken  up  by  the  carbonic 
acid. 

The  exact  mode  in  which  carbonic  acid  is  carried  into  the  blood  cannot  be  regarded 
as  finally  settled.  If  the  above  account  is  correct,  it  should  be  possible  by  the 
addition  of  blood  protein  to  sodium  bicarbonate  to  induce  this  latter  to  give  up  the 
whole  of  its  carbonic  acid  to  a  vacuum.  The  protein  would  however  have  to  be  pre- 
pared free  from  sodium,  and  this  ought  to  be  possible  by  dialysing  a  serum  or  hfemo- 
globin  solution  against  normal  saline  in  the  presence  of  excess  of  C02,  i.  e.  maintaining 
a  tension  of  this  gas  in  the  dialysing  fluid  of  something  over  100  mm.  Hg.,  since  only 
under  these  conditions  would  it  be  possible  to  free  sodium  from  its  attachment  to  the 
protein.  It  was  pointed  out  by  Bohr  that  haemoglobin  formed  a  combination  with 
carbonic  acid  and  that  the  dissociation  curve  of  this  compound  resembled  closely  that 
of  the  carbonic  acid  in  the  whole  blood.  According  to  Buckmaster,  carbonic  acid 
exists  in  the  blood  in  two  modes  of  combination,  viz.  as  sodium  bicarbonate  and  as 
carbon  dioxide  haemoglobin.  He  considers  that  the  function  of  the  sodium  bicar- 
bonate is  to  maintain  the  neutrality  of  the  blood  by  acting  as  a  '  buffer '  substance, 
while  the  haemoglobin  compound  is  responsible  for  all  the  transference  of  carbonic 
acid  which  takes  place  in  respiration.  If  however  the  crystallised  haemoglobin 
employed  contains  sodium  in  combination,  it  might  act  as  a  sodium  protein  system  in 
the  same  manner  as  we  have  assumed  for  the  whole  blood.  Further  evidence  is  required 
on  this  cpaestion. 

The  red  corpuscles  may  act  in  another  way  in  favouring  the  giving  up 
of  the  carbon  dioxide  of  the  plasma  to  a  vacuum.  There  is  evidence  that 
an  interchange  of  acid>  radicals  takes  place  between  the  corpuscles  and  the 
plasma  on  exposure  of  blood  to  varying  tensions  of  C02.  According  to 
Hamburger,  when  carbon  dioxide  is  passed  into  defibrinated   blood,  the 


THE  CHEMISTRY   OF  RESPIRATION 


111!) 


alkaline  reserve  of  the  plasma  increases  while  the  chlorides  diminish,  and 
the  reverse  change  must  take  place  when  the  carbonic  acid  tension  in  the 
blood  is  diminished  as  on  exposure  of  the  blood  to  a  vacuum. 


EXCHANGE   OF   GASES   IN   THE   LUNGS 

A  fluid  gives  oft"  gas  to  or  takes  up  gas  from  any  other  medium  with 
which  it  is  in  contact,  according  to  the  relative  pressures'  of  the  gas.  The 
question  arises  whether  the  physical  conditions  in  the  lungs  are  such  as  to 
account  for  the  absorption  of  oxygen  and  the  evolution  of  carbon  dioxide 
by  the  blood  in  its  passage  through  these  organs.  In  order  to  answer  this 
question  we  must  know  the  partial  pressures  or  tensions  of  oxygen  and  of 
•carbon  dioxide  in  the  alveolar 


air.  in  the  venous  blood  coming 
to  the  lungs,  and  in  the  arterial 
blood  leaving  the  lungs.  In  the 
alveoli  the  pressures  are  given 
by  the  analysis  of  alveolar  air. 
The  determination  of  the  gaseous 
tensions  in  the  blood  presents 
however  considerable  difficulty. 
It  is  necessary  to  bring  the  blood 
in  contact  with  gaseous  mixtures 
containing  various  proportions 
of  the  gas  whose  tension  in  the 
blood  it  is  desired  to  measure. 
By  making  various  experiments 
a  gaseous  mixture  will  be  found 
with  which  the  blood  is  in 
equilibrium.  If  we  know  before- 
hand the  amount  of  gas  in  this 

mixture,  we  know  its  tension  and  therefore  the  tension  of  the  gas  in  the 
liquid. 

Pfliiger's  aerotonometer  (Fig.  514)  consists  of  two  glass  tubes,  r  and  b,  contained  in 
a  vessel  filled  with  water  at  the  temperature  of  the  body.  The  upper  ends  of  the  tubes 
are  connected  by  the  tube  a  with  the  artery  or  vein  in  which  it  is  desired  to  estimate 
the  tension  of  the  blood  gases.  If,  for  instance,  we  wish  to  determine  the  tension  of 
C02  in  venous  blood,  where  we  expect  the  tension  to  amount  to  about  4  per  cent,  of  an 
atmosphere,  one  tube  R  is  filled  with  a  gaseous  mixture  containing  3  per  cent.  C02,  and 
the  other  tube  K  with  a  mixture  containing  5  per  cent.  C02.  a  ia  now  connected  with 
the  distal  end  of  the  jugular  vein  or  with  the  central  end  of  the  carotid  artery,  and 
blood  is  allowed  to  flow  in  a  thin  stream  down  the  walls  of  the  tubes  R  and  R,  thus 
presenting  a  large  surface  to  the  contained  gases.  The  blood  collects  in  the  lower 
narrower  portions  of  the  tubes,  and  runs  out  into  the  vessels  6,  6,  whence  after  defibrina- 
tion it  is  returned  at  intervals  into  the  veins  of  the  animal. 

In  all  such  instruments  the  main  difficulty  is  in  obtaining  a  sufficient 
surface  of  the  blood  exposed  to  the  gaseous  mixture.     The  interchange  of 


Fig.  514.     Pfliiger's  aerotonometer. 


1120  PHYSIOLOGY 

gases  is  thus  very  slow,  and  it  is  difficult  to  be  certain  at  any  time  that 
the  blood  and  the  gas  with  which  it  is  in  contact  are  really  in  equilibrium. 
Krogh  therefore  adopted  an  ingenious  device  of  limiting  the  volume  of  air 
to  a  small  bubble,  the  superficial  area  of  which  is  large  in  proportion  to 
its  bulk.  This  bubble,  after  it  has  been  in  a  stream  of  blood  for  some  minutes, 
is  transferred  to  a  special  capillary  tube  in  which  its  analysis  can  be  carried 
out  with  a  fair  degree  of  accuracy. 

The  performance  of  a  tonometer  may  be  expressed  by  the  ratio  of  the  surface  of 

blood  exposed  to  the  volume  of  the  air  used.    The  '  specific  surface  '  of  an  aerotonometer 

,  ,      area  in  so.  cm.         '  .„         '  ,  _„..      ,    .  .        , 

is  represented  by  .  .     The  specific  .surface  of  Pfluger  s  instrument  is  only 

volume  m  c.c. 

3*3  and  of  Bohr's  only  5-2.  In  Krogh's  microtonometer  the  absolute  volume  of  air 
employed  is  reduced  to  a  bubble  of  about  2  mm.  in  diameter,  having  a  volume  of  -004  c.c. 
and  a  surface  of  0*125  sq.  cm.,  so  that  its  specific  surface  is  30.  In  such  a  bubble  the 
equalisation  of  the  tensions  takes  place  with  extreme  rapidity  and  only  a  minute 
quantity  of  fluid  is  necessary.  The  microtonometer  consists  of  the  tonometer  proper 
and  the  apparatus  for  tho  micro-analysis  of  the  gas  bubble.  In  the  latter  the  measure- 
ment of  the  gas  bubble  is  carried  out  in  a  capillary  tube,  the  absorption  of  carbon  dioxide 
and  of  oxygen  being  effected  in  the  usual  way  with  potash  and  with  pyrogallic  acid. 
The  tonometer  is  represented  in  Fig.  515.  It  is  kept  in  a  small  water-bath  at  the  tem- 
perature of  the  blood  to  be  examined.  The  tonometer  is  filled  with  saline  solution  and 
contains  the  gas  bubble  2,  winch  can  be  drawn  up  by  means  of  the  screw  4  into  the 
narrow  graduated  tube  3,  where  its  volume  is  measured.  The  blood  from  the  artery  or 
vein,  in  which  we  wish  to  examine  the  tension  of  the  gases,  passes  by  a  cannula  through 
the  tube  1,  and  enters  the  tonometer  as  a  fine  jet.  It  forces  its  way  up  above  the  gas 
bubble,  which  is  pressed  a  little  down  by  the  current,  and  kept  oscillating  with  great 
rapidity.  From  the  tonometer  the  blood  flows  back  through  the  tube  7  and  is  collected 
in  a  vessel  where  it  can  be  measured  and  afterwards  drawn  off  and  reinjected  into  the 
animal  if  necessary.  Since  the  total  pressure  of  the  gases  in  the  blood  is  nearly  always 
negative,  it  is  necessary  to  keep  the  pressure  in  the  tonometer  also  negative.1  This  is 
accomplished  by  means  of  a  mercury  valve  and  can  be  regulated  to  any  desired  pressure. 
During  the  course  of  a  tonometric  experiment  the  volume  of  the  gas  bubble  is 
measured  from  time  to  time  by  drawing  it  up  into  the  graduated  tube,  and  the  pressure 
is  regulated  until  the  volume  of  the  bubble  remains  constant.  After  five  minutes 
gaseous  equilibrium  will  have  been  established  between  the  gas  bubble  and  the  sur- 
rounding blood,  and  it  is  necessary  then  only  to  draw  it  up  into  the  graduated  tube 
and  analyse  it  in  order  to  determine  the  tension  of  the  gases  in  the  blood.  Clotting 
of  the  blood  is  prevented  by  the  injection  of  hirudin. 

In  these  experiments  the  tension  of  the  air  in  the  alveoli  of  the  animal's 
lungs  or  in  the  bifurcation  of  the  trachea  was  determined  by  taking  samples 
of  the  air.  The  results  of  the  experiments  show  that  the  tension  of  the 
gases  in  arterial  blood  follows  closely  the  tension  of  the  corresponding  gases 
in  the  alveolar  air.  The  tension  of  carbon  dioxide  in  arterial  blood  is  either 
identical  with  or  very  slightly  above  the  tension  of  the  gas  in  the  alveolar 
air.  The  oxygen  tension  of  the  blood  is  always  lower  than  the  alveolar 
oxygen  tension,  and  the  difference  is  generally  1  to  2 — even  3  to  4 — per  cent, 
of  an  atmosphere.  The  results  of  a  series  of  determinations  of  the  tensions 
of  the  gases  in  the  blood  and  alveolar  air  respectively  are  given  in  Figs.  516 

1  Otherwise  the  whole  bubble  would  gradually  go  into  solution  and  disappear. 


THE   CHEMISTRY   OF   RESPIRATION 


1121 


and  517.  In  Fig.  517  a  and  b  (Krogh)  the  composition  of  the  alveolar  air 
artificially  altered  by  increasing  the  percentage  of  carbon  dioxide  and  of 
oxygen  respectively.  It  will  be  seen  in  each  case  that  there  was  a  corresponding 
alteration  of  the  tension  in  the  arterial  blood,  the  tension  of  carbon  dioxide 
being  higher  and  that  of  oxygen  lower  in  the  blood  than  in  the  air  through- 
out the  experiment.  We  have  no  direct  determinations  of  the  tensions  of  the 
gases  in  the  blood  of  man,  though  an  approximate  valuation  of  these  tensions 


Fib.  515.     a,  Krogh's  microtonoineter.     b,  upper  part  of  niicrotononieter  showing 
capillary  tube  into  which  the  bubble  is  returned  for  measurement  and  analysis. 

can  be  obtained  by  knowing  the  degree  to  which  the  arterial  and  venous 
blood  respectively  is  saturated  with  oxygen  or  carbon  dioxide.  An  indirect 
method  may  be  employed  to  measure  Hie  gaseous  tensions  in  the  venous 
blood  coming  to  the  lungs.  It  is  possible,  as  Loewy  has  shown,  to  block  the 
right  bronchus  in  man  by  introducing  a  cathether  through  the  larynx  and 
trachea,  so  that  the  renewal  of  air  in  the  right  half  of  the  lung  is  entirely 
stopped  for  some  time.  A  sample  of  air  in  the  blocked  lung  can  be  taken 
at  any  time  by  means  of  the  catheter.  The  interchange  of  gases  between 
alveolar  air  and  blood  will  go  on  until  the  tension  of  gases  in  the  air  is  the 
same  as  that  coming  to  the  blocked  portion  of  lung.  By  this  means  the 
tension  of  the  oxygen  in  the  venous  blood  was  found  to  be  5-3  per  cent.  =  37 
mm.  Hg.,  and  that  of  the  carbon  dioxide  6  per  cent.  =  46  mm.  Hg. 
71 


1122 


PHYSIOLOGY 


The  tensions  in  the  alveolar  air  of  man  may  be  taken  as  follows : 

Oxygen 107  mm.  Hg. 

Carbon  dioxide     .  .  .  .         .       40     „      „ 

As  the.  venous  blood  enters  the  lungs  there  is  thus  a  difference  of.  pressure 
0f  107  —  37  =  70  mm.  Hg.,  which  will  tend  to  cause  a  flow  of  oxygen  from 


Fig.  516.     Tensions  of  02  and  C02  in  alveoli  compared  with  those  in  arterial 

blood  of  rabbit. 

The  dottod  lines  represent  the  tensions  in  the  alveolar  air,  the  uninterrupted 

lines  the  tensions  of  the  gases  in  the  arterial  blood.     (Kboqh.) 


tto 

ioas 

ftr       x  % 

. 

•  1 

in  inspired 

\\ 

f 

l: 

\  '  ■ :- 
\  *  '■ 

*.-. 

1 

\v. 

■ 

0j 

*»5 

CO*. 

'            -t- 

+ 

Fig.  517.     Tensions  of  gases- in  alveolar  air  and  in  arterial  blood. 

A,  during  artificial  increase  of  oxygen  tension  in  alveoli;  B,  during  artificial 

increase  of  CO,  tension  in  alveoli. 

alveolar  air  to  blood  and  a  difference  of  46  —  40  =  6  mm.  Hg.,  tending 
to  cause  a  flow  of  carbon  dioxide  from  blood  to  alveolar  air.  Is  this  differ- 
ence sufficient  to  account  for  the  amount  of  gas  given  off  or  taken  up  by 
the  blood  in  its  passage  through  the  lungs  ?  In  a  state  of  medium  distension 
the  3000  c.c.  of  air  contained  by  the  lungs  have  been  estimated  to  occupy 
seven  hundred  million  alveoli,  each  of  which  has  a  diameter  of  0-2  mm., 
so  that  the  total  surface  over  which  the  blood  is  exposed  to  the  alveolar 


THE   CHEMISTRY   OF   RESPIRATION  1123 

air  amounts  to  90  square  metres.  This  is  a  minimal  figure,  since  no  account 
in  the  calculation  is  taken  of  the  augmentation  of  surface  caused  by  the 
fact  that  the  capillaries  project  into  the  lumen  of  the  alveolus;  and  by 
Hiifner  the  total  surface  exposed  is  estimated  at  140  square  metres.  The 
former  figure  however  amounts  to  about  1000  square  feet  and  is  equivalent 
to  the  floor-space  of  a  room  50  feet  long  by  20  feet  wide.  It  is  important 
to  realise  that  the  blood  passing  through  the  pulmonary  artery  suddenly 
spreads  out  into  a  layer  which  is  uot  more  than  one  blood  corpuscle  thick, 
and  is  exposed  to  the  air  over  this  huge  area,  whence  it  is  picked  up  again 
and  collected  into  the  pulmonary  veins.  Such  a  means  of  facilitating  rapid 
interchange  of  gases  between  the  blood  and  a  given  volume  of  air  we  cannot 
possibly  imitate  artificially.  The  thickness  of  the  tissue  separating  this 
layer  of  air  from  the  alveolar  air  is  on  the  average  -004  mm.  Loewy  and 
Zuntz  have  directly  determined  the  velocity  of  diffusion  of  carbon  dioxide 
and  nitrous  oxide  through  the  frog's  lung,  and  have  calculated  therefrom 
the  rate  at  which  oxygen  would  diffuse  through  a  similar  layer  of  tissue, 
taking  into  account  the  much  greater  solubility  of  carbon  dioxide  as  com- 
pared with  oxygen.  They  estimate  that,  under  a  constant  difference  of 
pressure  of  35  mm.  Hg.,  6-7  c.c.  of  oxygen  would  pass  in  a  minute  through 
each  square  centimetre  of  the  alveolar  wall.  Through  the  whole  surface 
of  the  lung  this  would  amount  to  an  absorption  of  6083  c.c.  oxygen.  The 
oxygen  actually  absorbed  by  a  man  at  rest  amounts  to  about  300  c.c.  per 
minute,  so  that  the  physical  conditions  allow  an  ample  margin  for  any  increase 
in  the  consumption  of  oxygen ;  in  fact,  a  difference  of  pressure  of  a  couple 
of  millimetres  would  suffice  to  cause  a  passage  of  the  250  c.c.  per  minute 
which  is  required  by  the  resting  man.  In  the  same  way  it  is  'easy  to  account 
for  the  passage  of  carbon  dioxide  in  the  reverse  direction.  This  gas  diffuses 
through  a  wet  membrane  about  twenty-five  times  as  rapidly  as  oxygen, 
so  that  a  difference  of  pressure  between  the  blood  and  the  alveolar  air 
amounting  to  only  -03  mm.  Hg.  would  suffice  to  cause  a  passage  outwards 
of  the  250  c.c.  normally  expired  per  minute. 

It  is  evident  that  the  only  limitation  for  the  absorption  of  oxygen  is 
given  by  the  power  of  the  haemoglobin  to  combine  with  the  oxygen  which 
passes  through  the  alveolar  wall  into  the  blood  plasma. 

U  we  look  at  the  dissociation  curve  of  the  oxyhemoglobin  in  mammalian 
blood  given  on  p.  1110,  we  see  that  the  amoimt  of  oxygen  which  can  be  taken 
up  by  hsemoglomh  in  the  presence  of  the  normal  tension  of  carbon  dioxide, 
i.  e.  40  mm.  Hg.,  begins  to  diminish  very  rapidly  when  the  pressure  of  the 
oxygen  falls  below  50  mm.  Hg.  Thus  at  40  mm.  oxygen  pressure  and  a 
carbon  dioxide  tension  of  40  nun.,  oxyhsemoglobin  is  about  65  per  cent, 
saturated,  and  at  30  mm.  it  is  only  50  per  cent,  saturated.  Under  normal 
circumstances  the  blood  leaves  the  lungs  over  90  per  cent,  saturated  with 
oxygen.  If  the  saturation  falls  to  60  per  cent,  we  should  expect  to  obtain 
evidence  of  failure  of  oxygen  supply  to  the  tissues.  According  to  Loewy 
the  oxygen  tension  in  the  alveoli  can  sink  to  between  30  and  35  mm.  Hg. 
before  any  signs  of  oxygen  lack  make  their  appearance.     These  results  were 


L124  PHYSIOLOGY 

obtained  by  exposing  a  man  in  a  state  of  complete  rest  to  reduced  pressure 
in  an  air-chamber.  Under  these  conditions  the  slightest  muscular  exertion 
would  at  once  tend  to  cause  distress  from  deficient  oxygen  supply.  The 
exact  percentage  of  oxygen  in  the  inspired  air,  which  would  give  an  alveolar 
oxygen  tension  of  30  to  35  mm.,  varies  with  the  depth  of  respiration.  Thus 
with  shallow  respiratory  movements  the  pressure  may  sink  to  35  mm.Hg. 
when  the  inspired  air  contains  as  much  as  12  per  cent,  oxygen.  If  the 
movements  be  deeper,  the  oxygen  content  of  inspired  air  may  be  reduced 
to  9  or  10  per  cent,  before  respiratory  distress  is  observed. 

The  view  that,  in  the  interchange  of  gases  in  the  lungs,  the  membrane  between  the 
blood  and  the  alveolar  air  play's  simply  a  passive  part  was  till  recently  by  no  means 
universally  accepted.  In  Bohr's  experiments  on  the  tension  of  oxygen  and  carbon 
dioxide  in  the  blood  as  determined  with  his  aeroto'nometer,  oxygen  tensions  were  often 
found  considerably  higher  in  the  blood  than  in  the  air  of  the  alveoli,  and  in  the  same 
way  the  carbon  dioxide  tension  of  the  blood  leaving  the  lungs  was  found  to  be  less  than 
the  carbon  dioxide  tension  of  the  alveolar  air.  Krogh's  experiments  show  conclusively 
however  that  these  results  are  not  reliable,  and  that  the  difference  between  the  tensions 
in  the  alveoli  and  in  the  blood  respectively  is  always  such  as  to  allow  of  the  passage  by 
diffusion  of  oxygen  inwards  and  carbon  dioxide  outwards  from  the  blood.  Moreover, 
as  Krogh  points  out,  the  structure  of  the  pulmonary  epithelium  lends  no  support  to 
the  view  that  it  acts  as  a  secreting  membrane.  In  mammals  the  cells  are  of  two  kinds, 
viz.  small  granular  nucleated  cells  lying  in  the  interstices  of  the  capillaries,  and  larger 
extremely  thin  structureless  plates,  without  nuclei,  covering  the  capillaries.  In  birds, 
where  the  gaseous  exchange  is  of  all  animals  the  most  rapid  and  efficient,  the  existence 
of  a  lung  epithelium  has  never  been  demonstrated,  and  the  capillaries  appear  to  be 
almost  completely  free  and  to  be  surrounded  with  air  on  both  sides. 

Bohr's  view  as  to  the  secretory  function  of  the  pulmonary  epithelium  was  supported 
as  concerns  the  intake  of  oxygen  by  Haldane.  This  observer  has  devised  a  method  of 
determining  the  oxygen  tension  of  the  blood  in  the  lungs  founded  on  the  use  of  carbon 
monoxide.  It  has  already  been  mentioned  that  carbon  monoxide  has  the  power  of  dis- 
placing oxygen  from  oxyhemoglobin  to  form  a  much  more  stable  compound,  carboxy- 
hernoglobin.  If  blood  be  shaken  up  with  a  mixture  of  oxygen  and  carbon  monoxide, 
the  haemoglobin  distributes  itself  between  the  two  gases.  In  order  however  to  get  an 
equal  distribution,  it  is  necessary  to  take  a  very  small  percentage  of  carbon  monoxide, 
owing  to  its  greater  avidity  for  hemoglobin.  Thus,  if  haemoglobin  solution  be  shaken 
up  with  air  containing  ;07  per  cent,  of  CO,  the  result  is  a  mixture  of  equal  parts  of  oxy 
and  carboxyhsemoglobin.     The  affinity  of  CO  for  haemoglobin  would  thus  appear  to  be 

21 
about  —  =  300  times  the  affinity  of  oxygen  for  hemoglobin. 

Carbon  monoxide  is  not  destroyed  in  the  body,  so  that  if  a  mixture  containing  a 
small  proportion  of  CO  be  breathed,  this  gas  will  be  taken  up  until  a  certain  percentage 
of  haemoglobin  is  converted  into  CO-hernoglobin  and  the  tension  'of  CO  in  the  tissues 
and  fluids  of  the  body  is  equal  to  that  of  the  inspired  air.  The  amount  of  haemoglobin 
which  is  converted  into  carboxyhsemoglobin  will  serve  as  a  measure  of  the  relative 
tensions  of  CO  and  oxygen  in  the  lungs.  If  the  oxygen  tension  of  arterial  blood  were 
the  same  as  that  of  the  alveolar  air,' we  should  expect  that,  with  a  given  percentage  of 
CO  in  the  air  breathed,  the  final  saturation  with  CO  of  the  blood  within  the  body  would 
be  the  same  as  the  saturation  of  blood  when  shaken  outside  the  body  with  air  con- 
taining the  same  percentage  of  CO  as  in  the  air  breathed.  It  was  found  by  Haldane 
however  that  in  all  cases  the  percentage  of  CO  hemoglobin  formed  was  much  less  in  the 
body  than  outside  the  body.  Thus  in  blood  shaken  up  with  air  containing  20'0  per  cent. 
oxygen  and  -045  per  cent.  CO,  the  amount  of  carbon  monoxide  hemoglobin  formed  was 
31  per  cent,  of  the  whole  hemoglobin.  When  the  same  mixture  was  inhaled  for  three 
or  four  hours  by  a  man,  the  percentage  of  CO  hemoglobin  in  his  blood  rose  only  to 


THE   CHEMISTRY   OF   RESPIRATION  1125 

20  per  cent.,  at  which  figure  it  remained  stationary.  This  would  correspond  to  an 
oxygen  tension  of  about  25  per  cent,  of  an  atmosphere,  whereas  we  have  already  seen 
that  the  oxygen  tension  in  the  alveoli  cannot  be  greater  than  15  per  cent.  He  therefore 
concluded  that  the  epithelial  cells  of  the  alveoli  play  an  active  part  in  the  respiratory 
interchange,  taking  up  the  oxygen  on  one  side  at  a  tension  of  15  per  cent,  and  piling  it 
up  on  the  other  until  the  pressure  in  the  blood  is  much  higher  than  that  in  the  alveolar 
air.  Theoretically  there  is  no  reason  to  deny  the  possibility  of  such  powers  to  the 
pulmonary  epithelium.  We  knew  that  the  secreting  cells  of  the  kidney  take  up  urea 
from  the  blood  which  contains  only  about  -02  per  cent,  of  this  substance,  and  excrete 
it  into  the  renal  tubule,  into  a  medium  containing  about  2  per  cent. ;  and  if  the  data 
given  by  Haldane  are  correct  we  must  ascribe  an  analogous  function  to  the  pulmonary 
epithelium.  These  data  however  were  obtained  by  a  colorimetric  method  working 
with  very  minute  quantities  of  blood,  and  lacked  the  support  of  control  experiments. 
As  a  result  of  further  experiments,  Haldane  has  modified  his  position  so  far  as  to  allow 
that  under  normal  conditions  the  absorption  of  oxygen  from  the  alveolar  air  takes  place 
in  accordance  with  the  difference  of  pressure,  i.  e.  by  a  process  of  diffusion.  He  is  still 
of  opinion  that  under  abnormal  conditions,  when  the  oxygen  tension  in  the  alveolar 
air  is  very  low,  there  is  an  active  absorption  and  transference  of  oxygen  to  the  blood 
on  the  part  of  the  pulmonary  epithelium.  Why  animals  should  evolve  a  function 
which  can  be  brought  into  play  only  on  climbing  mountains  seems  difficult  to  under- 
stand, and  it  does  not  seem  probable  that  a  reinvestigation  of  the  tensions  of  oxygen 
in  the  blood  under  such  conditions  by  Krogh's  method  will  lend  any  confirmation  to 
Haldane's  conclusions. 

An  analogy  has  been  drawn  between  the  processes  of  gas  interchange  in  the  lungs 
and  that  in  the  swim  bladder  of  the  fish.  Bohr  has  shown  that  the  gas  obtained  by 
puncturing  the  bladder  often  contains  considerable  excess  of  oxygen.  If  the  bladder 
be  punctured  and  the  fish  then  left  in  the  water,  the  gas  rapidly  reaccumulates,  and  it 
is  found,  on  tapping  a  second  time,  that  the  percentage  of  oxygen  is  largely  increased, 
and  may  amount  to  between  60  and  80  per  cent,  of  the  total  gases.  This  reaccumulation 
of  the  gases  does  not  take  place  if  both  vagi  are  cut,  and  is  therefore  ascribed  to  a  direct 
secretory  activity  on  the  part  of  the  epithelium  lining  the  swim  bladder  under  the 
influence  of  the  vagus  nerves.  Bohr,  as  the  result  of  experiments  by  himself  and  some 
of  his  pupils,  is  inclined  to  endow  the  vagus  nerves  in  the  higher  vertebrates,  including 
mammals,  with  an  analogous  regulatory  influence  on  the  gaseous  exchanges  in  the  lungs. 
As  regards  the  evolution  of  carbon  dioxide,  the  facts  elucidated  by  Haldane  himself 
would  make  one  hesitate  in  ascribing  any  special  secretory  activity  to  the  pulmonary 
epithelium.  We  find,  namely,  that  the  respiratory  centre  reacts  immediately  to  the 
slightest  increase  in  the  tension  of  the  carbon  dioxide  in  the  alveolar  air.  Since  this 
behaviour  of  the  respiratory  centre  is  independent  of  any  nervous  connections  between 
the  lungs  and  the  brain,  it  seems  to  indicate,  as  indeed  Krogh  has  found,  that  the  tension 
of  the  carbon  dioxide  in  the  blood  follows  closely  the  tension  of  the  carbon  dioxide  in 
the  alveolar  air.  Ii  the  carbon  dioxide  were  secreted  by  the  pulmonary  epithelium,  we 
should  expect  the  lungs  to  react  to  increased  carbon  dioxide  in  the  alveoli  by  simply 
increasing  their  work  so  as  to  maintain  the  tension  of  carbon  dioxide  in  the  blood  at  a 
constant  level.  This  at  any  rate  is  the  way  in  which  the  kidney  would  behave  under 
analogous  circumstances.  Moreover  there  is  no  likeness  between  the  thick  typical 
secreting  cells  of  the  '  red  gland,'  which  is  the  gas-secreting  part  of  the  swim  bladder, 
and  the  thin  structureless  plates  which  separate  the  capillaries  of  the  lungs  from  the 
alveolar  air. 


SECTION  III 

THE    REGULATION    OF   THE    RESPIRATORY 
MOVEMENTS 

Each  movement  of  inspiration  involves  the  co-ordinated  activity  of  a  large 
number  of  muscles.  Thus  the .  diaphragm  and  the  intercostal  muscles 
must  come  into  action  at  the  same  time,  and  the  extent  to  which  they 
contract  will  determine  the  depth  of  the  inspiration.  Similarly,  they  must 
cease  to  act  simultaneously  if  the  act  of  expiration  is  to  take  place.  The 
rhythm  and  extent  of  the  alternate  contractions  and  relaxations  of  the 
respiratory  muscles  are  determined,  as  we  have  seen,  by  the  needs  of  the 
organism  as  a  whole.  These  respiratory  movements  are  regulated  so  that 
the  total  ventilation  of  the  alveoli  shall  be  sufficient  to  meet  the  gaseous 
exchanges  of  the  body.  Whether  the  organism  consumes  250  or  1000  c.c.  of 
oxygen  per  minute,  the  respiratory  movements  keep  the  composition  of  the 
gas  in  the  alveoli  at  a  practically  constant  level. 

The  muscles  involved  both  in  inspiration  and  expiration  can  be  thrown 
into  activity  only  by  the  intermediation  of  nerves.  Each  act  of  inspiration 
involves  a  discharge  along  a  number  of  nerves,  e.  g.  the  facial  to  the  muscles 
moving  the  alse  nasi,  the  vagus  to  the  muscles  of  the  larynx,  the  branches 
of  the  cervical  and  brachial  nerves  to  the  muscles  of  the  neck,  the  phrenic 
nerves  to  the  diaphragm,  and  the  dorsal  nerves  to  the  intercostal  muscles. 
The  fibres  making  up  these  nerves  are  derived  from  nerve  cells  of  the  anterior 
horn,  situated  at  various  levels  in  the  medulla  and  spinal  cord.  In  each  act 
of  inspiration  or  expiration  the  activities  of  all  these  groups  of  cells  must  be 
brought  into  relation  among  themselves,  as  well  as  with  the  needs  of  the 
organism  for  oxygen  and  for  the  elimination  of  carbon  dioxide.  It  is 
conceivable  that  the  co-ordination  of  the  activities  of  the  various  motor 
nuclei  might  be  attained  by  the  provision  of  communicating  nerve  paths 
joining  the  centres  among  themselves,  and  by  a  sensibility  of  all  these  centres 
to  the  gaseous  contents  of  the  blood  as  well  as  to  the  influence  of  afferent 
impressions  from  the  periphery.  A  much  more  efficient  co-ordination 
however  would  be  effected  by  the  subjection  of  these  motor  nuclei  to  the 
action  of  some  specialised  portion  of  the  central  nervous  system,  which 
would  act  as  a  receiving  centre  for  afferent  impressions  from  the  lungs  and 
surface  of  the  body,  and  would  be  endowed  with  a  special  sensibility  to 
changes  in  the  composition  of  the  blood  circulating  through  its  vessels. 
Experiment  shows  that  the  latter  method  is  employed  in  the  organism  for 
the  regulation  of  the  respiratory  movements.   If  the  spinal  cord  be  cut  across 

1126 


REGULATION   OF  THE  RESPIRATORY  MOVEMENTS     1127 

below  the  seventh  cervical  nerve  roots,  the  action  of  the  intercostal  and 
abdominal  muscles  in  respiration  ceases  permanently,  although  respiration 
is  still  continued  by  the  rhythmic  activity  of  the  diaphragm  and  the  other 
muscles  supplied  by  nerves  leaving  the  central  nervous  system  above  the 
point  of  section.  Division  of  the  cord  at  the  first  or  second  cervical  nerve 
abolishes  the  action  of  the  diaphragm,  though  the  movements  of  the  muscles 
supplied  by  the  facial,  vagus,  and  spinal  accessory  nerves  continue.  A 
section  of  the  brain  stem  through  the  mid -brain  leaves  the  respiratory 
movements  unaltered,  and  the  same  absence  of  effect  as  concerns  these 
movements  may  often  be  obtained  when  a  section  is  carried  across  the  upper 
part  of  the  medulla  about  the  level  of  the  striw  acoustical.  We  must  con- 
clude from  these  experiments  that  the  motor  nuclei  of  the  cord  are  subject 
to  and  normally  thrown  into  activity  by  impulses  originating  in  the  medulla 
oblongata  and  transmitted  therefrom  down  the  spinal  cord. 

Many  experiments  have  been  made  with  the  idea  of  locating  the  position 
of  the  medullary  respiratory  centre  more  accurately.  The  first  experiments 
on  this  point  were  made  at  the  beginning  of  last  century  by  Legallois,  whose 
observations  were  confirmed  and  extended  by  Flourens.  These  observers 
described  the  respiratory  centre  as  limited  to  a  small  area  at  the  level  of  the 
apex  of  the  calamus  serif  tortus ,  which  they  designated  nceud  vital  on  account 
of  the  fact  that  destruction  of  this  area  was  at  once  fatal  by  paralysis  of 
respiration.  Later  experiments  have  shown  that  the  centre  is  not  quite  so 
circumscribed.  .In  the  first  place,  it  is  bilateral,  each  centre  presiding  more 
especially  over  the  muscles  of  the  same  side  of  the  body,  so  that  longitudinal 
section  in  the  middle  fine  does  not  destroy  the  respiratory  movements. 
Other  observers  have  located  the  centre  in  the  situation  of  the  solitary 
bundle  ('  respiratory  bundle  of  Gierke  '),  which  is  made  up  of  the  descending 
branches  of  the  vagus  nerve  after  they  have  entered  the  medulla,  while, 
according  to  Gad-,  the  respiratory  centre  is  diffused  over  a  considerable 
area  of  the  formatio  reticularis  on  either  side  of  the  medulla.  There  is  no 
doubt  that  this  centre  is  in  close  connection  with  the  central  terminations 
of  the  vagus  nerves. 

From  the  centre  on  each  side  the  efferent  impulses  to  the  motor  nuclei 
of  the  respiratory  muscles  pass  down  in  the  deeper  portions  of  the  lateral 
columns  of  the  cord.  Hemisection  of  the  cervical  cord,  e.g.  on  the  right 
side,  causes  cessation  of  the  contractions  of  the  diaphragm  on  the  same  side. 
There  must  however  be  commissural  fibres  joining  the  motor  nuclei  on  the 
two  sides.  If  the  right  phrenic  nerve  be  divided,  after  hemisection  on  the 
left  side,  the  left  half  of  the  diaphragm  at  once  commences  to  contract 
rhythmically  with  each  respiration  (Porter).  It  is  evident  that  the  cessation 
of  respiration  after  section  of  the  cord  is  not  due  to  a  condition  of  shock  of 
the  lower  spinal  centres,  since  it  is  possible  for  impulses  to  pass  down  the 
cord  and  to  cross  over  to  the  contra-lateral  diaphragm  nucleus  immediately 
after  hemisection  of  the  cord  on  the  side  of  the  nucleus. 

THE  QUESTION  OF  SPINAL  RESPIRATORY  CENTRES.  Several  physiologists 
c.  g.  Brown-S^quard,  Langcndorff,  and  Wertheimer,  have  described  respiratory  centres 


1128  PHYSIOLOGY 

in  the  spinal  cord.  There  is  no  doubt  that,  if  the  cord  be  cut  across  in  the  upper  cervical 
region  and  artificial  respiration  maintained  for  some  time,  cessation  of  the  respiration 
may  be  followed  by  rhythmic  contractions  of  the  respiratory  muscles.  These  are 
especially  marked  in  young  animals  and  if  the  activity  of  the  cord  has  been  heightened 
by  the  injection  of  small  doses  of  strychnine.  Careful  observation  of  the  movements 
shows  however  that  they  cannot  be  spoken  of  as  respiratory,  since  although  rhythmic, 
they  are  not  co-ordinate.  The  diaphragm  may  contract  either  simultaneously  or  in 
alternation  with  the  intercostals,  and  muscles  which  are  essentially  expiratory  at  the 
same  time  as  those  which  we  are  wont  to  regard  as  inspiratory.  These  experiments 
show  merely  that  the  motor  centres  of  the  cord  can  enter  into  rhythmic  activity  under 
the  influence  of  asphyxial  conditions.  The  movements  affect  the  muscles  of  the  limbs 
as  well  as  those  essentially  respiratory  in  function. 

THE   AUTOMATICITY   OF   THE   RESPIRATORY   CENTRE 

We  have  now  to  inquire  what  it  is  that  keeps  the  respiratory  centre  in 
activity.  Is  the  rhythmic  discharge  of  inspiratory  impulses  from  the  centre 
due  to  rhythmic  or  continuous  stimulation  of  afferent  nerves,  or  is  the  centre 
so  constructed  that  under  the  normal  conditions  of  its  environment  the 
metabolic  activity  of  its  constituent  parts  tends,  like  that  of  the  heart  cells, 
to  assume  a  rhythmic  character?  In  other  words,  is  the  activity  of  the 
centre  reflex  or  automatic  ?  It  has  been  found  by  Rosenthal  that  rhythmic 
respiratory  movements  are  maintained  even  after  complete  section  of  the 
brain  stem  at  the  level  of  the  superior  corpora  quadrigemina,  section  of  the 
cord  at  the  level  of  the  seventh  cervical  nerve,  and  division  of  both  vagi  and 
of  the  posterior  roots  of  all  the  cervical  spinal  nerves.  It  is  true  that  if  the 
sections  of  the  brain  stem  be  placed  as  low  as  the  strice  acousticce,  the  re- 
spiratory movements  are  profoundly  modified  and  give  place  to  a  series  of 
inspiratory  spasms.  We  might  argue  from  this  that  the  centre  was  capable 
of  a  very  imperfect  degree  of  automatic  action,  but  needed  the  stimulus  of 
afferent  impulses  from  the  vagi  or  from  the  higher  parts  of  the  brain  to 
render  these  actions  adequate  for  the  respiratory  needs  -of  the  organism. 

In  the  above  experiment  the  centre  cannot  be  regarded  as  free  from  all  afferent 
stimuli,  since  the  mere  closure  of  the  demarcation  current  in  the  cut  ends  of  the  nerves 
would  cause  a  certam  amount  of  excitation,  and  the  animal  does  not  survive  sufficiently 
long  to  allow  this  condition  to  pass  off.  Hering  has  shown  that  in  the  '  spinal  cord 
frog '  (?'.  e.  one  in  which  the  brain  has  been  destroyed)  section  of  all  the  posterior  roots 
absolutely  abolishes  all  mobility,  the  injection  of  strychnine  being  without  effect.  A 
typical  spasm  however  can  be  at  once  produced  by  exposing  and  stimulating  the 
stump  of  one  of  the  cut  posterior  roots.  We  might  suppose  that  the  respiratory  centre 
would  be  similarly  devoid  of  automatism  if  absolutely  free  from  afferent  stimuli.  It 
must  be  mentioned  however  that,  according  to  Sherrington,  it  is  possible  to  excite 
strychnine  or  asphyxial  spasms  in  a  dog  or  cat  with  isolated  spinal  cord,  in  which  all 
the  afferent  roots  below  the  transection  have  been  divided  six  or  seven  hours  previously. 
He  therefore  is  of  opinion  that  in  the  mammal  the  motor  nervous  mechanism  can  be  set 
into  activity  apart  from  the  incidence  of  afferent  impressions.  The  respiratory  centre 
tends  to  respond  to  all  stimuli,  continuous  or  rhythmic,  by  means  of  rhythmic  discharges, 
and  there  can  be  no  doubt  that,  if  we  take  the  medulla  in  connection  with  the  rest  of 
the  hind-  and  mid-brain,  we  are  justified  in  regarding  its  activity  as  automatic. 

The  automatic  activity  of  the  heart  is  intimately  dependent  on  the 
saline  constituents  of  the  blood.    It  may  be  abolished  or  diminished  by 


REGULATION  OF  THE  RESPIRATORY  MOVEMENTS     1129 

modifying  these  constituents,  and  can  be  maintained  for  a  considerable  length, 
of  time  by  perfusing  the  heart,  with  solutions  containing  inorganic  salts  in 
the  concentration  in  which  they  exist  in  the  blood  plasma.  When  we 
speak  of  the  automatic  activity  of  the  respiratory  centre,  we  imply  in  the 
same  way  that  its  activity  is  dependent  on  the  normal  composition  of 
the  blood  circulating  through  its  vessels.  In  this  case  however  it  is  the 
gaseous  contents  of  the  blood  which  are  of  supreme  importance.  If  the 
normal  ventilation  of  the  lungs  be  prevented,  as  by  ligature  of  the  trachea 
or  opening  both  pleural  cavities,  the  blood  becomes  more  and  more  venous. 
As  this  venous  blood  circulates  through  the  medulla,  the  activity  of  the  centre 
is  continually  increased,  until  finally  the  impulses  discharged  from  the 
centre  may  set  into  activity  practically  every  muscle  of  the  body,  producing 
asphyarial  convulsions.  On  the  other  hand,  the  activity  of  the  respiratory 
centre  can  be  diminished  or  even  abolished  if,  by  an  artificial  ventilation  of 
the  alveoli,  we  maintain  an  over-arterialisation  of  the  blood,  so  that  the 
fluid  passing  to  the  brain  contains  more  oxygen  and  less  carbon  dioxide 
than  is  the  case  under  normal  circumstances.  What  are  the  factors  involved 
in  this  chemical  regulation  of  respiration? 


THE   CHEMICAL   REGULATION   OF   THE   RESPIRATORY 
MOVEMENTS 

If,  the  nervous  centres  being  intact,  the  proper  aeration  of  the  respiratory 

eenl  re  be  interfered  .with  in  any  way,  the  respiratory  movements  increase  in 

ill  and  frequency,  and  if  the  disturbing  factor  be  not  removed  the 

animal  dies,  presenting  a  train  of  phenomena  which  are  classified  together 

under  the  term  '  asphyxia.' 

The  phenomena  of  asphyxia  may  be  divided  into  three  stages : 

(1)  In  the  first  stage,  that  of  Ityperpncea,  the  respiratory  movements 
are  increased  in  amplitude  and  in  rhythm.  This  increase  affects  at  first  both 
inspiratory  and  expiratory  muscles.  Gradually  the  force  of  the  expiratory 
movements  becomes  increased  out  of  all  proportion  to  the  inspiratory,  and 
the  first  stage  merges  into  : 

(2)  The  second,  which  consists  of  expiratory  convulsions,  in  which  almost 
every  muscle  of  the  body  may  be  involved.     Just  at  the  end  of  the  first 

consciousness  is  lost,  and  almost  immediately  after  the  loss  of  con- 
sciousness we  may  observe  a  number  of  phenomena  extending  to  almost  all 
the  functions  of  the  body,  some  of  which  have  been  already  studied.  Thus 
the  vaso-motOT  centre  is  excited,  causing  universal  vascular  constriction. 
There  is  often  also  secretion  of  saliva,  inhibition  or  increase  of  intestinal 
movements,  constriction  of  the  pupil,  and  so  on. 

(3)  At  the  end  of  the  second  minute  after  the  stoppage  of  the  aeration  of 
the  blood,  the  expiratory  convulsions  cease  almost  suddenly,  and  give  way  to 
slow  deep  inspirations.  With  each  inspiratory  spasm  the  animal  stretches 
itself  out  and  opens  its  mouth  widely  as  if  gasping  for  breath.  The  whole 
stage  is  one  of  exhaustion  :  the  pupils  dilate  widely,  and  all  reflexes   are 


1130  PHYSIOLOGY 

abolished.    The  pauses  between  the  inspirations  become  longer  and  longer, 
until  at  the  end  of  four  or  five  minutes  the  animal  takes  its  last  breath. 

If  we  increase  the  activity  of  the  centre  and  therefore  its  gaseous  inter- 
changes, by  warming  the  blood  in  the  carotid  arteries,  there  may  be  a 
considerable  quickening  of  respiration  unaccompanied  by  any  deepening,  a 
condition  which  is  spoken  of  as  tachypncea.  On  the  other  hand,  we  may  slow 
the  respiratory  movements  by  placing  a  small  piece  of  ice  on  the  floor  of  the 
fourth  ventricle. 

In  the  production  of  the  phenomena  of  asphyxia  two  factors  must  be  at 
work.  In  the  first  place,  there  is  an  accumulation -of  carbon  dioxide  in  the 
blood  bathing  the  centre,  or  an  increased  tension  of  this  gas  in  the  centres 
themselves,  either  as  a  result  of  deficient  excretion  or  increased  production. 
On  the  other  hand,  the  centre  is  deprived  of  oxygen,  either  by  failure  of 
renewal  of  the  oxygen  supply  or  by  increased  using  up  of  this  gas  in  the 
metabolism  of  the  centre.  The  question  arises,  which  of  these  two  changes 
is  responsible  for  the  different  physiological  events  which  characterise 
asphyxia  ?  At  various  times  these  phenomena  have  been  ascribed  either  to 
the  increased  tension  of  carbon  dioxide  or  to  the  diminished  tension  of 
oxygen  in  the  centre.  The  view,  that  the  normal  stimulus  to  the  respiratory 
centre  in  asphyxia  was  the  lack  of  sufficient  oxygen  and  that  the  normal 
activity  of  this  centre  was  determined  by  the  tension  of  oxygen  in  the  blood 
circulating  through  the  brain,  was  first  put  forward  by  Rosenthal.  When 
sufficient  oxygen  was  present,  the  centre,  according  to  this  observer,  would 
cease  to.  act,  so  that  a  condition  of  apncea  would  be  produced.  According 
to  Traube,  on  the  other  hand,  the  special  respiratory  stimulus  was  the 
excess  of  carbon  dioxide  in  the  blood,  and  this  view  was  supported  strongly 
by  Miescher.  The  tendency  of  recent  work,  especially  by  Haldane  and 
his  pupils,  has  been  to  show  that  there  is  an  element  of  truth  in  both  views 
— that  indeed  the  respiratory  centre  can  be  excited  either  by  excess  of 
carbon  dioxide  or  by  lack  of  oxygen,  but  that  its  sensitivity  to  carbon 
dioxide  is  by  far  the  more  important  factor  in  the  determination  of  the 
increased  respiratory  movements  in  asphyxia,  and  is  the  only  chemical 
factor  which  can  be  regarded  as  playing  any  part  in  the  regulation  of  the 
respiratory  movements  under  normal  conditions.  This  factor  is  well  brought 
out  if  we  investigate  the  effect  on  the  respiratory  movements  of  altering  the 
tensions  of  the  two  gases'  in  the  air  breathed .  If  by  this  means  we  succeed 
in  altering  the  tension  of  the  two  gases  in  the  alveolar  air,  we  may  assume  that 
the  tensions  of  the  gases  in  the  arterial  blood  leaving  the  lungs  are  altered  in 
the  same  ratio.  The  results  of  such  experiments  are  very  striking.  Even 
a  slight  increase  in  the  percentage  of  carbon  dioxide  in  the  air  causes  an 
increase  first  in  the  depth  and  later  on  in  the  rhythm  of  respiration  (Fig.  518). 
This  is  shown  in  the  following  Table  by  Haldane,  which  represents  the  average 
depth  and  frequency  of  the  respirations  when  the  subject  was  breathing 
normal  air  and  air  charged  with  varying  percentages  of  carbon  dioxide. 
A  rise  of  carbon  dioxide  in  the  atmosphere  to  2  per  cent,  increases  the  depth 
of  respirations  by  30  per  cent.,  and  the  total  alveolar  ventilation  by  50  per 


REGULATION  OF  THE   RESPIRATORY  MOVEMENTS     1131 

cent.  A  rise  of  carbon  dioxide  to  3  per  cent,  increases  the  total  ventilation 
of  the  alveoli  by  126  per  cent.  An  amount  of  carbon  dioxide  equivalent 
to  6  per  cent,  increases  the  depth  of  each  respiration  by  272  per  cent.,  and 
the  total  alveolar  ventilation  by  757  per  cent. 


Fig.  518.     Effect  of  COa  on  respiratory  movements  of  rabbit.     (Scott.) 

Upper  line,  tracing  of  diaphragm  slip  iHead's  method).  Lower  tracing,  carotid 
pressure.  During  the  first  period  indicated  on  tho  signal  line  the  animal  breathed 
9-fi  per  cent.  CO,  in  air,  and  during  the  second  period  10  per  cent.  C02  with  33  per 
cent,  oxygen.     Time  tracing  =  2  sees.     Scale  =  mm.  Hg.  blood  pressure. 


Percentage  COo  . 
in  inspired  air 

Average  depth 
of  respirations 

Average 
frequency  of 
respirations 
per  minute 

Ventilation  of  alveoli 
with  inspired  air 
(normal  =  100) 

CO,  percentage 
in  alveolar  air 

004 

673 

14 

100 

5-6 

0-79 

739 

14 

(6-60  litres  per  min.) 
116 

5-5 

202 

864 

15 

153 

5-6 

307 

1216 

15 

226 

5-5 

5- 14 

1771 

19 

498 

6-2 

6-02 

2104 

27 

857 

6-6 

If  we  examine  the  last  column  of  figures  in  this  Table,  representing  the 
percentage  of  CO,  in  the  alveolar  air,  it  will  be  seen  that,  in  spite  of  the  very 
large  variations  in  the  air  breathed,  the  alveolar  content  in  C02  remained 
practically  constant  until  the  C0a  in  the  atmosphere  was  increased  to  such 
;ui  extent  that  the  processes  of  compensation  were  no  longer  efficient.  We 
must  conclude  therefore  that  the  respiratory  centre  is  so  arranged  as  to 
react  to  the  slightest  increase  of  C02  tension  in  the  blood,  any  increase  in 
this  gas  giving  at  once  a  compensatory  increase  in  depth  and  frequency  of 
respiration,  so  that  the  alveolar  C02  content  may  be  maintained  almost 
constant. 

That  it  is  the  tension  of  C02  in  the  alveolar  air  and  therefore  in  the  blood 
bathing  the  centres,  and  not  the  percentage  amount  of  this  gas  which  is  the 
determining  factor,  is  shown  by  a  comparison  of  the  composition  of  the 


1132 


PHYSIOLOGY 


alveolar  air  under  different  atmospheric  pressures.  Thus,  when  the  subject 
of  the  experiments  from  which  the  above  Table  was  derived,  was  placed  in 
an  air-chamber  compressed  to  a  pressure  of  1261  mm.,  the  mean  percentage 
of  C02  in  the  alveolar  air  was  3-42,  corresponding  however  to  a  tension  of 

3-42  X    -      =  5-6  per  rent,  of  an  atmosphere,  a  figure  almost  identical 

with  those  given  in  the  last  column  of  this  Table.  At  the  top  of  Ben 
Nevis,  where  the  barometric  pressure  was  646  mm.,  the  percentage  of  C02  in 

the  alveolar  air  was  6-6,  corresponding  to  a  tension  of  6-6  X  —  =  5-2  per 

760  ' 


3000       2600        2200 


Fio.  519.  Effects  of  alterations  in  the  barometric  pressure  on  the  alveolar  CO, 
tension,  the  al'veolar  C02  percentage,  and  in  the  alveolar  O,  tension.  Note 
that  the  excitant  effects  of  O.  lack  are  not  seen  until  the  pressure  falls  below 
500  mm.  Hg.    (Boycott  and  Haldane.) 


cent,  of  an  atmosphere,  i.  e.  of  760  mm.  Thus  the  pressure  of  C02  in  alveolar 
air  remains  practically  constant  with  widely  varying  limits  of  atmospheric 
pressure  and  with  very  different  percentages  of  C0B  in  the  inspired  air, 
showing  that  the  reactions  of  the  organism  are  directed  so  as  to  maintain, 
by  alterations  in  the  respiratory  depth  and  rhythm,  a  constant  tension  of  this 
gas  in  the  alveoli  and  therefore  in  the  arterial  blood. 

Very  different  are  the  phenomena  observed  on  alteration  of  the  partial 
pressure  of  oxygen  (Fig.  519).  Here,  within  wide  limts,  the  partial  pressure 
of  oxygen  in  the  alveolar  air  is  determined  by  its  pressure  in  the  inspired  air. 
Thus,  if  we  take  the  same  series  of  observations  with  a  pressure  of  646  mm., 
the  percentage  of  oxygen  in  the  alveolar  air  was  13-19,  corresponding  to  a 

tension  of  13-19  X  —  =  10-4  per  cent.     At  an  atmospheric  pressure  of 

755  mm.  the  percentage  of  oxygen  in  the  alveolar  air  was  13-97,  corresponding 
to  a  tension  of  13-06  per  cent.,  which  we  may  take  as  the  normal  figure  at  the 


REGULATION   OF  THE  RESPIRATORY  MOVEMENTS     1133 

sea-level.    In  air  compressed  to  a  pressure  <>f  1261  mm.  the  percentage  of 

1261 
oxygen  was  16-79,  corresponding  to  a  tension  of  16-79  X  — —  =  26-8  per 

cent,  of  an  atmosphere  of  760  mm. 

Similar  results  are  obtained  by  altering  the  percentage  of  oxygen  in  the 
air  breathed.  The  oxygen  tension  or  percentage  in  the  inspired  air  can  be 
lowered  from  its  normal  of  20-93  to  12  or  13  per  cent,  without  altering 
in  any  way  the  depth  or  rhythm  of  respiration,  and  in  fact  without  any 
change  being  noticed  by  the  individual  who  is  the  subject  of  the  experiment. 
A  percentage  of  13  per  cent,  of  oxygen  corresponds  to  an  alveolar  content  in 


Fig.  5:20.     Effects  of  oxygon  lack.     (Scott.) 
Upper  tracing,  diaphragm  slip;  lower  tracing,  carotid  blood  pressure.     During 
time  indicated  by  signal,  5  per  cent,  oxygen  in  nitrogen  was  inhaled.     C  =  eon- 
vulsion. 

oxygen  of  8  per  cent.,  and  with  a  further  reduction  of  the  oxygen  content 
there  is  increased  pulmonary  ventilation  (Fig.  520),  but  the  diminution  in 
oxygen  may  be  pushed  to  such  an  extent  that  the  patient  becomes  blue  from 
the  deficient  aeration  of  his  haemoglobin,  without  any  considerable  distress 
being  caused.  In  fact  in  many  cases  the  subject  of  such  an  experiment  may 
lose  consciousness  suddenly  before  he  has  been  aware  of  any  serious  deficiency 
in  his  aeration. 

The  difference  in  the  sensitiveness  of  the  centre  to  increase  of  carbon  dioxide  and 
lack  of  oxygen  respectively  is  well  shown  by  an  experiment  of  Haldane's,  in  which  the 
same  person  breathed  in  and  out  of  a  bag,  in  the  first  place  allowing  the  carbon  dioxide 
produced  in  respiration  to  accumulate,  and  in  the  second  removing  the  carbon  dioxide 
In  means  of  soda  lime, so  that  the  sole  effect  of  respiration  was  to  produce  a  continual 
diminution  in  the  percentage  of  oxygen.     In  the  first  case,  when  the  carbon  dioxide  was 


il.'.l  PHYSIOLOGY 

allowed  to  accumulate,  it  was  found  that  extreme  and  intolerable  hyperpneca  was  pro- 
duced when  the  gaseous  content  of  the  bag  consisted  of  56  per  cent,  carbon  dioxide 
with  14-8  per  cent,  oxygen.  When  the  carbon  dioxide  was  absorbed,  it  was  possiblo 
to  breathe  in  and  out  of  the  bag  for  a  much  longer  period.  No  hyperpncea  was  pro- 
duced, and  the  experiment  was  stopped  as  soon  as  the  subject  was  becoming  blue  in 
the  face  and  experienced  slight  throbbing  in  the  head.  The  pulse  frequently  had  gone 
up  from  80  to  108.  The  bag  was  found  to  contain  no  carbonic  acid  and  only  8' 7  per 
cent,  oxygen.  In  another  similar  experiment  the  oxygen  had  been  reduced  to  6' 7  per 
cent,  before  it  was  necessary  to  stop  the  experiment. 

We  must  conclude  that  the  respiratory  centre  possesses  a  specific  sensi- 
bility for  carbon  dioxide,  which  determines  the  normal  depth  and  rhythm 
of  the  respiratory  movements.  Although  the  respiratory  centre,  in  com- 
mon with  the  rest  of  the  central  nervous  system,  is  sensitive  to  and  can  be 
excited  by  lack  of  oxygen,  this  quality  is  rarely  brought  into  play.  Under 
all  ordinary  circumstances,  an  increased  need  for  oxygen  is  associated  with 
an  increased  production  of  carbon  dioxide  in  the  oxidative  processes  of  the 
body,  and  the  augmentation  of  respiration,  produced  by  the  excitatory 
effect  of  a  small  excess  of  carbon  dioxide  tension  in  the  blood,  suffices  to 
provide  fully  for  the  increased'  needs  of  the  organism  for  oxygen.  The 
reactions  of  the  organism  have  not  been  evolved  in  order  to  adapt  it  to 
balloon  ascents  or  experiments  in  respiratory  chambers.  As  an  example  of 
a  normal  adaptation,  we  may  take  the  changes  in  respiration  which  occur 
in  an  animal  as  the  result  of  muscular  exercise.  During  their  activity  a 
large  amount  of  carbon  dioxide  is  produced  in  the  muscles.  The  blood 
passing  from  the  muscles  to  the  heart  will  not  be  able  to  get  rid  of  the  excess 
of  the  carbon  dioxide  in  passing  through  the  lungs,  and  will  reach  the 
respiratory  centre  more  highly  charged  with  this  gas,  the  tension  of  which 
will  be  raised.  The  respiratory  centre  is  thus  stimulated,  and  the  increased 
pulmonary  ventilation  thereby  produced  lowers  the  alveolar  carbon  dioxide 
pressure,  until  a  point  is  reached  at  which  an  equilibrium  is  maintained 
between  the  effect  of  the  increased  production  of  carbon  dioxide  in  raising 
the  arterial  carbon  dioxide  tension  and  that  of  the  increased  respiratory 
activity  in  lowering  it.  Under  these  circumstances  it  is  found  that  the 
increased  consumption  of  oxygen  in  the  contracting  muscles  is  more  than 
compensated,  so  that  the  oxygen  tension  in  the  alveoli  and  in  the  arterial 
blood  is  rather  above  than  below  normal. 

In  certain  experiments  Zuntz  and  Geppert  foimd  that,  during  muscular 
exercise,  the  respiratory  movements  were  increased  to  such  an  extent  as 
to  bring  the  tension  of  carbon  dioxide  in  the  arterial  blood  below  normal. 
In  these  experiments  the  muscular  contractions  were  produced  by  tetanis- 
ing,  through  the  spinal  cord,  the  lower  linibs  of  an  animal.  Under  these 
circumstances  the  activity  of  the  muscle  would  be  associated  with  a 
diminished  blood  flow,  so  that  the  contractions  would  be  carried  out  in  the 
absence  of  a  sufficient  supply  of  oxygen.  In  the  absence  -of  sufficient 
oxygen,  muscular  contractions  result  in  the  production,  not  of  carbon 
dioxide  but  of  lactic  acid ;  and  it  is  highly  probable  that  in  the  experiments 
in  question  there  was  a  discharge  of  acid  substances  into  the  blood,  diminish- 


REGULATION  OF  THE  RESPIRATORY  MOVEMENTS     1135 

ing  the  alkalinity  of  this  fluid  and  therefore  lowering  its  carrying  power  for 
carbon  dioxide.  As  a  matter  of  fact,  one  can  produce  dyspnoea  by  diminish- 
ing the  alkalinity  of  the  blood  by  the  injection  of  acids;  and  attacks  of 
dyspnoea  are  observed  in  the  later  stages  of  diabetes,  when  the  alkalinity 
of  the  blood  is  decreased  in  consequence  of  the  production  of  such  bodies 
as  oxybutyric  acid.  This  dyspnoea  has  been  ascribed  to  the  fact  that  a 
diminished  carrying  power  of  the  blood  for  carbon  dioxide  will  raise  the 
tension  of  this  gas  in  the  tissues  where  it  is  formed,  so  that  a  diminished 
alkalinity  of  the  blood  may  cause  a  higher  tension  of  carbon  dioxide  around 
the  respiratory  centre.  It  has  been  shown  by  Ryffel  that  even  a  short 
period  of  sufficiently  violent  muscular  exercise,  i.  e.  one  giving  rise  to 
dyspnoea,  causes  a  subsequent  increase  of  lactic  acid  in  the  urine,  and  that 
the  blood  itself  at  the  close  of  the  period  of  exercise  contains  a  demonstrable 
amount  of  this  acid.  Thus  in  one  case  the  urine,  passed  thirty  minutes 
after  running  one-third  of  a  mile  in  two  minutes,  contained  454  mg.  lactic 
acid  as  against  a  normal  excretion  of  between  3  and  4  mg.  lactic  acid 
per  hour.  In  another  experiment  blood  was  obtained  from  the  fore-arm 
before  exercise,  immediately  after  exercise,  and  three-quarters  of  an  hour 
later.  The  exercise,  which  consisted  of  running  rapidly,  lasted  two  minutes 
forty-five  seconds.     The  following  Table  represents  the  results  obtained  : 

Lactic  acid  per  100  c.c. 
Blood  before  starting       .....     12'5  mg. 
Blood  immediately  after  stopping     .  .         .     708    „ 

Blood  45  minutes  later    .....     15*9    „ 

The  production  of  lactic  acid  during  muscular  exercise  may  thus  be 
regarded  as  a  second  line  of  defence  for  the  organism,  tending  to  maintain 
the  increased  ventilation  of  the  lungs  even  when  the  supply  of  oxygen  is 
insufficient  to  oxidise  completely  the  materials  consumed  in  the  production 
of  the  muscular  energy.  This  acid  mechanism  is  however  employed  only 
when  the  supply  of  oxygen  lags  behind  the  respiratory  needs  of  the  body 
(cp.'Fig.  521).  Ordinary  exercise,  even  when  considerable  {e.g.  a  twenty- 
four  hours'  track  walking  race),  does  not  cause,  as  Ryffel  has  shown,  any 
appreciable  increase  in  the  ehmination  of  lactic  acid  by  the  urine.  Under 
normal  circumstances  the  depth  and  rhythm  of  respiration  depend  on  the 
carbon  dioxide  pressure  in  the  respiratory  centre,  a  rise  of  0-2  per  cent,  of 
an  atmosphere  in  the  tension  of  this  gas  in  the  alveoli  being  sufficient  to 
double  the  amount  of  alveolar  ventilation  during  rest. 

The  first  phase  in  the  phenomena  of  asphyxia  is  thus  conditioned  simply 
by  the  changes  in  the  carbon  dioxide  tension.  A  little  later  the  gradual 
exhaustion  of  oxygen  in  the  blood  round  the  centre  begins  to  make  itself 
felt.  The  respiratory  centre  shares  with  the  rest  of  the  central  nervous 
system  a  sensitiveness  to  the  absence  of  oxygen,  deprivation  of  oxygen 
having  first  an  excitatory  and  later  a  paralytic  effect.  In  asphyxia  the 
first  centres  to  feel  this  effect  are  those  of  the  cortex,  and  during  the  first 
stage  there  is  mental  excitation  terminating  rapidly  in  abolition  of  con- 
sciousness.   During  the  second  stage  there  is  a  discharge  of  energy,  which 


1136 


PHYSIOLOGY 


spreads  throughout  the  whole  nervous  system,  beginning  in  the  bulbar 
centres  and  causing  a  great  rise  of  blood  pressure  with  slowing  of  the  heart, 
and  extending  thence  to  all  the  spinal  centres  with  the  production  of  muscular 
spasms.  At  this  stage  too,  there  is  a  discharge  of  impulses  giving  contraction 
of  the  pupil,  and  a  discharge  along  the  whole  sympathetic  system,  producing 
the  various  phenomena  of  vasoconstriction,  erection  of  hairs,  sweating, 
salivation,  which  are  generally  brought  about  by  stimulation  of  different 
parts  of  this  system.  The  phenomena  of  the  third  stage  are  due  to 
exhaustion  of  the  nerve  centres,  accompanied  or  preceded  by  exhaustion 
and  dilatation  of  the  heart,  the  circulation  failing  before  the  excitation  of 
the  lower  centres  has  entirely  come  to  an  end.  In  this  third  stage  it  is 
impossible  bv  the  strongest  stimuli  to  evoke  any  reflex. 




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Fio.  521.     Dissociation  curve  of  oxyhemoglobin  in  defibrinated  cats'  blood. 

1,  cat  I,  after  partial  occlusion  of  trachea  and  fifteen  minutes  breathing  of  gas 
of  increasing  poverty  in  oxygen;  4,  cat  II,  at  beginning  of  experiment;  3,  cat  II, 
after  fifteen  minutes  gas  respiration ;  2,  after  twenty-one  minutes  ditto. 


Considerable  discussion  has  taken  place  as  to  the  exact  nature  of  the  stimulation 
brought  about  by  want  of  oxygen.  The  blood  of  animals,  which  have  been  killed  by 
asphyxia,  is  known  to  contain  reducing  substances,  so  that  oxygen  added  to  it  disappears 
and  cannot  be  recovered  in  a  vacuum.  Pfliiger  therefore  suggested  that  it  was  these 
reducing  substances  themselves  which  were  effective  exciting  agents.  It  was  shown 
many  years  ago  by  Hoppe-Seyler  and  his  pupils  that  in  conditions  of  chronic  oxygen 
starvation  there  was  an  excessive  production  of  lactic  acid  in  the  body,  and  we  have 
seen  that  the  same  is  true  for  the  isolated  muscle,  and  that  to  these  substances  has  been 
ascribed  the  excitation  of  the  respiratory  centre  which  takes  place  in  violent  muscular 
exercise  (Zuntz  and  Geppert).  Haldane  has  suggested  that  in  the  hyperpncea  and  con- 
vulsions, which  occur  as  the  result  of  breathing  mixtures  with  very  low  percentages  of 
oxygen,  the  effective  stimulus  is  also  lactic  acid.  Experiments  were  carried  out  by 
Ryffel  on  individuals  who  had  been  subjected  in  a  respiratory  chamber  to  very  low 
oxygen  tensions,  sufficient  to  cause  C3"anosis,  so  that  their  oxygen  alveolar  tension  was 
only  about  6  per  cent.  After  an  experiment  lasting  four  hours,  there  was  a  definite 
increase  of  lactic  acid  in  the  blood  of  the  forearm  (up  to  23"6  mg.  lactic  acid  per  100  c.c.). 
After  one  lasting  only  fifteen  minutes,  in  which  the  oxygen  shortage  became  very 
marked,  no  increase  could  be  detected.  When  we  expose  an  animal  such  as  a  rabbit  to 
low  percentages  of  oxygen,  the  hyperpnoea  so  produced  disappears  almost  immediately 


REGULATION   OF  THE  RESPIRATORY  MOVEMENTS     1137 

when  a  larger  percentage  of  oxygen  is  supplied  to  the  animal,  whereas  that  produced  by 
carbon  dioxide  excess  dies  awa}'  slowly  on  exposure  to  normal  conditions.  It  would  seem 
that,  when  the  exposure  to  low  oxygen  tensions  is  of  short  duration,  no  lactic  acid  is  pro- 
duced in  the  blood.  If  therefore  we  ascribe  the  hyperpneea  to  the  production  of  lactic 
acid,  we  must  locate  the  production  of  this  acid  in  the  respiratory  centre  itself.  There 
are  no  inherent  improbabilities  in  such  an  assumption,  but  it  is  difficult  at  present  to 
see  how  it  can  be  put  to  the  test  of  experiment. 

In  dealing  with  the  question  of  the  blood  alkalinity  we  denned  neutrality  as  a  con- 
dition in  which  there  were  equivalent  concentrations  of  H  and  OH  ions.  In  the  blood 
the   H    ion    concentration   is   about   0'3  X  10~7N.      The  alkalinity  is  expressed  by 

.     The  acids  and  bases  of  the  blood  serum  and  of  the  tissue  fluids 
concentration  H  ions 

lly  are  in  such  proportions  as  to  maintain  the  approximate  neutrality  of  these 
fluids  even  a"er  considerable  additions  of  acid  or  alkali.  Thus  hydrochloric  acid  may 
be  added  to  the  extent  of  025  N,  or  NaOH  to  the  extent  of  "005  N,  without  causing 
any  marked  alteration  in  the  reaction  of  the  blood.  Although  the  change  produced 
by  the  addition  of  acids  or  alkalies  is  so  minute,  it  is  appreciable  by  electrical 
methods,  and  it  may  still  more  readily  be  appreciated  by  and  act  as  a  stimulus  for  the 
pells  of  the  body  themselves.  Thus  we  have  not  yet  succeeded  in  determining  electric- 
ally the  change  in  hydrogen  ion  concentration  caused  by  the  change  from  arterial  to 
venous  blood.  If  however  blood  serum  be  saturated  with  carbon  dioxide  at  a  full 
atmosphere,  the  concentration  of  the  hydrogen  ions  rises  to  1"4  X  10-7N,  while  after 
removing  the  greater  part  of  the  carbon  dioxide  from  the  same  serum  by  the  passage  of  a 
stream  of  air,  the  concentration  of  the  hydrogen  ions  sinks  to  -008  x  10 ""  7N.  As  the 
respiratory  centre  responds  to  such  minute  changes  of  concentration  as  would  be 
expressed  by  a  difference  of  02  per  cent,  of  an  atmosphere  in  the  carbon  dioxide  tension 
of  the  circulating  blood,  it  must  possess  a  sensitivity  greater  than  any  of  our  physical 
means  for  measuring  the  concentration  of  hydrogen  ions  in  a  fluid.  We  may  approach 
this  delicacy  of  reaction  by  using  a  large  molecule  as  our  indicator.  Thus,  as  we  have 
seen,  the  dissociation  curve  of  haemoglobin  is  sensitive  to  the  change  in  reaction  caused 
by  raising  the  tension  of  carbon  dioxide  in  the  hemoglobin  solution  by  10  mm.  Hg. 
(cp.  Fig.  509). 

The  regulating  factor  in  the  blood  is  probably  not  carbon  dioxide  nor  any  special  acid, 
but  the  concentration  of  hydrogen  ions  in  this  fluid  or  in  the  cells  of  the  centre  itself. 
Such  a  conclusion  brings  under  one  head  all  the  several  factors  which  we  know  to  act 
upon  the  respiratory  centre,  namely,  tension  of  carbon  dioxide,  presence  of  acids  in  the 
blood — especially  lactic — and  considerable  diminution  of  oxygen  supply  to  the  cells. 
The  respiratory  centre  would  then  not  differ  qualitatively  from  any  other  part  of  the 
central  nervous  system.  Its  special  function  would  be  determined  simply  by  the  evolu- 
tion to  a  marked  degree  of  a  sensibility  to  hydrogen  ions  which  is  already  possessed  by 
the  whole  of  the  central  nervous  system  and  indeed  by  practically  every  tissue  of  the  body. 

We  may  conclude  that  mere  lack  of  oxygen  is  not  to  be  regarded  in 
itself  as  an  excitatory  agent.  Its  influence  will  be  rather  to  paralyse  all 
activity.  On  the  other  hand,  excitation  is  caused  by  the  products  of 
metabolism,  which  vary  according  as  the  oxygen  supply  is  ample  or 
insufficient  for  the  needs  of  the  cells.  In  the  former  case  activity  results 
in  the  production  of  carbon  dioxide,  in  the  latter  of  lactic  acid,  and  perhaps 
other  substances.  Both  these  are  acid  substances  and  their  production 
will  therefore  raise  the  concentration  of  the  hydrogen  ions  in  the  cells 
where  they  are  produced  as  well  as  in  the  blood.  The  nerve  centres  are 
extremely  sensitive  to  minute  changes  in  the  hydrion  concentration  either 
in  themselves  or  in  the  fluids  surrounding  them,  and  are  thrown  into  activity 
by  excess  of  these  ions  and  inhibited,  or  put  to  rest,  by  relative  deficiency 


1138 


PHYSIOLOGY 


of  the  ions.  In  their  relation  to  H  and  OH  ions  respectively  the 
medullary  centres  have  a  sensibility  five  times  as  great  as  the  spinal 
centres.  The  condition  of  apnoea,  which  is  associated  not  only  with 
cessation  of  respiratory  movements  but  also  with  fall  of  blood  pressure, 
may  be  ascribed  to  relative  increase  in  the  OH  ions  or  diminution  in  the 
H  ions. 

Since  the  animal  has  developed  a  mechanism  by  means  of  which  changes 
in  the  reaction  of  the  blood  can  be  rapidly  adjusted  by  varying  the  excre- 
tion oi  carbon  dioxide,  whilst  the  excretion  of  other  acids  is  relatively  sloW 
carbon  dioxide  may  be  regarded  as  the  normal  respiratory  hormone ;  and 
so  far  we  may  agree  with  Henderson  in  regarding  carbon  dioxide  as  maintain- 
ing the  activities  of  the  various  nerve  centres  at  their  normal  level.  But  it  is 
the  bydrion  concentration  which  appears  to  be  the  essential  factor,  and  the 
acid  substances  produced  during  oxygen  lack  are  equally  efficacious,  but  not 


Fia.  522.     Normal  tracing  of  diaphragm  slip  (Head's  method). 


so  convenient.  Thus  their  production  is  not  a  steady  process  like  that  of 
carbon  dioxide  but,  as  Mathison  pointed  out,  commences  suddenly  at  a  time 
when  the  executive  side  of  the  nerve  cell  is  feeling  the  effect  of  oxygen 
starvation,  so  that  the  cell  may  be  too  much  disorganised  to  respond  to 
stimulation.  "  The  broad  margin  of  safety  protecting  the  organism  against 
paralysis  of  its  cells  by  oxygen  starvation  is  assured  by  the  sensitiveness  of 
the  medullary  centres  to  hydrogen  ion  concentration  and  therefore  to  carbon 
dioxide  in  common  with  other  acids." 

On  the  other  hand,  it  must  be  remembered  that  excessive  production  of 
hydrogen  ions  may  finally  result  in  a  condition  of  paralysis,  which  in  the 
nervous  centres  is  expressed  by  narcosis.  These  effects  can  be  removed  only 
by  a  free  supply  of  oxygen.  The  concentration  at  which  these  results  occur 
varies,  as  we  have  seen,  in  different  parts  of  the  nervous  system  and  also  in 
different  tissues.  Thus  on  the  heart  a  slight  increase  in  H  ion  concentration 
causes  diminished  tone,  which  may  lead  to  dilatation  and  failure  of  this  organ. 
The  same  effect  is  produced  on  the  unstriated  muscle  fibre  of  the  blood 
vessels.  Since  in  the  heart  and  blood  vessels  the  reverse  effect  is  produced 
by  increasing  the  OH  ion  concentration,  it  is  evident  that  the  fine  of 
'  physiological '  neutrality,  at  which  neither  stimulation  nor  paralysis 
results,  must  vary  in  different  tissues. 


REGULATION   OF  THE  RESPIRATORY    MOVEMENTS     1139 

It  is  an  interesting  question  whether  the  electrical  excitation  of  nerves 
may  not  be  due  to  a  similar  alteration  in  the  hydrion  concentration  at  the 
cathode  which  is  the  seat  of  stimulation.  If  this  were  so,  all  the  activities 
of  protoplasm  might  be  regarded  as  determined  by  the  relative  concentration 
of  the  H  and  OH  ions  within  the  cells  or  in  the  medium  surrounding  the  cells. 


THE   REFLEX   NERVOUS   REGULATION   OF   RESPIRATION 

Although  the  specific  sensibility  of  the  respiratory  centre  to  C02  is  the 
most  important  factor  in  determining  the  depth  and  rhythm  of  the  respiratory 
movements,  these  movements  and  the  condition  of  the  respiratory  centre 
itself  are  modified  in  a  large  degree  by  impulses  arriving  at  the  centre  along 
both  vagi.  Through  other  sensory  nerves  of  the  body  the  respiratory 
movements  can  be  altered  'reflexly,  but  it  is  only  through  the  vagi  that  a  con- 
tinuous stream  of  impulses  passes  to  the  centre  under  normal  circumstances, 
so  that  every  respiratory  movement  is  modified  by  these  impulses. 

In  studying  the  nervous  mechanism  of  respiration,  it  is  necessaiy  to  have  some 
accurate  method  of  recording  the  respiratory  movements.  They  may  be  registered  by 
means  of  a  tambour  applied  to  the  chest,  communicating  with  another  tambour  provided 
with  a  lever,  which  is  arranged  to  write  on  a  blackened  surface;  or  a  side  tube  to  a 
cannula  in  the  trachea  may  be  connected  with  the  registering  tambour.  In  the  first 
case  movements  of  the  thorax  are  registered ;  in  the  second  changes  of  intra-pulmonary 
pressure.  These  methods  are  obviously  useless  when  it  is  wished  to  study  the  effects 
of  artificial  distension  or  collapse  of  the  lungs.  In  this  instance  we  may  use  the  method 
described  by  Head.  In  the  rabbit  a  slip  of  the  diaphragm  on  either  side  of  the  ensiform 
cartilage  is  so  disposed  that  the  end  of  it  may  be  freed  and  attached  by  a  thread  to  a 
lever  without  injury  to  its  blood-  or  nerve-supply.  It  is  found  that  this  slip  contracts 
synchronously  with  the  rest  of  the  diaphragm,  so  that  it  serves  as  a  sample  of  the 
diaphragm,  the  contractions  of  which  may  be  recorded  uninfluenced  by  passive  move- 
ments of  the  chest  wall  or  artificial  increase  of  intra-pulmonary  pressure. 

If,  while  the  respiratory  movements  are  being  recorded  in  one  of  the 
a  line-mentioned  ways,  both  vagi  be  divided,1  a  marked  change  in  the 
respirator}'  rhythm  is  at  once  seen.  The  first  effect  is  an  increased 
inspiratory  tonus,  but  this  rapidly  disappears,  and  the  respiratory  move- 
ments become  less  frequent  and  are  increased  in  amplitude.  If  now  the 
central  end  of  one  of  the  vagi  be  stimulated  with  an  interrupted  current,  the 
inspiration  may  be  quickened  or,  as  is  more  commonly  the  case,  the  in- 
spiratory movements  may  be  increased  at  the  expense  of  the  expiratory  so 
that  finally  a  condition  of  inspiratory  standstill  is  produced,  and  the  slip  of 
the  diaphragm  enters  into  prolonged  contraction. 

1  The  division  of  the  vagi  is  best  effected  by  putting  them  on  a  hooked  copper  wire, 
of  which  the  upper  end  is  inserted  in  a  freezing-mixture.  In  this  way  complete  func- 
tional division  of  the  nerves  is  obtained  without  any  excitation.  If  the  nerves  be  cut, 
a  certain  amount  of  stimulation  takes  place  in  consequence  of  the  closure  of  the  demarca- 
tion current  produced  by  the  cross-section. 


1140 


PHYSIOLOGY 


With  a  very  weak  stimulus  it  is  sometimes  possible  to  produce  augmenta- 
tion of  the  expiratory  movements  or  rather  inhibition  of  the  inspiratory,  and 
this  is  the  invariable  result  of  passage  of 
a  constant  current  through  the  vagus  in 
an  ascending  direction.  This  effect  may  be 
more  strikingly  brought  about  by  stimu- 
lation of  the  central  end  of  the  superior 
laryngeal  nerve,  which  produces  first  an 
inhibition  of  inspiration,  so  that  the  re- 
spiratory muscles  come  to  a  standstill  in 
the  position  of  expiration,  and  then  a 
forcible  contraction  of  the  expiratory  mus- 
cles. This  illustration  of  the  presence  of 
expiratory  fibres  in  the  superior  laryngeal 
nerve  is  not  confined  to  laboratory  experi- 
ence, but  is  constantly  occurring  in  every- 
day life.  The  superior  laryngeal  nerve 
supplies  sensory  fibres  to  the  mucous 
membrane  of  the  glottis,  and  we  know 
that  the  slightest  irritatiou  of  these  fibres 
— the  presence  of  a  crumb  or  a  particle  of 
mucus— causes  forcible  expiratory  spasms, 
with  spasmodic  closure  of  the  glottis,  which 
we  term  a  cough.1 

So  we  see  that  the  vagus  nerve  con- 
tains two  kinds  of  afferent  fibres,  or  at 
any  rate  afferent  fibres  with  two  distinct 
functions.  Stimulation  of  the  one  kind 
stops  inspiration  and  produces  expiration ;  stimulation  of  the  other  stops 
expiration  and  produces  inspiration.  Since  section  of  both  vagi  causes 
slowing  of  respiration,  impulses  which  exert  some  influence  on  the  re- 
spiratory centre  and  quicken  respiration  must  travel  up  the  vagi  from  the 
lungs.  The  respiratory  movements  cause  an  alternate  distension  and  con- 
traction of  the  lungs,  and  it  has  long  been  thought  that  it  is  these  changes 
in  the  volume  of  the  lungs  which  start  the  accelerating  impulses  that  travel 
up  the  vagus  nerves.  To  test  the  truth  of  this  hypothesis  it  is  necessary 
to  study  the  two  phases  of  respiration  separately;  that  is,  to  see  first  the 
result  on  the '  respiratory  impulses  of  distension  of  the  lungs,  and  secondly 
the  result  of  a  sudden  collapse  or  a  contraction  caused  by  sucking  air  out 
of  the  lungs.  The  effects  of  distension  or  collapse  of  the  lung  may  be  shown 
by  simply  closing  the  trachea  at  the  end  of  inspiration  or  of  expiration.  The 
results  of  such  an  experiment  are  shown  in  Fig.  523. 

1  It  must  not  be  imagined  that  the  fibres  of  the  superior  laryngeal  nerves  are  con- 
cerned in  the  reflex  maintenance  of  the  normal  respiratory  rhythm.  They  are  cited  here 
merely  because  the  result  of  their  stimulation  resembles  that  which  would  be  caused 
by  stimulation  of  the  analogous  expiratory  fibres  which  rim  in  the  trunk  of  the  vagus 
from  the  lungs  to  the  respiratory  centre. 


Fig.  523.  Effects  of  distension  and 
collapse  of  lung.  Both  curves  are 
described  by  a  lever  attached  to  a 
slip  of  the  diaphragm  of  a  rabbit. 
A  contraction  of  the  diaphragm 
(inspiration)  raises  the  lever;  dur- 
ing relaxation  of  the  diaphragm 
the  lever  falls. 

In  A,  the  trachea  is  closed  at  x, 
the  height  of  inspiration ;  a  pause 
follows,  during  which  the  lever 
gradually  sinks  until  an  inspiration 
(a  very  powerful  one)  sets  in. 

In  B,  the  trachea  is  closed  at  the 
end  of  expiration,  x;  there  follow 
powerful  inspirations.     (Foster.) 


REGULATION   OF  THE  RESPIRATORY  MOVEMENTS     1141 

A  still  more  marked  effect  is  produced  if  the  kings,  by  means  of  a  tube 
in  the  trackea,  be  artificially  inflated  or  if  air  be  sucked  out  of  them.  The 
inflation  produces  an  instantaneous  and  complete  relaxation  of  the  dia- 
phragm (Fig.  524)  which  by  clamping  the  tracheal  tube  may  be  prolonged 
for  several  seconds,  while  sucking  air  out  of  the  lungs  causes  a  tonic  contrac- 
tion of  the  diaphragm  (Fig.  525).  Somewhat  similar  results  may  be  obtained 
by  repeatedly  inflating  or  deflating  the  lungs  (positive  and  negative  ventila- 
tion). The  effects  here  are  complicated  by  the  fact  that  one  is  dealing  in 
both  cases  with  alternating  movements  of  the  lungs,  viz : — expansion  and 
contraction,  both  of  which  will  have  an  influence  on  the  respiratory  centre. 


Pos.  ventilation 


Fio*  524.     Positive  ventilation.     (Head.) 
Under  the  influence  of  positive  ventilation,  the  inspiratory  contractions  of  the 
diaphragm  become  less  and  less  till  they  disappear  completely. 


>■<■'„'.  ventil >i  urn 


FlG.  525.     Negative  ventilation.     (Head.) 
At  a  negative  ventilation   was  commenced.     The  expiratory  relaxation  of  the 
diaphragm  is  seen  to  become  more  and  more  incomplete,  until  it  finally  enters  into 
continued  contraction. 


Moreover  repeated  forcible  inflation  of  the  lungs  increases  the  ventilation 
of  the  pulmonary  alveoli,  thus  lowering  the  normal  carbon  dioxide  tension 
of  the  lungs.  As  a  result  of  repeated  ventilation  we  may  obtain  a  condition 
of  respiratory  standstill.  In  this  condition  however,  as  we  shall  see  later, 
the  determining  factor  is  rather  chemical  than  mechanical. 

These  inhibitory  and  augmentor  effects  of  changes  in  the  volume  of 
the  lung  must  also  result  from  the  normal  movements  of  these  organs  in 
respiration.  Let  us  consider,  for  instance,  what  will  happen  if  the  influence 
of  the  two  vagi  could  be  suddenly  thrown  in  after  these  nerves  have  been 
divided.  (This  experiment  can,  in  fact,  be  realised  more  or  less  completely 
if  the  functional  division  of  the  vagi  be  effected  by  cooling  or  by  ether 
narcosis.)  The  animal  would  be  breathing  slowly  and  deeply.  If  at  the 
beginning  of  an  inspiration  the  vagi  became  functional,  the  expansion  of  the 
lungs  caused  by  the  inspiratory  movement  would  send  inhibitory  impulses 


1142 


PHYSIOLOGY 


up  to  the  vagus  centre,  which  would  stop  the  movement  of  inspiration. 
The  movement  of  expiration  would  then  begin,  and  the  collapse  of  the  lungs 
thereby  produced  would  itself  send  impulses  up  the  vagi  which  would  tend 
to  excite  an  inspiratory  movement.  Both  inspiration  and  expiration  would 
therefore  be  shortened,  and  the  successive  movements  would  follow  one 
another  at  a  shorter  interval  than  if  the  vagi  were  not  functional.  In  this 
way,  under  normal  circumstances,  the  rhythm  of  the  respiratory  centre 
must  be  determined  reflexly  through  the  agency  of  the  vagi,  while  the  chief 
factor  in  determining  the  total  pulmonary  ventilation  is,  as  we  have  seen, 
the  carbon  dioxide  tension  ot  the  blood. 


RT  Lung 


artif  resp  app. 


LT  Lun 


Fig.  526.     Diagram  to  illustrate  Head's  experiment  on  the  effect  of  collapse  of  the 
lung.     R.c,  respiratory  centre;  R.v,  L.v,  right  and  left  vagi. 


In  the  foregoing  account  we  have  spoken  of  the  expiratory  and  inspiratory  effects 
of  the  vagus  as  if  they  were  of  equal  importance.  It  seems  probable  however  that  the 
inhibitory  or  expiratory  impulses  started  by  the  inspiratory  movement,  the  only  or 
the  more  active  part  of  normal  respiration,  play  a  more  prominent  part  in  the  regulation 
of  respiration  than  do  the  inspiratory  impulses ;  and  one  observer  (Gad)  goes  so  far  as 
to  deny  altogether  the  existence  of  two  kinds  of  respiratory  fibres  in  the  vagus.  Accord- 
ing to  Gad,  the  vagus,  as  regards  the  respiratory  centre,  is  a  purely  inhibitory  nerve. 
Hence  the  primary  effect  of  dividing  both  vagi  is  an  increased  inspiratory  tone.  This 
view  at  first  seems  paradoxical,  in  that  it  explains  the  final  slowing  of  respiration  after 
section  of  the  vagi  as  due  to  the  cutting  off  of  previous  inhibitory  impulses.  But  inhi- 
bition in  all  tissues  has  a  twofold  effect.  Although  the  immediate  effect  is  diminution 
of  activity,  yet  the  diminished  disintegration  necessarily  associated  with  lowered 
activity  means  an  increase  of  the  anabolic  at  the  expense  of  the  catabolic  processes  of 
the  tissues.  In  this  way  we  explained  the  diminished  excitability  occurring  in  a  nerve 
at  the  anode  of  a  constant  current,  and  it  will  be  remembered  that  the  secondary  result 
of  anelectroronus  was  increased  irritability  and  consequent  excitation  at  break  of  the 
constant  current.  The  same  sort  of  process  must  occur  in  the  respiratory  centre.  A 
continued  restraint  of  its  rhythmic  activity  must  lead  to  a  heaping  up  of  its  irritable 
material,  so  that  the  final  result  is  a  state  of  hyperexcitability  in  which  the  centre,  so  to 
speak,  boils  over  on  the  slightest  provocation. 

In  this  condition  a  cutting  off  of  the  inhibitory  impulses  must  at  first  increase  the 


REGULATION  OF  THE  RESPIRATORY  MOVEMENTS     1143 

activity  of  the  centre,  leading  to  the'  increased  inspiratory  tonus  already  described. 
But  unchecked  by  any  reigning  impulses,  the  centre  enters  upon  a  career  of  spendthrift 
activity.  Each  inspiratory  contraction  is  maximal,  but  the  centre,  exhausted  by  the 
effort,  has  to  wait  a  considerable  time  before  it  can  accumulate  sufficient  energy  for 
the  next;  hence  the  final  result  of  section  of  both  vagi  is  deepening  and  slowing  of 
respiration. 

Although  Gad  has  rendered  great  service  in  emphasising  the  importance  of  the 
inhibitory  or  expiratory  impulses  which  ascend  the  vagi,  there  is  no  doubt  that  he  went 
too  far  in  denying  the  existence  of  inspiratory  fibres  in  the  vagus.  This  is  shown  by  the 
following  experiment  of  Head.  According  to  Gad's  view,  collapse  of  both  lungs  implies 
simply  a  removal  of  the  normal  inhibitory  impulses  ascending  the  vagi,  and  is  therefore 
equivalent  to  division  of  these  two  nerves.  If  in  the  rabbit  the  left  vagus  be  divided,  a 
tube  can  be  introduced  into  the  left  bronchus,  and  artificial  respiration  can  be  performed 
by  alternate  inflation  and  collapse  of  the  left  lung,  without  in  any  way  affecting  the 
respiratory  centre,  all  connections  with  the  latter  being  destroyed  (v.  Pig.  526).  Mean- 
while the  animal  carries  out  normal  respiratory  movements,  which  can  be  recorded  by  the 
diaphragm  slip  method.     While  the  slip  is  contracting  regularly,  the  right  pleura  is 


Fn;.  527.  Effect  of  10'6  per  cent.  C02  in  a  mixture  containing  233  per  cent.  0„  on  a 
rabbit  with  both  vagi  divided.  The  gas  was  administered  between  the  arrows. 
Zero  line  of  blood  pressure  is  32  mm.  below  bottom  of  tracing.  Compare  this 
Figure  with  Fig.  518,  p.  1131.     (F.  H.  Scott.) 

opened  and  the  right  lung  allowed  to  collapse.  The  effect  of  this  collapse,  carried  up  by 
the  right  vagus  to  the  centre,  is  an  extreme  contraction  of  the  diaphragm,  and  since  the 
onset  of  asphyxia  is  prevented  by  the  artificial  respiration  carried  out  on  the  left  lung, 
the  tonic  standstill  of  the  diaphragm  may  last  over  a  minute.  In  this  case  therefore 
the  effect  of  collapse  of  one  lung  is  enormously  greater  than  that  produced  by  section 
of  both  vagi,  showing  that  the  effect  is  due,  not  to  abolition  of  the  ordinary  tonic  inhibi- 
tory stimuli,  but  to  excitation  of  special  inspiratory  fibres  in  the  vagus  by  the  collapse 
of  the  lung. 

By  means  of  the  string  galvanometer  it  is  possible  to  show  definitely  that  a  collapse 
of  the  lungs  does  set  up  a  nervous  impulse  travelling  up  the  vagus  nerves.  This  impulse 
must  be  inspiratory  in  character,  so  that  there  is  no  reason  to  deny  the  existence  of  both 
kinds  of  fibres  in  these  nerves.  The  effect  of  electrical  stimulation,  especially  with  an 
ascending  constant  current,  is  also  strong  evidence  in  the  same  direction. 

After  division  of  both  vagi  the  total  pulmonary  ventilation  does  not  as 
a  rule  undergo  any  marked  changes,  and  in  the  absence  of  anaesthesia  the 
aeration  of  the  blood  may  be  carried  out  almost,  if  not  quite,  as  well  as  in 
the  intact  animal.  The  importance  of  the  vagus  action  for  the  organism  is 
shown  however  if  we  put  an  increased  strain  on  the  respiratory  mechanism, 
as  for  instance  by  increasing  the  percentage  of  carbon  dioxide  in  the  air 
breathed.  In  the  intact  animal  this  procedure  leads  first  to  increased  depth 
and  later  to  increased  frequency  of  respiration,  the  total  ventilation  being 


1144 


PHYSIOLOGY 


thereby  augmented  to  such  an  extent  as  to'keep  the  alveolar  tension  of  carbon 
dioxide  almost  constant.  If  the  same  percentage  of  carbon  dioxide  be 
administered  to  an  animal  after  section  of  both  vagi,  the  effect  is  deepening 
of  respiration  but  not  quickening  (Fig.  527).  Each  inspiratory  movement 
however  is  already  considerable  so  that  the  margin  by  which  increase  of 
pulmonary  ventilation  is  possible,  by  increase  of  depth  of  respiration  alone, 
is  not  so  great  as  in  a  normal  animal.  Moreover,  since  no  quickening  of 
respiration  takes  place,  the  increased  ventilation  rapidly  becomes  inadequate 
for  the  maintenance  of  the  normal  alveolar  carbon  dioxide  tension.  In  the 
following  Table  the  total  amounts  of  pulmonary  ventilation,  obtained  on 
administration  of  mixtures  containing  carbon  dioxide  to  a  rabbit  before 
and  after  section  of  the  vagi,  are  compared. 


Rabbit,  3  kilos. 

Respiration  with  air  .... 
„                 4-2  per  cent.  C02 
„                  8-6  per  cent.  C02 
„                 air  ... 

Respirations    Vol.  of  each 
per  minute       respiration 

Total  ventilation 
per  minute 

e.c. 

72                19 

96  25 

97  29 
72                 20 

1368 

2400 
2813 
1440 

Vagi  Divided 

Respiration  with  air  . 

4-2  per  cent.  C0.2 
„                  8-6  per  cent.  CO, 

45 
45 

42 

29 
34 

38 

1305 
1530 
1596 

Whether  we  assume  that  the  prevailing  impulses  travelling  up  the 
vagi  are  purely  inhibitory  or  are  both  inhibitory  and  augmentor,  the  re- 
sultant effect,  by  reining  in  the  activity  of  the  centre,  is  to  economise  its 
energy  and  the  energy  of  the  respiratory  muscles.  The  result  of  the  vagal 
impulses  will  therefore  be  to  increase  the  excitability  of  the  respiratory 
centre  and  make  it  more  susceptible  to  slight  changes  in  the  carbon  dioxide 
tension  of  the  blood,  while  maintaining  a  sufficient  margin  of  energy  to 
meet  the  increased  needs  thrown  on  the  respiratory  mechanism  by  augmented 
metabolism,  such  as  occurs  in  violent  muscular  exercise. 

The  important  part  played  by  the  vagi  in  the  regulation  of  normal 
respiration  is  shown  still  more  strikingly  if  the  respiratory  centre  in  the 
medulla  be  separated  from  the  higher  parts  of  the  brain  before  the  section 
of  the  vagi  is  carried  out.  Separation  of  the  medulla  from  the  higher  parts 
of  the  brain,  as  by  section  just  behind  the  corpora  quadrigemina,  has 
practically  no  influence  on  the  respiratory  rhythm.  If  now  both  vagi  be 
divided,  the  normal  respiratory  movements  cease  entirely,  being  replaced 
by  a  series  of  inspiratory  spasms,  each  of  which  lasts  several  seconds  and 
is  followed  by  a  pause  of  half  to  one  minute's  duration.     These  spasms  are 


REGULATION  OF  THE  RESPIRATORY  MOVEMENTS      1145 

inadequate  for  the  proper  oxygenation  of  the  blood.  They  become  gradually 
less  and  less  frequent,  and  in  about  half  an  hour  the  animal  dies  of  asphyxia. 
We  must  conclude  'therefore  that  the  medullary  respiratory  centre  "with 
the  help  of  the  vagi  is  able  to  carry  out  normal  respiratory  movements.  If 
both  vagi  are  cut.  impulses  arrive  at  the  centre  from  the  higher  parts  of  the 
brain,  regulating  its  activity  and  enabling  it  to  carry  out  modified  but 
sufficient  respiratory  movements.  Removed  from  both  these  sources  of 
afferent  impulses,  the  centre  discharges  only  a  series  of  spasms  which  are 
totally  inadequate  for  the  renewal  of  the  blood  gases,  so  that  the  animal 
dies. 

We  may  summarise  these  results  as  follows  : 

Respiratory  centre  with  vagi — normal  respiration. 
Respiratory  centre  with  brain — modified  respiration. 
Respiratory     centre     alone — inadequate     spasmodic     contractions     of 
respiratory  muscles,  and  death  of  animal. 

The  nature  of  the  supplemental  action  of  the  mid-brain  on  the  medullary  respiratory 
centre  has  not  yet  been  made  out.  It  is  apparently  not  dependent  on  afferent  impulses 
arriving  at  the  brain,  since  section  of  no  cranial  nerve  affects  in  any  way  the  activity  of 
the  centres.  Certain  observers  have  described  '  accessory  respiratory  centres '  in  the 
mid-brain,  in  the  region  of  the  posterior  corpora  quadrigemina.  Stimulation  of  this 
part  causes  increase  in  the  rate  of  inspiratory  movements  and  finally  tonic  spasm  of  the 
diaphragm.  Expiratory  effects  have  been  produced  by  stimulation  of  the  anterior 
corpora  quadrigemina,  and  it  would  seem  that  a  section  has  to  pass  through  or  behind 
these  bodies  in  order  to  produce  the  results,  already  described,  of  cutting  off  the  higher 
centres  from  the  medulla  oblongata  after  division  of  the  vagi.  Other  localised  spots  in 
the  brain  from  which  effects  on  respiration  have  been  obtained  are  the  inner  wall  of  the 
optic  thalamus  and  the  root  of  the  olfactory  tract.  Further  experiments  are  necessary 
before  we  can  regard  any  of  these  centres  as  normally  involved  in  the  maintenance  or 
regulation  of  the  respiratory  movements. 

APNCEA.  If  artificial  respiration  be  maintained  so  as  to  produce  a 
somewhat  greater  ventilation  than  is  effected  by  the  normal  respiratory 
movements  of  the  animal,  a  standstill  of  respiration  is  brought  about.  This 
condition  is  called  apnoea.  The  first  explanation  of  this  standstill  was  that 
it  was  due  to  over-oxygenation  of  the  blood.  The  fact  that  it  could  be 
produced  by  artificial  ventilation  with  inert  gases,  such  as  hydrogen  and 
nitrogen,  as  well  as  the  discovery  of  the  inhibitory  influence  of  distension 
of  the  lungs  on  the  respiratory  centre,  led  Head  to  ascribe  it  to  the  summation 
of  a  series  of  inhibitory  stimuli.  In  these  experiments  however  the  fact 
was  forgotten  that  forced  ventilation  of  the  lungs  with  air  or  any  inert  gases 
will  reduce  the  carbon  dioxide  tension  in  the  blood  circulating  round  the 
pulmonary  alveoli  and  therefore  round  the  respiratory  centre.  A  respiratory 
pause  will  thus  ensue  and  last  until  the  increasing  accumulation  of  carbon 
dioxide  in  the  blood  raises  its  tension  to  the  normal  height,  at  which  the 
respiratory  centre  is  'set,'  so  to  speak,  to  respond  by  a  respiratory  dis- 
charge. If  the  carbon  dioxide  content  of  inspired  air  be  increased  to  about 
4-5  per  cent.,  it  is  impossible  to  produce  an  apnoeic  pause,  however  rapidly 
the  respiratory  movements  be  carried  out.     It  would  seem  therefore  that 


1146  PHYSIOLOGY 

ordinary  apnoea  is  entirely  due  to  deficiency  of  carbon  dioxide  tension  in  the 
respiratory  centre,  and  that  although  the  vagus  nerve  is  inhibitory  of 
respiration,  it  is  impossible  to  summate  a  series  of  vagus  inhibitions  by 
artificial  respiration  so  as  to  produce  a  lasting  cessation  of  respiratory 
movements.  The  chief  use  of  the  vagi  in  respiration  seems  to  be  for  main- 
taining, by  frequent  inhibitions,  the  excitability  of  the  respiratory  centre 
at  a  maximum. 

Miesoher  distinguished  three  types  of  apnoea,  viz.  : 

Apncea  vera,  due  to  the  washing  out  of  C02  from  the  lungs,  and  the  consequent 
reduction  of  the  tension  of  this  gas  in  the  blood. 

Apncea  vagi,  a  stoppage  of  respiration  caused  by  stimulation  of  the  inhibitory  fibres 
of  the  vagi.  This  stoppage  is  limited,  as  we  have  seen,  to  the  immediate  duration  of . 
the  stimulus  (whether  electric  or  produced  by  distension  of  the  lungs). 

Apncea  spuria.  Stoppage  of  respiration  by  stimulation  of  other  nervous  or  sensory 
surfaces.  Thus  when  a  duck  plunges  there  is  immediate  stoppage  of  respiration, 
which  may  last  four  or  five  minutes  if  the  animal  remains  so  long  under  water.  The 
same  stoppage  may  be  produced  by  pouring  water  on  the  beak. 


Fig.  528.     Forced  breathing  of  air  for  two  minutes,  followed  by  apnrea  for  two 

minutes,  and  periodic  ('  Cheyne-Stokes  ')  breathing  for  about  five  minutes. 

At  A,  sample  of  alveolar  air  contained  02,  11  "44  per  cent.;  C02,  5'58  per  cent. 

Second  sample  at  b,  02,   13-55  per  cent. ;    C02,  5-57   per  cent.      (Douglas  and 

Haldane.) 


•  CHEYNE-STOKES  '    BREATHING 

If  a  man  desires  to  hold  his  breath  for  some  time  he  takes  first  a  series 
of  deep  breaths.  The  result  is  to  dimmish  the  carbon  dioxide  tension  in  the 
alveoli  and  therefore  to  take  away  the  need  and  the  desire  to  breathe  until 
the  carbon  dioxide  tension  rises  to  normal  as  the  result  of  the  continued 
formation  of  carbon  dioxide.  By  continuing  forced  respiratory  movements 
for  a  minute  or  two,  the  carbon  dioxide  tension  both  in  the  alveoli  and  in 
the  blood  may  be  brought  down  to  a  very  considerable  extent.  As  a  result 
there  is  a  prolonged  period  of  apncea.  During  this  period  of  cessation  of 
respirations  however,  the  oxygen  is  being  used  up,  and  the  tension  of  this 
gas  in  the  alveoli  may  fall  to  such  an  extent  that  the  respiratory  centre  is 
excited  by  lack  of  oxygen  before  the  carbon  dioxide  tension  in  the  alveoli 
has  risen  to  its  normal  value.  As  a  result  of  the  excitation  by  oxygen  lack,  a 
few  breaths  are  taken,  the  carbon  dioxide  tension  is  once  more  lowered 
tod  the  stimulation  due  to  the  oxygen  lack  disappears.  There  is  thus 
again  a  cessation  of  respiration.  These  periods  of  cessation  alternate  with 
periods  of  respiration,  so  that  we  get  a  condition  of  periodic  breathing  which 
is  spoken  of  as  Cheyne-Stokes  respiration.      During  the  period  of  apncea 


REGULATION   OF   THE   RESPIRATORY   MOVEMENTS      1147 

resulting  on  forced  breathing,  the  great  diminution  of  oxygen  tension  in 
the  alveoli  is  shown  by  the  fact  that  the  subject  of  the  experiment  becomes 
blue,  and  may  indeed  lose  consciousness.  There  are  at  the  same  time 
rhythmic  changes  in  the  blood  pressure,  which  rises  towards  the  ends  of 
the  periods  of  the  apncea.  falling  during  the  periods  of  respiration.  The  first 
respiration  after  forced  breathing  is  due  to  oxygen  lack.  The  period  of 
apncea  may  therefore  be  considerably  prolonged,  if  the  onset  of  oxygen 
lack  be  postponed  b)7  increasing  the  tension  of  this  gas  in  the  alveoli  at 
the  commencement  of  the  apnceic  period.  By  forcibly  breathing  for  a 
period  of  two  minutes  in  an  atmosphere  of  oxygen,  men  have  succeeded  in 
holding  their  breath  for  as  long  a  period  as  eight  minutes  (Vernon). 

'  Cheyne-Stokes '  breathing  is  almost  invariably  observed  as  one  of  the  effects  of 
exposure  to  high  altitudes,  and  is  then  especially  marked  during  sleep.  It  is  often  present 
when  the  activity  of  the  respiratory  centre  is  depressed,  as  in  cases  of  uraemia  or  per- 
nicious ansemia.  Under  these  circumstances  *it  may  be  temporarily'  removed  by 
administering  cither  oxygen  or  carbon  dioxide  (in  small  percentage)  to  the  patient. 
The  oxygen  improves  the  condition  of  the  centre:  the  carbon  dioxide  acts  as  an  added 
Stimulus  and  louses  its  activity. 


SECTION  IV 

THE  EFFECTS  ON  RESPIRATION   OF  CHANGES   IN 
THE   AIR   BREATHED 

We  have  already  seen  that  a  moderate  increase  in  the  carbon  dioxide  per- 
centage of  the  air  breathed  (e.g.  np  to  4  per  cent.)  causes  a  proportional 
increase  in  the  ventilation  of  the  lungs,  so  as  to  maintain  the  tension  of  this 
gas  in  the  alveoli  at  the  normal  level.  The  same  effect  is  observed  whether 
the  mixture  breathed  contains  18  or  50  per  cent,  of  oxygen,  showing  that  the 
slight  diminution  in  oxygen  content  caused  by  mixing  the  air  with  carbon 
dioxide  is  in  no  way  responsible  for  the  effect.  If  the  amount  of  carbon 
dioxide  be  increased  to  12  or  15  per  cent.,  it  becomes  almost  impossible  to 
continue  the  inhalation  owing  to  the  spasm  of  the  glottis  produced  by  the 
irritant  effects  of  the  carbon  dioxide.  If  these  high  percentages  be  ad- 
ministered to  an  animal  by  a  tracheal  tube,  violent  dyspnoea  is  produced 
which  gradually  diminishes,  and  the  animal  passes  into  a  condition  of 
narcosis  in  which  the  respiratory  movements  become  less,  and  the  oxygena- 
tion of  the  blood  is  ineffectively  carried  out  even  hi  the  presence  of  excess  of 
oxygen.  The  administration  of  larger  percentages,  such  as  30  or  40  per 
cent.,  causes  rapid  death  and  failure  of  the  circulation  and  respiration,  often 
preceded  by  convulsions.  Coincident  with  the  increased  respiration  brought 
about  by  moderate  percentages  of  carbon  dioxide,  there  is  a  rise  of  blood 
pressure  determined  by  vascular  constriction.  With  high  percentages  of 
carbon  dioxide  the  curve  of  blood  pressure  obtained  resembles  that  produced 
by  lack  of  oxygen. 

Oxygen  itself  exercises  no  excitatory  effects  on  the  respiratory  move- 
ments. At  the  normal  atmospheric  pressure  the  tension  of  oxygen  in  the 
alveoli  is  about  107  mm.  Hg.,  a  pressure  which,  as  we  have  seen,  is  amply 
sufficient  to  saturate  the  haemoglobin  passing  through  the  vessels  of  the 
lungs.  Since  the  depth  and  frequency  of  respiration  are  determined  by  the 
carbon  dioxide  tension  in  the  alveoli,  no  alteration  in  respiration  will  be 
produced  by  increasing  the  tension  of  oxygen  in  the  air  breathed  above  its 
normal  amount.  The  respiratory  movements  in  an  atmosphere  of  pure 
oxygen  will,  in  the  normal  individual,  remain  unchanged. 

This  statement  is  true  only  for  the  healthy  individual.     If  from  failure  of  the  heart 
and  circulation,  from  diminished  oxygen  tension,  or  from  severe  loss  of  blood,  the  oxy- 

1148 


EFFECTS  ON  RESPIRATION   OF  CHANGES  IN  AIR    1149 

genation  of  the  blood  is  already  insufficient,  marked  amelioration  of  the  symptoms  may 
be  produced  by  inhalation  of  pure  oxygen.  Especially  is  this  noticeable  where  there  is 
failure  of  the  heart.  In  these  cases  the  heart,  already  affected,  is  unable  to  keep  up  an 
adequate  circulation  and  to  supply  itself  with  sufficient  oxygen.  A  vicious  circle  is  thus 
established  in  which  the  heart  tends  to  get  steadily  worse.  By  administration  of  oxygen 
an  adequate  supply  of  this  gas  to  the  heart  muscle  is  assured;  the  heart  beat  therefore 
becomes  more  effective  and  the  whole  circulation  is  improved  and  therewith  the  provision 
of  oxygen  to  the  body  at  large. 

If  a  warm-blooded  animal  be  immersed  in  a  chamber  and  submitted  to 
pure  oxygen  at  a  pressure  of  four  atmospheres,  it  dies  as  rapidly  as  if  it  were 
in  an  atmosphere  of  pure  nitrogen.  At  this  pressure  the  oxidative  processes 
of  the  body  as  well  as  the  intake  of  oxygen  into  the  lungs  are  absolutely 
abolished.  It  is  interesting  to  note  that  certain  other  oxidative  phenomena, 
e.  g.  the  spontaneous  oxidation  of  phosphorus,  also  cease  if  the  tension  of  the 
oxygen  be  sufficiently  high.  Exposure  of  an  animal  over  a  considerable 
period  of  time  to  a  pressure  of  oxygen  of  two  atmospheres  may,  as  Haldane 
and  Lorrain  Smith  have  shown,  set  up  severe  inflammation  of  the  lungs  and 
thereby  cause  death  indirectly. 

CHANGES  IN  TENSION  OF  OXYGEN.  If  a  man  breathe  a  mixture  of 
nitrogen  and  oxygen  free  from  carbon  dioxide,  and  the  oxygen  be  gradually 
diminished,  no  feeling  of  'want  of  breath'  may  be  experienced.  With 
percentages  of  oxygen  as  low  as  12  per  cent,  there  may  be  no  change  in  the 
respiration,  even  though  the  deficient  oxygenation  of  the  blood  may  be 
shown  by  the  blueness  of  the  lips  and  face.  If  the  oxygen  be  reduced  still 
lower,  a  certain  amount  of  hyperpncea  may  occur,  but  in  many  cases  the 
individual  experimented  on  may  not  feel  any  ill  effects  until  he  suddenly 
becomes  unconscious  from  lack  of  oxygen.  If  fresh  oxygen  be  not  supplied 
this  unconsciousness  may  be  followed  by  convulsive  movements  and  death. 
If  the  administration  of  low  percentages  of  oxygen,  e.  g.  about  10  to  12 
per  cent,  of  an  atmosphere,  be  continued  for  some  time,  the  subject  of  the 
experiment  may  suffer  considerable  discomfort.  One  of  the  signs  of  oxygen 
lack  is  often  severe  headache,  and  this  may  be  accompanied  by  vomiting  or 
nausea  and  by  a  feeling  of  discomfort  in  the  precordial  region.  Many 
experiments  have  been  made  both  on  animals  and  man  by  submitting  them 
to  a  lowered  atmospheric  pressure  in  chambers  specially  built  for  the 
purpose.  The  limit  to  which  the  pressure  may  be  reduced  varies  in  different 
individuals,  the  variations  being  determined  by  the  type  of  respiratory 
movement  of  the  individual  in  question,  since  on  the  depth  of  respiration 
depends  the  relation  between  the  tension  of  oxygen  in  the  alveoli  and  that 
in  the  inspired  air.  The  lowest  limit  at  which  life  is  possible  corresponds 
to  an  oxygen  tension  in  the  alveoli  of  27  to  30  mm.  Hg. 

MOUNTAIN  SICKNESS.  The  phenomena,  just  described  as  ensuing  on 
exposure  of  an  animal  to  low  oxygen  tensions  in  a  respiratory  chamber  for 
some  length  of  time,  are  exactly  similar  to  those  which  are  regarded  as 
characteristic  of  mountain  sickness.  The  following  Table  shows  the 
diminution  in  the  atmospheric  pressuie  at  varying  heights  above  the  level 
of  the  sea  : 


1150 


PHYSIOLOGY 


Height  above  sea  level, 

Barometer 

Per  cent,  of  au 

in  metres 

mm.  Hg. 

atmosphere 

0 

760 

100 

1000 

670 

88 

2000 

593 

78 

3000 

524 

69 

4000 

463 

61 

5000 

410 

54 

6000 

357 

47 

7000 

320 

42 

At  a  height  of  5000  metres  the  pressure  of  the  air  is  reduced  to  little 
over  half  an  atmosphere,  and  the  oxygen  tension  is  therefore  only  about 
11  per  cent,  of  an  atmosphere.  It  must  be  remembered  that  in  most  cases 
of  mountain  sickness,  in  addition  to  this  absolute  oxygen  lack,  there  is 
increased  consumption  of  oxygen,  owing  to  the  muscular  exercise  involved 
in  climbing.  Moreover  a  greater  volume  of  the  alveolar  air  must  consist 
of  Carbon  dioxide  if  the  tension  of  this  gas  is  to  be  kept  constant  (cp.  Fig.  519, 
p.  1132).  Since,  diminished  oxygen  tension,  within  fairly  wide  limits,  does 
not  excite  any  corresponding  increase  in  the  respiratory  movements,  there 
must,  at  these  heights,  be  an  actual  diminution  in  the  oxygen  tension  in  the 
alveoli.  This  diminution  in  tension  is  shown  by  a  series  of  observations 
carried  out  by  Zuntz  on  himself  and  fellow- workers  at  different  localities. 
It  may  be  noted  that  on  Monte  Rosa,  where  the  oxygen  tension  in  the 
alveoli  was  reduced  to  between  37  and  57  mm.  Hg.,  as  against  the  normal  101 
to  105  nun.  Hg.,  all  the  members  of  the  party  were  suffering  from  mountain 
sickness. 


Height 

Ub'ivr  sra 

level, 
in  metres 

02 
tension 
of  air 

Alveolar  O-j  tensior 

A 

B 

c 

D 

1 

F 

104 

Berlin    . 

54 

157 

105 

101 

105 

103 

Brienz  . 

500 

148 

84-5 

94 

80 

88 

86 

91 

Brienzer  Rothorn    . 

2130 

121 

68 

66 

64 

62 

66 

71 

Col  d'Olen      . 

2900 

110 

57 

— 

— 

60 

68 

68 

Monte  Rosa   . 

4560 

89 

— 

46 

49 

61 

37 

57 

As  a  result  of  the  oxygen  starvation  there  is  inadequate  supply  of  this 
gas  to  the  heart,  so  that  the  circulation  tends  to  fail,  especially  on  making 
the  slightest  muscular  movements.  At  the  same  time  the  oxygen  starva- 
tion of  the  brain  produces  failure  of  judgment  and  inability  to  carry  out  or  to 
co-ordinate  muscular  movements  properly.  The  symptoms  as  a  rule  do  not 
increase  until  death  results,  so  that,  although  there  is  an  oxygen  starvation 
of  the  body,  there  must  be  some  means  by  which  the  respiration  is  modified 
so  as  to  obtain  a  sufficiency  of  this  gas  for  the  lowered  requirements  of  the 
body.     That  the  adaptation  is  effective  is  shown  by  the  fact  that  most 


EFFECTS  ON  RESPIRATION   OF  CHANGES  IN  AIR    1151 

individuals,  if  they  remain  at  a  height,  gradually  recover  from  the  mountain 
sickness  and  may  finally  be  able  to  carry  out  muscular  movements  with 
almost  as  great  precision  and  force  as  they  could  previously  on  the  plains. 
The  mechanism,  by  which  increased  ventilation  of  the  lungs  is  attained,  is 
that  already  mentioned  (p.  1136)  in  dealing  with  the  effects  of  lack  of  oxygen, 
namely,  the  production  of  acid  substances  in  the  body.  The  respiratory 
centreisthus  stimulated  by  these  acid  substances,  especially  lactic  acid,  as  well 
as  by  the  carbon  dioxide  tension  of  the  blood ;  and  the  joint  action  of  these 
two  substances  (which  probably  co-operate  in  raising  the  hydrion  concen- 
tration of  the  blood)  determines  the  marked  increase  in  the  lung  ventilation. 
Since  the  carbon  dioxide  is  no  longer  the  sole  factor  responsible  for  the 
ventilation,  the  tension  of  this  gas  in  the  alveolar  air  is  diminished. 

ACAPNIA.  This  diminution  of  carbon  dioxide  tension  in  the  blood  and  alveolar  air 
has  been  regarded  by  Mosso  as  the  essential  factor  in  the  causation  of  mountain  sickness 
and  has  been  designated  acapnia.  It  may  be  absent  however  in  the  most  marked 
cases  of  mountain  sickness,  where  the  respiratory  centre  has  failed  to  respond  to  the 
additional  acid  stimulation ;  and  it  may  be  present  to  a  marked  degree  in  individuals 
who  are  experiencing  none  of  the  ill-effects  of  this  "disorder. 

Another  important  means  of  rapid  adaptation  is  by  means  of  the  circula- 
tion. This  is  noticeable  even  in  the  case  of  persons,  sitting  quietly  in  a 
gas  chamber,  who  are  subjected  to  gradually  lower  pressures.  It  is  evident 
that  a  deficient  passage  of  oxygen  from  the  alveoli  to  the  blood  may,  so 
far  as  the  tissues  and  heart  are  concerned,  be  accommodated  for  by  in- 
creasing the  rapidity  of  the  circulation,  and  this  is  effected  by  a  quickening 
pulse  rate.  The  following  Table  shows  the  changes  in  the  pulse  rate 
caused  by  exposure  to  varying  pressures  in  a  gas  chamber : 

Pui.se  in  Gas  Chamber 

Pres*nre  PuLse 

720 64 

650 72 

424 84 

This  quickening  of  the  pulse  is  to  be  observed  also  in  the  trained  mountain 
soldier,  in  individuals  in  whom  there  is  no  lowering  of  the  alveolar  carbon 
dioxide  tension,  so  that  apparently  in  such  cases  the  whole  adaptation  to 
altered  conditions  is  by  means  of  the  circulation.  In  cases  where  adaptation 
fails,  it  is  in  the  circulation  that  the  failure  is  most  marked,  so  that  the 
symptoms  of  severe  mountain  sickness  resemble  closely  those  produced  by 
rapid  heart  failure.  Dilated  heart,  cyanosis,  muscular  weakness,  vomiting, 
mental  torpor,  inco-ordination,  delirium,  may  all  be  observed  in  both  cases. 
The  disturbance  of  the  central  nervous  system  is  shown  by  the  almost 
invariable  occurrence  at  great  heights  of  Cheyne-Stokes  breathing. 

If  the  animal  is  able  to  withstand  the  immediate  effects  of  exposure  to  a 
rarefied  atmosphere,  a  process  of  adaptation  comes  into  play  which  finally 
fits  him  for  discharging  his  functions  normally  even  at  the  high  altitude. 
From  the  lack  of  sensibility  of  the  respiratory  centre  to  small  changes  in 


1152 


PHYSIOLOGY 


oxygen  tension,  any  diminution  in  oxygen  tension  must  cause  a  corresponding 
diminution  in  the  degree  of  saturation  of  the  haemoglobin  of  the  blood.  This 
change  in  oxygen  saturation  is  at  once  felt  by  the  blood-forming  organs. 
As  an  immediate  effect  of  change  to  a  region  of  low  atmospheric  pressure, 
there  is  a  relative  increase  in  the  blood  corpuscles  due  to  a  concentration 
of  the  blood  and  a  diminution  of  its  plasma.  Simultaneously  however 
the  blood-forming  organs  enter  into  a  condition  of  increased  activity,  so 
that  after  a  stay  of  four  or  five  weeks'  duration  at  a  height,  both  corpuscles 
and  haemoglobin  are  considerably  increased  in  total  amount.  The  following 
Table  shows  the  average  number  of  red  corpuscles  contained  in  one  cubic 
millimetre  of  blood  from  the  inhabitants  of  regions  at  varying  altitudes  : 


Height  above  sea 

level, 

in  metres 

Red  corpuscles 

Cliristiauia    . 

0 

4,970,000 

Zurich 

412 

5,752,000 

Davos  . 

1560 

6,551,000 

Arosa   . 

1800 

7,000,000 

Cordilleras     . 

4392 

8,000,000 

There  is  of  course  a  limit  to  the  power  of  adaptation,  a  limit  which  varies 
in  different  individuals.  Thus  for  some  men  it  is  impossible  to  stay  any 
length  of  time  in  the  high  settlements  in  the  Andes,  while  others,  after  two 
or  three  weeks'  discomfort,  become  perfectly  inured  to  their  new  conditions. 
It  seems  doubtful  however  whether  any  of  the  present  race  of  men  could 
become  adapted  to  permanent  residence  at  a  height  over  5000  metres,  and 
though  for  a  certain  length  of  time  by  bringing  into  play  the  reserve 
mechanisms  already  described,  they  may  raise  themselves  to  a  height 
considerably  above  5000  metres,  it  seems  questionable  whether  without 
artificial  means,  such  as  the  inhalation  of  oxygen,  it  will  be  possible  for 
any  man  to  attain  the  highest  points  on  the  earth's  surface,  or  at  any  rate 
to  arrive  there  by  his  own  unaided  efforts.  The  highest  summits  in  the 
Himalayas  have  a  height  approaching  that  attained  by  Tissandier  with  his 
two  companions  in  his  famous  balloon  ascent,  namely,  8600  metres.  In  this 
ascent,  although  oxygen  inhalation  was  used  (somewhat  ineffectively),  two 
of  the  party  succumbed. 

The  stimulating  effect  of  oxygen  lack  on  the  blood-forming  organs 
extends  also  to  the  muscular  system,  so  that  one  of  the  effects  of  a  residence 
in  high  altitudes  is  increased  assimilation  of  nitrogen.  For  a  time  the 
nitrogen  output  is  less  than  the  nitrogen  intake,  and  there  is  an  actual 
building  up  of  new  tissue.  The  condition  of  the  individual  is  similar  to  that 
of  a  growing  animal,  a  fact  which  may  explain  the  admirable  results  of  a 
mountain  holiday.  We  can  hardly  imagine  that  the  power  of  the  organism 
to  react  in  this  way  was  evolved  through  generations  of  mountain  climbing. 
We  are  probably  here  making  use  of  an  adaptation  which  has  been  evolved 
for  the  purpose  of  retrieving  loss  of  blood  by  haemorrhage,  such  as  must  have 


EFFECTS  ON  RESPIRATION  OF  CHANGES  IN  AIR    1153 

been  of  continual  occurrence  in  the  struggle  of  individual  against  individual, 
which  has  resulted  in  the  survival  of  the  animals  of  to-day. 

ALTERATIONS  IN  THE  NITROGEN  TENSION.  The  nitrogen  of  the 
atmosphere  plays  no  part  in  the  metabolism  of  the  body,  and  must  be 
regarded  as  a  purely  inert  gas.  It  is  a  matter  of  indifference  whether  under 
normal  atmospheric  pressure  we  breathe  an  atmosphere  of  pure  oxygen  or 
one  containing  one-fifth  part  of  this  gas  diluted  with  four-fifths  of  nitrogen. 
The  very  inertness  of  nitrogen  may  be  of  danger  to  the  body  under  certain 
conditions.  If  a  man  or  an  animal  be  exposed,  as  in  a  diving-bell,  to  a 
pressure  of  three,  four,  or  six  atmospheres,  the  respiratory  functions  are 
unaffected,  but  the  amount  of  nitrogen  dissolved  in  the  fluids  of  the  body 
is  increased  in  direct  proportion  to  the  pressure.  If  the  pressure  be  now 
suddenly  released,  the  nitrogen,  which  cannot  be  used  up  by  the  tissues,  is 
given  off  from  the  body  fluids  in  the  form  of  bubbles,  just  as  carbonic  acid 
gas  rises  in  bubbles  from  soda-water  when  the  pressure  is  removed  by  with- 
drawing the  cork  from  the  bottle.  These  bubbles  occurring  in  all  the 
capillaries  obstruct  the  flow  of  blood,  and  therefore,  if  the  evolution  of  gas  is 
sufficiently  large,  the  animal  dies  in  convulsions.  A  similar  evolution  of  gas 
may  occur  in  the  spinal  cord,  giving  rise  to  destruction  of  the  cord  and 
paralysis  ('  divers'  palsy ').  In  order  to  prevent  this  sudden  evolution  of 
gas  it  is  necessary  that  the  change  from  the  high  pressure  to  the  ordinary 
atmospheric  pressure  should  be  carried  out  gradually,  so  as  to  give  the 
blood  plasma,  supersaturated  with  nitrogen,  time  to  get  rid  of  its  excess  of 
nitrogen  without  the  formation  of  bubbles. 

OTHER  GASES.  Hydrogen  and  methane  are,  like  nitrogen,  indifferent 
gases.  They  may  be  respired  if  mixed  with  20  per  cent,  of  oxygen,  and 
either  of  the  gases  may  be  used  instead  of  nitrogen  to  dilute  the  oxygen  that 
we  breathe,  without  harm  or  inconvenience. 

Carbon  monoxide  is  rapidly  poisonous  by  its  action  on  the  red  corpuscles. 
It  combines  with  haemoglobin,  forming  CO-haemoglobin,  a  compound  which 
is  much  more  stable  than  oxyhaemoglobin.  The  blood  is  therefore  deprived 
of  its  oxygen  carrier,  and  the  animal  dies  of  asphyxia.  We  have  seen 
however  that  the  displacement  of  oxygen  by  CO  is  not  absolute,  but  only 
relative.  Hence,  although  the  avidity  of  CO  for  haemoglobin  is  140  times 
that  of  oxygen,  we  can  convert  the  CO  back  into  oxyheemoglobin  by  in- 
creasing the  mass  influence  of  the  oxygen.  This  may  be  done  by  giving  the 
poisoned  animal  pure  oxygen  to  breathe,  or  even  oxygen  under  pressure. 
In  pure  oxygen  at  a  pressure  of  two  atmospheres  an  animal  can  breathe  and 
live,  even  though  the  whole  of  its  haemoglobin  is  converted  into  CO-haemo- 
globin, the  amount  of  oxygen  which  is  simply  dissolved  by  the  blood  plasma 
being  sufficient  at  this  pressure  for  the  respiratory  needs  of  the  animal 
(Haldane). 

Other  gases  which  have  special  poisonous  properties  are  hydrocyanic 
acid,  sulphuretted  hydrogen,  phosphuretted  hydrogen  (PH3),  arseniuretted 
hydrogen,  etc. 

IRRESPIRABLE  GASES  are  those  which  are  so  irritating  that  they 
73 


1154  PHYSIOLOGY 

produce  spasm  of  the  glottis.    Such  are  ammonia,  chlorine,  sulphur  dioxide, 
nitric  oxide,  and  many  others. 

VENTILATION 

A  point  of  practical  importance  is  the  securing  to  each  individual  of 
sufficient  fresh  air,  so  that  he  may  always  have  a  plentiful  supply  of  oxygen, 
and  may  be  relieved  of  his  waste  products.  It  is  found  that  a  dwelling-room 
becomes  unpleasant  and  stuffy  when  the  percentage  amount  of  C02  has 
reached  0-1  per  cent.  This  stuffiness  is  supposed  to  be  due  to  organic 
exhalations  from  the  skin,  lungs,  and  alimentary  canal,  some  of  which  have 
a  poisonous  effect,  giving  rise  to  headache  and  sleepiness.  Since  these 
cannot  be  measured,  it  is  taken  as  a  cardinal  rule  in  ventilation  that  the 
amount  of  C02  should  never  rise  above  0-1  per  cent. 

Since  in  questions  of  ventilation  we  have  generally  to  deal  with  trades  in 
which  the  metric  measure  is  not  used,  it  may  be  convenient  to  give  the  data 
as  to  carbon  dioxide  production  and  the  amount  of  air  required  in  cubic  feet. 

An  adult  man  gives  off  about  0-6  cubic  foot  of  C02  every  hour  Hence 
in  that  time  he  raises  the  amount  of  C02  in  1000  cubic  feet  of  air  from  "04 
per  cent,  (the  normal  amount  in  the  atmosphere)  to  0-1  per  cent.  He  must 
therefore  be  supplied  with  2000  cubic  feet  of  air  per  hour  in  order  to  keep 
the  amount  of  C02  down  to  -07  per  cent. 

(Ordinary  air  contains  -04  per  cent.  CO,,  therefore  2000  cubic  feet  would 
contain  0-8  cubic  foot  C02,  which  with  the  0-6  cubic  foot  given  off  by  the 
man  would  be  1-4,  which  is  -07  per  cent.) 

In  order  that  the  air  may  be  easily  renewed  without  giving  rise  to  exces- 
sive draught,  a  certain  amount  of  cubic  space  must  be  allotted  to  each  man. 
Each  adult  should  have  in  a  room  1000  cubic  feet  of  space,  and  be  supplied 
every  hour  with  2000  to  3000  cubic  feet  of  air. 


SECTION  V 

THE  MECHANISMS   OF   OXIDATION   IN   THE  TISSUES 

The  blond  in  its  passage  through  the  capillaries  takes  up  carbon  dioxide 
from  the  tissues,  giving  oxygen  to  the  latter  in  exchange.  This  interchange 
is  determined  by  the  differences  in  tension  of  the  gases  on  the  two  sides  of 
the  capillary  wall.  Whereas  the  tension  of  oxygen  in  the  plasma  varies 
from  loo  mm.  Hg.  in  arterial  to  25  mm.  Hg.  in  venous  blood,  the  tension  of 
oxygen  in  the  tissues  outside  the  vessels  in  most  cases  approaches  0,  as  is 
shown  by  Ehrlich's  methylene-blue  experiment  described  on  p.  111-1.  On 
the  other  hand,  the  tension  of  carbon  dioxide  in  the  tissues,  as  judged  from 
the  examination  of  fluids  such  as  bile  and  urine,  varies  from  6  to  10  per  cent, 
of  an  atmosphere.  The  continuous  flow  of  oxygen  into,  and  of  carbon 
dioxide  away  from,  the  tissues  points  to  the  constant  occurrence  of  oxidative 
changes  in  the  tissue  cells.  By  the  blood  the  tissues  receive  not  only  oxygen 
but  also  foodstuffs,  namely,  proteins  or  amino-acids,  fats,  and  sugars, 
derived  from  the  alimentary  canal  or,  in  starvation,  from  other  parts  of  the 
body.  The  activity  of  the  tissues,  whether  motor  as  in  the  case  of  muscle, 
or  secretory  as  in  the  case  of  glands,  is  derived  from  the  energy  set  free  in 
the  partial  or  complete  oxidation  of  these  foodstuffs,  which  occurs  within 
the  active  cells  themselves.  A  study  of  the  mechanism  of  oxidation  in  the 
body  involves  therefore  a  consideration  of  the  processes  which  take  place 
within  the  confines  of  each  cell.  The  question  is  by  no  means  an  easy  one. 
Although  we  speak  of  the  'burning'  of  foodstuffs,  and  compare  the  pro- 

in  the  body  to  those  which  take  place  in  combustion,  e.g.  in  a  candle- 
flame,  the  analog}  is  after  all  a  very  rough  one.  In  the  first  place,  the  food- 
stuffs, even  after  absorption,  belong  to  a  class  of  substances  which  have  been 

led  as  dysoxidisabh,  since  they  present  no  tendency  to  combine  with 
ordinary  atmospheric  oxygen.  Thus  sugars,  proteins,  or  fats,  if  guarded 
from  microbial  infection,  may  be  kept  for  years  exposed  to  the  air  without 
irgoing  any  change.  It  is  true  that  in  certain  eases,  e.g.  in  alkaline 
solutions  of  sugar,  we  may  obtain  slow  absorption  of  oxygen  and  oxidation 
of  the  sugar.  The  changes  are  however  slight  and  limited  in  extent.  All 
these  foodstuffs  are  susceptible  of  combustion  if  raised  to  a  sufficiently  high 
temperature,  but  in  the  animal  body  the  processes  of  oxidation  have  to  go 
.mi  at  a  temperature  varying  between  5°  and  40°  C,  and  in  a  solution  which 
is  almost  neutral  in  reaction.  It  might  be  said  that  at  the  temperature  of 
an  ordinary  flame  th.'  combustion  of  tin'  foodstuffs  is  immediate  and 
Complete,  whereas  in  the  body  the  oxidation  takes  place  by  stages.     Recent 

1155 


1156  PHYSIOLOGY 

research  has  tended  to  remove  this  point  of  distinction  by  pointing  out  that 
even  in  an  explosion  of  a  mixture  of  methane  and  oxygen  there  is  a  series 
of  intermediary  products,  and  that  the  whole  process,  if  analysed,  is  made 
up  of  stages  in  which  hydrolysis  and  oxidation  go  on  simultaneously,  so 
that  on  this  account  it  is  difficult  to  cause  a  combination,  even  of  hydrogen 
and  oxygen,  in  the  complete  absence  of  any  watery  vapour.  The  oxidations 
in  the  body  are  strictly  limited  both  in  nature  and  extent.  The  mere  fact 
that  a  substance  is  readily  or  even  spontaneously  oxidisable  (autoxidisable) 
affords  no  guarantee  that  it  will  undergo  oxidation  in  the  animal  body. 
Thus  phosphorus  or  pyrogallol  taken  by  the  mouth  can  be  recovered  in  an 
unoxidised  form  from  the  urine.  Carbon  monoxide  is  excreted  unchanged. 
There  must  apparently  be  some  definite  relationship  between  the  molecular 
structure  of  the  foodstuffs  and  that  of  the  cells  of  the  body.  Thus  ordinary 
proteins,  which  undergo  complete  oxidation,  contain  large  quantities  of 
leucine.  This  substance  is  laevorotatory  and  is  designated  Meucine.  If 
Meucine  be  administered  to  rabbits  it  is  completely  oxidised.  If  its  isomer 
(Z-leucine,  resembling  it  in  every  particular,  so  far  as  we  can  see,  except  in 
its  relation  to  polarised  light,  be  administered  to  a  rabbit,  the  greater  part 
of  the  substance  passes  through  the  body  unchanged.  In  the  same  way 
there  are  sixteen  sugars  of  the  formula  C6H1206.  Of  these  only  four,  namely, 
glucose,  fructose,  galactose,  and  mannose,  can  be  oxidised  in  the  animal 
body.  Other  sugars  differing  in  so  slight  a  degree  from  these  four  as, 
e.  g.,  Z-glucose  or  Z-fructose,  camiot  be  utilised  by  the  body.  Not  only  must 
there  be  a  distinct  relation  between  the  structure  of  the  cell  and  the  molecular 
structure  of  the  foodstuff  supplied,  but  there  must  be  different  mechanisms 
for  the  foodstuffs  and  their  derivatives.  Thus  in  certain  cases  of  disease 
or  of  abnormal  nutrition  the  body  may  lose  absolutely  the  power  of  utilising, 
%.  e.  of  oxidising,  a  whole  class  of  foodstuffs.  In  severe  diabetes,  or  after 
destruction  of  the  pancreas,  glucose  behaves  in  the  body  as  if  it  were  one 
of  the  artificial  unassimilable  sugars.  The  normal  oxidation  of  fats  probably 
proceeds  by  stages  in  each  of  which  two  atoms  of  carbon  undergo  oxidation. 
The  penultimate  stage  in  the  oxidation  of  any  of  the  higher  fatty  acids  is 
thus  oxvbutyric  acid.  In  complete  carbohydrate  starvation,  for  some 
reason  or  other  the  body  loses  its  power  of  completing  this  last  stage,  so 
that  the  oxybutyric  acid  undergoes  no  further  oxidation,  and  either  accumu- 
lates in  the  body  or  is  excreted  combined  with  bases  in  the  urine.  In  the 
normal  individual  tyrosine,  whether  administered  separately  or  in  combina- 
tion in  protein,  is  completely  oxidised,  the  benzene  ring  being  broken  up. 
In  certain  rare  cases  of  disordered  metabolism  the  patient,  who  is  otherwise 
apparently  well,  is  unable  to  effect  the  total  oxidation  of  tyrosine,  which 
is  therefore  excreted  as  homogentisic  acid,  after  undergoing  only  the  first 
stage  of  its  normal  transformation  in  the  body.  These  various  mechanisms 
are  adjusted  in  each  case  to  the  functional  activity  of  the  cell  and  are  limited 
therefore,  not  by  the  supply  of  oxygen  or  of  foodstuff  to  be  oxidised,  but 
by  the  necessities  of  the  cell,  i.  e.  the  adaptations  induced  in  it  by  its  environ- 
mental changes.     In  discussing  the  mechanism  of  intracellular  oxidation 


THE  MECHANISM  OF  OXIDATION   IN  THE  TISSUES    1157 

we  have  therefore  to  consider  in  the  first  place  how  the  dysoxidisable 
foodstuffs  are  made  to  combine  with  the  molecular  oxygen  diffusing  into 
the  cells  from  the  blood  in  the  capillaries;  in  the  second  place  the  means 
by  which  these  oxidative  changes  are  strictly  limited  in  accordance  with 
the  necessities  of  the  cell ;  and  finally  the  nature  of  the  specific  oxidative 
mechanisms  for  each  land  of  foodstuff  and  for  the  various  stages  in  the 
oxidation  of  each  foodstuff. 

We  are  very  far  as  yet  from  being  able  to  give  a  definite  answer  to  any 
one  of  these  questions.  Even  in  the  first  problem,  namely,  the  oxidation 
of  dysoxidisable  substances,  we  have  to  confine  ourselves  almost  exclusively 
to  speculation  on  possibilities.  Although  these  substances  will  not  unite 
with  the  oxygen  of  the  air,  in  which  the  combining  activities  of  the  oxygen 
are  satisfied  by  the  combmation  of  two  atoms  to  form  one  molecule,  many 
of  them  readily  undergo  oxidation  if  subjected  to  the  action  of  '  atomic ' 
oxygen  or  '  active  '  oxygen ;  and  it  has  been  suggested  that  the  problem  of 
the  oxidation  of  the  body  is  really  bound  up  with  the  question  as  to  the 
mode  of  activation  of  the  molecular  oxygen  derived  from  the  oxyhemoglobin. 
Thus  Hoppe-Seyler  suggested  that  the  activation  of  oxygen  might  occur 
through  the  intermediation  of  reducing  substances.  He  supposed  that 
reducing  substances  might  be  formed  under  the  influence  of  ferments  by 
hydrolytic  splitting  of  the  foodstuffs.  A  reducing  substance  is  one  that 
has  sufficient  affinity  for  oxygen  at  the  ordinary  temperature  to  tear  asunder 
the  bonds  which  unite  two  atoms  of  oxygen  to  form  one  molecule,  and  to 
combine  with  one  or  both  of  the  atoms  so  set  free.  If  the  combination  is 
with  only  one  atom,  the  other  atom  of  the  oxygen  molecule  is  set  free  in  an 
active  form,  and  is  therefore  able  to  oxidise  dysoxidisable  substances  which 
may  be  present.  Thus,  when  a  mixture  of  ammonia  and  pyrogallol  is 
exposed  to  the  atmosphere,  the  oxygen  is  rapidly  absorbed,  forming  a  dark 
brown  solution,  pyrogallol  being  therefore  a  reducing  agent.  But  at  the 
same  time  a  certain  amount  of  the  ammonia  (a  dysoxidisable  substance) 
undergoes  oxidation  with  the  formation  of  nitrite.  In  the  slow  spontaneous 
oxidation  of  phosphorus,  which  occurs  on  exposing  this  substance  to  the 
atmosphere,  ozone,  020,  is  always  formed.  As  a  type  of  the  formation  of 
reducing  substances  in  hydrolytic  fermentations  may  be  adduced  the  butyric, 
acid  fermentation,  in  which  sugar  is  converted  into  butyric  acid,  carbonic 
acid,  and  hydrogen  : 

C6H1206  =  C4H802  +  2C02  +  2H2. 

The  hydrogen  produced  in  this  process  would  act  as  a  reducing  agent. 
There  is  no  doubt  that  reducing  substances  are  formed  under  normal  circum- 
stances in  the  tissues,  as  is  shown  by  the  methylene-blue  experiment,  and 
it  is  possible  that  such  reducing  substances  may  aid  in  activating  oxygen 
and  in  bringing  about  certain  oxidative  processes.  The  activation  of 
oxygen  would  however  not  explain  the  specific  character  of  the  various 
oxidations,  and  the  accurate  gradation  of  these  oxidations  to  the  necessities 
of  the  cell.     In  many  cases  reducing  substances  may  themselves  act  as 


1158  PHYSIOLOGY 

carriers  of  oxygen,  and  their  action  be  more  or  less  specific.  If  for  instance 
glucose  be  boiled  with  an  ammoniacal  solut  inn  of  cupric  hydrate,  it  undergoes 
oxidation,  the  cupric  being  reduced  to  cuprous  hydrate.  Cuprous  hydrate 
in  ammoniacal  solution  is  a  reducing  .substance;  it  absorbs  oxygen  from 
the  air  and  is  reconverted  to  cupric  hydrate.  A  small  amount  of  cupric 
hydrate  therefore,  in  the  presence  of  air,  may  act  as  a  carrier  of  oxygen  from 
the  air  to  the  sugar  and  may  thus  oxidise  indefinitely  large  quantities  of 
sugar.  In  the  same  way,  if  indigo  in  alkaline  solution  be  boiled  with  sugar, 
it  undergoes  reduction  with  the  formation  of  a  colourless  compound.  On 
shaking  the  decolorised  solution  with  air,  it  absorbs  oxygen  with  the  reproduc- 
tion of  indigo,  so  that  here  again  minute  quantities  of  indigo  blue  may  servo 
to  oxidise  large,  quantities  of  glucose.  The  mode  of  action  of  these  oxygen 
carriers  resembles  closely  that  of  the  various  ferments  which  effect  the 
transference  of  water  from  the  menstruum  to  the  substrate  {e.g.  trypsin. 
invertase,  etc.).  These  hydrolytic  ferments  differ  from  ordinary  hydrolytic 
agents,  such  as  dilute  acids,  in  the  specific  character  of  their  action.  Trypsin, 
for  instance,  will  hydrolyse  polypeptides  of  a  type  corresponding  to  those 
which  make  up  the  ordinary  food  products,  but  is  powerless  to  hydrolyse 
polypeptides  composed  of  artificial  amino-acids  which  are  the  optical  isomers 
of  those  occurring  in  the  body.  It  seems  possible  that  we  might  explain  the 
specific  oxidations  occurring  in  the  cell  by  assuming  the  presence  of  a  number 
of  ferments,  oxidases,  which  would  act  as  oxygen  carriers,  but  each  of  which 
would  be  able  to  act  only  on  a  certain  type  of  foodstuff  or  on  molecules 
of  a  given  configuration. 

Such  oxidative  ferments  have  been  described  as  existing  in  many  animal 
and  vegetable  extracts.  Many  species  of  fungus  contain  a  ferment  known 
as  tyrosinase,  from  the  fact  that,  when  it  is  added  to  solutions  of  tyrosine  in 
the  presence  of  air,  the  tyrosine  is  oxidised  with  the  formation  of  a  brown 
pigment.  The  same  ferment  is  able  to  effect  the  oxidation  of  other  aromatic 
substances.  The  browning  of  a  freshly  cut  potato  or  apple  on  exposure  to 
the  air  is  similarly  ascribed  to  the  oxidation  of  a  chromogen  by  the  oxygen 
of  the  air,  through  the  intermediation  of  an  oxidase  present  in  the  cells. 
If  benzyl  alcohol  or  salicyl  aldehyde  be  added  to  a  suspension  of  liver  cells 
in  blood,  and  air  be  allowed  to  bubble  through  the  mixture  for  some  time, 
the  alcohol  or  aldehyde  is  oxidised  to  the  corresponding  acid.  In  the  same 
way  xanthine  (C5H4N402)  added  to  a  mixture  of  spleen  pulp  and  defibrinated 
I  ili  K  >d  is  converted  into  uric  acid  (C5H4N403). 

Bach  and  Chodat  have  shown  that  in  many  cases  the  oxidase  is  not  a 
single  substance,  but  a  mixture  of  an  organic  peroxide  with  a  ferment, 
peroxidase,  which  has  the  property  of  splitting  off  atomic,  i.  e.  active  oxygen, 
from  the  peroxide.  These  peroxidases  have  the  same  effect  on  hydrogen 
peroxide.  They  must  be  distinguished  from  the  ferment  caialase,  which  is 
present  in  almost  all  animal  and  vegetable  tissues,  and  which  effects  a  rapid 
decomposition  of  hydrogen  peroxide  with  the  formation  of  molecular 
oxygen  : 

2H202  =  2H20  +  02. 


THE   MECHANISM   OF  OXIDATION   IN  THE  TISSUES    1159 

In  the  case  of  a  peroxidase  the  equation  would  be  represented  : 
H20„  =  H20  +  O'. 

In  chemistry  many  reactions  are  known  in  which  the  part  of  a  peroxidase 
is  played  by  an  inorganic  catalyst.  Thus  hydrogen  peroxide  effects  a  slow 
oxidation  of  many  organic  substances,  but  the  oxidation  is  enormously 
hastened-  if  to  the  mixture  be  added  a  trace  of  a  ferrous  salt  (Fenton's 
reaction).  The  same  part  may  be  played  by  salts  of  manganese,  and  it  is 
interesting  to  note  that  manganese  forms  an  essential  constituent  of  the 
peroxidase  laccase,  which  is  present  in  many  plants  and  is  responsible  for 
the  formation  of  the  Japanese  lacquer.  It  effects  a  specific  oxidation  of 
hydroquinone  and  pyrogallol.  The  oxidations  carried  out  by  the  use  of 
hydrogen  peroxide,  with  or  without  a  catalyst  or  peroxidase,  present  a 
close  resemblance  to  the  oxidations' occurring  in  the  animal  body.  Thus 
Dakin  has  shown  that  saturated  fatty  acids,  even  the  higher  members  of 
the  series,  are  gradually  oxidised  if  warmed  gently  with  hydrogen  peroxide 
in  the  presence  of  ammonia;  and  the  course  of  the  reaction  resembles  in 
many  respects  that  which,  on  other  grounds,  we  have  assumed  to  take  place 
in  the  normal  metabolism  of  the  body. 

We  have  no  evidence  that  hydrogen  peroxide  is  formed  at  any  time  in 
the  body,  though  there  is  some  reason  to  assume  its  formation  in  the  process 
of  carbon  assimilation -in  the  green  leaf.  If  we  adopt  the  views  of  Bach  and 
Chodat,  we  must  assume  that  every  animal  cell  contains  organic  peroxides 
as  well  as  peroxidases,  or  else  that  it  can  under  physiological  conditions 
form  these  substances.  Since  there  is  also  evidence  of  the  presence  of 
reducing  substances  in  the  cells,  we  may  conveniently  assume,  with  Ehrlich. 
that  distinct  side-chains  of  the  protoplasmic  molecule  have  specific  affinities 
for  oxygen.  When  all  these  affinities  are  saturated,  these  side-chains  will 
act  as  peroxides,  parting  with  their  oxygen  with  extreme  ease,  whereas 
when  the  greater  number  are  imsaturated,  the  resultant  effect  will  be  that 
of  a  reducing  agent.  The  same  protoplasmic  molecule  may  therefore, 
according  to  its  state  of  saturation  with  oxygen,  act  either  as  an  oxidising 
or  reducing  agent,  and  can  effect,  probably  through  the  intermediation  of 
specifically  adapted  oxidases,  the  oxidation  of  the  various  foodstuffs  stored 
up  as  the  paraplasm  of  the  cell.  Since  the  oxidative  processes  are  deter- 
mined, not  by  the  presence  of  oxygen  but  by  the  functional  activities  of 
the  tissue,  welmust  assume  that  the  peroxidases  are  not  preformed  in  the 
cell,  but  exist  as  precursors,  zymogens,  from  which  they  can  be  set  free  in 
accordance  with  the  necessities  of  the  cell. 

It  is  probable  that  many  of  the  foodstuffs  or  other  proximate  con- 
stituents are  not  directly  accessible  to  oxidation,  and  that  the  first  step  in 
their  utilisation  is  a  process  of  cleavage  or  hydrolysis,  which  itself  involves 
the  presence  of  specific  ferments.  Thus,  so  far  as  we  can  tell,  the  amino-acids 
undergo  deamination  before  oxidation.  They  can  thus  be  stored  up  in  the 
cell  either  free  or  in  the  form  of  protein,  and  present  no  point  of  attack  to 
oxygen  until  the  process  of  hydrolysis  and  deamination  has  taken  place.  This 
course  of  events  is  certainly  true  for  some  of  the  members  of  the  purine  group. 


CHAPTEE  XVII 

RENAL    EXCRETION 

SECTION  I 

THE  COMPOSITION  AND  CHARACTERS  OF  THE  URINE 

The  main  product  of  the  oxidation  of  carbon,  namely,  carbon  dioxide,  is 
discharged  by  the  lungs  and  to  a  slight  extent  by  the  skin.  Water,  taken 
as  such  with  the  food  but  also  derived  to  a  slight  extent  from  the  oxidation 
of  hydrogen,  is  got  rid  of  by  the  lungs,  skin,  and  kidneys.  The  salts  of 
heavy  metals,  e.g.  iron,  bismuth,  mercury,  when  administered,  are  excreted 
for  the  most  part  by  the  alimentary  canal.  A  certain  proportion  of  the 
pigmentary  waste  products  of  the  body,  derived  from  the  breakdown  of  the 
blood  pigment,  is  also  eliminated  with  the  faeces.  With  these  exceptions, 
practically  all  the  waste  products  resulting  from  metabolism  are  excreted 
in  the  urine  by  the  kidneys.  We  have  thus  to  seek  in  the  composition  of 
this  fluid  the  last  chapter  in  the  metabolic  history  of  a  large  number  of  the 
constituents  of  the  body.  Since  moreover  the  kidneys  may  excrete  almost 
any  substance  which  circulates  through  their  blood  vessels,  many  of  the 
intermediate  metabolites  may  be  found  in  minute  quantities  in  the  urine 
and  may  be  isolated  by  working  up  large  quantities  of  this  fluid. 
Under  pathological  conditions  these  metabolites  may  appear  in  the 
urine  in  larger  amounts  and  serve  then  as  an  index  to  some  inter- 
ference with  the  later  stages  in  the  metabolism  of  fats,  carbohydrates,  or 
proteins. 

The  composition  of  the  urine  must  therefore  be  a  variable  one,  according 
to  the  activity  of  the  body,  the  quantity  and  nature  of  the  food  taken,  and 
the  relative  amount  of  water  escaping  by  the  kidneys,  lungs,  and  skin 
respectively.  But  just  as  we  can  describe  a  normal  diet  for  an  adult  man 
of  average  weight,  so  we  can  describe  an  average  composition  for  the  urine. 
The  history  of  the  urinary  constituents  has  been  given  for  the  most  part  in 
the  chapter  dealing  with  the  metabolism  of  the  proximate  constituents  of 
the  food.  It  will  be  useful  however  to  enumerate  in  this  chapter  the  various 
constituents  of  the  urine  and  to  summarise  their  properties,  preparation, 
and  normal  significance. 

The  urine  of  man  is  a  clear  yellow  fluid  which  froths  when  shaken.  On 
standing,  a  cloud  of  mucus  is  deposited,  consisting  of  a  very  small  amount 
of  nucleoprotein  derived  from  the  epithelial  lining  of  the  bladder  and  urinary 

1160 


THE  COMPOSITION  AND  CHARACTERS  OF  THE  URINE     1161 

passages.  In  concentrated  urine  a  deposit  occurs  on  cooling.  This  deposit 
dissolves  when  the  urine  is  warmed,  and  consists  of  urates.  Under 
certain  circumstances  urine  is  turbid  as  it  is  passed,  but  in  this  case  the 
turbidity  generally  consists  of  earthy  phosphates  and  is  not  cleared  up 
by  heating. 

The  colour  of  the  urine  varies  with  its  concentration.  After  severe 
sweating  the  amount  of  water  excreted  by  the  kidneys  is  small,  and  the 
urine  is  therefore  concentrated  and  of  high  colour.  After  copious  draughts 
of  liquid  the  urine  may  be  very  pale  and  dilute. 

Ordinary  urine  has  an  aromatic  odour,  but  this  varies  largely  with  the 
character  of  the  food.  Many  food  substances  give  characteristic  odours, 
which  may  depend  on  alterations  undergone  by  them  in  their  passage 
through  the  body. 

The  specific  gravity  of  the  urine  is  proportional  to  its  concentration. 
Normally  it  is  1016  to  1020,  though  it  may  rise  as  high  as  1040  or  sink  as 
low  as  1002. 

The  molecular  concentration  of  the  urine  is  almost  always  greater  than 
that  of  the  blood.  Its  osmotic  pressure  may  be  measured  by  determining 
the  depression  of  freezing-point.  The  A  of  urine  normally  varies  between 
0-87  and  2-71  (A  of  blood  =  0-56).  After  copious  draughts  of  water  the 
depression  of  freezing-point  in  the  urine  may  be  less  than  that  of  serum,  and 
may  be  as  small  as  0-25. 

The  reaction  of  urine  is  generally  described  as  acid.  It  is  acid  to  litmus 
and  to  phenolphthalein.  This  is  due  to  the  fact  that  neutral  constituents 
of  the  food  give  rise  to  acid  end-products  in  metabolism.  The  sulphur  of 
proteins  is  converted  into  sulphuric  acid  and  the  phosphorus  of  lecithin 
into  phosphoric  acid.  .  There  is  thus  a  predominance  of  acid  radicals  over 
bases  in  ordinary  urine.  This  statement  however  applies  only  to  man  and 
to  carnivora.  In  the  food  of  herbivora  there  is  a  predominance  of  alkaline 
bases.  Vegetable  acids,  e.g.  tartaric,  malic,  and  citric  acids,  midergo 
oxidation  to  carbonic  acid  in  the  body,  so  that  their  bases  leave  the  body  as 
alkaline  carbonates.  The  urine  of  such  animals  therefore  contains-  an 
excess  of  alkaline  carbonates,  and  is  alkaline  in  reaction  and  froths  on  the 
addition  of  an  acid.  If  a  herbivorous  animal  be  starved  so  that  it  has  to 
live  on  its  own  tissues,  it  becomes  for  the  time,  so  to  speak,  carnivorous, 
and  its  urine  becomes  clear  and  acid.  The  urine  of  man  can  be  made 
alkaline  by  the  ingestion  of  large  quantities  of  vegetables  or  fruits.  Under 
such  circumstances  the  urine  as  passed  is  generally  turbid  from  the  presence 
of  precipitated  earthy  phosphates.  In  determining  the  reaction  of  urine  it 
is  usual  to  adhere  to  one  indicator,  e.g.  phenolphthalein,  and  to  give  the 
acidity  in  terms  of  decinormal  acid,  naming  the  indicator  used.  The 
acidity  (i.  e.  the  concentration  of  H  ions)  can  also  be  determined  by  the 
electrical  method.  In  this  way  Hoeber  found  the  acidity  of  human  urine 
to  vary  between  4*7  x  10  ~7  and  100  X  10  ~7.  On  the  average  it  was 
49  X  10_7in  the  litre. 

THE    AVERAGE    COMPOSITION    OF     THE     URINE.     Several    analyses 


1162  PHYSIOLOGY 

of  the  day's  urine  under  varying  conditions  of  food  have  already  been  given 
(v.  pp.  802,  823).  The  following  may  be  taken  as  a  fair  average  for  an  adult 
man  on  ordinary  mixed  diet : 

Total  amount  of  urine  =  1500  c.c. 

This  contains  about  60  grm.  of  solids,  of  which  25  grm.  are  inorganic  and 
35  grm.  organic.     These  are  distributed  as  follows  : 


Inorganic  Constituents 

Organic  Constituents 

Sodium  chloride    . 

15'0  grm. 

Urea  ..... 

300  grm 

Sulphuric  acid 

.       2-5      „ 

Uric  acid     .... 

0-7     „ 

Phosphoric  acid     . 

.       2-5     „ 

Creatinine   .... 

1-0     „ 

Potassium    . 

•       3-3     „ 

Hippuric  acid 

0-7     „ 

Ammonia 

.       0-7     „ 

Other  substances 

2-6     „ 

Magnesia 

•       0-5     „ 

Lime   .... 

•       0-3     „ 

Other  substances  . 

•       0-2     „ 

The  quantity  of  urine  will  naturally  vary  with  the  water  leaving  the 
body  by  the  kidneys,  and  therefore  according  to  the  habit  of  the  individual 
with  regard  to  the  intake  of  fluids  and  with  his  occupation.  Thus  after 
copious  sweating  the  total  amount  may  fall  to  400  c.c.  in  the  course  of  the 
day.  If  large  draughts  of  liquid  be  taken  it  may  rise  to  3000  c.c.  or  more. 
There  are  also  diurnal  variations  in  the  amount  secreted,  depending  probably 
largely  on  the  circulation  through  the  kidneys.  The  secretion  is  at  a  mini- 
mum during  sleep,  and  especially  between  2  and  4  o'clock  in  the  morning. 
It  is  at  its  maximum  during  the  first  hours  after  rising,  and  increases  generally 
after  each  meal.  Muscular  exercise  may  also  give  an  initial  increase  owing 
to  the  greater  vigour  of  the  circulation  associated  with  exercise.  If  the 
exercise  is  severe  enough  to  cause  sweating  or  is  carried  to  fatigue,  there 
may  be  a  consequent  diminution  in  the  amount  of  urine  secreted. 


THE   INORGANIC   CONSTITUENTS   OF   THE   URINE 

(«)  ACID  RADICALS.  The  chlorides  of  the  urine  are  derived  almost 
entirely  from  the  chlorides  of  the  food.  Though  essential  constituents  of 
the  body  fluids,  it  does  not  seem  that  the  chlorides  enter  into  organic  com- 
bination with  the  constituents  of  the  cells.  The  output  of  chlorides,  which 
normally  varies  from  6  to  10  grm.  CI.  in  the  course  of  the  day,  will  therefore 
depend  on  the  amount  of  chlorides  taken  in  with  the  food.  If  these  be 
withdrawn  altogether,  the  chlorides  may  almost  disappear  from  the  urine, 
although  the  circulating  blood  contains  practically  the  same  amount  of 
chlorides  as  in  the  normal  individual,  showing  that  the  body  retains  the 
chlorides  necessary  for  the  proper  carrying  out  of  the  vital  processes  as 
long  as  possible.  Chlorides  may  also  disappear  from  the  urine  temporarily 
under  various  pathological  conditions.  This  is  especially  marked  in  cases 
of  acute  pneumonia. 


THE  COMPOSITION  AND  CHARACTERS   OF  THE  URINE    1163 

Sulphates.  The  salts  of  sulphuric  acid  do  not  form  an  important  con- 
stituent of  the  food.  The  sulphates  of  the  urine  are  derived  almost  entirely 
from  the  oxidation  of  the  sulphur  of  the  protein  molecule.  The  output  of 
sulphates  is  therefore,  like  that  of  urea,  an  index  of  protein  metabolism. 
As  the  nitrogen  of  the  urine  goes  up,  so  the  sulphates  will  increase.  On  an 
average  diet  the  ratio  of  urinary  nitrogen  to  S03  is  about  5:1;  though, 
owing  to  the  varying  content  of  different  proteins  in  the  sulphur,  this  ratio 
will  alter  with  the  nature  of  the  protein  taken  as  food.  The  daily 
output  of  sulphuric  acid  varies  between  1-5  and  3  grm.  S03.  The  greater 
part  of  the  sulphate  is  present  as  sulphates  of  the  alkaline  metals.  A  certain 
proportion,  about  10  per  cent.,  is  present  in  the  form  of  conjugated  or 
ethereal  sulphates,  chiefly  indoxyl  sulphate.  A  small  proportion  of  the 
sulphur  excreted  in  the  urine  is  present  in  unoxidised  form  as  so-called  neutral 
sulphur.  The  neutral  sulphur  probably  includes  a  number  of  different 
bodies,  among  which  sulphocyanates  and  cystine  are  the  best  known. 

Inorganic  sulphates  can  be  precipitated  from  the  urine  by  the  addition  of  hydro- 
chloric acid  and  barium  chloride.  On  filtering  off  this  precipitate,  the  filtrate  contains 
the  ethereal  sulphates.  On  boiling,  the  hydrochloric  acid  decomposes  these  substances, 
setting  free  sulphuric  acid,  which  combines  with  the  excess  of  barium  present  and  is 
precipitated  as  barium  sulphate.  This  second  precipitate  therefore,  when  weighed, 
gives  the  amount  of  ethereal  sulphates  present.  To  determine  the  neutral  sulphur,  the 
fluid  after  the  separation  of  both  kinds  of  sulphates  is  treated  with  sodium  carbonate 
to  precipitate  the  barium,  filtered,  and  the  filtrate  evaporated  to  dryness.  The  residue 
is  then  ignited  with  potassium  nitrate,  cooled,  and  extracted  with  water.  By  this 
treatment  all  the  neutral  sulphur  is  converted  into  sulphates,  which  can  be  thrown  down 
from  the  solution  with  barium  chloride  and  weighed  in  the  usual  way. 

Phosphates.  The  phosphates  of  the  urine  are  derived  partly  from  the 
phosphates  of  the  food,  partly  from  the  oxidation  of  the  organic  phosphorus- 
containing  constituents  of  the  food  and  of  the  tissues,  e.g.  nuclein,  lecithin, 
etc.  If  the  food  contains  much  calcium  and  magnesium,  the  amount  of 
phosphates  excreted  by  the  urine  diminishes,  since  these  substances  are 
excreted  with  the  faeces  as  calcium  and  magnesium  phosphates.  According 
to  the  diet  therefore,  phosphoric  acid  may  be  excreted  either  by  the  intestine 
or  by  the  kidneys.  The  amount  of  phosphates,  reckoned  as  P»05,  excreted 
in  the  course  of  the  day  may  vary  between  1  and  5  grm.  In  the  urine  the 
phosphates  exist  as  a  mixture  of  the  mono-  and  di-sodium  phosphates,  the 
relative  amounts  of  the  two  varying  with  the  acidity  of  the  urine.  If  the 
urine  is  neutral  or  alkaline  there  is  very  often  a  deposit  of  earthy  phosphates. 
Whether  this  deposit  is  present  or  not.  depends  on  the  varying  solubility  of 
the  different  calcium  and  magnesium  phosphates.  Thus  the  mono-mag- 
nesium phosphate  MgH4(P04)2  and  the  mono-calcium  phosphate  CaH4(P04)2 
are  both  fairly  soluble  in  water,  and  their  solubility  is  increased  by  the 
presence  of  neutral  salts.  With  increased  acidity  of  the  urine  the  proportion 
of  the  two  bases  present  in  these  forms  is  diminished.  The  di-magnesium 
and  di-calcium  phosphates  are  only  slightly  soluble  in  water,  and  the  latter 
would,  if  present  in  the  urine,  be  deposited.  One  may  indeed,  in  slightly 
acid  urine,  find  the  di-calcium  phosphate  occasionally  present  as  a  crystalline 


1164  PHYSIOLOGY 

deposit.  On  heating  the  urine  the  di-calcium  phosphate  breaks  up  into  a 
mono-calcium  phosphate  and  a  tri-calcium  phosphate,  while  the  acidity  of 
the  urine  is  increased  by  the  solution  of  the  mono-calcium  phosphate. 
Alkaline  urine  will  always  present  a  precipitate  of  tri-calcium  phosphate 
Ca3(P04)2.  When  normal  urine  is  allowed  to  stand,  the  urea  is  converted 
by  the  presence  of  micro-organisms  into  ammonium  carbonate,  and  the 
urine  becomes  alkaline.  Under  such  conditions  we  may  often  find  a 
crystalline  precipitate  of  ammonium  magnesium  phosphate,  NH4MgP04, 
the  so-called  '  triple  phosphate.' 

(b)  THE  BASES  OF  THE  URINE.  The  bases  include  potash,  soda, 
ammonia,  magnesia,  and  lime. 

The  amount  of  potash  excreted  in  twenty-four  hours  varies  between  1-9 
and  3-2  grm.,  according  to  the  nature  of  the  food  taken.  With  a  large  meat 
diet,  which  contains  considerable  quantities  of  potassium,  the  output  of 
this  base  is  increased.  In  fasting  there  is  also  an  increase  in  the  output  of 
potash,  owing  to  the  utilisation  of  the  tissues  of  the  body  which  themselves 
are  rich  in  potassium. 

The  amount  of  sodium  excreted  in  the  twenty-four  hours  varies  on 
the  average  between  4  and  5  grm.,  but  depends  very  largely  on  the  quantity 
of  sodium  chloride  taken  with  the  diet. 

The  alkaline  earths,  lime  and  magnesia,  are  invariably  present  in  urine, 
but  in  much  smaller  quantities  than  the  alkaline  metals.  The  average 
amount  of  these  two  bases  in  the  twenty-four  hours  varies  in  each  case 
between  0-1  and  0-2  grm.  Their  output  by  the  urine  is  no  criterion  of 
the  amount  taken  in  with  the  food  or  absorbed  from  the  intestines,  since 
both  these  bases  may  be  re-excreted  into  the  gut  and  appear  as  insoluble 
phosphates  in  the  faeces. 

Normal  human  urine  always  contains  a  small  amount  of  ammonia,  on 
an  average  between  0*6  and  0-8  grm.  in  the  twenty-four  hours.  As  we 
have  already  seen,  in  dealing  with  the  origin  of  urea  in  the  body,  the  quantity 
of  ammonia  in  the  urine  is  an  index  to  the  excess  of  acids  over  bases  which 
have  to  be  excreted  by  this  fluid.  Thus  it  is  easily  possible  to  increase  the 
proportional  amount  of  ammonia  in  the  urine  by  the  administration  of 
mineral  acids.  An  increase  of  the  proportion  of  nitrogen  excreted  as 
ammonia,  apart  from  the  administration  of  acids  with  the  food,  is  an 
important  indication  of  the  formation  of  abnormal  acid  substances  in  meta- 
bolism. Thus  in  diabetes,  when  the  last  stages  of  fat  oxidation  are  in 
default,  so  that  the  oxy-fatty  acids,  /?-oxybutyric  and  aceto-acetic  acids, 
accumulate  in  the  body,  there  is  always  a  considerable  rise  in  the  ammonia 
of  the  urine. 

It  is  usual  to  reckon  iron  among  the  bases  which  may  be  excreted  by  the 
urine.  The  amount  of  this  substance  in  the  urine  is  extremely  small,  as  a 
rule  less  than  5  mg.  in  the  day.  It  affords  no  clue  to  the  iron  metabolism 
of  the  body,  since  the  main  channel  of  excretion  of  this  substance  is  the 
intestine. 


THE  COMPOSITION  AND  CHAEACTERS   OF  THE  URINE    1165 


ORGANIC   CONSTITUENTS   OF   THE   URINE 

Almost  all  these  constituents  contain  nitrogen,  which  in  man  is  dis- 
tributed anion"  the  various  urinary  constituents  as  follows  : 


Urea 
Ammonia 
Creatinine 
Uric  acid 


85-90  per  cent. 
2-4 
3 
1-3 


About  6  per  cent,  of  the  urinary  nitrogen  is  in  the  form  of  other  substances, 
such  as  hippuric  acid,  pigments,  etc. 


UREA  or  CARBAMIDE,  C0\Ntt"  can  be 
./OH 


regarded    as    derived    from 


carbonic  acid,  CO^  ^^  by  the  replacement  of  each  OH  group  by  an  NH2 

group.    It  is  isomeric  with  ammonium  cyanate,  NH4CNO.    If  a  solution 

of  potassium  cyanate  and  ammonium  chloride  be  warmed  together  and 

evaporated,   crystals  -of  urea  may  be 

obtained    in    long    colourless    prisms 

(Fig.    529)     without     any     water    of 

crystallisation.    It  is  soluble  in  water 

and    alcohol,    and   insoluble   in   ether. 

Its  solutions  are  neutral  in  reaction, 

but    it    forms    crystalline    salts    with 

strong     acids.     Thus     urea     nitrate. 

which  is  produced  by  treating  strong 

solutions    of    urea    with    concentrated 

nitric  acid,  forms  microscopic  rhombic 

plates  which  are  extremely  insoluble, 

so  that  their  formation  may  be  used 

as  a  test  for  urea  (Fig.  530).     With 

oxalic    acid    urea    solutions    yield    an 

insoluble     oxalate,     also     in     typical 

crystals.      Urea    when    heated    melts 

at  about  130°  C.      On  further  heating 

it     undergoes     decomposition,     giving 

off   ammonia   and   forming   biuret,   as 

follows  : 


("Kg 


co<^ 

co<n3, 


NH., 


Urea  Nitrate.     Urea  oxalate. 


At  the  same  time  a  certain  amount  of  cyanic  acid  is  formed,  and  this 
polymerises  to  cyanuric  acid,  H3C3N3O3.  On  heating  with  alkalies  or  with 
strong  acids,  urea  undergoes  hydrolysis,  with  the  production  of  carbon 
dioxide  and  ammonia  : 

CON2H4  +  H20  =  CO,  +  2NH3. 

The  same  change  is  effected  in  urea  by  certain  micro-organisms,  e.  g.  the 


1166  PHYSIOLOGY 

micrococcus  ureae,  which  is  responsible  for  the  ammoniacal  change  which 
occurs  in  urine  when  exposed  to  the  air. 

Urea,  being  the  chief  nitrogenous  constituent  of  the  urine,  is  the  most 
important  index  to  the  protein  metabolism  of  the  body.  As  we  have  seen, 
urea  may  be  regarded  as  partly  exogenous,  partly  endogenous.  The  greater 
part  of  the  30  grin,  excreted  by  a  normal  individual  in  the  course  of  the  day  is 
derived  directly  from  the  proteins  of  the  foods,  as  a  result  of  the  deamination 
of  the  amiuo-acids,  which  occurs  shortly  after  their  absorption.  The 
ammonia  thus  formed  is  combined  with  carbonic  acid  and  carried  to  the 
liver,  where  the  ammonium  carbonate  undergoes  dehydration  with  the  pro- 
duction of  urea.  Its  amount  will  therefore  be  directly  proportional  to  the 
amount  of  protein  taken  as  food.  A  smaller  proportion  is  derived  from 
the  breakdown  of  the  tissues  of  the  body.  This  endogenous  moiety  may 
undergo  considerable  increase  under  any  conditions  which  cause  a  rapid  dis- 
integration of  the  tissues.  Thus  in  febrile  conditions  there  is  a  large  rise  in 
the  urea  output,  even  in  a  starving  individual. 

In  order  to  prepare  urea  from  urine,  advantage  may  be  taken  of  the  insolubility  of 
its  combination  with  nitric  acid.  Urine  is  concentrated  to  about  one-sixth  of  its'  bulk. 
It  is  then  cooled  and  treated  with  twice  its  volume  of  pure  concentrated  nitric  acid, 
care  being  taken  to  keep  the  whole  mixture  cool.  Urea  nitrate  is  precipitated.  The 
precipitate  is  collected,  dried  roughly  by  pressing  between  filter  paper,  and  then  rubbed 
up  with  fresh  barium  carbonate.  Barium  nitrate  is  formed  and  urea  set  free.  The 
whole  mass  is  dried  and  treated  with  hot  absolute  alcohol,  in  which  the  barium  nitrate 
is  insoluble.  On  filtering  off  the  barium  nitrate  a  pure  solution  of  urea  is  obtained 
from  which  the  urea  will  crystallise  on  allowing  the  alcohol  to  evaporate. 

CREATININE.  Creatinine  is  a  normal  constituent  of  urine,  in  which 
it  occurs  in  quantities  of  0-8  to  1-3  grm.  in  the  twenty-four  hours.  It  is 
easily  produced  from  creatine  by  boiling  the  latter  with  strong  hydrochloric 
acid,  when  a  process  of  dehydration  occurs.     Creatine  has  the  formula  : 

NH2 

I 
NH  =  C— N(CH3)CH,-COOH. 

On  dehydration  it  is  converted  into  creatinine  : 

NH 1 

I  I 

NH  =  C— N(CH3)CH2CO 

Creatinine  may  be  obtained  from  urine  in  the  following  way.  The  urine  is  made 
alkaline  with  milk  of  lime  and  treated  with  calcium  chloride  and  filtered.  The  filtrate 
is  slightly  acidified  with  acetic  acid  and  evaporated  on  the  water  bath  to  a  syrupy  con- 
sistence. A  little  sodium  acetate  is  added  and  the  mixture  extracted  with  alcohol.  The 
filtered  alcoholic  extract  is  now  treated  with  a  concentrated  neutral  alcoholic  solution  of 
zinc  chloride.  A  crystalline  precipitate  of  creatinine  zinc  chloride  is  produced.  After 
two  days  this  precipitate  is  collected  on  a  filter,  washed  with  alcohol,  dissolved  in  water, 
and  then  boiled  for  a  quarter  of  an  hour  with  lead  hydrate.  The  mixture  is  then  filtered 
and  the  filtrate  evaporated  to  dryness.  The  dry  residue  is  now  extracted  with  cold 
alcohol  and  filtered.  On  allowing  the  alcohol  to  evaporate,  crystals  of  creatinine 
separate  out  (Fig.  531).     It  gives  the  following  tests: 


THE  COMPOSITION  AND  CHARACTERS  OF  THE   URINE    1167 

(1)  WEYL'S  TEST.  On  treating  a  solution  of  creatinine  with  a  small  quantity  of 
very  dilute  sodium  nitroprusside  solution  and  then  with  weak  caustic  alkali,  a  rich 
ruby  red  colour  is  produced  which  gradually  changes  to  yellow.  On  now  adding  acetic 
acid  and  warming,  the  solution  becomes  green  and  then  blue,  and  finally  a  precipitate 
of  Prussian  blue  is  formed. 

(2)  JAFFE'S  TEST.  On  treating  a  solution  of  creatinine  with  a  few  drops  of  a 
watery  solution  of  picric  acid  and  dilute  caustic  potash,  an  intense  red  colour  is  produced. 
This  reaction  is  made  use  of  for  the  quantitative  estimation  of  creatinine  in  the  urine. 

Like  the  other  nitrogenous  constituents,  creatinine  can  be  regarded 
as  partly  exogenous,  partly  endogenous  in  origin.  The  exogenous  part  is 
derived  from  the  creatine  contained  in  meat.     When  meat  is  excluded  from 


Fig.  531.     Creatinine.     (Funke.) 


Fig.  532.     Uriu  acid.     (Funke. 


the  diet,  the  output  of  creatinine  becomes  remarkably  constant  and  is  little 
affected  by  the  total  amount  of  proteins  taken,  the  amount  excreted  during 
.starvation  being  practically  identical  with  that  excreted  on  a  full  protein 
diet.  It  is  said  to  be  increased  during  febrile  conditions  and  as  a  result  of 
violent  muscular  exercise. 

URIC  ACID.     Uric  acid  is  2-6-8-trjoxypurine. 

HN— CO  N  =  C(OH) 


OC   C— NHX 


HN— C— NH' 


>CO 


(HO)C     C— NHs 

II      II 
N— C  —  N/ 


>C(OH) 


Uric  acid  forms  small  rhombic  crystals.  The  crystalline  form  varies 
considerably  in  the  presence  of  impurities.  The  different  forms  of  uric 
acid  crystal  which  may  occur  in  the  urine  are  shown  in  the  accompanying 
figure  (Fig.  532).  It  is  extremely  insoluble  in  pure  water,  one  part  of  uric 
acid  requiring  39,000  parts  of  water  at  18°  C.  for  its  solution.  It  is  easily 
soluble  in  concentrated  sulphuric  acid  and  alkalies. 

It  may  be  prepared  from  human  urine  or  from  guano,  which  consists  almost  entirely 
uf  urates.  In  order  to  prepare  it  from  guano,  this  is  dissolved  with  the  aid  of  heat  in 
dilute  sodium  carbonate,  filtered,  and  the  filtrate  treated  with  a  few  drops  of  concen- 
trated hydrochloric  acid  and  boiled.     On  allowing  to  cool,  the  uric  acid  crystallises  out. 


1168  PHYSIOLOGY 

From  urine  uric  acid  may  be  obtained  by  adding  one-fiftieth  of  its  volume  of  concen- 
trated hydrochloric  acid  and  allowing  to  stand  for  two  days.  The  uric  acid  is  thrown 
down  in  small  dark  red  or  brown  crystals.  They  can  be  collected  on  a  filter,  dissolved 
in  alkali,  decolorised  by  boiling  with  animal  charcoal,  and  the  pure  acid  thrown  down 
as  before  by  means  of  hydrochloric  acid. 

A  more  convenient  method  of  preparation  from  human  urine  is  based  on  the  fact 
that  ammonium  urate  is  insoluble  in  concentrated  solutions  of  ammonium  chloride 
(Hopkins).  The  urine  is  saturated  with  crystals  of  ammonium  chloride  and  a  few  drops 
of  strong  ammonia  added.  A  gelatinous  precipitate  of  ammonium  urate  is  produced. 
This  is  collected  on  a  filter,  washed  off  with  a  minimum  amount  of  hot  water  into  a 
beaker,  and  a  few  drops  of  hydrochloric  acid  added.  The  mixture  is  boiled  and  then 
allowed  to  cool,  when  the  pure  acid  crystallises  out. 

TESTS   FOR   URIC   ACID 

(1)  MUREXIDE  TEST.  If  a  small  quantity  of  uric  acid  be  treated  with  a  little 
strong  nitric  acid  and  the  whole  evaporated  to  dryness  on  the  water-bath,  an  orange- 
red  residue  is  obtained,  which  on  treatment  with  ammonia  yields  a  fine  purple  colour. 
If  a  drop  of  sodium  hydrate  be  now  added  the  purple  changes  to  blue.  Instead  of  nitric 
acid,  bromine  water  may  be  employed. 

(2)  SCHIFF'S  TEST.  If  uric  acid  be  dissolved  in  a  little  soda  and  a  drop  be  placed 
on  filter  paper  previously  moistened  with  silver  nitrate,  a  yellow  or  brown  spot  is 
produced. 

(3)  On  boiling  urie  acid  with  Fehling's  solution  for  some  time,  a  yellowish  precipitate 
of  cuprous  hydrate  is  produced. 

(4)  An  alkaline  solution  of  uric  acid  on  treatment  with  a  few  drops  of  a  solution  of 
phosphomolybdic  acid  gives  a  dark  blue  precipitate  with  a  metallic  lustre,  consisting 
of  microscopic  prismatic  crystals. 

(5)  With  sodium  hypobromite  uric  acid  is  decomposed,  giving  off  about  half  of  its 
nitrogen  as  the  free  gas. 

URATES.  Of  the  four  hydrogen  atoms  in  uric  acid,  two  can  be  replaced 
by  metallic  radicals.  Uric  acid  thus  acts  as  a  weak  dibasic  acid.  It  forms 
three  orders  of  salts,  namely,  the  neutral  urates,  the  bi-urates,  and  the 
quadri-urates.  The  neutral  urates,  M'2U,  are  very  unstable,  and  exist  only 
in  the  presence  of  caustic  alkalies.  They  are  decomposed  even  by  the 
carbonic  acid  of  the  atmosphere.  The  bi-urates,  MHU,  are  the  most  stable 
of  the  urates.  They  may  be  prepared  by  dissolving  uric  acid  with  the  aid 
of  heat  in  weak  solutions  of  the  alkaline  carbonates,  from  which  they 
separate,   on  cooling,   in  stellar  crystals. 

The  quadri-urates  have  the  formula  H2U,  MHU.  They  may  be  pre- 
pared by  boiling  uric  acid  with  dilute  solutions  of  potassium  acetate.  On 
cooling  the  mixture  the  quadri-urate  separates  as  an  amorphous  precipitate 
or  in  crystalline  spheres.  The  quadri-urates  are  extremely  unstable,  and  in 
the  presence  of  water  are  broken  up  into  the  bi-urates  and  free  uric  acid. 
It  is  probable  that  under  normal  conditions  the  greater  part  of  the  uric  acid 
in  the  urine  is  present  in  the  form  of  a  quadri-urate  (Roberts),  and  the  so- 
called  lateritious  deposit,  the  brick-red  amorphous  precipitate  of  urates 
which  occurs  in  concentrated  urine  on  cooling,  consists  of  these  quadri- 
urates.  The  exact  condition  of  the  urate  however  will  depend  on  the 
reaction  of  the  urine.  A  bi-urate,  with  acid  sodium  phosphate,  is  decom- 
posed with  the  formation  of  uric  acid  in  the  following  way  : 

MHO  +  MH2P04  =  H2U  +  M2HP04. 


THE  COMPOSITION  AND  CHAKACTERS  OF  THE  URINE    1169 

Thus  the  quadri-urates  present  in  the  urine  immediately  after  its  secre- 
tion will  tend  to  undergo  spontaneous  decomposition  into  uric  acid  and  the 
bi-urate,  and  the  latter  itself  may  be  decomposed  with  the  formation  of 
uric  acid  and  alkaline  phosphate.  We  thus  see  that  when  the  urine  is  acid, 
i.  e.  when  there  is  a  predominance  of  acid  phosphates,  there  will  be  a  tendency 
to  the  precipitation  of  uric  acid  in  the  urinary  passages.  If  however  the 
di-sodium  phosphate  be  in  excess,  the  uric  acid  may  be  kept  in  solution  as 
the  quadri-urate  or  even  as  the  bi-urate. 

The  uric  acid  of  the  urine  is  derived  almost  entirely  from  the  purine 
metabolism  of  the  body.  The  uric  acid  may  be  endogenous  or  exogenous, 
i.  e.  may  be  derived  from  the  breaking  down  of  the  nucleins  of  the  cells  or 
by  a  direct  transformation  of  the  nucleins  contained  in  the  food.  The 
amount  passed  daily  varies  between  0-4  and  1  grin.,  according  to  the  nature 
of  the  diet.  It  is  not  absent  from  the  urine  even  during  complete  starvation. 
It  is  increased  when  foods  are  ingested  rich  in  nucleins,  such  as  liver  or  sweet- 
breads, or  in  any  other  precursors  of  uric  acid,  e.g.  hypoxanthine,  such  as 
meat  or  meat  extract.  We  have  no  evidence  that  the  urinary  uric  acid 
in  the  mammal  is  formed  by  synthesis,  though  this  is  the  manner  in  which 
the  greater  part  of  the  uric  acid  excreted  by  birds  and  reptiles  is 
formed. 

Small  traces  of  purine  bases  also  occur  in  urine,  namely,  xanthine,  hypo- 
xanthine, and  adenine.  When  tea  and  coffee  are  taken  the  methyl-prxrines 
may  occur,  namely,  caffeine,  theobromine,  and  their  derivatives. 

HIPPURIC  ACID  is  a  frequent,  though  not  a  constant,  constituent  of 
human  urine.  It  is  derived  from  benzoic  acid  or  from  an  aromatic  sub- 
stance which  on  oxidation  can  give  rise  to  benzoic  acid.  In  the  kidneys 
the  benzoic  acid  is  conjugated  with  glycine  to  form  hippuric  acid.  The 
amount  of  hippuric  acid  excreted  in  the  day  may  vary  between  0-1  and 
1  grm.  After  a  diet  rich  in  fruit  or  vegetables  its  amount  may  rise  to  2  grm. 
It  is  present  in  considerable  quantities  in  the  urine  of  herbivora  and  may  be 
most  easily  prepared  from  horses'  urine.     Hippuric  acid  has  the  formula  : 

C6H5CO 

I 
HNCH2COOH 

It  can  be  obtained  in  niilk-white  crystals  (Fig.  533),  which  are  only  slightly 
soluble  in  cold  water,  but  easily  soluble  in  alcohol,  ether,  and  acetic  acid. 
It  is  insoluble  in  petroleum,  ether,  and  benzol.  On  heating,  it  is  broken  up 
into  benzoic  acid  and  glycine.  On  heating  with  concentrated  nitric  acid, 
it  forms  nitro-benzol,  which  can  be  recognised  by  its  characteristic  smell  of 
bitter  almonds. 

In  order  to  extract  it  from  the  urine,  the  urine  is  made  alkaline  with  sodium  car- 
bonate, filtered,  and  the  filtrate  evaporated  to  a  syrupy  consistence.  This  is  then  treated 
with  alcohol,  the  alcohol  evaporated,  and  the  residue  repeatedly  extracted  with  acetic 
ether.  The  acetic  ether  is  collected,  evaporated  to  dryness,  and  the  residue  repeatedly 
extracted  with  petroleum  ether  to  remove  the  benzoic  acid  and  fat.  What  is  left  behind 
is  hippuric  acid,  which  can  be  purified  by  recrystallisation  from  alcohol  or  ether. 
74 


1170 


PHYSIOLOGY 


AMINO-ACIDS.  According  to  Levene  and  van  Slyke,  amino-acids  are 
always  present  in  the  urine,  and  contribute  about  1-5  per  cent,  of  the  total 
nitrogen. 

OTHER  AROMATIC  SUBSTANCES.  The  chief  of  these  is  the  so-called 
'  urinary  indican  '  or  potassium-indoxyl-sulphate.  This  is  derived  from  the 
indol  produced  in  the  intestines  from  the  tryptophane  contained  in  the 
proteins  of  the  food,  the  change  being  effected  by  the  influence  of  the  micro- 
organisms of  putrefaction.     The  amount  of  the  conjugated  sulphates  in 

the  urine  is  thus  an  index  of  the  extent 
of  putrefaction  in  the  intestines.  In 
dogs,  when  the  intestine  has  been 
disinfected  by  repeated  doses  of  calo- 
mel, the  conjugated  sulphates  entirely 
disappear  from  the  urine.  Urinary 
indican  has  the  formula  : 


■COSO,OK 


Fig.  533.     Hippuric  acid.     (Funke.) 


HC      C        CH 

C       N 
H      H 


In  addition  to  the  tests  for  conjugated  sulphates  mentioned  earlier,  the  indoxyl- 
sulphate  can  be  detected  by  various  methods  dependent  on  the  formation  of  indigo  blue. 
The  urine  is  treated  with  an  equal  volume  of  concentrated  hydrochloric  acid  and 
several  cubic  centimetres  of  chloroform  added.  A  solution  of  chloride  of  lime  is 
now  added  drop  by  drop,  shaking  after  the  addition  of  each  drop.  A  bluo  colour  is 
produced  which  is  extracted  by  the  chloroform.  It  is  important  not  to  add  too  much 
chloride  of  lime,  as  otherwise  the  blue  colour  first  produced  will  be  destroyed  by  further 
oxidation. 

THE  URINARY  PIGMENTS.  Normal  urine  gives  no  definite  absorption 
bands.  It  owes  its  colour  to  the  presence  of  a  yellow  pigment,  urochrome. 
In  order  to  separate  urochrome  from  urine,  the  urine  is  saturated  with 
crystals  of  ammonium  sulphate  and  filtered.  The  filtrate,  which  still 
contains  nearly  all  the  colour  of  the  urine,  is  shaken  up  with  alcohol,  which 
withdraws  the  greater  part  of  the  colouring  matter.  On  concentrating  the 
alcohohc  solution  and  pouring  it  into  an  equal  volume  of  ether,  an  amor- 
phous brown  precipitate  falls,  which  is  the  urochrome.  Urochrome,  on 
treatment  with  aldehyde,  yields  a  pigment  closely  similar  to  urobilin.  On 
the  other  hand,  urobilin,  treated  with  potassium  permanganate,  is  converted 
into  a  substance  practically  identical  with  urochrome.  Urochrome  must 
therefore  be  derived  from  the  same  source  as  urobilin. 

Urobilin  is  rarely  present  in  normal  urine,  and  then  only  in  the  form  of 
a  chromogen,  from  which  it  must  be  set  free  by  acidification.  In  certain 
pathological  conditions,  especially  in  cirrhosis  of  the  fiver,  urobilin  may 
occur  in  the  urine  in  considerable  quantities. 


THE  COMPOSITION  AND   CHAKACTERS   OF  THE  URINE     1171 

In  order  to  extract  urobilin  from  such  urine,  the  urates  are  first  precipitated  by 
saturation  with  ammonium  chloride,  and  the  filtrate  is  then  saturated  with  ammonium 
sulphate  and  a  drop  of  sulphuric  acid  added.  On  shaking  the  fluid  up  with  a  mixture 
of  two  parts  ether  and  one  part  chloroform,  the  urobilin  is  taken  up  by  the  latter. 
The  ether-chloroform  solution  is  separated  off  and  shaken  up  with  caustic  soda,  when 
the  urobilin  passes  entirely  into  the  alkaline  solution. 

Urobilin  in  solution  gives  a  single  absorption  band  between  the  lines  b 
and  F,  i.  e.  at  the  junction  of  the  green  and  blue  of  the  spectrum.  On 
treating  with  zinc  chloride  and  ammonia  its  solutions  show  a  well-marked 
green  fluorescence.  The  urobilin  of  urine  is  identical  with  stereo bilin,  the 
colouring  matter  of  the  foeces.  It  is  formed  from  bile  when  the  latter 
decomposes,  and  is  probably  produced  in  the  intestines  by  the  action  of 
mioro-organisms  on  bile  pigment. 

Other  pigments  which  may  occur  in  urine  are  uroerythrin  and  hsema- 
toporphyrin.  Uroerythrin  gives  the  pink  colour  to  urate  sediments.  Its 
chemical  nature  is  not  known.  It  is  distinguished  by  the  fact  that  on 
addition  of  caustic  soda  the  pink  colour  is  changed  to  green.  On  suspending 
the  red-coloured  precipitate  of  urates  in  hot  water  and  extracting  with  amyl 
alcohol,  a  pink  solution  is  obtained  which  shows  two  absorption  bands  in 
the  green  part  of  the  spectrum. 

Hwmatoporphyrin  is  present  only  in  very  small  amounts  in  normal  urine, 
but  under  certain  conditions,  especially  after  poisoning  with  sulphonal,  it 
may  occur  in  such  large  quantities  as  to  give  the  urine  a  deep  purple  colour. 
Under  these  circumstances  it  is  found  in  the  form  of  alkaline  haematopor- 
phyrin  and  gives  the  characteristic  absorption  bands  of  the  latter. 

Urorosein  is  a  name  that  has  been  given  to  a  pigment  which  is  formed 
when  the  urine  is  treated  with  strong  mineral  acids.  It  is  probably  an 
indol  derivative.  It  gives  a  single  absorption  band  between  the  lines 
d  and  e. 

ABNORMAL   CONSTITUENTS   OF   THE   URINE 

A  very  large  number  of  substances  occur  in  the  urine  in  minute  traces  and  may  be 
detected  when  large  quantities  of  this  fluid  are  worked  up  at  one  time.  Most  of  the 
so-called  pathological  constituents  may  be  detected  in  this  way  in  normal  urine.  It  is 
only  when  they  occur  in  easily  detectable  amounts  that  their  presence  becomes  of  any 
significance. 

COAGULABLE  PROTEIN.  Under  normal  circumstances  urine  is  free  from  any 
coagulable  protein  except  the  small  traces  of  mucinous  material,  nucleoprotein,  which 
uivts  the  cloudiness  to  the  urine.  If  the  kidney  cells  are  damaged  by  disease,  by  inter- 
ference with  their  blood  supply,  or  by  circulating  poisons,  the  glomerular  epithelium 
permits  the  passage  of  a  certain  amount  of  the  proteins  of  the  plasma.  Under  these 
circumstances,  if  small  pieces  of  the  kidney  be  plunged  into  boiling  water,  the  coagulated 
protein  may  be  seen  in  Bowman's  capsule.  The  presence  of  coagulable  protein  (generally 
spoken  of  as  albumin)  in  the  mine  is  significant  of  the  pathological  conditions  of  the 
kidney  associated  with  Bright's  disease.  A  small  trace  will  generally  be  found  in 
the  urine  which  is  passed  shortly  after  taking  muscular  exercise.  Under  this  condition 
the  presence  of  albumin  in  the  urine  has  no  pathognomonic  significance. 

The  proteins  generally  found  are  identical  with  those  of  the  blood  plasma  and  con- 
sist of  serum  albumin  and  serum  globulin.  Their  presence  in  the  mine  may  be  detected 
by  the  precipitate  produced  on  boiling.     In  carrying  out  this  test  a  few  cubic  centi- 


1172 


PHYSIOLOGY 


Fig.  534.     Glucosazone. 


metres  of  saturated  salt  solution  should  be  added  and  one  or  two  drops  of  dilute  acetic 
acid.  A  more  delicate  test  is  that  known  as  Heller's.  Some  strong  nitric  acid  is  placed 
in  a  test-tube  and  the  urine  is  poured  carefully  down  the  side  of  the  tube  so  as  to  form  a 
layer  on  the  surface  of  the  nitric  acid.     If  albumin  be  present,  a  white  ring  is  formed  at 

the  junction  of  the  two  liquids. 

SUGAR.  Normal  urine  eon- 
tains  about  one  part  per  thousand 
of  glucose.  In  diabetes  the  power 
of  assimilating  carbohydrates  is 
diminished  or  destroyed.  The 
amount  of  sugar  in  the  blood  is 
increased,  and  sugar  appears  in 
large  quantities  in  the  urine.  The 
sugar  is  practically  always  glucose. 
Lactose  may  occur  in  the  urine  of 
mil  sing  women  even  in  conditions 
of  health.  Since  both  these  sugars 
will  reduce  Fehling's  solution,  it 
becomes  important  to  be  able  to 
distinguish  between  them. 

The  following  tests  are  used  for 
the  detection  of  abnormal  amounts 
of  sugar  in  the  urine  : 

(1)  FEHLING'S     TEST.     The 
urine  is  boiled  with  Fehling's  solu- 
tion (an  alkaline  solution  of  copper 
sulphate  to  which  Rochelle  salt  has  been  added  to  keep  the  cupric  hydrate  in  solution). 
Under  the  action  of  glucose  or  lactose  the  cupric  hydrate  is  reduced  to  an  insoluble 
cuprous  hydrate,  which  forms  a  yellow  or  red  precipitate. 

(2)  The  phenylhydrazine  test  may  be  carried  out  as  follows :    2  c.c.  of  50  per  cent. 

acetic  acid,  saturated  with  sodium 
acetate,  and  two  drops  of  phenylhy- 
drazine are  added  to  5  c.c.  of  urine. 
The  mixture  is  evaporated  down  to 
3  c.c,  rapidly  cooled,  and  again 
warmed  in  a  water  bath.  It  is  then 
allowed  to  cool  slowly.  Crystals  of 
the  corresponding  ozazone  separate 
out  in  the  hot  liquid  in  the  case  of 
glucosazone,  on  cooling  in  the  case 
of  lactosazone  (Figs.  534,  535). 

(3)  The  most  convenient  way  of 
distinguishing  between  lactose  and 
glucose  is  by  adding  a  little  yeast 
to  the  urine  in  an  inverted  trst- 
tube.  If  glucose  be  the  sugar  pre- 
sent, it  is  fermented  by  the  yeast 
with  the  production  of  carbon 
dioxide,  which  collects  at  the  top 
of  the  test-tube. 

In  rare  circumstances  fructose  or 
laevulose,  or  pentose  may  be  found 
in   the   urine.      The  former  would  be  detected  by  the  fact  that  it  rotates  polarised 
light  to  the  left  instead  of  the  right,  as  is  the  case  with  glucose. 

GLYCURONIC  ACID.  Small  traces  of  this  are  present  in  normal  urine.  It  occurs 
as  a  conjugated  acid  after  the  administration  of  various  substances,  e.  g.  camphor  and 
chloral.     If  phenol,  indol,  or  scatol  be  given  to  an  animal  which  is  receiving  very  little 


Fig.  535.     Lactosazone.     (Plimmek.) 


THE  COMPOSITION  AND  CHARACTERS   OF  THE   URINE    1173 

protein  in  its  diet,  these  substances  will  leave  the  body  conjugated,  not  with  sulphuric 
acid,  but  with  glycuronic  acid.  Glycuronic  acid  may  be  regarded  as  the  first  product 
of  oxidation  of  glucose,  having  the  formula  : 

COOH 

I 
(CHOH)4 

I 
CHO 

It  reduces  Fehling's  solution  and  rotates  the  plane  of  polarised  light  to  the  left. 

OXY-FATTY  ACIDS  AND  ACETONE.  These  substances  occur  often  associated 
with  glucose  in  diabetes,  especially  towards  the  end  of  the  disease.  They  represent  the 
penultimate  stages  in  the  oxidation  of  the  fats.  Their  relation  to  one  another  is  seen 
from  their  formula"  : 

CHo  CHg  •  CHg 

I  I 

CO 

I 

CH, 


CHOH 

1 

CO 

i 

CH2 

I 

CH2 

1 

COOH 

Oxybutyric  acid 

COOH 

Aceto-acetic  acid 

They  may  also  occur  in  any  condition  of  carbohydrate  starvation,  relative  or  absolute. 
Thus  they  are  found  in  the  urine  during  absolute  starvation  as  well  as  in  individuals 
on  a  pure  fat  and  protein  diet.  The  two  acids  are  generally  found  associated  in  the 
urine. 

The  presence  of  aceto-acetic  acid  may  be  detected  as  follows  : 

(1)  To  some  urine  add  ferric  chloride  as  long  as  a  precipitate  of  ferric  phosphate  con- 
tinues to  form.  Filter  this  off  and  to  the  filtrate  add  a  few  more  drops  of  ferric  chloride. 
If  the  acid  be  present  a  claret  colour  is  produced. 

(2)  On  heating  with  dilute  alkali,  aceto-acetic  acid  is  decomposed,  with  the  pro- 
duction of  acetone.  This  may  be  detected  by  its  odour  or  by  distilling  off  a  small 
proportion  of  the  fluid  and  testing  the  distillate  in  the  following  ways : 

(a)  On  the  addition  of  sodium  hydrate  and  iodine  and  warming,  iodoform  is  formed. 

(6)  Legal's  test.  A  few  drops  of  freshly  prepared  sodium  nitroprusside  solution  is 
added  and  the  7nixture  rendered  alkaline  with  sodium  hydrate.  A  deep  red  colour  is 
formed.     On  acidifying  with  acetic  acid  this  colour  is  changed  to  a  reddish  purple. 

CYSTINE.  This  substance,  which  is  a  normal  product  of  the  hydrolysis  of  proteins, 
is  found  as  a  constant  constituent  to  the  amount  of  half  a  gramme  a  day  in  the  urine  of 
certain  individuals.  The  condition  of  cystinuria  represents,  like  alcaptonuria,  an  inborn 
error  of  metabolism.  It  is  found  in  the  child  and  persists  throughout  life.  In  such 
cases  the  cystine  may  give  rise  to  urinary  deposits  or  even  to  a  urinary  calculus. 

HOMOGENTISIC  ACID.  This  is  an  aromatic  acid  having  the  composition  of 
dioxyphenyl  acetic  acid.     Its  formula  is  as  follows : 

OH 
/\ 

I         I  CH2.COOH 
OH 

It  occurs  as  a  constituent  of  the  urine  of  certain  individuals,  who  are  said  to  be 
affected  with  alcaptonuria.  The  urine  of  these  cases  is  remarkable  for  its  resistance  to 
putrefactive  changes.  It  slowly  darkens  on  exposure  to  the  air,  and  on  the  addition  of 
alkali  and  shaking  with  air  it  becomes  rapidly  brown  or  black.  It  reduces  Fehling's 
solution,  so  that  the  presenco  of  sugar  may  be  suspected.     Such  urine  contains  homogen- 


1174 


PHYSIOLOGY 


tisic  acid  in  a  quantity  of  3  to  6  grm.  per  day.  The  amount  of  the  acid  excreted  varies 
with  the  protein  food  taken.  It  seems  that  in  these  cases  the  power  of  the  organism  to 
break  up  tyrosine  and  phenylalanine  is  entirely  absent.  If  either  of  these  substances  be 
administered  by  the  mouth,  it  is  converted  almost  quantitatively  into  homogentisic  acid, 
which  appears  in  the  urine.  Individuals  with  alcaptonuria  continue  to  secrete  homo- 
gentisic acid  during  starvation,  so  that  the  tyrosine  and  phenylalanine  set  free  in  the 
course  of  tissue  disintegration  undergo  the  same  fate  as  when  they  are  derived  from  the 
food.  Alcaptonurics  apparently  suffer  no  ill  effects  as  a  result  of  their  abnormal 
metabolism.     The  tyrosine  and  phenylalanine  can  be  absorbed  and  play  their  part 

in  building  up  the  proteins  of  the  tissues, 
but  the  process  or  ferment  is  wanting  which 
is  responsible  for  the  further  break-up 
of  the  first  product  of  their  oxidation, 
namely,  homogentisic  acid. 


URINARY   DEPOSITS 

In    addition    to    formed    elements, 
such  as  blood  corpuscles,  bacteria,  or 
pus  cells,  which  may  occur  in  abnor- 
mal urine,  the  following  deposits  may 
be  found  : 
(a)  In  Acid   Urine.     (1)  Amorphous  urates  occur  generally  as  a  brick- 
red  amorphous  deposit  thrown  down  as  the  urine  cools.    It  is  redissolved 
on  warming  the  urine,  and  consists  generally  of  the  quadri -urates.     The 


crystals.     (Fbey 


Fig.  537.     Urinary  deposit,  containing  uric 
acid,  sodium  urate,  and  calcium  oxalate. 


Fio.  538.     Deposit  of   '  triple  '   phosphate 
and  ammonium  urate.     (Ftjnke.) 


acid  urate  of  sodium  and  of  ammonium  may  occasionally  occur  in  star- 
shaped  clusters  of  needles  or  as  spherules  with  small  crystals  adhering  to 
them. 

(2)  Uric  acid.  Whetstone,  dumb-bell,  or  sheaf  -like  aggregations  of 
crystals,  generally  deeply  pigmented  so  as  to  resemble  cayenne  pepper 
(Fig.  536). 

(3)  Calcium  oxalate  (Fig.  537).     Colourless,  transparent,  highly  refrac- 


THE  COMPOSITION   AND  CHARACTERS   OF  THE  URINE    1175 


Insoluble  in  acetic  acid,  soluble 


The 


five  octahedral  crystals  (envelope-shaped), 
in  hydrochloric  acid. 

(4)  Ammonium   magnesium   phosphates    (in   faintly   acid    urine), 
crsytals    have    been    compared    to 
knife-rests  or  coffin-lids   (Fig.  538). 
They  are  soluble  in  acetic  acid. 

(5)  Calcium  hydrogen  phosphate. 
CaHP04.  These  are  rare.  They 
form  large  prismatic  crystals  often 
arranged  in  rosettes.  Easily  soluble 
in  dilute  acetic  acid.  On  adding  a 
solution  of  ammonium  carbonate,  the 
crystals  are  eaten  away  and  form  an 
amorphous  deposit. 

(6)  Tyrosine,  fine  needles  in  star- 
shaped  bundles,  and  cystine,  in 
regular  hexagonal  plates,  ma)''  occur 
under  very  rare  circumstances. 

(b)  In  Alkaline  Urine.  (1)  The  commonest  precipitate  consists  of 
earthy  phosphates,  amorphous,  easily  soluble  in  dilute  acetic  acid. 

(2)  Ammonium  magnesium  phosphate  or  triple  phosphate  is  common 
in  mine  which  has  undergone  ammoniacal  fermentation. 

(3)  Acid  ammonium  urate  (Fig.  539)  may  also  occur  in  alkaline  urine. 
On  treatment  with  HC1  it  is  dissolved  and  uric  acid  in  crystals  slowly 
separates  out. 


Fig.  539.     Ammonium  urate. 


QUANTITATIVE   ESTIMATION   OF   THE   CHIEF   URINARY 
CONSTITUENTS 

It  may  be  useful  here  to  summarise  the  most  trustworthy  methods  which  are  employed 
for  the  estimation  of  the  chief  urinary  constituents.1 

The  TOTAL  '  ACIDITY  '  of  the  urine  is  measured  by  titrating  it  against  decinormal 
alkali  in  the  presence  cf  an  indicator,  such  as  phenolphthalein.  The  indistinctness  of 
the  end-point  is  due  to  the  presence  of  calcium  salts  and  ammonium  salts.  Folin  there- 
fore recommends  that  the  titration  be  carried  out  in  the  presence  of  potassium  oxalate, 
which  diminishes  the  error. 

Method.  To  25  c.c.  urine  add  15  to  20  grm.  potassium  oxalate  and  1  to  2  drops  of 
phenolphthalein.     Shake  thoroughly  for  one  or  two  minutes,  and  whilst  the  solution 

is  still  cold  from  the  effect  of  the  oxalate,  titrate  with        NaOH  until  a  permanent  pink 
remains. 

TOTAL  NITROGEN.  In  all  metabolic  experiments,  the  determination  of  the  total 
nitrogen  of  the  food,  the  mine,  and  the  faces  is  indispensable.  In  each  case  Kjeldahl's 
method  is  employed.  This  method  depends  on  the  fact  that  all  the  nitrogenous  sub- 
stances met  with  in  the  body,  when  heated  for  a  considerable  time  with  concentrated 
sulphuric  acid,  undergo  oxidation,  the  nitrogen  being  finally  converted  into  ammonia. 
On  adding  alkali  to  the  mixture,  the  ammonia  is  set  free  from  its  combination  with  the 


1  Fuller  details  will  be  found  in  Plimmer's  Practical  Physiological  Chemistry,  from 
which  most  of  the  methods  here  given  are  taken. 


L176  PHYSIOLOGY 

sulphuric  acid  and  can  be  distilled  off  and  received  into  a  vessel  containing  a  known 
amount  of  deeinormal  acid.  By  titrating  this  acid  after  the  operation  we  can  determine 
the  quantity  of  ammonia  which  has  been  produced.  To  carry  out  this  method  5  c.c. 
of  urine  are  heated  with  20  c.c.  sulphuric  acid  and  a  small  quantity  of  copper  sulphate 
and  potassium  sulphate.  The  copper  sulphate  is  to  aid  the  oxidation  of  the  organic 
substances,  the  potassium  sulphate  is  to  raise  the  boiling-point  of  the  mixture.  The 
boiling  is  continued  for  half  an  hour.  The  flask  is  then  cooled  and  half  filled  with  dis- 
tilled water.  A  special  form  of  distillation  tube  (Fig.  540)  is  now  attached  by  a  rubber 
cork  which  fits  tightly,  but  just  before  this  is  done  an  excess  of  strong  caustic  soda 
sufficient  to  neutralise  the  concentrated  sulphuric  acid  is  run  in  under  the  acid.  The 
other  end  of  the  distillation  tube    is  at  once  arranged  to  dip  under  the  surface  of  a 

measured  quantity  of  standard  acid  (e.  g.  10  c.c.  H2S04),  diluted  with  water,  and  con- 
tained in  a  fiOO  c.c.  Erlenmeyer  flask.  The  flask  is  then  shaken  and  heated.  In  about 
a  quarter  of  an  hour  the  ammonia  is  completely  distilled  off,  and  its  amount  can  be 

determined  by  titrating  the  acid  in  the  flask  with  NaOH,  methyl  orange  being  used 
as  indicator. 

UREA.  The  method  usually  adopted  for  estimating  the  urea  is  that  devised  by 
Hiifner.  It  depends  on  the  fact  that  urea  is  decomposed  by  an  alkaline  hypobromite 
with  the  production  of  CO;  and  nitrogen.  In  the  presence  of  an  excess  of  alkali  the  C02 
is  absorbed,  and  the  nitrogen  may  be  collected  and  measured,  and  serves  as  an  index 
of  the  amount  of  urea  present.     The  reaction  which  occurs  is  as  follows  : 

CO(NH2)2  +  3NaBrO  +  2NaOH  =  3NaBr  +  N2  +  Na2C03  +  3H20. 

60  grm.  22-4  litres  =  28  grm. 

1  grm.  372  c.c. 

Actually  however  only  354-33  c.c.  nitrogen  are  evolved  by  1  grm.  urea. 

The  disadvantage  of  this  method  is  that  other  substances,  such  as  ammonia,  creati- 
nine, and  uric  acid,  give  off  a  certain  amount  of  their  nitrogen  with  sodium  hypobromite, 
so  that  the  method  is  not  strictly  accurate,  though  enough  so  for  most  clinical  purposes. 
In  actually  carrying  out  the  method  5  c.c.  cf  urine  are  treated  with  25  c.c.  of  freshly 
prepared  solution  of  sodium  hypobromite,  and  the  nitrogen  evolved  is  coDected  in  a 
graduated  tube  over  water. 

Urease  Method.  A  still  simpler  method  is  to  employ  urease,  a  ferment  contained 
in  soy  bean,  which  splits  urea  with  hydrolysis  into  ammonia  and  carbonic  acid.  Five  c.o. 
of  urine  with  25  c.c.  of  water,  and  half  a  grm.  of  powdered  soy  bean  are  placed  in  a 
cylinder,  which  is  kept  at  about  40°  C.     Air  is  drawn  through  the  mixture  and  then 

through  25  or  50  c.c.  of        sulphuric  acid  for  half  to  one  hour.      One  grm.  anhydrous 

sodium  carbonate  is  then  added  to  break  up  any  ammonium  salts,  and  air  drawn  through 
as  before  for  another  half  hour.  Titration  of  the  acid  then  gives  the  amount  of  ammonia 
liberated,  from  which,  after  subtraction  of  the  ammonia  originally  present  in  the  urine, 
the  percentage  of  urea  may  be  calculated. 

Folin's  Method.  In  Kjeldahl's  method  all  the  nitrogenous  constituents  of  the  urine 
are  converted  into  ammonia  by  boiling  with  strong  sulphuric  acid.  This  conversion 
occurs  with  extreme  readiness  in  the  case  of  urea,  so  that  by  using  a  weaker  acid  and 
carefully  regulating  the  temperature  the  hydrolysis  may  be  confined  practically  to  the 
urea  itself.     This  is  the  principle  of  Folin's  method  of  estimating  urea. 

Five  cubic  centimetres  of  urine  are  measured  into  a  200  c.c.  Erlenmeyer  flask.  Five 
cubic  centimetres  of  concentrated  hydrochloric  acid,  20  grm.  crystallised  magnesium 
chloride,  a  piece  of  paraffin  the  size  of  a  small  hazel  nut,  and  finally  2  or  3  drops  of  a 
1  per  cent,  solution  of  alizarin  red  in  water  are  added.  A  special  safety  tube  is  then 
inserted  into  the  neck  of  the  flask  and  the  mixture  boiled  until  each  returning 
drop  from  the   safety  tube   produces   a   very  perceptible  bump.     The   heat   is   then 


THE  COMPOSITION   AND   CHARACTERS   OF  THE   URINE     1177 


reduced  somewhat,  and  the  heating  is  continued  for  a  full  hour.    The  alizarin  red  is  used 
in  order  to  ensure  that  the  contents  of  the  flask  do  not  become  alkaline.     At  the  end 
of  an  hour  the  contents  of  the  flask  are  put  into  a  litre  flask  with  about  700  c.c.  water 
and  20  c.c.  of  a  10  per  cent,  sodium  hydrate, 
and  the  ammonia  is  then   distilled   off  into  a 
measured  quantity  of  acid.     The  results  obtained 
in  this  way  will  give  us  the  total  amount  of 
urea   together   with   any   ammonia   which   was 
preformed  in  the  urine.     It  is  therefore  neces- 
sary also  to  determine  the  amount  of  this  pre- 
formed ammonia. 

ESTIMATION  OF  AMMONIA.  In  Folin's 
method  for  the  estimation  of  ammonia,  this  is 
set  free  by  the  addition  of  weak  alkali  (sodium 
carbonate)  and  is  then  removed  from  the  urine 
at  ordinary  room  temperature  by  passing  a  strong 
current  of  air  through  the  liquid.  The  issuing 
current  of  air  carrying  the  ammonia  passes 
through  a  measured  quantity  of  decinormal 
acid.  If  the  air  current  be  strong  enough, 
one  and  a  half  hours  is  sufficient  to  remove  the 
whole  of  the  ammonia  from  25  c.c.  of  urine.  The 
decinormal  acid  is  then  titrated  and  the  amount 
of  the  ammonia  reckoned.  In  carrying  out  the 
method  25  c.c.  of  urine  is  measured  into  a 
cylinder  30  to  40  cm.  high,  and  about  a  gramme 
of  sodium  carbonate  and  some  petroleum  (to  prevent  foaming)  are  added.  The  upper 
end  of  the  cylinder  is  then  closed  by  a  doubly  perforated  rubber  stopper  through  which 
pass  two  glass  tubes,  only  one  of  which  is  long  enough  to  reach  below  the  surface  of 
the  liquid.  The  shorter  tube,  about  10  cm.  in  length,  is  connected  with  a  calcium 
chloride  tube  filled  with  cotton,  and  this  in  turn  is  attached  to  a  glass  tube 
extending  to  the  bottom  of  a  wide-mouthed  bottle,  capacity  about  500  c.c,  which 
contains  20  c.c.  decinormal  acid  in  200  c.e.  of  water. 

A  more  convenient  method  for  the  estimation  of  ammonia  is  that  originally  pro- 
posed by  Schiff  and  recently  worked  out  by  Malfatti.  It  depends  on  the  fact  that,  when 
a  neutral  solution  of  an  ammonium  salt  is  treated  with  formaldehyde,  combination 
occurs  with  the  formation  of  hexamethylene  tetramine  (urotropine)  and  the  liberation 
of  a  corresponding  amount  of  acid,  which  can  be  estimated  by  titrating  with  decinormal 
alkali.     The  reaction  which  occurs  is  as  follows  : 


Fig.  540. 


6CH,0  +  2(NH4)2S04 

Formaldehyde 


6H20  +  N4(CH2)6  +  2H2S04. 

Hexamethylene  tetramine 


In  carrying  out  this  method  25  c.c.  of  urine  are  measured  by  means  of  a  pipette  into  a 
flask  or  beaker  and  diluted  with  five  times  its  volume  of  water.  Four  or  five  drops  of 
phenolphthalein  are  then  added  and  decinormal  sodium  hydrate  is  run  in  until  there  is 
a  slight  permanent  pink  colour.  The  amount  of  alkaline  solution  necessary  to  produce 
this  colour  is  a  measure  of  the  acidity  of  the  urine.  Ten  cubic  centimetres  of  formalin, 
diluted  with  three  volumes  of  water  and  previously  neutralised  to  phenolphthalein 
with  decinormal  alkali,  are  then  added.  The  colour  disappears  owing  to  the  setting 
free  of  the  acid  radicals  previously  combined  with  ammonia.  Decinormal  alkali  is  then 
run  into  the  mixture  until  a  permanent  pink  colour  is  again  obtained.  The  number  of 
cubic  centimetres  of  the  decinormal  alkali  required  in  this  second  case  corresponds  to 
the  amount  of  decinormal  ammonia  previously  present  in  the  25  c.c.  of  urine.     . 

This  method  gives  somewhat  higher  figures  than  the  method  of  Folin  just  described, 
owing  to  the  fact  that  the  small  traces  of  amino-acids,  which  may  be  present  in  the  urine, 
react  to  formalin  in  a  very  similar  way.  The  difference  does  not  exceed  10  per  cent., 
so  that  the  method  is  amply  delicate  for  clinical  purposes. 


1178  PHYSIOLOGY 

CREATININE.  In  Folin's  method  for  the  determination  of  creatinine,  which  is 
now  universally  employed,  advantage  is  taken  of  the  colour  reaction  given  by  creatinine 
(and  by  no  other  normal  urinary  constituent)  with  picric  acid  in  alkaline  solution 
(Jaffre's  reaction),  the  colour  being  compared  with  that  of  a  standard  potassium 
bichromate  solution.  The  reagents  employed  are  decinormal  potassium  bichromate 
containing  24-55  grm.  per  litre;  saturated  picric  acid  solution  containing  about  12  grm. 
per  litre ;  and  a  10  per  cent,  solution  of  sodium  hydrate.  For  the  comparison  of  the 
colours  a  Duboscq  colorimeter  is  employed. 

Ten  cubic  centimetres  of  urine  are  measured  into  a  500  c.c.  flask;  15  c.c.  of  picric 
acid  and  5  c.c.  of  sodium  hydrate  are  then  added  and  the  mixture  allowed  to  stand  for 
five  minutes.  Some  of  the  potassium  bichromate  solution  is  placed  into  one  of  the 
cylinders  of  the  colorimeter  and  its  depth  accurately  adjusted  to  the  8  mm.  mark. 
At  the  end  of  five  minutes  the  contents  of  the  500  c.c.  flask  are  diluted  up  to  500  c.c. 
with  water,  and  some  of  the  mixture  placed  into  the  other  cylinder  of  the  colorimeter, 
and  the  two  colours  are  then  compared.  The  calculation  of  the  results  is  very  simple. 
If,  for  example,  it  is  found  that  it  takes  9-5  mm.  of  the  unknown  urine  picrate  solution 
to  equal  the  8  nun.  of  the  bichromate,  then  the  10  c.c.  of  urine  contains 

10  X         =  8-4  me.  creatinine. 


ESTIMATION  OF  URIC  ACID.     The  best  method  for  this  purpose  is  a  slight  modi- 
fication by  Folin  of  the  method  devised  by  Hopkins. 
For  this  method  the  following  reagents  are  required  : 

(1)  A  solution  of  ammonium  sulphate,  uranium  acetate,  and  acetic  acid,  made  up  as 

follows  :  500  grm.  ammonium  sulphate,  5  grm.  uranium  acetate,  and  60  c.c.  10  per 
rent,  acetic  acid  are  dissolved  in  650  c.c.  water.  The  volume  of  this  solution  is 
almost  exactly  1000  c.c. 

(2)  Ten  per  cent,  ammonium  sulphate  solution. 

n 

(3)  r-  potassium  permanganate  solution  made  by  dissolving  1-581  grm.  pure  potassium 

permanganate  in  one  litre  of  water;    1  c.c.  =  '00375  grm.  uric  acid. 

Measure  200  c.c.  urine  with  a  pipette  into  a  500  c.c.  flask  and  add  50  c.c.  of  the 
ammonium  sulphate  and  uranium  acetate  reagent.  Mix  the  solutions  and  allow  to 
stand  for  about  half  an  hour  so  as  to  let  the  precipitate  settle.  This  precipitate 
contains  a  mucoid  substance  (and  phosphates)  which,  if  not  thus  removed,  renders  the 
subsequent  filtration  and  washing  of  the  ammonium  urate  precipitate  very  slow.  Filter 
off  the  supernatant  liquid  through  a  dry  filter  into  a  dry  vessel,  and  measure  out  125  c.c. 
(  =  100  c.c.  urine)  of  this  with  pipettes  into  a  beaker.  Add  5  c.c.  concentrated  ammonia, 
mix  well,  and  allow  to  stand  covered  with  paper  for  twelve  to  twenty-four  hours. 

Carefully  decant  the  supernatant  liquid  upon  a  filter,  wash  the  precipitate  of  ammo- 
nium urate  on  to  the  filter  with  10  per  cent,  ammonium  sulphate,  and  wash  this  once 
or  twice  with  the  same  reagent  to  remove  the  chlorides  as  completely  as  possible. 

Remove  the  filter  from  the  funnel,  open  it,  and  with  a  fine  stream  of  water  wash 
the  ammonium  urate  precipitate  into  a  beaker.  To  the  ammonium  urate  precipitate, 
suspended  in  about  100  c.c.  water,  add  15  c.c.  strong  sulphuric  acid  and  titrate  at  once, 
without  cooling,  with  the  potassium  permanganate  solution.  At  first  every  small 
addition  of  the  permanganate  is  decolorised  before  it  diffuses  through  the  liquid,  but 
towards  the  end  the  decolorisation  is  slower,  and  the  permanganate  should  be  added 
two  drops  at  a  time  until  a  faint  pink  colour  is  seen  throughout  the  whole  solution. 
The  amount  of  uric  acid  can  then  be  calculated,  1  c.c.  of  the  permanganate  solution  being 
equivalent  to  "00375  grm.  uric  acid. 

CHLORIDES.  The  chlorides  of  urine  are  estimated  by  Volhard's  method.  The 
principle  of  this  method  consists  in  precipitating  the  chlorides  by  excess  of  a  standard 
solution  of  silver  nitrate  in  the  presence  of  nitric  acid.  The  excess  of  silver  is  then 
estimated  in  an  aliquot  part  of  the  filtrate  with  a  solution  of  potassium  or  ammonium 


THE  COMPOSITION  AND  CHARACTERS  OE  THE  URINE     1179 

sulphocyanate  which  has  been  previously  standardised  against  the  silver  solution,  a 
ferric  salt  being  used  as  indicator. 

The  following  solutions  are  required : 

(1)  Standard  silver  nitrate  solution  either        or  so  that  1  c.c.  corresponds  to  -01  grm. 

NaCl.  ' 

(2)  Potassium  sulphocyanate  solution  (8  grm.  per  litre). 

(3)  Pure  HN03  free  from  chlorides. 

(4)  A  saturated  solution  of  iron  alum. 

The  potassium  sulphocyanate  solution  must  be  standardised  against  the  silver  nitrate 
solution.  This  is  carried  out  as  follows  :  Place  10  c.c.  AgN03  solution  with  a  pipette 
in  a  beaker,  add  5  c.c.  pure  HN03,  5  c.c.  iron  alum  solution,  and  80  c.c.  water.  Now 
run  in  the  sulphocyanate  solution  from  a  burette  until  a  permanent  red  tinge  is  obtained. 
Note  the  amount  required  for  the  10  c.c.  AgN03  solution. 

The  method  of  analysis  is  carried  out  as' follows:  Place  10  c.c.  urine  in  a  100  c.c. 
measuring  flask  with  a  pipette.  Then  add  about  4  c.c.  pure  nitric  acid  and  10  or  20  c.c. 
with  a  pipette  of  the  standard  silver  nitrate  solution.  Now  fill  up  to  the  mark  with 
distilled  water,  mix  thoroughly,  and  filter  into  a  dry  vessel  through  a  dry  paper.  Take 
exactly  50  c.c.  of  the  filtrate  with  a  pipette  and  titrate  with  the  sulphocyanate  solution 
until  a  permanent  red  colour  is  obtained,  iron  alum  having  been  added  before  the  titra- 
tion is  commenced.     Calculation  of  results  : 

50  c.c.  filtrate  =  8  c.c.  KCNS 
.-.  100  c.c.       „        =  25  c.c.      „ 
Now  a:  c.c.  KCNS  =  lOc.c.  AgN03 

.-.  25  c.c.      „       =  10  x  —  AgNO, 

x  i 

This  is  the  excess  not  utilised  to  precipitate  the  chlorides 

10  x  25\ 
.•.  (20  —  1  =  amount  of  AgN03  solution  used. 

F^om  this  the  amount  in  grammes  of  NaCl  passed  in  the  urine  in  twenty-four  hours 
can  be  calculated. 

ESTIMATION  OF  PHOSPHATES.  The  method  depends  upon  the  precipitation 
of  all  the  phosphates  by  a  standard  solution  of  uranium  acetate  or  uranium  nitrate  in 
the  presence  of  sodium  acetate  and  acetic  acid  as  (Ur02)HP04.  The  determination  of 
the  end-point,  when  soluble  uranium  salt  is  in  solution,  is  shown  by  means  of  potassium 
ferrocyanide,  or  by  cochineal  tincture  which  becomes  green. 

The  following  reagents  are  required  : 

(1)  Acid  sodium  acetate  solution  (100  grm.  NaAc,  30  grm.  HAc,  1000  c.c.  H20). 

(2)  Cochineal  tincture  (5  grm.  cochineal  extracted  for  several  days  with  150  c.c.  alcohol 

and  100  c.c.  water  and  then  filtered). 

(3)  Standard  uranium  solution  (1  c.c.  =  '005  grm.  P205  or  5  mg.). 

This  must  be  prepared  by  standardising  against  a  standard  phosphate  solution. 
Generally  sodium  phosphate  is  employed ;  about  12  grms.  are  weighed  out  and  dissolved 
in  1000  c.c.  watei  ;  50  c.c.  of  this  solution  are  evaporated  to  dryness,  incinerated,  and 
weighed  as  pyrophosphate.  From  the  weight  of  this  the  amount  of  P205  in  50  c.c.  can 
be  calculated  and  the  remainder  of  the  solution  can  be  diluted,  so  that  50  c.c.  contain 
0'1  grm.  P206.  It  is  simpler  to  use  acid  potassium  phosphate,  KH2P04,  which  can  be 
weighed  directly  and  dissolved  in  water,  so  that  50  c.c.  contain  0T  grm.  P205.  Fifty 
cubic  centimetres  of  this  solution  are  titrated  with  the  uranium  solution  (30  grm.  in 
one  litre)  in  the  manner  described  below,  and  the  uranium  solution  is  then  diluted  so 
that  1  c.c.  =  5  mg.  P205. 

The  method  of  analysis  is  carried  out  as  follows  :   Place  50  c.c.  urine  with  a  pipette 


1180  PHYSIOLOGY 

in  a  100  c.c.  beaker,  add  5  c.c.  acid  sodium  acetate  solution  and  a  few  drops  of  cochi- 
neal tincture.  Heat  the  urine  to  boiling  and  run  in  slowly  the  standard  uranium 
acetate  solution  from  a  burette  as  long  as  a  precipitate  is  formed.  Again  heat  to 
boiling  and  add  the  uranium  solution  drop  by  drop,  until  the  red  colour  is  changed  to 
green.  This  end-point  can  also  be  tested  by  taking  out  a  drop  and  placing  it  in  contact 
with  a  drop  of  potassium  ferrocyanide  solution  or  on  a  little  heap  of  this  substance 
finely  powdered  on  a  white  piece  of  porcelain.  A  brown  colour  or  precipitate  is 
formed  when  excess  of  soluble  uranium  salt  is  present  in  the  solution.  (A  few  more 
drops  may  be  required  to  reach  this  point  than  to  turn  the  cochineal  green.) 

The  principle  of  the  estimation  of  sulphates  has  already  been  described  (p.  1163). 
It  is  not  advisable  to  attempt  this  volumetrieally. 


SECTION  II 


THE    SECRETION    OF   URINE 

With  the  single  exception  of  hippuric  acid,  all  the  constituents  of  the  urine 
are  formed  in  parts  of  the  body  other  than  the  kidneys.  *  Extirpation  of 
both  kidneys  leads  to  an  accumulation  of  these  specific  urinary  con- 
stituents in  the  blood  and  tissues.  The  work  of  the  kidney  is  therefore 
confined  to  an  excretion  of  preformed  constituents.  Considered  from  a 
broad  standpoint,  the  function  of  this  organ  is  the  preservation  of  the  normal 
composition  of  the  circulating  blood. 
Whenever  the  latter  contains  an  abnor- 
mal constituent  or  any  of  its  normal 
constituents  are  present  in  abnormal 
quantities,  the  kidney  excretes  the  sub- 
stance in  question  until  the  composition 
of  the  blood  is  restored.  We  have  to 
determine  the  conditions  which  influence 
the  quantity  and  quahty  of  the  urine 
secreted  by  the  kidneys,  and  to  ascribe 
to  each  element  in  these  organs  its  proper 
share  in  the  total  work  of  the  kidney. 

In  no  other  organ  of  the  hody  are  our  views 
as  to  function  so  intimately  dependent  on  our 
knowledge  of  structure  as  in  the  kidney.  This 
organ  is  a  branched  tubular  gland  consisting 
in  man  of  ten  to  fifteen  nearly  equal  divisions, 
known  as  the  Malpighian  pyramids.  In  certain 
animals,  such  as  the  rabbit  and  rat,  only  one 
pyramid  is  present.  It  is  divided  into  an  outer 
portion  or  cortex,  an  inner  portion,  the  medulla, 
and  between  these  the  '  boundary  layer,'  con- 
taining the  larger  branches  of  the  renal  blood 
vessels  (Fig.  541).  From  the  outer  boundary 
of  the  Malpighian  pyramids  of  the  medulla,  a 

number  of  processes,  the  medullary  rays,  pass  out  into  the  cortex  towards  the  surface 
of  the  kidney.  All  parts  of  the  kidney  are  made  up  of  branched  tubules  embedded  m 
scanty  connective  tissue  and  richly  supplied  with  blood  vessels.  Each  tubule  begins 
by  a  blind  dilated  extremity  in  the  cortex,  known  as  Bowman's  capsule,  which  surrounds 
a  bunch  of  capillary  blood  vessels,  the  glomerulus,  the  two  together  formmg  the  Mal- 
pighian body  From  Bowman's  capsule  a  short  neck  leads  into  a  proximal  convo- 
luted tubule,  and  this  into  a  y-shaped  portion  which  passes  down  in  a  medullary  ray 

1181 


'ia.  541.     Section  of  human  kidney. 
(Cadi  at.) 
a,  cortex;  b,  medulla  or  Malpighian 
pyramids;    c,    papilla;     d,    ureter; 
e,  e,  boundary  zone. 


1 182 


PHYSIOLOGY 


into  the  underlying  portion  of  the  medulla,  and  consists  of  straight  descending  and 
ascending  limbs  and  the  loop  of  Henle.  The  ascending  limb  passes  into  a  distal  convo- 
luted tubule,  and  this  by  a  '  junctional  tubule  '  joins  with  a  number  of  others  to  form  a 
straight  '  collecting  tubule.'  Several  of  these  unite  to  form  the  papillary  ducts,  which 
open  on  the  surface  of  the  papilla  in  the  expanded  part  of  the  renal  duet  or  ureter 
(Fig.  542).  The  whole  tubule  consists  of  epithelium  lying  on  a  basement  membrane; 
the  epithelium  varies  in  structure  in  different  parts  of  the  tubule.  The  bunch  of 
glomerular  capillaries  is  covered  with  a  very  thin  layer  of  endothelial  cells,  and  a  similar 
layer  forms  the  lining  of  Bowman's  capsule.  The  convoluted  tubules  contain  cells 
which  are  roughly  cubical  or  cylindrical  in  cross-section,  but  do  not  present  very 
definite  cell  outlines.  These  cells,  which  are  similar  in  the  two  sets  of  convoluted 
tubules,  have  long  been  distinguished  as  '  rodded  epithelium  '  (Fig.  543)  on  account  of 
the  ease  with  which  a  radial  disposition  of  rods  or  granules  is  demonstrated  in  their 
protoplasm.     As  ordinarily  prepared,  the  free  margin  of  these  cells,  where  they  abut 


/    Boundary  zone 


Diagram  showing  courso  of  urinary  tubules,  and  the  distribution 
of  blood  vessels.     (From  Yeo.) 


on  the  lumen,  is  irregular.  This  appearance  is  due  to  the  readiness  with  which  the 
cells  undergo  alteration  under  the  influence  of  different  fixing  reagents,  especially  of 
such  as  contain  water.  When  properly  fixed  it  is  seen  that  the  rodded  structure,  as 
described  by  Heidenhain,  is  due  to  rows  of  granules  arranged  vertically  to  the  basement 
membrane.  Moreover  the  free  margin  of  the  cells,  instead  of  being  irregular,  consists  of 
a  well-marked  striated  border,  formed  of  a  number  of  very  fine  hairs  closely  set  together 
and  springing  from  a  row  of  granules  in  the  peripheral  part  of  the  cell  (Fig.  544).  The 
hairs,  which  make  up  the  striated  border  (sometimes  called  the  '  brush  border '),  have 
not  been  observed  to  present  ciliary  movement,  and  are  probably  comparable  with  the 
similar  structures  found  clothing  the  free  border  of  the  epithelium  of  the  intestinal 
villus.  Such  cells  are  characteristic  features  of  the  epithelium  lining  the  urinary  organs 
in  all  types  of  animals,  and  are  well  marked  in  the  nephridia  of  worms.  Besides  these 
rows  of  granules,  other  granules  are  found,  especially  towards  the  free  margin  of  the  cell 
and  round  about  the  nucleus.  Some  of  the  granules  appear  to  be  of  a  fatty,  others  of 
a  protein  character. 

The  descending  limb  of  Henle's  loop  is  narrow,  and  possesses  flattened  epithelial 
cells,  while  the  ascending  limb  presents  an  epithelium  similar  to  that  of  the  convoluted 
tubules,  but  with  less  marked  striation.     The  junctional  and  collecting  tubules  are 


THE   SECRETION   OF  URINE  1183 

lined  with  cubical  or  columnar  cells  with  a  clear  protoplasm.  The  marked  differences 
between  the  structure  of  these  various  parts  point  to  a  differentiation  of  function  and 
division  of  labour  among  them  in  the  preparation  of  the  fully  formed  urine.  This  con- 
clusion is  borne  out  by  a  study  of  the  blood  supply  of  the  kidney.     The  large  renal 


r 


Fie.  543.     A  portion  of  convoluted  tubule  with  '  rodded  '  epithelium. 
(Heidenhain.) 

artery  divides  in  the  pelvis  into  four  or  fivje  branches,  which  pass  up  to  the  boundary 
zone  and  there  give  off  arteries  in  different  directions;  those  which  run  towards  the 
surface  are  the  interlobular  arteries.  Each  of  these,  which  is  an  end  artery  presenting 
no  anastomoses  with  its  fellows,  gives  off  on  all  sides  short  wide  branches,  which  pass 
to  the  glomeruli  and  constitute  the  vasa  afferentia  of  these  bodies.  Each  vas  afferens 
has  a  thick  muscular  wall.  The  glomerulus  itself  consists  of  a  number  of  anastomosing 
A 


^■1  >v> 

k> 

/•;%; 

13 

A&$ 

•->>&  * 


^H 


FlG.  544.     C -     ion    ol  convoluted  tubules  from  kidney  of  rat.     (Sauek.) 

a,  during  Blight  secretion;  b,  during  maximal  secretion. 

wide  capillaries  invested  by  an  extremely  thin  wall,  which  is  sometimes  said  to  consist 
simply  of  a  protoplasmic  film  devoid  of  nuclei.  The  glomerular  capillaries  are  collected 
together  to  form  an  efferent  vessel,  the  vas  efferens,  which  is  narrower  than  the  vas 
afferens  but,  like  the  latter,  presents  a  well-marked  muscular  coat.  The  vas  efferens 
breaks  up  again  into  a  second  set  of  capillaries,  which  ramify  round  the  tubules  of  the 
cortex  and  communicate  with  a  similar  network  round  the  tubules  of  the  medulla.  The 
medullary  pyramids  are  also  provided  with  blood  by  a  plexus  of  capillaries  taking  their 
origin  from  little  bunches  of  vessels,  the  vasa  recta  (v.  Fig.  542),  which  leave  the  concave 
side  of  the  arterial  arches  of  the  boundary  zone  to  run  towards  the  papilla,  and  receive 
also  a  few  vessels  which  spring  from  the  vasa  afferentia  of  the  cortical  vessels.     From  the 


1184  1'IIYSIOLOGY 

capillaries  of  the  tubules  the  blood  is  collected  again  into  veins,  which  leave  the  kidnej 
partly  by  the  cortex  and  capsular  vessels,  partly  by  lame  venous  trunks  which  join  to 
form  the  renal  vein  at  the  hilurn  of  the  kidney.  The  kidney  is  richly  supplied  with 
nerves,  which  arc  chiefly  distributed  to  the  muscular  walls  of  its  blood  vessels.  Some 
ant  hois  have,  described  a  fine  nerve- plexus  surrounding  the  tubules  and  sending  branches 
between  and  into  the  cells  of  the  convoluted  tubules  themselves. 

The  main  points  in  the  above  description  of  the  structure  of  the  kidney 
were  made  out  by  Bowman  in  1840,  and  suggested  the  theories  of  urinary 
secretion  both  of  Bowman  and  of  Ludwig  (1844),  theories  which  have 
furnished  the  basis  of  all  our  subsequent  investigation  of  the  subject.  Both 
observers  appreciated  the  great  difference  between  the  membrane  covering 
the  glomerular  loop  and  the  lining  membrane  of  the  tubule,  and  both  drew 
attention  to  the  difference  in  the  circulation  in  these  two  portions  of  the 
kidney.  The  glomerular  capillaries,  supplied  with  blood  through  a  short 
wide  artery  and  drained  by  an  efferent  vessel  smaller  than  the  afferent, 
would  represent  a  region  of  very  high  capillary  blood  pressure,  whereas  the 
pressure  in  the  capillaries  surrounding  the  tubules  must  be  low  and  similar 
to  that  in  other  capillary  regions.  Bowman  therefore  suggested  that  the 
urine  consisted  of  two  parts,  namely,  one  part  containing  the  water  and 
salts  produced  by  a  process  of  filtration  through  the  walls  »f  the  glomerular 
capillaries,  and  another  part,  containing  the  specific  urinary  constituents, 
urea,  uric  acid,  etc.,  secreted  by  the  cells  probably  of  the  convoluted  tubules. 
To  Ludwig,  on  the  other  hand,  it  seemed  possible  at  first  to  account  for  the 
whole  process  of  formation  of  urine  without  the  assumption  of  any  active 
intervention  on  the  part  of  the  cells  of  the  tubules.  He  imagined  that  the 
whole  of  the  urinary  constituents  passed  from  the  blood  to  the  urinary 
tubule  in  the  glomerulus  by  a  process  of  filtration.  The  glomerular  transu- 
date would  represent  therefore  a  very  dilute  urine  containing  the  crystalloids 
of  the  blood  in  the  same  concentration  as  in  the  blood  and  with  no  more 
urea  than  the  blood  itself  contained.  The  great  difference  in  urea  content 
between  the  blood  and  the  fully  formed  urine  he  ascribed  to  a  process  of 
concentration  takmg  place  in  the  fluid  in  its  passage  through  the  tubules,  in 
which  water  and  certain  of  the  salts  were  reabsorbed,  a  process  of  reabsorp- 
tion  conditioned  by  the  difference  hi  protein  content  between  the  urine  within 
the  tubules  and  the  lymph  under  low  pressure  on  the  outside  of  the  tubules. 
We  know  now  that  in  its  original  form  the  theory  of  Ludwig  is  untenable. 
If  a  process  of  concentration  occurs  within  the  tubules,  it  must  invobre^ 
the  performance  of  work  by  the  cells  lining  these  tubules,  and  could  not  take 
place  as  a  result  of  mere  differences  of  colloid  content  between  the  two  fluids. 
It  was  shown  long  ago  by  Hoppe-Seyler  that,  if  urine  be  dialysed  against 
serum,  there  is  a  passage  of  water,  not  from  urine  to  serum,  but  from 
serum  to  urine,  i.  e.  the  latter  is  much  more  concentrated  than  the  former. 
The  movement  of  water  from  one  fluid  to  another  through  a  colloid  mem- 
brane depends  on  the  relative  osmotic  pressures  of  the  two  fluids,  and  this 
in  turn  is  determined  by  the  molecular  concentration  of  the  two  fluids.  It 
is  easy  to  estimate  the  molecular  concentration  of  any  sample  of  serum  <>r 
urine.     The  method  which  is  most  convenient  is  to  determine  the  depression 


THE  SECRETION  OF  URINE 


1185 


of  freezing-point  in  the  two  fluids.  Whereas  senim  ordinarily  freezes  at 
—  0-56°  C.  to  —  0-59°  0.,  the  freezing-point  of  urine  is  generally  lower  and 
may  vary  from  this  figure  to  as  much  as  —  4-5°  C.  For  the  production 
therefore  of  urine  from  blood  plasma,  a  certain  amount  of  work  has  to  be 
done,  and  the  seat  of  this  work  we  can  locate  only  in  the  cells  of  the  kidney. 
We  may  determine  the  rmnmvm work,  necessary  to  form  a  certain  amount  of 
urine  of  a  given  concentration,  by  measuring  the  amount  of  heat  that  must 
be  imparted  to  the  blood  plasma  in  order  to  reduce  it  to  the  same  concentra- 
tion and  volume,  or  we  can  calculate  it  if  we  know  the  freezing-points  of  the 
two  fluids.  A  depression  of  freezing-point  A  =  —  1°  C.  corresponds  to  an 
osmotic  pressure  of  122-7  metres  of  water.  To  concentrate  100  c.c.  of  a 
saline  fluid,  such  as  urine,  so  as  to  halve  its  bulk  and  double  its  depression  of 
freezing-point,  e.g.  from  —  1°  C.  to  —  2°  C,  would  therefore  require  the 
expenditure  of  work  equivalent  to  that  which  would  be  required  to  compress 
100  c.c.  of  a  gas  at  a  pressure  of  122' 7  metres  of  water  to  half  its  bulk. 

In  this  way  can  be  determined  the  work  necessary  to  change  a  fluid  of  A  =  —  0-56 
(such  as  plasma)  to  one  of  —  2-3  (urine).  The  work  done  in  forming  200  e.c.  of  urine 
of  this  concentration  from  fluid  plasma  would  amount  to  42-9  kgm.  metres.  But  the 
c  mcentration  in  the  kidney  does  not  occur  in  this  simple  fashion.  If  we  compare  the 
c  imposition  of  blood  plasma  with  that  of  urine,  we  see  that  almost  every  constituent  is 
changed  in  different  proportions. 

Relative  Compositions  of  Blood  Plasma  and  Normal  Urine  in  Man  (Cushny) 


Blood  plasma 
per  cent. 

Urine  per  cent. 

Change  in 

concentration 

in  kidney 

Water        ..... 

90-93 

95 



Proteins,  fats  and  other  colloids 

7-9 

— 

— 

Dextrose  .... 

01 



— 

Urea 

0-03 

2 

60 

Uric  Acid 

0002 

005 

25 

Na  . 

0-32 

0-35 

1 

K     . 

002 

0-15 

7 

NH4 

0001 

0-04 

40 

Ca    . 

0008 

0015 

2 

Mg  . 

00025 

0006 

2 

CI    . 

0-37 

0-6 

2 

PO, 

0009 

0-27 

30 

so4 

0003 

0-18 

60 

If  we  added  up  the  work  required  to  produce  the  change  in  concentration  of  each 
constituent,  we  should  arrive  at  a  figure  probably  ten  times  as  great  as  that  given  above. 
The  large  amount  of  work  done  under  some  conditions  by  the  kidneys  in  the  formation 
of  urine  is  indicated  by  measurements  of  the  oxygen  consumption  of  this  organ.  This 
may  amount  to  -04  to  -06  c.c.  per  gramme  per  minute,  and  in  some  forms  of  diuresis  may 
rise  to  as  much  as  -28  c.c.  per  gramme  per  minute.  It  is  worthy  of  note  that  this  rise 
in  oxygen  consumption  is  found  when  the  diuresis  is  caused  by  the  intravenous  injection 
of  urea,  sodium  sulphate,  or  phlorhizin,  but  not  when  the  diuresis  is  brought  about  by 
the  injection  of  water,  Ringer's  solution  or  sodium  chloride. 
75 


IJ86  PHYSIOLOGY 

The  abandonment  of  Lud wig's  view  as  to  the  mechanism  of  the  concentra- 
tion does  not  however  place  his  theory  out  of  court.  The  question  will 
still  have  to  be  discussed  whether  the  chief  object  of  the  tubules  is  the  con- 
centration of  the  fluid  produced  in  the  glomeruli,  or  whether  they  add  to  this 
fluid  by  a  further  secretory  process,  or  whether  they  may  not  possibly 
possess  both  functions  and  in  their  various  parts  alter  the  fluid  flowing 
through  them  either  by  addition  or  by  withdrawal  of  water  or  dissolved 
constituents.  The  common  point  in  the  two  theories  is  the  sharp  distinc- 
tion which  is  drawn  between  the  nature  of  the  glomerular  activity  and  the 
nature  of  the  activity  of  the  tubules.  The  questions  which  we  have  to 
decide  by  experiment  are  : 

(1)  The  nature  of  the  glomerular  activity  and  the  conditions  which 
determine  the  amount  of  fluid  formed  by  the  glomeruli,  and  especially 
whether  the  energy  required  for  the  formation  of  the  glomerular  fluid  is 
furnished  by  the  heart  through  the  blood  pressure  within  the  capillaries  or 
by  the  endothelium  covering  these  capillaries. 

(2)  The  function  of  the  tubules,  whether  they  secrete  or  absorb,  and 
what  part  is  played  in  these  processes  by  the  various  segments  of  the  tubules, 
which  differ  so  widely  in  their  histological  characters. 


FUNCTIONS   OF   THE   GLOMERULI 

It  is  generally  assumed,  as  the  best  explanation  of  known  facts  with 
regard  to  the  secretion  of  urine,  that  a  watery  exudation  free  from  protein  is 
formed  in  the  glomeruli,  and  that  this  becomes  concentrated  on  its  way 
through  the  tubules,  either  by  the  absorption  of  water  and  certain  salts  or  by 
the  secretion  and  addition  of  urea,  uric  acid,  etc.  as  well  as  such  salts  as 
acid  phosphates.  As  to  the  nature  of  the  glomerular  functions  two  opinions 
have  been  held.  According  to  the  Ludwig  school,  the  process  is  one  simply 
of  filtration,  in  which,  under  the  pressure  of  the  blood  in  the  glomerular 
capillaries,  the  water  and  crystalloid  constituents  of  the  plasma  are  filtered 
through  the  glomerular  epithelium,  leaving  behind  the  protein  constituents. 
According  to  Heidenhain,  the  process  cannot  be  regarded  as  one  simply  of 
filtration,  but  involves  the  secretory  activity  of  the  glomerular  epithelium. 
If  the  glomerular  urine  is  a  filtrate,  it  must  resemble  blood  plasma  in  practi- 
cally all  particulars  except  its  protein  content,  since  the  blood  pressure,  which 
is  the  only  force  causing  filtration,  is  too  small  to  effect  any  appreciable 
separation  of  salts.  On  the  other  hand,  a  certain  nunimum  difference  of 
pressure  between  the  two  sides  of  the  membrane  must  be  present  in  order  to 
separate  the  colloids  from  the  other  constituents  of  the  plasma.  We  have 
seen  in  Chapter  iv  (p.  141)  that,  in  order  to  produce  a  filtrate  containing  only 
water  and  salts  from  serum,  a  minimum  difference  of  pressure  of  30  mm.  Hg. 
is  necessary,  corresponding  to  the  osmotic  pressure  of  the  colloidal  con- 
stituents of  the  blood  plasma  or  serum.  Thus  in  order  to  produce  a  filtrate, 
free  from  protein,  from  the  blood  plasma  circulating  through  the  glomerular 
capillaries,  the  pressure  of  the  urine  in  the  tubules  and  ureter  must  always 


THE  SECRETION   OF  URINE  U8F- 

be  at  least  30  mm.  lower  than  the  pressure  of  the  blood  in  the  glomeruli.  A 
direct  determination  of  the  latter  figure  is  not  possible.  The  anatomical 
arrangements  are  such  as  to  bring  this  pressure  up  to  a  high  point.  Not  only 
are  the  vasa  afferentia  very  short,  but  the  vasa  efl'erentia  are  only  two- 
thirds  of  the  diameter  of  the  vasa  afferentia.  Moreover  the  sudden  increase 
of  bed,  which  ensues  as  the  blood  passes  from  the  vas  afferens  to  the  bundle 
of  capillaries,  must  itself  cause  a  rise  of  pressure  in  the  latter,  due  to  the 
transformation  of  the  kinetic  energy  of  the  moving  fluid  into  the  statical 
energy  represented  by  pressure  on  the  walls  of  the  vessels. 

This  point  can  be  rendered  clearer  by  the  following  considerations.  If  fluid  is  flowing 
in  a  tube  of  continuous  bore  ab  (Fig.  5-45)  there  will  be  a  continuous  fall  of  pressure 
from  a  to  b.  If  however  in  the  tube  abc  the  segment  b  be  of  much  greater  diameter 
than  the  segments  a  and  c,  although  while  the  fluid  is  at  rest  the  pressures  will  be  equal 
at  all  points  of  the  system,  as  soon  as  the  fluid  moves  from  a  to  c,  although  there  is  a  fall 
of  pressure  between  a  and  c,  a  manometer  attached  to  6  may  show  an  actual  greater 
pressure  than  a  manometer  inserted  at  a.  Fluid  is  flowing  from  a  place  of  lower  to  a 
place  of  higher  pressure.     The  apparent  paradox  is  due  to  the  fact  that  the  energy 


pressure 


1  pressure 


causing  the  fluid  to  move  from  a  to  b  is  of  two  kinds.  It  equals  fmi'2  -f-  P>  »•  e.  repre- 
sented by  the  kinetic  energy  of  the  moving  mass  of  fluid  as  well  as  the  difference  of 
pressure  between  any  two  points  of  the  tube.  The  total  energy  will  diminish  con- 
tinuously from  a  to  c,  and  is  used  in  overcoming  the  resistance  of  the  system.  We  may 
say  then  that  the  sum  of  these  two,  namely,  %mv2  -f-  P,  is  greater  at  a  than  b,  and  is 
greater  at  6  than  c  ;  but  as  the  fluid  passes  from  the  narrow  tube  a  into  the  wide  tube  b, 
there  is  a  sudden  fall  of  its  velocity  and  a  consequent  diminution  of  the  factor  \rriv2-. 
In  order  to  provide  for  a  continuous  fall  in  the  total  energy  of  the  fluid,  namely,  \mv%  -f- 
P,  the  diminution  in  the  factor  \mv%  must  cause  a  corresponding  increase  in  the  factor 
P,  i.  e.  in  the  lateral  pressure  exercised  by  the  fluid  on  the  vessel  wall.  As  the  total 
diameter  of  the  bed  of  the  stream  in  the  capillaries  may  be  twenty  times  that  of  the  bed 
in  the  vas  afferens,  the  velocity  of  the  blood  in  these  capillaries  will  be  only  one-twentieth 
of  that  in  the  artery  and  the  kinetic  energy  of  the  blood  only  one  four-hundredth.  It 
is  possible  therefore  that  the  pressure  exercised  by  the  blood  on  the  walls  of  the  capil- 
laries may  be  even  greater  than  that  in  the  interlobular  arteries,  and  this  effect  will  be 
still  further  aided  by  the  narrow  diameter  of  the  vas  efferens.  Although  therefore  the 
pressure  in  the  ordinary  capillaries  of  the  body  is  probably  not  greater  than  20  to  30  mm. 
Hg.,  the  glomerular  capillaries  might  present  a  pressure  little  inferior  to  that  in  the  main 
arteries  of  the  body. 

The  pressure  in  the  ureter  is  under  normal  circumstances  approximately 
nil,  whereas  that  in  the  glomerular  capillaries  is  probably  not  more  than 
20  mm.  Hg.  below  that  in  the  main  arteries  of  the  body,  so  that  there  is  a 
difference  of  pressure  on  the  two  sides  of  the  membrane  more  than  sufficient 
to  cause  a  constant  filtration  of  a  protein-free  fluid  from  the  blood  plasma 


1188  PHYSIOLOGY 

coursing  through  these  capillaries.  On  raising  the  pressure  on  the  tubule 
side,  the  filtration  ought  to  come  to  an  end  when  t  lie  pressure  approaches 
a  figure  which  is  30  to  40  mm.  Hg.  below  that  in  the  glomerular  capillaries. 
A  number  of  observers  have  found  that  urinary  secretion  ceases  when  the 
blood  pressure  falls  to  between  40  and  50  mm.  Hg.  The  urinary  secretion 
can  be  stopped  by  raising  the  pressure  in  the  tubules  by  means  of  ligature 
of  the  ureter.  On  applying  the  ligature  the  secretion  continues  for  a  time 
until  the  pressure  in  the  ureter  rises  up  to  a  certain  point,  when  the  secretion 
comes  to  an  end.  In  one  experiment  the  following  pressures  were  obtained 
in  a  dog  which  was  secreting  urine  copiously  under  the  action  of  diuretin. 
Manometers  were  connected  both  with  the  carotid  artery  and  with  the 
ureters  so  that  no  outflow  of  urine  was  possible. 

Arterial  pressure  .  Ureter  pressure 

140 72 

138 92 

133 88 

In  this  experiment  therefore  secretion  came  to  an  end  with  a  difference 
of  pressure  between  ureter  and  arteries  of  between  40  and  50  mm.  Hg. 

The  absolute  pressure  attained  within  the  ureter  in  any  given  experiment  after  liga- 
ture of  these  tubes  will  vary  with  several  factors.  In  the  first  place,  if  the  minimum 
secreting  pressure  is  really  conditioned  by  the  colloid  content  of  the  blood  plasma,  it 
will  be  less  the  smaller  the  proportion  of  colloids  in  the  plasma.  In  some  experiments 
(.Magnus)  a  flow  of  urine  was  observed  with  a  blood  pressure  as  low  as  18  mm.  Hg.,  but 
in  this  case  the  blood  was  extremely  dilute  as  the  result  of  the  continuous  injection  into 
the  blood  vessels  of  normal  salt  solution.  Barcroft  and  Knowlton  have  shown  that  the 
diuresis  brought  about  by  injection  of  saline  (Ringer's)  solution  is  inhibited  by  mixing 
with  the  saline  fluid  colloids,  such  as  gelatin  and  gum,  which  possess  an  osmotic  pressure. 
Colloids  such  as  starch,  with  no  measurable  osmotic  pressure,  have  no  such  effect. 

On  the  other  hand,  the  ureters,  or  at  any  rate  the  urinary  tubules,  cannot  be  regarded 
as  absolutely  water-tight.  Not  only  are  the  cells  of  these  tubules  capable  of  taking  up 
fluid,  but  it  is  probable  that  at  high  pressures  a  certain  amount  of  actual  filtration  takes 
place  between  these  cells.  This  process  of  reabsorption  will  tend  to  diminish  the  actual 
pressure  of  the  fluid  in  the  ureters,  so  that  the  secretion  of  urine  may  apparently  come 
to  a  standstill  when  there  is  still  a  difference  of  pressure  between  blood  and  urine  con- 
siderably over  50  mm.  Hg.  Under  such  circumstances  the  ureter  pressure  will  be  higher, 
and  the  difference  of  pressure  between  urine  and  blood  less,  the  more  rapid  the  formation 
of  urine  by  the  glomeruli.  In  a  number  of  experiments  by  V.  E.  Henderson,  it  was 
found  that  the  figure  B.P.  —  U.P.  tended  to  approximate  40  mm.  Hg.  the  more  rapid 
the  secretion  of  urine  was.  With  a  slow  secretion  the  flow  of  urine  apparently  ceased 
when  there  was  as  much  as  80  mm.  Hg.  difference  of  pressure  on  the  two  sides  of  the 
glomerular  membrane. 

We  may  conclude  that,  for  the  production  of  any  urine  by  the  kidney, 
a  certain  minimum  difference  of  pressure  is  necessary  between  the  blood  in 
the  glomeruli  and  the  urine  in  the  tubule,  and  that  this  difference  becomes 
less  the  smaller  the  protein  content  of  the  blood.  Since  the  only  work 
required  in  the  formation  of  a  protein-free  filtrate  from  the  blood  is  that  due 
to  the  osmotic  pressure  of  the  proteins  themselves,  and  the  observed  difference 
of  pressure  during  secretion  is  greater  than  this  osmotic  pressure,  we  are 
justified  in  concluding,  provisionally  at  any  rate,  that  the  mechanical  factors 


THE   SECRETION   OF  URINE  1189 

present  at  the  upper  end  of  the  urinary  tubule  are  sufficient  to  account  for  the 
production  of  a  glomerular  transudate  free  from  protein,  but  containing  the 
same  proportion  of  water  and  salts  as  the  blood  plasma  circulating  through 
the  capillaries. 

If  the  process  occurring  in  the  glomeruli  is  simply  one  of  filtration,  three 
conditions  must  be  realised  : 

(1)  The  amount  of  filtrate,  so  long  as  the  ureter  pressure  is  constant, 
must  depend  on  the  pressure  and  rate  of  flow  of  the  blood  in  the  glomerular 
capillaries,  and  must  fall  or  rise  with  the  lattet. 

(2)  The  constitution  of  the  fully  formed  urine  as  it  appears  in  the  ureters, 
after  modification  by  addition  or  subtraction  on  the  part  of  the  tubular  cells, 
must  approximate  more  closely  to  the  supposed  glomerular  transudate, 
containing  the  same  proportion  of  salts  as  the  blood  plasma,  the  more  rapidly 
the  formation  of  the  glomerular  transudate  takes  place  :  i.  e.  the  quicker  the 
flow  of  urine  the  more  nearly  must  its  composition,  reaction,  and  osmotic 
pressure  resemble  those  of  the  blood  serum. 

(3)  The  total  quantity  of  solids  excreted  in  any  given  time  must  be 
increased  with  any  increase  in  the  urinary  flow.  For,  whatever  the  activity 
of  the  tubules,  the  glomeruli  must  blindly  turn  out  a  certain  proportion  of 
solids  with  every  cubic  centimetre  of  fluid  that  they  form. 

We  may  deal  first  with  the.  influence  of  alterations  in  the  renal  blood 
supply  on  the  flow  of  urine.  Ligature  of  the  renal  vein  diminishes  and  soon 
stops  the  flow  altogether.  Since  this  procedure  must  cause  a  large  rise  of 
pressure  in  the  capillaries  of  the  kidney,  this  result  was  regarded  by  Heiden- 
hain  as  disproving  any  possibility  of  the  glomerular  process  being  of  the 
nature  of  a  filtration.  At  any  given  time  however,  the  glomeruli  contain  but 
little  blood.  With  total  cessation  of  the  renewal  of  this  blood,  their  contents 
will  rapidly  become  so  concentrated  that  they  will  be  little  more  than  a  mass 
of  red  corpuscles.  No  filtration  of  water  and  salts  can  take  place  unless  there 
is  a  continual  renewal  of  the  fluid  on  the  blood  side  of  the  filter. 

On  the  other  hand,  alterations  in  the  blood  supply  to  the  kidney, 
determined  by  changes  on  the  arterial  side,  have  pronounced  effects  on  the 
amount  of  urine  formed.  The  pressure  in  the  glomerular  capillaries  and  the 
rate  of  flow  through  these  capillaries  can  be  increased  in  either  of  two  ways  : 

fa)  By  increase  of  the  driving  force,  i.  e.  the  general  blood  pressure ; 

(b)  By  a  diminution  of  the  resistance  to  the  flow  of  blood  through  the 
kidneys,  as  by  dilatation  of  the  vessels  of  this  organ. 

The  blood  flow  through  the  kidney  can  be  investigated,  either  by  record- 
ing the  total  volume  of  this  organ,  or  by  determining  the  amount  of  blood 
which  leaves  it  through  the  renal  vein,  according  to  the  methods  described 
in  Chapter  xiii. 

It  is  necessary  at  the  same  time  to  take  a  record  of  the  arterial  blood 
pressure  by  means  of  a  mercurial  manometer.  It  is  evident  that  an  expan- 
sion of  the  kidney  may  be  caused  by  a  rise  of  general  arterial  pressure  or, 
the  latter  remaining  constant,  by  a  dilatation  of  the  kidney 'vessels;  and, 
conversely,  a  fall  of  kidney  volume  may  be  due  either  to  a  fall  of  general 


1190 


PHYSIOLOGY 


blood  pressure  or  to  a  constriction  of  the  renal  blood  vessels.  By  taking 
these  two  records  it  is  possible  to  tell  whether  a  given  increase  of  blood  flow 
through  the  organ  is  of  local  or  of  general  causation,  i.  e.  is  active  or  passive. 
Thus  the  volume  of  the  kidney  gives  us  an  indirect  clue  to  the  pressure  in 
and  the  flow  through  the  kidney  vessels.  The  flow  through  the  vessels 
can  be  determined  directly  either  by  a  cannula  in  the  inferior  vena  cava,  all 
veins  other  than  the  renal  being  clamped,  or  by  Brodie's  method,  already 
described  (p.  1037). 

The  results  of  the  experiments  carried  out  by  these  methods  can  be 
represented  in  the  following  tabular  form  : 


Procedure 

General  blood 
pressure 

Eenal  vessels 

Kidney  volume 

Urinary  flow 

Division  of  spinal  cord  in 

Falls  to 

Relaxed 

Shrinks 

Ceases 

neck  .... 

40  mm. 

Stimulation  of  cord 

Rises 

Constricted 

Shrinks 

Diminished 

Stimulation  of  cord  after 

Rises 

Passively 

Swells 

Increased 

section  of  renal  nerves 

dilated 

Stimulation  of  renal  nerves 

Unaffected 

Constricted 

Shrinks 

Diminished 

Stimulation  of  splanchnic 

Rises 

Constricted 

Shrinks 

Diminished 

nerve 

Division  of  one  splanchnic 

nerve :         .          .          . 

(a)  In  dog 

Unaffected 

Dilated 

Swells  ( ?) 

Increased 

(6)  In  rabbit    . 

Falls 

Relaxed 

Shrinks  ( ?) 

Diminished 

Plethora 

Rises 

Dilated 

Swells 

Increased 

Haemorrhage 

Falls 

Constricted 

Shrinks 

Diminished 

It  will  be  seen  that  in  every  case,  where  an  increased  blood  flow  attended 
with  a  rise  of  blood  pressure  in  the  glomerular  capillaries  is  brought  about, 
the  urinary  flow  is  at  the  same  time  increased. 

Another  factor,  altering  the  ease  with  which  filtration  of  watery  fluid 
and  salts  would  take  place  through  the  glomerular  capillaries,  would  be  the 
composition  of  the  blood  plasma.  Any  dilution  of  this  plasma  must  render 
filtration  more  easy,  while  a  concentration  would  make  it  more  difficult. 
As  a  matter  of  fact  hydremia,  and  especially  hydraemic  plethora  caused  by 
injection  of  normal  saline  into  the  circulation,  evoke  an  increased  flow  of 
urine.  A  smaller  effect  is  produced  by  injection  of  defibrinated  blood,  and 
if  the  blood  has  been  previously  concentrated  by  depriving  the  animals  of 
water,  there  may  be  little  or  no  increase  in  flow,  in  consequence  of  the  high 
osmotic  pressure  of  the  proteins  of  the  plasma  injected. 

If  the  glomerular  function  is  that  of  mere  filtration,  we  should  expect 
that  the  more  rapidly  the  process  occurs,  the  more  nearly  would  the  urine 
which  is  turned  out  into  the  ureters  resemble  the  blood  plasma  in  com- 
position, reaction,  and  osmotic  pressure,  since  the  glomerular  filtrate  hurried 
through  the  tubules  would  have  very  little  time  to  undergo  any  changes 
resulting  in  its  concentration.  If,  on  the  other  hand,  the  diuresis  produced 
by  salt  or  sugar  solutions  is  to  be  ascribed  to  a  stimulation  of  the  renal 


THE   SECRETION   OF  URINE  1191 

epithelium,  the  differences  between  blood  plasma  and  urine  should  be 
greatest  at  the  height  of  the  diuresis,  when  the  concentration  of  the  specific 
stimulant  is  also  at  its  highest.  The  following  experiment  shows  that  the 
more  rapid  the  secretion  of  urine,  the  more  closely  does  its  concentration, 
as  indicated  by  its  osmotic  pressure  and  depression  of  freezing-point  (A), 
approximate  that  of  the  blood  plasma. 

A  dog  received  40  grm.  of  dextrose  dissolved  in  40  c.c.  of  water.  The 
following  Table  represents  the  relative  concentrations  of  urine  and  blood 
serum  at  different  stages  in  the  diuresis  thereby  produced  : 


Time 

TJriDe 

Rate  of  flow 

A  of  urine 

A  of  blood-serum 

11.30-12 

10  c.c. 

3-3 

2-360 

0-625  (at  12.0) 

From  12.0  to  12.7  injected  40  grm.  dextrose  into  jugular  vein 

12.7  -12.15 

35  c.c.                     45 

1-210 



12.16-12.20 

20  c.c.                     50 

0-975 

0-700  (at  12.16) 

12.20-12.30 

52  c.c.                     52 

0-835 

— 

12.30-12.40 

45  c.c.                    45 

0-825 

0-700  (at  12.30) 

12.40-12.50 

22  c.c.                    22 

0-830       J 

0-675  (at  12.40) 
0-675  (at  12.50) 

A  still  closer  approximation  of  the  concentration  of  the  urine  to  that  of  the 
plasma  was  obtained  by  Galeotti  in  some  experiments  in  which  the  modifying 
influence  of  the  tubular  epithelium  on  the  glomerular  transudate  had  been 
prevented  by  poisoning  the  animal  with  corrosive  sublimate,  which  causes 
destruction  of  the  epithelium  but  is  said  to  leave  the  glomeruli  intact. 

Since  the  glomerular  transudate  must  have  a  concentration  approxi- 
mately identical  with  that  of  the  blood  plasma,  it  would  be  impossible  for 
a  urine  formed  by  mere  filtration  to  have  a  concentration  less  than  that 
of  the  blood  plasma.  It  is  however  of  frequent  occurrence  that,  after 
copious  potations  of  tea  or  light  beer,  urine  is  passed  with  an  osmotic  pressure 
and  a  molecular  concentration  considerably  below  that  of  the  blood.  In 
one  case  Dreser  obtained  a  urine  with  a  freezing-point  of  A  =  0-160  O,  and 
the  same  result  has  been  obtained  on  one  or  two  occasions  when  the  diuresis 
has  been  produced  by  the  administration  of  caffeine.  If  we  assume  that  this 
hypotonic  fluid  is  formed  by  the  glomeruli,  we  must  at  once  give  up  any  idea 
of  the  process  in  these  structures  being  essentially  one  of  filtration.  But 
the  fine  adaptation  of  the  kidney  to  slight  changes  in  the  composition  of 
the  blood  is  apparently  an  endowment  of  the  tubular  epithelium;  and  in 
those  cases  where  large  quantities  of  hypotonic  urine  are  passed,  there  is 
not  at  any  time  any  appreciable  change  either  in  the  composition  of  the 
blood  or  in  its  total  volume.  Water  is  absorbed  from  the  alimentary  canal 
and  is  almost  immediately  excreted  by  the  kidneys.  When  we  attempt  to 
produce  the  same  effect  by  infusion  of  large  quantities  of  water  or  hypotonic 
solutions  into  the  blood  stream,  we  get  a  flow  of  urine  apparently  deter- 
mined entirely  by  the  circulation  through  the  kidney  and  having  a  con- 
centration not  inferior  to  that  of  the  blood.     The  passage  of  hypotonic  urine 


1192  PHYSIOLOGY 

can  be  ascribed  to  a  modification  of  the  glomerular  transudate  as  it  passes 
through  the  tubules,  a  modification  which  may  be  due  either  to  the  absorption 
of  salts  from  the  fluid,  or  to  a  secretion  of  water  or  extremely  dilute  salt 
solution  by  the  cells  of  the  tubules  themselves.  Possibly  both  processes  are 
involved. 

Certain  other  observations  accord  with  our  hypothesis  that  in  Bowman's  capsule  a 
fluid  is  transuded  having  the  same  molecular  concentration  as  blood  plasma,  and  there- 
fore considerably  less  concentrated  than  normal  urine.  Ribbert  succeeded  in  extir- 
pating the  whole  of  the  medullary  portion  of  the  kidney  in  the  rabbit,  leaving  the  cortex 
intact,  and  found  in  this  case  that  during  the  survival  of  the  animal  the  urine  passed  was 
much  more  dilute  than  normal.  In  cases  where,  while  the  glomeruli  remain  intact, 
there  is  destruction  of  the  tubular  epithelium  either  in  consequence  of  disease  or,  as 
in  Galeotti's  experiments,  as  a  result  of  poisons,  we  are  accustomed  to  obtain  a  dilute 
copious  urine;  and  the  continual  passage  of  such  urine  is  in  man  regarded  as  a  sign  of 
one  form  of  renal  disease. 

The  experimental  facts  which  we  have  passed  in  review  do  not  therefore 
negative  the  view  that  the  glomerular  epithelium  plays  the  part  of  a  passive 
filter  in  the  formation  of  tirine,  and  that  the  energy  of  the  process  by  which 
'  urine  '  is  produced  in  Bowman's  capsule  is  entirely  furnished  by  the  heart 
in  driving  the  blood  at  a  high  pressure  through  the  glomerular  capillaries. 

It  is  important  however  to  remember  that,  however  passive  it  may  be 
in  the  formation  of  urine,  the  filtering  membrane  is  composed  of  living  cells, 
which  may  alter  and  lose  their  powers  of  filtration  or  their  powers  of  retaining 
the  colloid  constituents  of  the  blood  plasma  under  any  influences  which 
impair  their  vitality.  Thus  obstruction  of  the  renal  artery  for  half  a  minute 
may  suppress  the  formation  of  urine  in  the  kidneys  for  half  to  several  hours, 
and  the  urine,  when  again  formed,  is  found  to  contain  coagulable  protein 
('  albumin  ')  which  can  be  shown  to  have  transuded  through  the  glomerular 
epithelium.  The  filtering  properties  of  the  membrane  may  be  impaired  to 
a  lesser  degree  by  slowing  the  circulation  of  the  blood  through  the  kidneys. 
In  the  venous  congestion  of  heart  disease,  the  presence  of  albumin  in  the 
urine  is  of  frequent  occurrence.  The  same  effect  on  the  permeability  of  the 
epithelium  may  be  produced  by  many  kinds  of  poisons,  mineral  or  microbial, 
circulating  in  the  blood. 


FUNCTIONS   OF   THE   RENAL   TUBULES 

Whatever  the  nature  of  the  glomerular  activity,  it  is  evident  that  the 
multiform  epithelium  of  the  tubules  may  alter  the  glomerular  transudate, 
either  by  the  absorption  or  by  the  secretion  of  water  or  solid  constituents. 
We  may  deal  with  the  evidence  for  the  occurrence  of  these  two  processes 
separately. 

SECRETION  BY  THE  RENAL  TUBULES.  Although  it  is  impossible 
to  collect  the  secretion  of  the  glomeruli  apart  from  that  of  the  tubules,  the 
arrangement  of  the  blood  vessels  in  certain  animals  enables  us  to  influence 
separately  the  circulation  to  these  two  parts  of  the  kidney.  The  amphibian 
kidney  receives  a  blood  supply  from  two  sources.      A  number  of  renal 


THE  SECRETION  OF  URINE 


1193 


Test- 

Kidney 
Renal  pgrral 

ArU  abdom.v- 


Aorfa 


Vena  cava 


Renal  arteries 


Femoral 


Fid  546. 


arteries  leaving  the  aorta  enter  the  kidney  and  supply  the  whole  of  the 
glomeruli,  the  vasa  eSerentia  from  which  pass,  as  in  the  mammalian  kidney, 
into  the  intertubular  capillaries.  These  are  also  supplied  with  blood  of 
venous  character  by  the  renal  portal  vein.  If  all  the  renal  arteries  be  divided 
or  ligatured,  the  glomeruli,  as  was  shown  by  Nussbaum,  are  entirely  cut  out 
of  the  circulation,  though  the  tubules  continue  to  receive  venous  blood 
through  the  renal  portal  vein.  Nussbaum  stated  that  ligature  of  all  the 
renal  arteries  caused  cessation  of  the  urinary  secretion,  which  could  be 
reinduced  by  injection  of  urea. 
He    concluded    that    urea    with  Faf  bod 

water  was  secreted  by  the 
tubules,  whereas  peptone,  sugar, 
and  haemoglobin  were  turned 
out  by  the  glomeruli.  Beddard 
showed  that  these  results  of 
Nussbaum  must  have  been  due 
to  the.  fact  that  he  had  not 
obstructed  the  whole  of  the  renal 
arteries.  One  or  two  of  these 
small  vessels  will  suffice  to 
supply  blood  to  a  considerable 
number  of  the  glomeruli.  After 
complete  obstruction  of  the 
arteries,  no  urinary  flow  could  be 
induced  even  with  subcutaneous 

injection  of  urea.  But  the  cutting  off  of  the  arterial  blood  supply  from  the 
tubules  caused  a  rapid  destruction  of  the  tubular  epithelium,  so  that  the 
result  of  the  experiment  could  not  be  taken  as  negativing  the  possibility  of 
this  epithelium  having,  when  in  a  normal  state  of  nutrition,  some  secretory 
power.  He  therefore  carried  out,  with  Bain  bridge,  another  series  of  ex- 
periments of  the  same  description,  in  which  the  frogs,  after  ligature  of  the 
renal  arteries,  were  kept  in  an  atmosphere  of  pure  oxygen.  Under  these 
circumstances  sufficient  oxygen  diffused  into  the  blood  of  the  renal  portal 
win  to  maintain  an  adequate  supply  of  this  gas  to  the  tubules.  No  desquam- 
ation of  the  epithelium  resulted,  and  injection  of  urea  produced  a  small 
flow  of  urine  even  when,  by  subsequent  injection  of  the  blood  vessels,  it  was 
proved  that  every  glomerulus  had  been  cut  out  of  the  circulation. 

In  the  cells  of  the  convoluted  tubules  various  kinds  of  granules  and  of  vacuoles  may 
be  distinguished.     Gurwitsch  divides  these  vacuoles  into  three  classes; 

(1)  Large  granules  staining  densely  with  osmic  acid,  and  probably  rich  in  lecithin. 

(2)  Smaller  very  numerous  granules  consisting  of  some  form  of  protein  material. 

(3)  Large  vacuoles  lying  close  to  the  free  margins  of  the  cells,  whose  contents  do 
not  undergo  coagulation  with  the  ordinary  fixing  reagents,  and  therefore  are  free  from 
protein,  fat,  or  mucin.  These  vacuoles  are  especially  marked  in  kidneys  which  are 
secreting  at  a  great  rate,  in  consequence  of  the  injection  of  saline  diuretics  or  of  large 
quantities  of  normal  salt  solution.  They  have  been  regarded  as  excretory  vacuoles,  and 
as  containing  water  or  saline  fluids  which  have  been  collected  by  the  cells  and  are 
being  passed  on  by  them  to  the  lumen  of  the  tubules. 


The  vascular  supply  to  the  kidney 
in  the  frog. 


1194  PHYSIOLOGY 

In  a  secreting  gland  such  as  the  parotid,  there  is  a  marked  change  in  the  appearance 
of  the  granules  according  as  the  gland  is  resting  or  actively  secreting.  No  such  changes 
have  been  discovered  in  the  granules  of  the  renal  cells,  and  the  vacuoles  that  have  been 
described  might  be  either  in  process  of  secretion  or  might  be  evidence  of  copious  absorp- 
tion of  watery  fluids  from  the  lumen  of  the  tubule. 

As  a  rule  it  is  impossible  to  trace  any  definite  constituent  of  the  urine 
on  its  way  through  the  cells  of  the  tubules.  But  if  massive  doses  of  uric  acid 
in  piperazin  be  injected  intravenously  into  a  rabbit,  the  kidneys,  taken 
twenty  to  sixty  minutes  after  the  injection,  present  tubules  full  of  uric  acid 
concretions.  In  the  medullary  portion  of  the  kidney  this  uric  acid  precipitate 
is  confined  to  the  lumen  of  the  tubules,  but  in  the  convoluted  tubules  granules 
of  uric  acid  are  to  be  found  in  the  epithelial  cells,  especially  towards  their 
inner  border. 

Under  the  same  circumstances  masses  of  uric  acid  crystals  are  also 
found  in  the  connective  tissues  between  the  tubules.  It  is  therefore  impos- 
sible to  be  certain  that  the  granules  observed  within  the  epithelial  cells 
are  in  process  of  excretion  or  are  being  absorbed  from  the  lumen.  Modem 
methods  have  failed  to  substantiate  the  older  observations  as  to  the  occur- 
rence of  uric  granules  under  normal  conditions  in  the  cells  of  the  convoluted 
tubules  of  the  bird's  kidney. 

Heidenhain  has  attempted  to  throw  light  on  the  excretive  functions  of 
the  kidney  by  studying  the  mechanism  by  means  of  which  it  excretes  certain 
dyestuffs,  such  as  sulphindigotate  of  soda  ('  indigo  carmine ').  If  the 
indigo  be  injected  into  the  veins,  it  is  excreted  in  a  concentrated  form, 
both  by  the  liver  and  by  the  kidney,  so  that  the  urine  assumes  a  dark  blue 
colour.  If  the  animal  be  killed  when  the  excretion  of  the  pigment  is  at 
its  height,  and  the  kidneys  be  rapidly  fixed  with  absolute  alcohol  (which 
precipitates  the  dyestuff),  all  parts  of  the  kidney  present  a  blue  colour, 
which  is  especially  marked  in  the  medulla.  Under  these  circumstances  the 
urine,  which  is  being  excreted  by  the  glomeruli,  rapidly  carries  down  the 
dyestuff,  wherever  it  may  be  turned  out,  into  the  tubules  of  the  pyramids. 
In  order  to  discover  the  exact  locality  of  the  cells  involved  in  its  excretion, 
we  must  stop  the  glomerular  transudate  by  some  means  or  other.  This 
stoppage  of  the  urinary  flow  can  be  effected  in  two  ways,  viz.  by  section  of 
the  spinal  cord  in  the  neck,  so  as  to  reduce  the  blood  pressure  to  about 
40  mm.  Hg.,  i.  e.  below  the  minimum  necessary  for  the  production  of  urine, 
or  by  cauterising  portions  of  the  surface  of  the  kidney  by  means  of  silver 
nitrate.  If  the  indigo  be  injected  into  the  veins  after  section  of  the  cord, 
and  the  animal  be  killed  half  an  hour  later,  and  the  kidneys  fixed  with 
absolute  alcohol,  they  are  found  to  be  of  a  bright  blue  colour,  although  no 
urine  has  been  secreted.  On  cutting  into  the  kidneys  the  colour  is  seen  to 
be  confined  to  the  cortex,  and  on  making  microscopic  sections  granules  of 
the  pigment  are  found  within  the  lumen  and  in  the  epithelial  cells  of  the 
convoluted  tubules.  If  the  kidneys  have  been  cauterised,  the  stain  is 
confined  to  the  convoluted  tubules  of  the  cortex  only  under  those  areas 
which  have  been  cauterised,  and  where  the  glomerular  functions  have  been 
abolished. 


THE  SECRETION   OF   URINE  1195 

All  these  appearances  are  susceptible  however  to  another  explanation. 
If  indigo  carmine  is  turned  out  by  the  glomerulus  it  will  be  so  dilute  that 
unless  very  large  doses  are  injected  the  glomerulus  will  not  be  stained.  As 
the  glomerular  transudate  descends  the  tubules  it  undergoes  concentration. 
The  precipitation  of  the  dyestufl  in  the  tubules  may  be  simply  a  result  of  this 
concentration,  and  the  granular  deposit  in  the  cells  may  be  evidence  not 
of  secretion  but  of  absorption  of  the  dyestufi  by  the  cells.  In  fact  we 
must  acknowledge  that  the  evidence  for  secretion  by  the  cells  of  the  con- 
voluted tubules  is  very  defective.  Since  all  the  microscopic  appearances 
observed  after  the  injection  of  dyestufi  are  susceptible  of  two  explanations, 
there  remains  only  the  experiment  of  Nussbaum,  as  repeated  by  Bainbridge 
and  Beddard,  as  evidence  of  secretion  on  the  part  of  the  tubular  epithelium  ; 
and  this  evidence  would  lose  its  weight  if  one  or  two  glomeruli  in  the  operated 
kidney  still  received  some  blood  supply,  even  though  they  failed  to  be 
injected  with  the  injection  mass  used  at  the  end  of  the  experiment  for  conr 
trolling  the  completeness  of  occlusion  of  the  renal  arteries. 

ABSORPTION  BY  THE  RENAL  TUBULES.  The  experiments  of  Ribbert, 
mentioned  above,  in  which  removal  of  the  medullary  portion  of  the 
kidney  led  to  the  formation  of  an  increased  quantity  of  a  more  watery  urine, 
points  to  the  possession  by  the  tubules  of  a  power  of  absorbing  water.  We 
have  other  evidence  that  this  power  of  resorption  is  not  confined  to  water, 
but  may  affect  also  the  dissolved  constituents  of  the  glomerular  transudate. 
It  was  pointed  out  by  Meyer  that,  if  two  salts  such  as  sodium  sulphate  and 
sodium  chloride  were  present  at  the  same  time  in  the  glomerular  transudate, 
any  process  of  resorption  should'afiect  chiefly  the  more  diffusible  salt,  namely, 
sodium  chloride.  Such  a  differential  resorption  would  account  for  the  much 
greater  diuretic  power  of  sodium  sulphate  as  compared  with  sodium  chloride. 
In  certain  experiments  Cushny  produced  a  diuresis  by  the  injection  of 
equal  parts  of  equivalent  NaCl  and  Na2S04  solutions  into  the  veins  of  a 
rabbit.  An  increased  flow  of  urine  was  produced  which  lasted  two  hours 
and  a  half.  The  chlorides  of  the  urine  rose  with  the  diuresis  and  reached 
their  maximum  at  the  height  of  the  urinary  flow.  They  then  sank,  and  hi 
some  experiments  had  practically  disappeared  from  the  urine  towards  the 
end  of  the  observation.  The  concentration  of  the  sulphates  however  con- 
tinued to  rise  in  the  urine  to  the  end  of  the  experiment.  Thus  in  the  first  of 
two  identical  experiments,  when  the  rabbit  was  killed  at  the  height  of  the 
diuresis,  the  serum  contained  0-547  per  cent,  chlorine  and  0-259  per  cent, 
sulphate,  while  the  urine  contained  0-372  per  cent,  chlorine  and  0-546  per 
cent,  sulphate.  In  the  second,  in  which  the  rabbit  was  killed  when  the  rate 
of  the  urinary  flow  had  considerably  diminished,  the  serum  contained  0-493 
per  cent,  chlorine  and  0-191  per  cent,  sulphate,  while  the  urine  contained 
■094  per  cent,  chlorine  and  2-0  per  cent,  sulphate.  'These  results  are  illus- 
trated in  Fig.  547. 

The  difference  between  the  two  salts  can  be  made  still  more  striking  if 
the  process  of  secretion  be  slowed  by  increasing  the  pressure  within  the 
tubules  by  partial  obstruction  of  one  ureter.    Thus  in  one  experiment, 


1190 


PHYSIOLOGY 


where  diuresis  was  produced  by  the  injection  of  30  c.c.  of  a  solution  con- 
taining 5-85  per-cent.  NaCl  +  14-2  per  cent.  Na2S04,  the  right  ureter  was 
partially  clamped  so  as  to  make  the  right  kidney  secrete  against  a  pressure 
of  31  mm.  Hg.     The  following  results  were  obtained  : 


Urine  c.c. 

Cl.  grm.            SOj  grm. 

4.37  till  4.47 

|  Left  kidney  .... 
I  Right  kidney 
Difference  (absorption)   . 

24 
8 
16 

00809     !     0-1080 
0-0142          00667 
00677          00413 

We  must  conclude  that  the  tubular  epithelium  possesses  the  power  of 
modifying  the  glomerular  transudate,  not  only  by  the  absorption  of  water 
but  also  by  the  absorption  of  dissolved  constituents,  and  that  the  relative 


1, 

'1 A 

J   V 

|    Y 

i 

/ 

1 

1 1 

\  \ 

\ 

/ 

\ 

O 

s 

\ 

\ 

N 

V 

^4— 

— 

-.. 

I*  -1U  4-5  60  75  50  IOS  ISO  135 

Fig.  547.     Curves  showing  excretion  of  urine  (thick  line),  of  sulphate  molecules 

( '  „\  thin  line),  and  of  Cl  molecules  (        - ,  dotted  line),  after  injection  of  50  c.c. 

of  a  solution  containing  1-775  grm.  Cl  and  4-8grm.  S04  per  100  c.c.     The  black 
line  along  the  base  marks  the  duration  of  the  injection.     (Cttshny.) 


permeability  of  the  cells  to  the  constituents  is  at  any  rate  one  factor  in  deter- 
mining the  substances  absorbed.  It  is  not  however  the  only  factor.  The 
function  of  the  kidney  is  to  preserve  the  normal  constitution  of  the  body 
fluids  by  turning  out  those  substances  which  are  abnormal  or  present  in  too 
great  an  amount.  The  behaviour  of  the  tubule  cells  with  regard  to  any  «iven 
substance  will  therefore  depend  to  a  certain  extent  on  the  previous  nutritive 
history  of  the  body. 

If  for  instance,  in  consequence  of  the  administration  of  sodium  chloride 


THE  SECRETION   OF  URINE  1197 

in  large  quantities  to  the  animal  during  the  few  days  preceding  the  experi- 
ment, the  body  is  overloaded  with  this  salt,  it  becomes  an  abnormal  con- 
stituent and  the  kidney  secretes  a  urine  far  richer  hi  sodium  chloride  than  is 
the  blood  plasma.  Moreover,  when  diuresis  is  produced  in  such  an  animal 
by  the  injection  of  equivalent  quantities  of  sodium  chloride  and  sodium 
sulphate,  there  is  no  diminution  of  the  NaCl  hi  the  urine  towards  the  end  of 
the  diuresis,  but  its  percentage  rises  steadily  as  the  rate  of  urinary  flow 
diminishes.  On  the  other  hand,  a  total  deprivation  of  sodium  chloride 
extending  over  several  days,  although  not  altering  to  any  large  extent  the 
percentage  amount  of  this  salt  in  the  blood  plasma,  leads  to  a  total  dis- 
appearance of  the  salts  from  the  urine,  the  whole  of  the  sodium  chloride 
present  in  the  glomerular  transudate  being  absorbed  on  its  way  through  the 
urinary  tubules. 

It  has  been  suggested  that  the  effects  of  certain  diuretics  on  the  kidney, 
such  as  caffeine,  diuretine,  or  theocine,  may  be  largely  conditioned  not  so 
much  by  their  influence  on  the  glomerular  circulation  as  by  a  paralytic  effect 
on  the  absorptive  functions  of  the  tubules.  According  to  Loewi,  on  injec- 
tion of  caffeine  or  diuretine,  the  increase  of  total  amount  of  urine  is  not 
accompanied  by  any  diminution  in  the  percentage  amount  of  NaCl.  Perhaps 
however  the  strongest  evidence  in  this  direction  is  afforded  by  an  experi- 
ment of  Pototzky.  A  rabbit  had  been  fed  on  a  diet  almost  totally  devoid 
of  chlorides,  and  was  therefore  excreting  a  urine  containing  only  -08  per 
cent.  NaCl.  Under  the  influence  of  diuretine  the  urine  was  increased  and 
the  concentration  of  the  NaCl  rose  to  0-64  per  cent.  The  same  increase  in 
the  percentage  amount  of  sodium  chloride  in  the  urine  has  also  been  observed 
after  the  injection  of  theocine,  which  has  therefore  been  specially  recom- 
mended as  a  diuretic  in  cases  of  dropsy,  where  a  diminution  of  the  salt 
content  of  the  body  is  a  valuable  means  for  the  diminution  of  the  dropsical 
Hi  rid  present  iu  the  tissue  spaces. 


THE   RENAL   MECHANISM 

What  conclusions  can  we  draw  from  this  mass  of  experimental  data 
as  to  the  functions  of  the  kidney  as  a  whole,  and  as  to  the  part  played  by 
its  various  constituent  elements  in  the  secretion  of  urine?  The  amazing 
adaptability  of  its  functions  to  the  needs  of  the  organism  has  been  abund- 
antly illustrated  in  the  facts  with  which  we  have  dealt.  Its  ordinary  activity 
is  determined  by  the  production,  as  a  result  of  the  normal  processes  of  meta- 
bolism, of  soluble  non-volatile  substances  in  every  cell  of  the  body.  These 
substances,  together  with  the  excess  of  water  taken  in  with  the  food  above 
that  lost  by  respiration  and  cutaneous  transpiration,  arc  turned  out  by  the 
kidney  as  urine.  The  activity  of  this  organ  must  therefore  be  determined  in 
the  first  place  by  chemical  stimuli.  If  we  accept  a  secretory  function  for 
the  tubules,  we  may  assume  that  the  kidney  reacts  to  the  slightest  deviation 
from  normal  of  the  blood  composition  in  two  directions  : 

(1)  Under  the  influence  of  certain  substances,  such  as  urea,  uric  acid, 


1198  PHYSIOLOGY 

or  water,  the  cells  of  the  convoluted  tubules  may  take  up  the  substance, 
which  is  in  excess,  from  the  surrounding  lymph  and  accumulate  it  in  vacuoles, 
which  are  discharged  on  the  inner  surface  of  the  cells  into  the  lumen  of  the 
tubules. 

(2)  Besides  this  specific  secretory  activity  of  the  cells  of  the  convoluted 
tubules,  the  tubules  as  a  whole  are  certainly  endowed  with  the  power  of 
absorbing  both  water  and  dissolved  substances  from  the  fluid  in  their  lumen. 
Whether  this  absorptive  power  is  limited  to  the  cells  of  Henle's  loop,  as 
was  first  suggested  by  Ludwig,  or  occurs  also  in  the  cells  of  the  convoluted 
tubules,  as  might  be  imagined  from  the  close  analogy  between  the  structure 
of  these  cells  and  that  of  the  intestinal  epithelium,  we  have  not  sufficient 
evidence  to  decide.  We  do  know  however  that  the  quality  of  the  absorp- 
tion is  strictly  regulated  according  to  the  needs  of  the  organism,  so  that  the 
constituents  which  are  precious  are  reabsorbed  for  service  in  the  body,  while 
those  which  are  in  excess  or  are  of  no  value  to  the  organism  are  allowed  to 
pass  out  into  the  ureters.  The  process  of  resorption  is  indeed,  as  is  shown 
by  Cushny's  experiments,  largely  dependent  on  the  physical  qualities  of 
the  substances  undergoing  absorption,  and  especially  on  the  permeability 
of  the  renal  cells  to  these  substances.  The  physical  conditions  are  however 
subordinated  to  the  physiological,  so  that  a  salt  so  diffusible  as  potassium 
iodide  is  left  in  the  fluid,  while  sodium  chloride  may  be  reabsorbed  in  large 
quantities. 

The  necessity  for  the  endowment  of  the  tubular  epithelium  with  a  resorp- 
tive  function  as  well  as  any  secretory  function  it  may  possess  is  determined 
by  the  presence  at  the  beginning  of  the  tubule  of  a  mechanism — the  glo- 
merulus, devoid  of  the  fine  selective  power  or  chemical  sensibility  which 
characterises  the  cells  of  the  convoluted  tubules.  The  production  of  urine  by 
the  glomerulus  is  regulated  entirely  by  the  pressure  and  velocity  of  the  blood 
through  its  capillaries  and  by  the  colloid  content  of  the  blood  plasma.  We 
may  assume  that  in  Bowman's  capsule  there  is  under  normal  conditions  a 
constant  production  of  a  fluid,  free  from  protein  but  having  the  same 
crystalloid  concentration  as  the  blood  plasma.  With  any  rise  of  general 
blood  pressure  the  amount  of  this  transudate  is  increased ;  with  any  fall  it  is 
diminished.  The  small  qualitative  changes,  which  are  constantly  occurring 
in  the  blood  as  the  result  of  the  taking  of  food  or  the  activity  of  different 
organs,  probably  produce  but  little  effect  on  the  amount  of  glomerular  fluid. 
Only  indirectly,  as  the  result  of  these  events  on  the  general  blood  pressure, 
or  possibly  in  consequence  of  the  production  of  substances  having  a  vaso- 
dilator effect  on  the  renal  vessels,  will  the  amount  of  the  urine  turned  out 
by  the  glomeruli  be  affected.  These  structures  therefore  have  the  twofold 
fimction  of  regulating  the  total  amount  of  circulating  fluid  and  of  providing 
an  indifferent  fluid  which  will,  so  to  speak,  flush  the  kidney  tubules  and 
carry  down  any  constituents  excreted  in  a  concentrated  form  by  the  cells 
of  these  tubules.  The  constant  production  of  a  glomerular  transudate 
might  result,  especially  in  terrestrial  animals,  in  the  loss  to  the  organism  of 
water  or,  under  certain  nutritive  conditions,  of    substances  indispensable 


THE   SECRETION   OF  URINE 


1199 


as  normal  constituents  of  the  serum,  such  as  sodium  chloride,  which  could 
not  be  made  good  at  the  expense  of  the  food.  It  is  for  this  reason  that  an 
absorptive  mechanism  sensitive  to  and  reflecting  the  nutritive  condition 
of  the  whole  body,  especially  as  concerns  water  and  salts,  should  be  present 
in  the  tubules. 

According  to  Cushny,  the  whole  of  the  changes  by  which  the  glome- 
rular transudate  is  transformed  into  urine  may  be  ascribed  to  processes 
of  absorption  occurring  in  the  tubules,  there  being  no  need  to  assume  the 
possession  of  any  secretory  functions  by  this  part  of  the  kidney.  He  would 
indeed  deny  any  fine  discrimination  to  the  kidney,  since  the  fluid  absorbed 
is  always  the  same  whatever  the  needs  of  the  organism  at  the  moment.  In 
the  following  Table  are  given  the  changes  which  must  be  effected  in  the 
glomerular  transudate  in  order  to  transform  it  into  urine. 


67  litres  plasma 
contain 

62  litres 
filtrate 
contain 
in  all 

61  litres  re-absorbed 
fluid  contain 

1  litre  urine 
contains 

cent.             ™aI 

Per 
cent. 

Total 

Per- 
cent. 

Total 

Water 

'92              62 1. 

62  1. 

_ 

611. 

95 

950  c.c. 

Colloids  . 

8           5360     gr. 

Dextrose 

01           67     gr. 

67     gr. 

011 

67     gr. 

— 

— 

Uric  Acid 

0002          1-3   „ 

13   „ 

00013       0-8   „ 

005 

0-5  gr. 

Sodium   . 

0-3          200      „ 

200      „ 

0-32 

196      „ 

0-35 

3-5   „ 

Potassium 

002          13-3   „ 

13-3   „ 

0019 

118    „ 

015 

15   „ 

Chloride 
Urea 

0-37        248      „ 
003          20      „ 

248      „ 
20      „ 

0-40 

242      „ 

0-6 
20 

60   „ 
20   „ 

— 

— 

Sulphate 

0003           1-8   „ 

18   „ 

— 

— 

018 

1-8   „ 

It  will  be  seen  that,  while  there  is  no  absorption  of  urea  and  of  sulphate, 
the  whole  of  the  dextrose  is  absorbed,  a  portion  of  the  uric  acid  and  the 
greater  part  of  the  sodium,  potassium  and  chloride.  The  absorbed  fluid  thus 
resembles  strongly  Locke's  fluid.  According  to  this  view  the  constituents 
of  the  glomerular  transudate,  i.  e.  the  diffusible  constituents  of  the  blood 
plasma,  may  be  divided  into  two  classes,  'threshold  substances'  and 
'  no-threshold  substances,'  the  former  being  only  excreted  in  the  urine  so 
far  as  they  exceed  a  certain  threshold  value,  while  the  others  are  excreted 
in  proportion  to  their  absolute  amount  in  the  plasma.  Thus,  of  the  threshold 
substances,  the  dextrose  of  the  plasma  is  normally  below  the  threshold, 
and  is  therefore  not  present  in  normal  urine.  The  sodium  chloride  also 
comes  within  the  threshold  class,  but  its  threshold  is  more  frequently 
exceeded  in  normal  conditions,  and  the  excess  is  then  ehminated.  When 
the  sugar  of  the  plasma  rises,  as  in  diabetes,  to  0-3  per  cent.,  it  appears  in 
the  urine  and  then  undergoes  concentration  just  as  urea  does.  Thus,  so  far 
as  concerns  the  cells  of  the  tubules,  the  no-threshold  substances  are  nut 
absorbed  and  must  all  escape  by  the  ureter,  whereas  the  threshold  bodies 


1200  PHYSIOLOGY 

arc  absorbed  in  different  proportions  determined  by  their  normal  values  in 
the  plasma.  The  tubules  absorb  from  the  glomerular  filtrate  a  slightly 
alkaline  fluid  containing  sugar,  amino-acids,  chlorides,  sodium  and  potassium 
in  approximately  the  same  proportions  as  they  are  present  in  normal  plasma. 
"  Thus  the  tubules,  out  of  the  glomerular  filtrate,  return  to  the  blood  the 
fluid  best  adapted  for  the  tissues,  and  allow  the  rest  to  escape.  If  the  plasma 
is  too  rich  in  sugar  or  chloride,  the  filtrate  also  contains  those  substances 
at  or  above  the  threshold  value.  The  tubules  however  return  them  at  the 
optimal  or  threshold  concentrations  and  the  remainder  passes  into  the 
ureters.  If  much  water  has  been  ingested  and  the  filtrate  is  correspondingly 
dilute,  the  subtraction  of  the  optimal  solution  leaves  the  excess  water  in 
the  urine  along  with  the  urea  and  other  waste  products  "  (Cushny). 

The  power  of  absorption  possessed  by  the  cells  of  the  tubules  is  not 
indefinitely  large,  and  the  urine  can  therefore  never  exceed  a  certain  con- 
centration at  which  its  osmotic  pressure  just  equals  the  absorptive  power 
of  the  cells.  This  hmiting  concentration  differs  in  different  animals,  the  cat 
being  able  to  absorb  against  a  resistance  of  fifty  to  sixty  atmospheres,  while 
the  human  kidney  cannot  concentrate  against  a  resistance  of  more  than 
twenty-five  atmospheres.  The  presence  of  any  inabsorbable  substance  in 
the  glomerular  fibrate,  e.g.  urea,  sodium  sulphate,  or  phosphate,  must 
therefore  limit  the  absorption  owing  to  the  osmotic  resistance  they  offered 
to  the  absorptive  powers  of  the  cells.  These  substances  will  therefore  act 
as  diuretics.  In  the  same  way  the  threshold  substances  will  act  as  diuretics, 
provided  that  they  are  present  in  the  plasma  in  proportions  above  the 
plasma,  so  that  they  can  no  longer  be  absorbed  by  the  cells  of  the  tubules. 
It  has  been  objected  by  Heidenhain  and  others  to  this  view  that,  if  we 
exclude  the  occurrence  of  secretion  by  the  cells  of  the  tubules,  we  must 
assume  that,  of  the  seventy  litres  passing  the  glomeruli  in  the  course  of 
twenty-four  hours,  no  less  than  sixty-eight  litres  must  be  reabsorbed  in  the 
tubules  in  the  formation  of  two  litres  of  urine.  But  Cushny  points  out  that 
we  have  many  analogies  to  this  process  in  the  body.  Thus  the  hver  throws 
into  the  duodenum  500  c.c.  of  fluid  in  twenty-four  hours,  all  of  which  is  re- 
absorbed with  the  exception  of  a  little  pigment.  The  urine  of  birds  passes 
down  the  ureter  as  a  clear  fluid,  but  in  the  cloaca  almost  all  the  water  is 
absorbed,  leaving  a  thick  paste  of  urine.  Nor  is  the  work  out  of  proportion 
to  the  mechanism  provided.  In  a  cat  fed  on  meat,  100  c.c.  of  urine  con- 
tained as  much  solids  as  twelve  litres  of  plasma  filtrate,  so  that  for  twelve 
litres  filtered  through  the  glomeruli  11-9  were  reabsorbed  in  the  tubules. 
Since  each  kidney  contains  about  16,000  glomeruli,  the  amount  of  fluid 
filtered  by  each  glomerulus  would  amount  to  about  -055  c.c.  per  hour.  Of 
this  more  than  "0144  c.c.  was  absorbed  in  passing  along  3  cm.  of  tubule, 
leaving  less  than  1  mg.  per  hour  from  each  capsule  to  enter  the  collecting 
tubule  (Cushny).  This  cannot  be  regarded  as  too  severe  a  task  either  for 
tha  glomeruli  or  for  the  tubules. 


THE  SECRETION   OF   URINE  1201 


ACTION   OF   DIURETICS 

Attempts  have  been  made  to  solve  the  problem  of  renal  secretion  by 
studying  the  action  of  diuretics,  i.e.  substances  which,  injected  into  the 
blood  stream  or  absorbed  from  the  alimentary  canal,  increase  the  secretion 
of  urine.  These  attempts  have  generally  ended  in  trying  to  explain  the 
action  of  diuretics  by  the  theory  preferred  by  the  experimenter.  A  large 
increase  in  the  urinary  flow  can  be  brought  about  by  the  intravenous  injection 
of  saline  diuretics  such  as  sodium  sulphate  or  potassium  nitrate,  of  neutral 
crystalloids  such  as  urea  or  sugar.  An  increased  production  of  urine  may 
be  due  to  augmented  glomerular  transudation  or  to  increased  secretion,  or  to 
diminished  absorption  in  the  tubules ;  and  in  many  cases  both  mechanisms 
may  be  involved. 

Three  factors  might' be  concerned  in  promoting  an  increased  glomerular 
transudation.    These  are: 

(1)  A  rise  of  pressure  in  the  glomerular  capillaries. 

(2)  Acceleration  of  the  blood  flow  through  the  capillaries. 

(3)  Diminution  of  the  amount  of  proteins  in  the  blood  plasma. 

When  a  concentrated  solution  of  salt  is  injected  into  the  circulation,  the 
osmotic  pressure  of  the  plasma  is  .raised  and  water  passes  from  the  tissue 
cells  into^the  blood  stream,  in  consecnience  of  the  osmotic  differences 
between  the  blood  and  cells  so  induced.  As  a  result  the  total  volume  of  the 
circulating  fluid  is  increased  by  the  addition  to  it  of  water  derived  from  the 
tissues,  i.  e.  a  condition  (if  hydraemic  plethora  is  set  up,  just  as  if  a  large  bulk 
of  normal  saline  fluid  had  been  injected  into  the  circulation.  So  long  as 
tliis  hydraemic  plethora  continues,  so  long  is  there  a  rise  both  in  arterial  and 
venous  pressures  and  in  the  velocity  of  the  circulating  blood.  The 
kidney  placed  in  an  oncometer  shows  a  great  increase  in  volume.  While 
the  plethora  lasts  there  are  mechanical  conditions  at  work  in  the  kidneys, 
i.  e.  rise  of  pressure,  greater  rate  of  flowr,  and  diminished  concentration 
of  plasma — all  of  which  would  concur  in  producing  an  increased  glomerular 
transudation.  With  certain  salts,  such  as  sodium  chloride,  the  diuresis 
may  be  coterminous  with  the  hydraemic  plethora,  but  with  other  members 
of  this  class,  such  as  grape  sugar,  the  diuresis  always  outlasts  the  plethora,  so 
that  the  continued  augmentation  in  the  secretion  of  urine  leads  to  an  actual 
concentration  and  diminution  of  the  volume  of  the  circulating  blood,  as  is 
shown  in  Fig.  548.  If  the  kidney  be  placed  in  an  oncometer,  it  is  found  that 
the  dilatation  of  the  kidney  outlasts  the  plethora,  and  comes  to  an  end  only 
with  the  cessation  of  the  increased  urinary  flow.  Since  however  increased 
secretion  of  urine  involves  dilatation  of  the  tubules,  and  therefore 
swelling  of  the  whole  kidney,  the  rise  of  the  oncometer  during  diuresis 
is  no  proof  that  there  is  still  a  greater  circulation  through  the  kidney. 
In  fact,  however  much  glomerular  change  may  be  concerned  in  the  initial 
increase  in  the  urinary  flow,  the  terminal  increase  must  be  ascribed  to  the 
effects  of  the  injected  substances  on  the  tubules.  As  we  have  already  seen, 
every  substance  which  is  not  absorbed  by  the  tubules  from  the  glomerular 

7<; 


1202 


PHYSIOLOGY 


filtrate  must  act  as  a  diuretic,  since  it  will  oppose  osmotic  resistance  to  the 
absorbing  powers  of  the  cells.  Thus  the  no-threshold  substances,  urea, 
and  sodium  sulphate,  nitrate,  and  phosphate,  will  act  as  diuretics  in  any  con- 
centration. The  threshold  substances  will  act  as  a  diuretic  so  long  as  their 
concentration  in  the  plasma  surpasses  their  normal  threshold  value. 


i 

^ 

Ar 

+ 

t.  HP 

mm 

Hffi 

Haeiii 



-- 

Percent. 

1 

\  / 

,'\ 

K 

t* 

0* 

V 

a> 

\ 

1 

o 

- 

c 

_| 

1 

Urine 

1 

SO       LW        luij      1 10      UV     130      U0 


Fig.  548.  A  comparison  of  the  effects  of  intravenous  injection  of  30  grm.  glucu.se 
in  concentrated  solution  on  the  arterial  blood  pressure,  the  concentration  of  the 
blood,  the  kidney  volume,  and  the  urinary  flow.     Abscissa  =  time  in  minutes. 

With  regard  to  the  specific  diuretics,  such  as  caffeine,  the  question  is 
not  quite  so  clear.  In  most  cases  injection  of  caffeine  in  the  rabbit  brings 
about  a  dilatation  of  the  kidney  and  a  proportional  increase  in  the  secretion 
of  urine.  But  cases  have  been  recorded  in  which  expansion  of  the  kidney 
occurred  without  any  increase  in  urinary  flow,  and,  on  the  other  hand, 
augmented  urinary  flow  without  any  increase  in  the  kidney  volume  or 
even  in  the  rate  of  blood  flow  through  the  kidney  (as  determined  by  Brodie's 
method).  The  general  rule  however  is  that  a  greater  rate  of  blood  flow  is 
obtained  pari  passu  with,  the  increased  urinary  flow ;  and  a  consideration 
of  certain  peculiarities  in  the  renal  circulation  must  prevent  us  from  laying 


THE   SECRETION   OF   URINE 


1203 


too  much  stress  on  apparent  exceptions  to  the  rule.  To  the  blood  entering 
the  kidneys  by  the  renal  arteries  two  ways  are  open.  The  blood  may  pass 
through  the  vasa  afferentia,  through  the  glomeruli  and  tubular  capillaries, 
back  to  the  renal  vein.  On  the  other  hand,  it  may  escape  the  glomeruli 
altogether,  and  pass  through  the  vasa  recta  directly  into  the  intertubular 
capillaries  and  so  into  the  renal  veins.  It  is  a  common  experience,  in 
injecting  the  blood  vessels  of  the  kidneys  •post-mortem,  to  find  the  renal 
arteries,  intertubular  capillaries,  and  veins  filled  to  distension  with  the 
injection  mass,  but  hardly  any  in  the  glomeruli.  One  must  assume  in  such 
a  case  thai  there  has  been  spasmodic  contraction  of  the  muscular  coats  of 
the  vasa  afferentia  (cp.  Fig.  549).    The  normal  amount  of  blood  might 


5=  ^§^ 


Via.  f>4'J.  Diagram  (after  Morat)  to  illustrate  the  effect  of  active  changes  in  the 
\.i  ;a  afferentia  and  efferent  ia  on  the  pressure  in  the  glomerular  capillaries. 
If  the  vas  afferens  constricts,  the  pressure  will  be  represented  by  the  lower 
dotted  line.  On  the  other  hand,  constriction  of  the  vas  efferens  would  raise 
the  pressure  in  the  glomerulus  till  it  almost  equalled  that  in  the  renal  artery, 
as  is  shown  by  the  upper  dotted  line. 
A,  arteries;  o,  glomerular  capillaries ;  c,  tubular  capillaries ;  v,  vein. 


therefore  circulate  through  the  kidney  without  any  flowing  through  the 
filtering  apparatus,  i.e.  the  glomeruli.  On  the  other  hand,  a  dilatation  of 
the  afferent  vessels  and  a  slight  constriction  of  the  efferent  vessels  would 
cause  a  considerable  rise  of  pressure  in  the  glomerular  capillaries,  and  a 
consequent  increased  transudation,  without  necessarily  altering  to  any 
marked  extent  the  total  circulation  of  blood  through  the  whole  organ.  The 
changes  hi  the  afferent  and  efferent  vessels  of  the  glomeruli  are  however 
beyond  our  control  or  powers  of  observation,  so  that  it  is  impossible  to 
devise  at  the  present  time  any  crucial  experiment  which  might  decide  the 
nature  of  the  process  occurring  in  the  glomeruli. 

On  the  other  hand,  it  seems  probable  that  many  diuretics — of  which 
ca  Heme  may  be  i  me — act  by  altering  the  activity  of  the  tubules.  If  we  accept 
the  idea  that  the  main  function  of  these  structures  is  that  of  secretion,  we 
may  assume  that  the  diuretics  increase  their  secretory  power.  It  is  more 
simple  however  to  assume  that  any  action  these  substances  possess  on  the 
tubules  is  one  of  paralysis,  complete  or  partial,  of  their  powers  of  absorption. 
Thus  the  action  of  phlorhizin  may  be  assumed  to  paralyse  the  absorptive 
powers  of  the  tubular  cells  for  glucose — i.  e.  to  reduce  glucose  for  this  par- 
ticular kidney  to  the  state  of  a  no-threshold  substance.     The  glucose  in  the 


J204  PHYSIOLOGY 

glomerular  transudate,  in  passing  through  the  tubules,  may  thus  be  con- 
centrated sixty  to  a  hundred  times.  Since  glucose  is  made  in  the  body 
and  supplied  to  the  circulating  blood  in  proportion  to  the  needs  of  the 
body,  so  as  to  maintain  its  concentration  in  the  plasma  at  a  definite  height, 
the  loss  of  sugar  in  the  urine  will  be  continued,  and  the  percentage  in  the 
plasma  will  not  tend  to  diminish  progressively  with  the  increased  secretion 
of  urine,  as  would  occur  for  example  in  the  case  of  urea.  We  may  assume 
that  different  diuretics  have  similar  powers  of  paralysis  on  the  absorptive 
mechanisms  of  the  tubules,  either  general,  or  confined  as  in  the  case  of 
phlorhizin  to  one  or  other  of  the  normal  constituents  of  the  plasma. 


SECTION  III 

THE    PHYSIOLOGY   OF   MICTURITION 

The  urine  as  it  is  formed  passes  through  the  ureters  to  the  bladder,  where 
it  gradually  accumulates,  and  is  voided  at  intervals. 

The  ureters  are  muscular  tubes  lined  by  transitional  epithelium.  The 
muscular  coat  is  composed  of  three  layers  of  unstriated  fibres,  a  middle 
circular  coat  lying  between  external  and  internal  longitudinal  coats.  If 
the  ureter  be  exposed  in  the  living  animal,  contraction  waves  are  seen  to 
pass  along  its  muscular  coat  from  the  pelvis  of  the  kidney  to  the  bladder, 
driving  the  contained  fluid  in  front  of  them.  The  frequency  of  the  con- 
tractions  is  increased  by  warming  the  ureter,  and  to  a  certain  extent  by 
distension,  so  that  the  waves  are  more  frequent  when  the  secretion  of  urine 
is  profuse.  The  ureters  enter  the  bladder  at  or  near  its  base,  at  the  two 
posterior  angles  of  the  region  known  as  the  trigonum.  Their  entrance  is 
oblique,  so  that  a  valvular  orifice  is  formed,  which  effectively  prevents 
reflux  of  urine  from  "bladder  to  ureter.  Khythmic  waves  of  contraction  are 
observed  also  in  the  excised  ureters,  when  these  are  kept  warm  in  normal 
siiline  solution.  By  Engelmann  they  were  regarded  as  myogenic,  since  they 
were  present  in  the  middle  third  of  the  ureter,  which  he  imagined  to  be 
entirely  free  from  ganglion  cells.  As  a  matter  of  fact  ganglion  cells  are 
found  throughout  the  ureter,  though  in  larger  numbers  at  its  two  ends.  The 
ureters  are  supplied  with  nerve  fibres  from  the  splanchnic  nerves  by  way 
of  the  renal  plexus,  and  at  their  lower  ends  from  the  hypogastric  nerves. 
Stimulation  of  the  latter  as  a  rule  increases  the  rhythm  of  the  contraction 
presented  by  the  lower  end  of  the  ureter.  The  splanchnic  nerves  have  been 
-luted  to  produce  either  acceleration  or  inhibition  of  the  contractions  at  the 
upper  end;  their  action  is  however  uncertain.  It  is  by  the  rhythmic 
advancing  waves  of  contraction  of  the  ureter  that  the  urine  is  continuously 
passed  on  to  the  bladder,  so  that  the  pelvis  of  the  kidney  is  kept  empty  of 
fluid  whatever  the  position  of  the  animal. 

The  bladder  is  lined  by  transitional  epithelium,  closely  adherent  to  the 
underlying  muscular  coat.  It  is  usual  to  describe  in  the  latter  three  layers 
of  muscular  fibres  : 

(1)  An  outer  layer  composed  of  bundles  running  longitudinally  from 
the  neck,  of  the  bladder  to  the  fundus,  sometimes  distinguished  by  the 
name  of  the  detrusor  urince.  At  the  neck  of  the  bladder  these  bundles  send 
some  fibres  to  be  attached  to  the  pubes  as  the  pubo-vesical  muscles.  On 
t  he  dorsal  surface  some  bundles  in  the  male  pass  mi  to  t  he  prostate  and  the 

1205 


]206  PHYSIOLOGY 

urerlira,  while  in  the  female  I  hey  end  in  the  tough  connective  tissue  in  the 
met  liio-vaginal  septum. 

(2)  The  middle  layer,  which  is  the  thickest  of  the  three,  is  composed 
of  fibres  arranged  circularly  and  forming  a  continuous  layer. 

(3)  The  inner  layer  is  thin  and  incomplete,  and  is  composed  of  anasto- 
mosing bundles  of  fibres  with  meshes  in  between  them  which  are  covered 
by  the  folds  of  the  mucous  membrane.  The  bundles  of  fibres  run  freely 
from  one  layer  to  the  other,  and  there  is  no  doubt  that  the  name  of  detrusor 

ought  physiologically  to  be  applied  to 
the  whole  of  the  three  coats,  which  act 
as  one  in  diminishing  the  capacity  of 
the  bladder.  At  the  base  of  the  blad- 
der the  structure  of  the  wall  is  modified 
over  the  triangular  region  lying  between 
the  orifices  of  the  ureters  and  of  the 
Ureter--  '\^f  y/  urethra  (the  trigonum)  by  the  differen- 

tiation here  of  fibres  which  serve  as  a 

sphincter   and   prevent   the   escape   of 
Prostate-    -^W     s  ,-»        ,i     ,  •  ,. 

-j&Sz^^Smssu^         urine.     Over  the  trigonum  the  mucous 

8l^  membrane    of   the    bladder   is   smooth 

\  and  closely  adherent  to  the  subjacent 

Fio.  550.  muscular  fibres,  which  themselves  are 

much  more  closely  packed  than  the  rest 

of  the   bladder  wall.     From    these   muscular   fibies  the  most  important 

sphincter,  the  sphincter  trigoni,  is  formed.     Bandies  of  muscle  fibres  pass 

from  the  trigonal  muscle  obliquely  forwards  and  downwards  (the  individual 

being  considered  in  the  civet  posture),  and  form  a  loop  around  the  orifice 

of  the  bladder,  lying  on  the  ventral  side  of  the  bladder  below  and  quite 

distinct  from  the  thick  coat  of  circular  fibres  belonging  to  the  bladder  itself 

(ss,  Fig.  550). 

This  sphincter  is  the  most  important  mechanism  for  the  retention  of 
urine.  If  a  catheter  be  passed  into  the  urethra  no  urine  escapes  until  its 
orifice  has  actually  entered  the  bladder.  The  wall  of  the  urethra  is  sur- 
rounded by  circular  muscular  fibres  which,  by  their  tonic  contraction,  will 
also  tend  to  prevent  the  escape  of  urine  along  the  canal.  This  urethral 
muscle  is  strengthened  by  two  sphincter  muscles  which  are  voluntary  and 
composed  of  striated  fibres.  The  chief  one,  which  has  been  named  by 
Kalischer  the  sphincter  urogenitalis  but  is  better  known  as  the  compressor 
urethras,  forms  a  flat  ring  around  the  second  part  of  the  urethra,  extending 
in  the  male  from  the  prostate  to  the  bulb,  where  its  function  is  taken  up 
by  the  bul bo-cavern osus. 

The  bladder  is  therefore  supplied  with  a  powerful  muscular  wall,  the 
contraction  of  which  will  cause  its  evacuation,  and  with  sphincters  of  two 
kinds,  one  involuntary,  the  sphincter  trigoni,  at  the  upper  neck  of  the 
bladder,  and  two  voluntary,  the  sphincter  urogenitalis  and  buJbo-cavernosus 
muscles,  which  can  empty  the  lower  parts  of  the  urethra. 


THE  PHYSIOLOGY   OF   MICTURITION 


1207 


The  nerve  supply  of  the  bladder  (Fig.  552)  is  derived  from  two  main 
sources,  namely,  from  the  upper  four  lumbar  nerves  through  the  sympa- 
thetic svstem,  and  from  the  second  and  third  sacral  nerves  by  means  of 


>n\><;<tiiUili< 


Circular  coat 
T-ongitudinal  coat 

Sphincter  trigoni 


Circjlar  coat 
Longitudinal  coat 


Sphincter  Iriga 


l  'ircular  coat 
Longitudinal  coat 


Sphincter  trigoni 
l-ougitudiual  muscle 


I'ig.  561.     Sagittal  sections  through  neck  of  bladder. 

(Metznkr  after  Kalischer.) 

\.   in   middle  line  (male);   B,  slightly  to  left  of  middle  lino  (male); 

C,  ditto  (female). 

the  pelvic  viscera]  nerves  or  nervi  erigenles.  The  upper  lumbar  nerves 
send  white,  rami  communicantes  to  the  lateral  chain  of  the  sympathetic, 
and  thence  to  the  collateral  ganglia,  which  are  grouped  round  the  inferior 
mesenteric  artery  to  form  the  inferior  mesenteric  ganglion.  Most  of  the 
fibres  end  in  this  collection  <>i  ganglion  cells,  and  a,  new  relay  of  axons  passes 


1208 


PHYSIOLOGY 


by  two  main  trunks,  the  hypogastric  nerves,  into  the  pelvis  on  each  side  of 
the  rectum  and  ends  in  a  plexus,  the  hypogastric  plexus,  at  the  base  of  the 
bladder.  From  this  plexus  fibres  pass  to  the  bladder  wall.  The  pelvic 
visceral  nerves  are  derived  from  the  second  and  third  sacral  nerves.  They 
make  no  connection  with  the  sympathetic  system,  but  pass  directly  to  the 


3rd  lamb  pert. 


Sup.  mes.  nerves  .  . 

Median  mes.  nerves 

Inf.  mes.  nerves  .. 

Inf.  mes.  ganglion  , 

Hypogastric  nerves 


Fig.  552.     Nerve  supply  to  bladder  of  eat.     (Nawrocki  and  Skabitschewsky.) 

hypogastric  plexus  and  are  carried  with  branches  of  this  plexus  to  the  neck 
of  the  bladder.  The  fibres  do  not  run  directly  from  the  spinal  cord  to  their 
ending  in  the  bladder  wall,  but  make  connection  with  cells  situated  peri- 
pherally, partly  in  the  hypogastric  plexus,  but  chiefly  in  the  walls  of  the 
bladder  itself.  Both  sets  of  fibres  supply  also  the  rectum  and  the  colon, 
and  carry  efferent  impulses  to  the  bladder.  Afferent  impulses  from  the 
bladder  travel  chiefly  in  the  pelvic  visceral  nerves. 


THE  PHYSIOLOGY  OF  MICTURITION  1209 

THE   FILLING   OF   THE    BLADDER 

Under  normal  circumstances  the  sphincters  at  the  neck  of  the  bladder  are 
in  a  state  of  tonic  contraction,  presenting  a  resistance  to  the  emptying  of 
tins  organ  which  will  vary  according  to  their  degree  of  contraction.  Thus  it 
requires  a  considerably  greater  pressure  in  the  bladder  to  overcome  the 
resistance  of  the  sphincters  during  life  than  after  death  of  the  animal.  In 
some  cases  after  death  they  may  permit  the  passage  of  urine  when  the 
pressure  of  the  bladder  is  only  about  20  mm.  water,  whereas  in  the  normal 
animal  the  pressure  has  as  a  rule  to  be  at  least  160  mm.  of  water  before  any 
escape  takes  place.  The  urine  therefore  as  it  is  secreted  must  accumulate 
and  distend  the  bladder.  The  bladder  wall  reacts  to  a  distending  force 
in  the  manner  which  is  characteristic  of  all  muscular  tissue,  especially 
lmstriated.  An  extending  force  applied  to  an  unstriated  muscle  fibre  has 
a  double  effect.  In  the  first  place,  if  the  stretching  force  is  applied  very 
slowly,  a  considerable  increase  in  length  of  the  muscle  may  occur  with  the 


U  3 


20"  ► 

Fig.  553.     Tracings  of  rhythmic  contractions  of  urinary  bladder. 
('Sherrington.) 

application  of  a  very  small  amount  of  force.  If  however  the  force  be 
applied  more  rapidly,  the  sudden  increase  of  tension  acts  as  a  direct  excitant 
to  the  muscle,  causing  it  to  enter  into  contraction,  which  may  be  tonic  or 
rhythmic.  The  effect  of  the  entry  of  urine  into  the  empty  bladder  on  the 
tension  in  this  organ  will  depend  therefore  on  the  rapidity  with  which  the 
kidneys  are  secreting.  Under  normal  circumstances  micturition  occurs 
in  man  when  the  intravesical  pressure  has  risen  to  about  150  mm.  water. 
Under  these  conditions  the  bladder  will  contain  between  230  and  250  c.c. 
of  urine.  If  however  the  secretion  of  urine  has  occurred  very  rapidly,  the 
same  pressure  may  be  attained  with  a  much  smaller  bladder  content,  and  if 
the  bladder  be  artificially  distended  by  the  injection  of  fluid  through  a 
catheter,  50  c.c.  of  fluid  may  suffice  to  raise  the  pressure  to  this  level.  As  the 
urine  is  slowly  secreted,  the  bladder  wall  at  first  gives  to  the  incoming  fluid, 
so  that  a  considerable  amount  can  be  stored  without  any  marked  rise  of  pres- 
sure Later  on  the  pressure  begins  to  rise  more  rapidly,  and  finally  attains 
a  pressure  of  between  120  and  150  mm.  water.  At  this  point  the  second 
effect  of  the  stretching  of  the  muscular  wall  makes  its  appearance.  A  mano- 
meter connected  with  the  bladder  shows  a  series  of  rhythmic  contractions 
of  the  muscular  wall  (Fig.  553^,  each  lasting  about  a  minute,  at  first  slight 


1210  PHYSIOLOGY 

in  extent,  but  becoming  more  marked  as  the  distension  of  the  bladder 
augments.  In  a  bladder  entirely  cut  off  from  its  connection  with  the 
central  nervous  system,  these  automatic  rhythmic  contractions  gradually 
increase  in  force  until  one  of  them  suffices  to  overcome  the  resistance  pre- 
sented by  the  tonically  contracted  sphincter.  A  partial  emptying  of  the 
bladder  therefore  takes  place,  but  the  pressure  falls  below  that  necessary  to 
overcome  the  resistance  of  the  sphincter  before  the  bladder  has  been  quite 
emptied,  so  that  there  is  always  under  these  circumstances  a  certain  amount 
of  residual  urine  left  in  the  bladder.  This  is  the  condition  found  in  animals 
where  the  lower  part  of  the  spinal  cord  has  been  extirpated,  or  in  man  where 
the  same  part  of  the  central  nervous  system  has  been  destroyed  as  the  result 
of  accident  or  disease. 


THE    MECHANISM    OF    EVACUATION    OF   THE    BLADDER 

In  the  denervated  bladder  the  factor  finally  causing  partial  evacuation 
is  the  gradual  increase  in  the  intravesical  tension  from  the  accumulation  of 
fluid  in  this  viscus.  The  same  factor  is  prepotent  in  determining  the  onset 
of  normal  micturition  in  an  animal  with  the  nervous  connections  of  its 
bladder  intact.  Apart  from  the  control  of  the  higher  centres,  micturition 
will  take  place  each  time  that  the  tension  in  the.  bladder  has  reached  a 
certain  height,  i.  e.  about  15  cm.  water,  the  amount  of  fluid  in  the  bladder 
at  the  time  depending  on  the  one  hand  on  the  rate  at  which  the  fluid  has 
entered  this  organ  from  the  ureters,  on  the  other  hand  on  the  irritability 
of  the  bladder  wall  itself  and  of  the  nervous  centres  concerned  with  its  motor 
innervation.  The  effect  of  the  gradual  accumulation  of  fluid  and  rise  of 
tension  is  twofold.  In  the  first  place,  it  acts  on  the  bladder  wall,  causing 
rhythmic  contractions  of  ever-increasing  intensity;  in  the  second  place,  the 
mere  stretching  of  the  bladder  originates  impulses  in  the  sensory  nerve- 
endings  in  its  wall,  which  are  reinforced  at  every  rise  of  tension  caused 
by  the  rhythmic  contractions.  These  impulses  travel  up  to  the  spinal 
centres,  and  are  summated  until  they  result  in  a  sudden  discharge  of  efferent 
impulses  of  two  kinds,  namely  : 

(1)  Motor  impulses  to  the  whole  musculature  of  the  fundus  of  the 
bladder  (the  detrusor  in  its  widest  sense) ; 

(2)  An  inhibition  of  the  tonic  contraction  of  the  sphincter.  This  in- 
hibition may  be  determined  by  inhibitory  impulses  travelling  to  the  sphincter 
and  causing  its  relaxation,  or  by  the  central  inhibition  of  the  impulses 
normally  going  to  the  sphincter  and  maintaining  its  tonic  contraction.  The 
resultant  of  these  two  processes,  the  contraction  of  the  detrusor  and  the 
relaxation  of  the  sphincter,  is  a  complete  emptying  of  the  bladder,  and  the 
act  is  completed  by  the  contraction  of  the  involuntary  and  voluntary 
muscles  surrounding  the  urethra  and  causing  complete  expulsion  of  the 
contents  of  this  tube. 


THE  PHYSIOLOGY  OF  MICTURITION  1211 


THE   INNERVATION   OF   THE   BLADDER 

ACTION  OF  THE  PELVIC  VISCERAL  NERVES.  In  all  animals  ex- 
citation of  the  peripheral  end  of  one  pelvic  visceral  nerve  causes  a  strong 
contraction  of  the  same  side  of  the  bladder,  involving  all  its  coats  and  some- 
thnes  extending  to  a  slight  extent  to  the  contralateral  half  of  the  bladder. 
When  both  pelvic  nerves  are  stimulated  simultaneously,  contraction  of  both 
sides  of  the  bladder  causes  a  considerable  rise  of  pressure  in  its  interior 
(Kg.  554)  which  is  always  sufficient  to  overcome  the  resistance  of  the 
sphincter  and  to  cause  a  complete  emptying  of  the  bladder.  There  is  no 
doubt  therefore  that  these  nerves  are  the  most  important  for  the  act  of 
micturition.  As  to  the  action  of  these  nerves  however  on  the  sphincter,  the 
results  of  different  experimenters  are  somewhat  at  variance.  In  the  cat 
there  seems  1"  !><•  no  doubt  thai  inhibition  of  the  sphincter  may  result  from 


Fig.  554-.     Curve  showing  rise  of  pressure  in  tin:  bladder  caused  l>\  .stimulation 

of  S,  sacral  nerves ;  h,  hypogastric  nerves.     (  Fagck.) 

The  scale  indicates  centimetres  of  water. 

stimulation  of  the  pelvic  visceral  nerves.  On  the  other  hand  Fagge, 
working  on  the  dog,  found  that,  although  micturition  was  excited  by  the 
stimulation  of  these  nerves,  the  expulsion  of  urine  did  not  occur  until  the 
intravesical  tension  had  reached  the  point  at  which  the  resistance  of  the 
sphincter  could  be  overcome  without  any  alteration  of  its  state  of  con- 
traction, i.  e.  the  point  at  which  fluid  injected  into  the  bladder  through 
the  ureter  began  to  escape  from  the  urethra  without  stimulation  of  any 
nerves  whatever. 

Observation:;  on  man  would  support  the  view  that  an  active  relaxation  of 
the  sphincter  trigoni  is  a  necessary  part,  of  the  act  of  micturition.  Thus  in 
experiments  by  Reyfisch  a  rigid  catheter  was  introduced  into  the  bladder, 
which  was  fully  distended  with  fluid.  On  withdrawing  the  catheter  until  its 
opening  lay  just  outside  the  bladder  in  the  posterior  urethra,  the  flow  of 
urine  stopped.  The  man  however  was  able  to  micturate  directly  he  was 
told  to,  and,  to  stop  again  at  will.  It  was  impossible  in  this  case  for 
any   of   the    urethral    muscles  to   be   concerned,   since   the   rigid   catheter 


1212  PHYSIOLOGY 

impeded  their  action.  The  relaxation  of  the  sphincter  must  therefore 
be  brought  about  by  impulses  descending  the  pelvic  visceral  nerves, 
which  we  may  regard  as  motor  to  the  detrusor  and  inhibitory  to  the 
sphincter  of  the  bladder. 

Section  of  the  nerve  on  one  side  causes  no  abnormality  in  micturition. 
After  three  weeks,  stimulation  of  the  intact  nerve  causes  contraction  of  the 
whole  bladder,  owing  to  the  outgrowth  of  preganglionic  fibres  from  the  sound 
trunk  to  the  decentralised  ganglia  of  the  opposite  side  (Elliott).  Section  of 
both  nerves  paralyses  micturition,  but  power  of  partial  evacuation  of  the 
bladder  may  return  in  a  few  weeks.  If  now  the  hypogastrics  be  cut,  or 
even  the  sacral  cord  extirpated,  the  bladder  is  not  completely  paralysed,  but 
its  evacuation  becomes  unconscious  and  incomplete. 

ACTION  OF  THE  HYPOGASTRIC  NERVES.  These  nerves,  which 
are  derived  from  the  sympathetic  system,  show  marked  differences  in  their 
action,  according  to  the  animal  which  is  the  subject  of  investigation.  In 
the  dog  the  hypogastric  nerves  cause  a  strong  contraction  of  the  muscle 
fibres  at  the  base  of  the  bladder,  especially  of  the  trigonum  and  of  the 
sphincter  trigoni.  When  these  nerves  are  stimulated  simultaneously  with 
the  pelvic  visceral  nerves,  a  great  rise  of  intravesical  tension  may  be  induced 
without  any  flow  of  urine  taking  place.  In  some  cases  prolonged  stimulation 
of  these  nerves  in  the  dog  causes  apparently  an  active  relaxation  of  the 
sphincter  of  the  bladder.  On  the  other  hand,  in  the  rabbit  and  the  cat 
these  nerves  cause  an  inhibition  of  the  bladder  wall.  In  other  animals 
they  may  excite  either  contraction  or  relaxation  (or  both)  of  the  detrusor. 
They  always  contain  motor  fibres  to  the  sphincter  of  the  bladder  as  well  as ' 
to  the  constrictor  fibres  surrounding  the  urethra.  Where  this  effect  is 
tonic,  micturition  must  be  associated  with  a  central  inhibition  of  their  tonic 
activity.  On  the  other  hand,  the  retention  of  urine  and  the  distension  of 
the  bladder  may  be  aided  by  a  reflex  dilatation  of  the  bladder  wall  and  a 
reflex  constriction  of  the  sphincter,  in  each  case  excited  through  these  nerves. 
Normally  therefore  both  sets  of  nerves  are  called  into  action.  The  hypo- 
gastrics play  an  especially  active  part  during  the  accumulation  of  mine 
in  the  bladder,  while  the  pelvic  visceral  nerves  are  necessary  for  the  complete 
evacuation  of  the  bladder  which  occurs  at  micturition. 


THE    CENTRAL    CONTROL    OF    THE    BLADDER 

The  nerve  centre  which  presides  over  the  tonus  and  contraction  of  the 
bladder  is  situated  in  the  lumbo-sacral  spinal  cord.  If  this  centre  and  its 
connections  be  intact,  micturition  may  be  carried  out  normally  even  after 
section  of  the  cord  in  the  dorsal  region.  The  centre  can  be  excited  reflexly 
by  stimulation  of  almost  any  sensory  nerve,  such  as  the  sciatic  or  the  fifth 
nerve.  In  many  cases  where,  in  consequence  of  obstruction  to  the  passage 
of  impulses  from  the  higher  parts  of  the  central  nervous  system,  micturition 
is  delayed,  this  act  may  be  excited  by  the  application  of^cold  or  hot 
sponges  to  the  perineum,  and  it  is  well  known  that  almost  any  irritation 


THE  PHYSIOLOGY   OF  MICTURITION  1213 

of  the  pelvic  organs  in   children    may  give    rise    to    reflex    involuntary 
micturition. 

In  the  adult  the  processes  of  retention  and  evacuation  of  urine  are 
modified  and  controlled  by  voluntary  effort.  The  normal  action  of  the 
sphincter  mechanism  may  be  aided  by  the  contraction  of  the  perineal 
muscles  which  keep  the  urethra  closed.  The  reflex  process  of  evacuation 
may  be  set  in  motion  by  voluntary  contraction  of  the  abdominal  muscles, 
by  which  the  pressure  in  the  bladder  is  increased  and  the  normal  sphincter 
act  lob  overcome.  It  is  probable  too  that  the  individual  has  a  certain  degree 
of  voluntary  power  over  the  unstriated  muscles  of  the  bladder,  and  that  the 
contraction  of  the  muscular  wall  may  be  directly  augmented  by  impulses 
proceeding  from  the  cortex  to  the  upper  part  of  the  lumbar  cord.  This  view 
is  favoured  by  the  fact  that  stimulation  of  the  crus  cerebri  has  been  observed 
to  cause  contraction  of  the  detrusor  urinse.  In  this  experiment  the  abdo- 
im  11  was  opened,  so  there  could  be  no  question  of  the  contraction  of  the 
abdominal  muscles. 


CHAPTER  XVIII 

THE  SKIN  AND  THE  SKIN  GLANDS 

In  all  classes  of  animals  the  skin  performs  two  functions.  In  the  first  place, 
it  serves  to  protect  the  more  delicate  underlying  parts  from  injury  and 
from  penetration  or  invasion  by  foreign  organisms.  In  the  second  place, 
it  serves  as  a  sense  organ,  and  is  richly  supplied  with  nerves,  by  means  of 
which  the  activities  of  the  body  as  a  whole  may  be  brought  into  relation 
with  the  changes  going  on  in  the  environment  and  affecting  the  external 
surface  of  the  body.  In  warm-blooded  animals  the  skin  plays  an  important 
part  in  the  regulation  of  the  body  temperature,  since  the  loss  of  heat  from 
the  body  must  occur  almost  entirely  through  its  surface.  In  the  present 
chapter  we  have  to  deal  only  with  the  first  and  third  of  these  functions. 

The  development  of  the  skin  as  an  organ  of  protection  shows  wide  modification  in 
various  classes  of  animals.  Thus  it  may  become  the  seat  of  formation  of  horny  plates, 
as  in  the  alligator ;  of  poisonous  glands,  as  in  the  toad ;  or  of  mucous  glands,  as  in  many 
varieties  of  fishes.  In  warm-blooded  animals  the  development  of  hair  from  the  deeper 
layers  of  the  epidermis  serves  to  diminish  the  loss  of  heat.  Since  the  hair  follicles  are 
richly  supplied  with  nerve  fibres,  the  hairs  act  also  as  organs  of  sensation.  In  man, 
where  the  hairs  are  rudimentary  except  in  certain  localities,  practically  only  this 
tactile  function  is  retained.  The  external  layer  of  the  skin  in  man  consists  of  a  tough 
horny  layer  formed  by  the  kcratinisation  of  the  external  layers  of  cells  of  the  epidermis. 
The  skin  is  composed  of  two  parts,  the  epidermis  and  the  cutis  (Fig.  555).  The  epidermis 
is  a  stratified  squamous  epithelium.  The  deeper  layers  form  the  rete  mucosum,  being 
soft  and  protoplasmic,  while  the  superficial  layers  forming  the  cuticle  are  hard  and  horny. 
The  most  superficial  layer  of  the  rete  mucosum  is  formed  of  flattened  cells  filled  with 
granules  of  a  material  staining  deeply  with  kaeraotoxylin  and  eosin,  known  as  eleidin. 
This  layer  is  called  the  stratum  granulosum.  Immediately  superficial  to  this  layer  is 
another  in  which  the  cells  are  indistinct.  The  cells  are  clear  in  section  and  form  what 
is  known  as  the  stratum  lucidum.  These  two  layers  evidently  constitute  the  inter- 
mediate stages  in  the  transformation  of  the  cells  of  the  rete  mucosum  into  the  horny  scales 
which  make  up  the  superficial  cuticle.  The  cutis  or  coriurn  is  composed  of  dense  con- 
nective tissue,  which  becomes  more  open  in  texture  in  its  deeper  part,  where  it  merges 
into  the  subcutaneous  connective  tissue.  The  most  superficial  layer  of  the  corium  is 
prolonged  into  minute  papilla;  over  which  the  epidermis  is  moulded.  These  papillae 
contain  for  the  most  part  capillary  vessels;  a  few  contain  touch  corpuscles,  special 
organs  of  tactile  sensation.  The  blood  vessels  of  the  skin  form  a  close  capillary  network 
immediately  at  the  surface  of  the  cutis,  sending  up  loops  into  the  papillae.  All  parts 
of  the  skin,  except  the  palms  of  the  hands  and  the  soles  of  the  feet,  are  beset  with  hair 
follicles.  The  hair  follicles  are  small  pits  which  extend  downwards  into  the  deeper 
part  of  the  corium,  being  downgrowths  of  the  rete  mucosum.  The  hair  grows  from 
a  small  papilla  of  cells  at  the  bottom  of  the  follicle,  the  part  of  the  hah-  lying  within  the 
follicle  being  known  as.  the  hah'  root.  The  hair  itself  consists  of  long  tapering,  horny 
cells,  the  nuclei  of  which  are  still  visible,  though  the  cell  substance  has  been  almost 
entirely  converted  into  keratin. 

1214 


THE   ,SK1N    AIN1)   THE   SKIN   (i LANDS 


1215 


In  order  to  keep  the  cuticle  supple  and  preserve  it  from  the  drying 
effects  of  the  atmosphere,  it  is  kept  constantly  impregnated  with  a  fatty 
material  known  as  sebum.  This  material  is  formed  by  the  sebaceous  glands, 
which  are  distributed  all  over  the  surface  of  the  skin  wherever  hair  follicles 
are  to  be  found,  the  mouths  of  the  glands  opening  into  the  hair  follicles.  A 
sebaceous  gland  is  a  pear-shaped  body,  consisting  of  a  secreting  part  and  a 
short  neck  opening  into  the  follicle.  The  gland  proper  is  composed  of  a 
solid  mass  of  cells.     The  outermost  cells  are  flattened  and  generally  show 


Stratum 
corneum 
Stratum 
lucidum 
Stratum 
'j^anulosum 


'•  -Jss 


* 


Ecto 
mucodum 


i'lc;.  550.  Vertical  section  through  the  skin  of  the  palmar  side  of  the  linger,  showing 
two  papilla  (one  of  which  contains  a  tactile  corpuscle)  and  the  deeper  layer  of 
the  epidermis.     Magnified  about  200  diameters.     (Scuafee). 

signs  of  proliferation.  The  cells  lying  internal  to  these  are  much  larger, 
and  their  protoplasm  is  transformed  into  a  network,  in  the  meshes  of  which 
are  granules  which  may  show  the  reaction  of  fat.  Further  inwards  the 
protoplasmic  network  diminishes  in  amount,  wliile  the  fatty  granules  increase 
in  size,  so  that,  in  the  lumen  adjoining  the  duct,  we  find  only  a  mass  of  cell 
debris  and  masses  of  fatty  material.  It  has  often  been  thought  that  the 
secretion  of  sebum  depended  simply  on  a  fatty  degeneration  of  the  cells. 
The  granules  however,  when  they  first  appear,  stain  with  acid  fuchsin 
rather  than  osmic  acid,  and  one  must  regard  the  formation  of  sebum  as  an 
act  of  true  secretion ,  in  which  the  secretory  granules  are  gradually  trans- 
formed into  the  special  constituents  of  the  sebum.  For  it  must  be  noted 
that  the  sebum  is  not  a  true  fat,  nor  does  it  correspond  in  composition  with 


1216  PHYSIOLOGY 

the  lai  found  in  other  parts  of  the  body.  It  is  true  that  it  contains  fatty 
acids.  Imi  these  are  lor  ihe  most  part  in  combination,  not  with  glycerin  bill 
with  higher  alcohols,  including  cholesterol.  A  somewhat  similar  material, 
known  as  wool-fat  or  lanoline,  may  be  extracted  from  wool  as  well 
as  from  the  feather-glands  of  water  birds,  such  as  the  goose  and  duck,  ll 
must  be  regarded  rather  as  a  wax  than  a  fat.  It  presents  many  advantages 
over  ordinary  fat  as  a  protective  salve  for  the  surface  of  the  body.  In  the 
first  place,  it  can  take  up  a  large  amount,  as  much  as  100  per  cent.,  of  water. 
In  the  second  place,  it  is  not  attacked  by  micro-organisms,  so  that  it  does 
not  tend  to  become  rancid  or  to  furnish  a  nidus  for  the  growth  of  these 
organisms  on  the  surface  of  the  body. 

The  secretion  of  sebum  is  a  continuous  process,  though  it  is  probably 
quickened  in  conditions  of  increased  vascularity  of  the  skin.  The  extrusion 
of  the  products  of  secretion  is  determined  by  the  presence  of  unstriated 
muscle  fibres,  the  arrector  pili,  which  pass  from  the  surface  of  the  cutis 
obliquely  over  the  outer  surface  of  the  sebaceous  gland.  When  these  muscle 
fibres  contract,  the  hair  is  erected  and  a  certain  amount  of  the  sebum 
squeezed  out  on  to  the  root  of  the  hair  and  the  surrounding  skin.  This 
contraction  will  occur  whenever  cold  is  suddenly  applied  to  the  skin.  The 
contracted  condition  of  all  the  muscles  of  the  hair  follicles  is  shown  by  the 
'  goose-skin  '  produced  under  such  circumstances.  There  is  no  evidence 
that  the  secretion  of  sebum  is  in  any  way  under  the  control  of  the  central 
nervous  system. 

THE  SWEAT  GLANDS.  Under  normal  circumstances  in  temperate 
climates  the  greater  part  of  the  water  taken  in  with  the  food  in  the  course 
of  the  day  is  excreted  by  the  kidneys,  a  smaller  proportion  leaving  by  the 
lungs  and  by  the  surface  of  the  skin.  On  an  average  we  may  say  that  about 
700  c.c.  are  got  rid  of  through  the  skin.  The  excretion  of  water  by  the  skin 
is  however  mainly  determined  by  the  need  for  regulating  the  temperature 
of  the  body,  so  that  the  amount  leaving  in  this  way  depends  on  the  heat 
production  of  the  body  or  on  the  external  temperature,  and  is  very  little 
affected  by  alterations  in  the  quantity  of  fluid  drank.  A  certain  amount  of 
water  is  constantly  evaporated  from  the  surface  of  the  body  as  the  so-called 
'  insensible  perspiration.'  If  a  man's  body  be  enclosed  in  a  vessel  through 
which  a  current  of  air  is  parsed,  and  the  temperature  of  the  air  gradually 
raised,  it  will  be  noted  that  the  amount  of  water  given  off  rises  slowly  up 
to  a  certain  degree  and  then  rises  rapidly.  The  sudden  kink  in  the  curve 
is  due  to  the  setting  in  of  the  activity  of  the  sweat-glands,  and  we  are 
therefore  justified  in  regarding  the  insensible  perspiration  as  being  de- 
termined by  evaporation  of  water  from  the  surface  of  the  cuticle  itself,  apart 
altogether  from  the  sweat  glands.  These  are  distributed  over  the  whole 
surface  of  the  skin,  and  are  especially  abundant  on  the  palm  of  the  hand 
and  on  the  sole  of  the  foot.  They  are  composed  of  single  imbranched 
coiled  tubes,  which  lie  in  the  subcutaneous  tissue  and  send  their  ducts  up 
through  the  cutis,  to  open  on  the  surface  by  corkscrew-like  channels  which 
pierce  the  epidermis.  The  secreting  part  of  the  tube  consists  of  a  basement 
membrane  fined  by  a  double  layer  of  cells;    the  innermost  of  these  are 


THE  SKIN  AND  THE  SKIN  GLANDS  1217 

cubical  and  represent  the  secreting  cells  proper.  Between  the  secreting 
cells  and  the  basement  membrane  is  a  layer  of  unstriated  muscle  fibres. 
The  duct  of  the  gland  has  an  epithelium,  consisting  of  two  or  three  layers  of 
cells  with  a  well-marked  internal  cuticular  lining,  but  there,  is  no  muscular 
layer. 

The  sweat  formed  by  these  glands  is  the  most  dilute  of  all  animal  fluids. 
As  collected  it  generally  contains  epithelial  scales  and  some  admixture  of 
sebum.  After  filtration  it  forms  a  clear  colourless  fluid  of  a  specific  gravity 
of  about  1003.  It  contains  over  99  per  cent,  of  water.  Among  the  solid 
constituents  sodium  chloride  is  the  most  prominent — it  may  contain  from 
0-3  to  0-5  per  cent,  of  this  salt.  It  is  generally  hypotonic  as  compared  with 
the.  blood  plasma.  It  may  also  contain  small  traces  of  protein.  This 
constituent  is  especially  marked  in  the  horse.  It  generally  contains  also  a 
small  quantity  of  urea,  which  may  become  a  prominent  constituent  in  cases 
of  renal  disease.  The  quantity  of  sweat  excreted  in  the  day  is  very  variable. 
The  secretion  is  under  the  control  of  the  central  nervous  system  and  is 
almost  entirely  adapted  to  the  regulation  of  the  body  temperature.  The 
nervous  mechanism  can  be  set  into  activity  either  centrally  or  reffexly. 
The  most  usual  factor  is  a  rise  of  the  body  temperature.  If  a  man  sit  in  a 
warm  room,  e.  <j.  of  a  Turkish  bath,  the  secretion  of  sweat  commences  as  soon 
as  the  temperature  of  the  body  has  attained  a  height  of  0-5°  to  1°  C.  above 
normal.  In  the  case  of  muscular  exercise  the  temperature  will  generally  be 
found  to  be  raised  if  it  be  taken  at  the  instant  that  sweating  has  commence*d. 
The  effect  of  rise  of  temperature  may  however  be  either  local  or  central, 
so  that  one  arm  enclosed  in  a  hot-air  bath  may  sweat  while  the  rest  of  the 
body  is  dry.  Under  ordinary  circumstances  the  central  stimulation  by  the 
warm  blood  is  the  predominant  factor.  This  is  shown  by  an  experiment 
of  Luchsinger.  In  the  cat  sweating  is  to  be  observed  only  on  the  hairless 
pads  of  the  front  and  hind  paws.  If  one  sciatic  nerve  be  cut  and  the  animal 
be  placed  in  a  warm  chamber,  sweating  will  commence  as  the  temperature  of 
the  animal  rises  in  the  three  intact  paws,  while  the  paw  with  the  nerve  cut 
will  be  quite  dry.  Sweating  moreover,  as  has  been  shown  by  Kalm,  may 
be  induced  in  the  cat's  paws  by  warming  the  blood  passing  through  the 
carotid  arteries  on  its  way  to  the  brain,  at  a  time  when  the  temperature  of 
the  blood  circulating  through  the  rest  of  the  body,  including  the  paws  them- 
selves, has  undergone  no  alteration.  Sweating  may  also  be  aroused  by 
asphyxia,  and  this  result  is  formd  even  in  the  spinal  cat,  i.  e.  after  separation 
of  the  spinal  centres  from  the  medulla.  The  secretion  of  sweat  resulting 
from  stimulation  of  the  sweat  nerves,  although  generally  associated  with 
increased  vascularity  of  the  skin,  is  not  in  any  way  dependent  thereon. 
Thus  even  in  the  amputated  linib,  stimulation  of  the  sciatic  nerve  may  cause 
the  appearance  of  drops  of  sweat  on  the  pad  of  the  foot.  If  the  sciatic  nerve 
be  stimulated  in  the  intact  animal,  the  secretion  of  sweat  which  is  produced 
is  associated  with  constriction  of  the  vessels  of  the  skin,  due  to  simul- 
taneous stimulation  of  the  vaso-constrictor  nerves  running  in  the  sciatic 
nerve. 

As  Langley  has  shown,  the  sweat  nerves  run  entirely  in  the  sympathetic 
77 


1218  PHYSIOLOGY 

system.  Leaving  the  cord  by  the  white  rami  conununicantes  from  the 
second  dorsal  to  the  third  or  fourth  lumbar  nerves,  they  pass  into  the 
sympathetic  chain.  Here  the  first  relay  of  fibres  ends  in  connection  with  the 
cells  of  the  sympathetic  ganglia,  and  a  fresh  relay  of  fibres,  which  are  non- 
medullated,  pass  from  the  cells  along  the  grey  rami  into  the  various  spinal 
nerves,  to  be  distributed  to  the  whole  surface  of  the  skin.  The  secretion  of 
sweat  by  the  sweat  glands  may  be  roused  by  the  injection  of  pilocarpine  even 
after  division  of  the  sweat  nerves,  so  that  this  drug  must  act  peripherally 
on  the  glands.  The  action  of  pilocarpine,  as  well  as  the  effects  of  artificial 
stimulation  of  the  sweat  nerves,  is  abolished  by  the  administration  of 
atropine. 

THE  GASEOUS  EXCHANGES  OF  THE  SKIN.  In  any  animal  with  a 
thin  moist  skin,  such  as  the  frog,  the  absorption  of  oxygen  and  the  excretion 
of  C02  from  the  skin  may  be  sufficient  for  the  proper  aeration  of  its  blood, 
so  that  it  may  continue  to  five  after  the  extirpation  of  its  lungs.  In  man 
there  is  also  a  continuous  output  of  C02  through  the  skin,  but  the  amount 
leaving  the  body  in  this  way  is  negligible  compared  with  that  which  is 
exhaled  through  the  lungs.  The  loss  of  C02  by  the  skin  rises  with  increase 
of  external  temperature.  Thus  at  a  temperature  of  29°  to  33°  C.  the  C02 
output  by  the  skin  is  about  0-35  grm.  per  hour,  i,  e.  about  8-4  grm.  in  the 
twenty -four  hours.  When  the  external  temperature  rises  above  33°  O, 
the  C02  output  increases,  so  that  at  34°  it  is  doubled  and  at  38-5°  it  may 
amount  to  as  much  as  1-2  grm.  per  hour  (Schierbeck).  It  is  just  at  this 
temperature  of  33°  C.  that  a  secretion  of  sweat  begins  to  be  noticeable,  so  it 
has  been  suggested  that  the  increased  C02  output  may  be  due  directly  to  the 
increased  work  and  metabolism  of  the  sweat  glands  during  their  activity. 

ABSORPTION  BY  THE  SKIN.  In.  order  to  test  the  alleged  influence  of 
baths  containing  medicinal  substances  in  solution,  many  experiments  have 
been  made  to  determine  whether  absorption  is  possible  by  the  skin.  It 
may  be  regarded  as  established  that  the  uninjured  skin  is  impermeable 
for  watery  solutions  of  salts  or  other  substances.  On  the  other  hand,  it  is 
possible  to  produce  a  certain  amount  of  absorption  by  the  inunction  of 
substances  dissolved  in  fatty  vehicles.  Thus  the  administration  of  mercury 
is  often  carried  out  by  the  inunction  of  mercurial  ointments,  and  the  fact  that 
mercurial  salivation  may  be  produced  in  these  conditions  shows  that  a  certain 
amount  of  the  mercury  must  have  been  absorbed.  It  is  difficult  to  imagine 
that  any  appreciable  amount  of  cod  liver  oil  will  be  available  for  the  nutrition 
of  the  infant  when  this  substance  is  administered  by  rubbing  it  on  the  skin. 
On  the  other  hand,  the  moist  mucous  surfaces,  such  as  the  conjunctiva  or 
the  mucous  membrane  of  the  respiratory  passages,  as  well  as  raw  surfaces  of 
the  skin,  e.g.  which  have  been  deprived  of  their  epidermal  layer  by  the 
application  of  blisters,  permit  of  the  rapid  passage  of  substances  in  watery 
or  oily  solution. 


CHAPTER  XIX 

THE   TEMPERATURE   OF   THE   BODY  AND    ITS 
REGULATION     ' 

In  dealing  with  the  chemical  changes  in  the  body  as  a  whole  we  have  seen 
that  the  sum  of  the  metabolic  processes  is  associated  with  the  evolution 
of  heat.  In  man,  under  normal  circumstances,  while  doing  moderate  work, 
the  total  energy  requirements  amount  to  about  3000  Calories.  The  whole 
of  this  is  derived  from  the  oxidation  of  the  food,  the  combination  of  its 


1  JO 
100 
90 
SO 

SO 

50 
40 
30 

\ 

\ 

\ 

^ 

0  5/0/5  20  IS  30         35  40  45         SO  55         SO 

7CMPERA  TURC 

Fio.  550.     Effect  of  temperature  on  the  C02  output  of  a  lupin  seedling. 
Ordinates  =  milligrammes  CO,  per  hour.     Abacissfe  =  temperature  in  degrees  Centigrade. 

carbon  and  hydrogen  with  oxygen  to  form  C02  and  water,  with  the  evolu- 
tion of  the  corresponding  amount  of  energy.  Of  this  energy  only  a  small 
proportion,  on  the  average  about  one-twentieth,  leaves  the  body  as  mechani- 
cal energy,  the  rest  being  evolved  in  the  form  of  heat  and  being  expended 
in  the  maintenance  of  the  body  temperature,  or  in  the  warming  of  the 

surrounding  medium. 

1219 


1220 


I'NYNIOLOOY 


The  evolution  of  heat  is  not  confined  to  the  higher  animals,  but  is  com- 
mon to  all  living  beings.  It  is  very  evident,  for  instance,  in  the  germina- 
tion of  peas  or  barley.  The  atmosphere  of  a  bee-hive  is  often  ten  degrees 
above  that  of  the  surrounding  atmosphere.  Whenever  we  can  excite 
increased  activity  in  an  organ,  we  are  able  to  show,  except  in  the  single  case 
of  the  nerve  impulse,  that  such  activity  is  associated  with  the  evolution  of 
heat.  This  heat  is  derived  from  the  chemical  changes  which  proceed  in  the 
living  cells.  Since  all  chemical  processes  are  quickened  by  rise  of  tempera- 
ture, we  should  expect  to  find  that  the  heat  produced  in  the  metabolic 
processes  of  organisms  would  tend  in  itself  to  quicken  these  processes.  In 
most  chemical  reactions  a  rise  of  about  10°  C.  would  increase  the  velocity  of 
reaction  from  two  and  a  half  to  three  times,  and  the  same  rule  is,  within 
the  limits  of  stability  of  living  tissues,  found  to  hold  good  for  them  also.  The 
diagram  (Fig.  556)  shows  the  influence  of  temperature  on  the  chemical 
changes  in  a  lupin  seedling,  as  measured  by  the  output  of  C02  per  hour  per 
100  grni.  of  plant.  A  marked  increase  in  the  rate  of  chemical  decomposi- 
tion is  shown  to  follow  a  rise  of  temperature ;  but  about  40°  C.  the  rate  of 
change  is  at  an  optimum,  and  thereafter  rapidly  declines,  owing  to  the  fact" 
that  the  living  tissues  are  being  killed  by  the  excessive  temperature. 

Hence  in  the  animal  organism  we  shall  expect  to  find  that  the  rate  of  the 
metabolism  is  also  proportional  to  the  temperature  of  the  animal.  This 
is  universally  the  case  whether  we  are  dealing  with  warm-blooded  or  cold- 
blooded animals.  In  cold-blooded  animals  the  temperature  of  the  body, 
and  therefore  the  rate  of  its  metabolism  and  the  amount  of  its  heat  produc- 
tion, is  proportional  to  the  external  temperature  (Fig.  557).  The  following 
Table  gives  the  average  C02  output  per  hour  of  five  lizards  placed  in  a 
chamber  which  could  be  maintained  at  varying  temperature  : 


Temperature 
of  bath 

Temperature  of 
lizards  (average) 

CO-  produced 
in  one  hour 

50°  C. 

5-5°  C. 

•0246 

90°  C. 

9-2°  Q 

•0790 

15-0°  C. 

15-2°  C. 

•0981 

20-5°  C. 

20-4°  C. 

•1023 

250°  C. 

24-5°  C. 

•1193 

300°  C. 

29-3°  C. 

•1440 

350°  C. 

34-8°  C. 

•1814 

390°  C. 

38-5°  C. 

•5454 

It  might  be  thought  that  such  a  reaction  in  change  of  temperature  would 
result  in  a  vicious  circle.  Since  the  animal  is  continually  producing  heat  and 
thus  raising  its  temperature  above  that  of  its  surroundings,  one  might  expect 
to  find  that  the  higher  the  external  temperature  the  greater  would  be  the 
difference  between  this  and  the  temperature  of  the  animal,  until  finally  the 
latter  would  rise  to  such  a  height  that  the  animal  would  die  of  heat-stroke, 
its  tissues  being  destroyed  by  the  actual  temperature  attained.  A  certain 
protection  is  afforded  to  most  cold-blooded  terrestrial  animals  by  the  fact 


TEMPERATURE  OF  THE  BODY  AND   ITS  REGULATION    1221 


that  their  surface  is  moist,  and  that  with  a  rise  of  external  temperature  the 
rate  of  evaporation  on  the  surface  increases,  so  that  the  increase  in  the  rate 
of  cooling  by  evaporation  more  than  corresponds  to  the  rate  of  increase  in 
the  heat  production,  which  would  tend  to  raise  the  body  temperature.  Most 
of  these  animals  however  escape  from  any  extreme  rise  of  external  tempera- 
ture by  burrowing  underground  or  taking  to  the  water,  while  in  plants  a  rise 
of  external  temperature  assists  transpiration  to  such  an  extent  that  the 
temperature  of  the  plant  is  generally  several  degrees  below  that  of  the 
surrounding  atmosphere.    The  extreme  variability  in  the  metabolism  of 


30' 


40 


10°  20" 

•External  temp.  C.° 

Fig.  557.     Effect  of  alterations  in  the  temperature  of  the  surrounding  medium 
on  output  of  C02  in  cold-blooded  (poikilothermic)  animals.     (C.  J.  Martin.) 

such  animals  implies  a  state  of  dependence  of  all  the  activities  of  the  body  on 
the  environment,  which  would  prevent  the  utilisation  to  the  full  of  the 
available  sources  of  energy.  An  animal  whose  metabolism  was  more  or 
less  independent  of  the  surrounding  temperature  must  have  a  great  ad- 
vantage over  an  animal  liable  to  have  his  activities  reduced  and  paralysed 
by  a  sudden  spell  of  cold  weather ;  this  greater  independence  of  the  environ- 
ment, which  is  characteristic  of  elevation  of  type,  has  been  achieved  by  the 
warm-blooded  animals  including  man.  Such  animals  are  often  spoken  of  as 
hommothermic,  i.  e.  animals  possessing  a  uniform  temperature,  in  contra- 
<lisi  inction  to  the  cold-blooded  animals,  which  are  'poikilothermic  and  possess 
a  temperature  varying  with  that  of  their  surroundings. 

Amongst  the  warm-blooded  animals  the  body  temperature  may  be 
very  different  according  to  the  species.  In  birds  it  is  generally  from  39° 
to  10°  C. ;  in  mammals  it  varies  from  35°  to  40°  C.  The  temperature  of 
man  varies  within  slight  limits  about  37°  C.  (98-4°  F.). 


1222  PHYSIOLOGY 

THE   DIURNAL   VARIATIONS   IN   THE   BODY   TEMPERATURE 

In  any  animal  the  seat  of  heat  production,  e.  g.  a  contracting  muscle, 
must  be  warmer  than  an  inactive  tissue,  and  this  again  than  a  tissue  from 
which  heat  is  being  rapidly  abstracted,  such  as  the  skin.  Owing  however 
to  the  rapidity  of  the  circulation  of  the  blood,  the  temperature  of  the  internal 
organs  can  be  regarded  as  approximately  uniform.  The  temperature  of  man 
is  usually  taken  in  the  mouth,  rectum,  or  axilla.  In  the  case  of  the  mouth 
the  temperature  is  liable  to  fluctuation  with  the  rate  of  breathing,  the  mouth 
being  cooled  by  the  passage  of  the  air  through  the  nasal  cavities.  There  is 
also  probably  loss  of  heat  through  the  cheeks.  In  order  to  determine  the 
temperature  in  this  situation,  the  mouth  should  be  kept  shut  for  a  few 
minutes  and  then  the  bulb  of  the  thermometer  inserted  under  the  tongue, 
and  the  lips  kept  closed  on  the  stem  of  the  thermometer  for  five  minutes. 
Except  in  cases  where  the  cutaneous  vessels  are  much  dilated,  the  tempera- 
ture of  a  thermometer  in  the  axilla  takes  a  considerable  time  to  rise  to  that 
of  a  thermometer  in  the  mouth ;  it  should  never  be  left  less  than  ten  minutes 
in  this  situation .  The  following  Table  represents  the  temperature  of  different 
parts  of  the  body  : 

SURFACE 

Skin  covered  with  clothes     ..... 
Naked  skin  in  bath  at  5°  C. 

25°  C 

Muscles  12  mm.  below  tiie  Surface 
In  bath  at  5°  C.  ... 

„       „    25°  C 


33c 

to  35° 

C. 

17° 

C. 

26-5c 

C. 

36-3° 

C. 

36-9° 

C. 

The  body  temperature  of  man  shows  variations  of  several  tenths  of 
a  degree  according  to  the  time  of  day  at  which  the  temperature  is  taken. 
The  highest  temperature  is  obtained  about  six  or  seven  in  the  evening,  and 
the  lowest  at  about  four  or  five  o'clock  in  the  morning.  With  these  diurnal 
changes  in  temperature  are  associated  parallel  oscillations  in  the  rate  of 
metabolism  as  shown  by  the  ehrnination  of  carbon  dioxide.  They  are 
probably  determined  by  the  changes  in  the  movement  and  tension  of  the 
muscles  occurring  during  the  waking  hours.  If  the  habits  of  a  man.  or 
animal  be  reversed,  so  that  he  sleeps  in  the  daytime  and  performs  his  normal 
vocation  by  night,  it  is  possible  to  reverse  also  the  direction  of  the  diurnal 
variations  in  temperature.  The  temperature  may  be  also  affected  tem- 
porarily by  various  acts,  such  as  the  taking  of  food  or  muscular  work;  the 
influence  of  the  latter  factor  is  often  very  marked.  In  many  individuals  a 
hard  game  at  tennis  suffices  to  raise  the  temperature  to  39°  C.  (102°  ¥.),  and 
even  the  healthiest  individual  will  show  some  change  in  his  temperature 
as  the  result  of  exercise.  Pembrey  found  that  the  act  of  marching  led  to  a 
considerable  rise  in  temperature,  a  rise  which  is  apparently  responsible  for 
the  discomfort  and  fatigue  observed  under  such  circumstances.  Such  a 
change  in  the  body  temperature  is  merely  temporary  in  its  effects,  and 
insignificant  in  comparison  with  the  wonderful  uniformity  of  temperature 


TEMPERATURE  OF  THE  BODY  AND  ITS  REGULATION    1223 

observed  in  men  of  all  races  and  of  all  climes  under  most  varying  conditions 
of  food  and  activity. 

Just  as  there  are  limits  to  the  power  of  the  organism  to  regulate  its 
temperature  when  there  is  an  excessive  formation  of  heat  in  the  body,  so 
there  are  limits  to  the  regulation  of  temperature  to  severe  alterations  in  the 
temperature  of  the  external  medium.  Thus  if  the  body  is  subjected  to 
excessive  external  cold,  or  the  loss  of  heat  be  increased  by  absence  of  clothes, 
by  depriving  an  animal  of  its  fur,  or  by  immersion  in  a  cold  bath,  the  tempera- 
ture of  the  body  may  sink  continuously.  This  fall  of  temperature  in  the 
higher  animals  is  very  soon  followed  by  paralysis  of  the  highest  nerve  centres 
and  loss  of  consciousness.  The  centres  in  the  medulla  are  later  on  affected, 
so  that  the  respiration  is  slowed  and  the  blood  pressure  falls.  If  the  tem- 
perature does  not  fall  too  low,  it  is  possible  to  revive  the  animal  or  man  by 
checking  the  loss  of  heat  or  by  supplying  artificial  warmth.  Recovery  has  in 
fact  been  observed  in  men  in  whom,  as  a  result  of  exposure,  the  body  tem- 
perature had  fallen  to  24°  C.  In  the  same  way  exposure  to  extreme  heat, 
especially  associated  with  muscular  exercise  and  increased  production  of 
heat  in  the  body,  may  cause  a  rise  of  the  body  temperature.  A  man  or 
animal,  whose  temperature  is  raised  above  the  normal,  is  said  to  be  in  a 
state  of  pyrexia.  A  rise  of  2°  or  3°  C.  is  associated  with  all  the  phenomena 
which  characterise  fever,  i.  e.  quickening  of  pulse  and  respiration,  malaise, 
headache,  and  loss  of  muscular  power.  If  the  temperature  rise  to  a  greater 
degree  than  this,  the  patient  may  lose  consciousness,  and  death  ensues  at  a 
temperature  of  about  44°  C. 

The  very  small  variation,  presented  by  the  body  temperature  in 
mammals,  even  under  the  influence  of  considerable  variation  in  external 
temperature  or  in  the  production  of  heat  in  the  body,  connotes  an  accurate 
adaptation  between  the  production  of  heat  in  the  body  and  the  loss  of 
heat  from  the  body.  The  regulation  of  the  temperature  can  be  effected 
either  by  regulation  of  heat  production,  by  alteration  in  the  rate  of  loss  of 
heat,  or  by  a  combination  of  both  mechanisms.  It  will  be  convenient  to 
deal  with  these  two  methods  of  regulation  under  separate  headings. 


THE  PRODUCTION  OF  HEAT  IN  THE  BODY 

The  reactions  mainly  responsible  for  heat  production  in  the  body  are 
those  associated  with  oxidation ;  the  processes  of  disintegration,  such  as  are 
effected  by  means  of  hydrolytic  ferments,  account  for  a  very  small  part  of 
the  heat  evolved. 

In  these  processes  of  oxidation  all  the  organs  participate,  the  most 
important,  especially  in  relation  to  the  regulation  of  heat  production,  being 
the  skeletal  muscles.  These  represent  more  than  half  the  total  weight  of 
the  soft  tissues  of  the  body,  and  even  during  rest  are  the  seat  of  oxidative 
processes  and  therefore  of  heat  formation.  Heat  formation  varies  with  the 
state   of  tone  of  the   muscles  and  is  largely  increased  with  every  active 


1224 


PHYSIOLOGY 


contraction.  The  effect  of  muscular  activity  on  the  total  output  of  energy 
of  the  body  is  well  represented  in  the  Table  given  on  p.  684. 

It  is  probable  that,  in  relation  to  their  size  at  any  rate,  the  glands  are 
still  more  effective  as  heat  producers.  The  liver  and  the  blood  flowing 
from  the  liver  have  been  stated  to  present  a  higher  temperature  than  any 
other  part  of  the  body.  On  the  other  hand,  the  nervous  system,  although 
dependent  on  a  constant  supply  of  oxygen  for  its  activities,  does  not  appear 
to  be  the  seat  of  extensive  metabolic  changes,  nor  does  the  heat  produced  in 
this  system  play  any  great  part  in  maintaining  the  temperature  of  the  body. 

The  skeletal  muscles  are  controlled  by  the  central  nervous  system ;  if 
separated  from  their  centres  in  the  cord  they  become  flaccid  and  rapidly 
atrophy.  The  heat  production  in  the  muscles  is  therefore  also  dependent  on 
their  connection  with  the  central  nervous  system.  If  this  connection  be 
severed  either  by  curare  or  section  of  the  cord,  or  if  the  reflex  play  of  impulses 
on  the  muscles  be  abolished  by  anaesthetics,  the  animal  will  react  like  a  cold- 
blooded animal .  The  total  metabolism  of  the  body  and  the  total  production 
of  heat  sink  to  a  minimum,  and  are  diminished  by  application  of  cold,  or 
increased  by  application  of  warmth,  to  the  surface  of  the  body.  On  the 
other  hand,  in  the  intact  animal  changes  of  temperature  in  the  environment 
provoke,  reflexly  by  their  action  on  the  muscles,  changes  in  the  opposite 
direction.  Thus  exposure  to  cold  increases  and  to  heat  diminishes  muscular 
metabolism  and  the  heat  production  of  the  body. 

The  effects  of  variations  in  the  external  temperature  on  the  metabolism 
of  warm-blooded  animals  are  well  shown  in  the  experiment,  from  which 
the  following  Tables  are  taken,  on  the  C02  output  in  the  ornithorhynchus 
and  in  the  rabbit  (Martin)  : 


1.  Ornithorhynchus.    Weight,  693  grm.  ; 

Surface,  876  so. 

CENTEMS. 

Temperature              Temperature 

of                                 of 
environment                   animal 

Difference  in 
temperature, 
animal  and 
environment 

COo  per  hour, 
in  grammes 

COo  per  hour 

per  1000 
8Q.  centima., 
in  grammes 

5 

31-8 

26-8 

1-090 

1-244 

10 

320 

220 

■722 

•825 

20 

32-6 

12-6 

•405 

■463 

32                         33-6 

1-6 

•336 

■383 

35                         35-3 

•3 

■377 

•430 

2.  Rabbit.    Weight,  750  grm. 

Temperature 

of 
environment 

Temperature 

of 

animal 

Difference  in 
temperature, 
animal  and 
environment 

COj  per  hour, 
in  grammes 

COs  per  hour 

per  1000 
sq.  centims., 
in  grammes 

5 

37-5 

32-5 

1-426 

1-543 

10 

38-0                       28-0 

1-038 

1124 

20 

38-7                        18-7 

•912 

■987 

35 

40-5                         5-5 

•766 

•829 

40 

41-6                          1-6 

•897 

•971 

TEMPERATURE   OF  THE  BODY  AND   ITS  REGULATION    1225 

In  the  former  animal,  where  the  regulation  of  the  temperature  of  the 
body  is  effected  almost  entirely  by  changes  in  heat  production,  the  effect 
of  warming  the  environment  of  the  animal  on  the  C02  output  is  extremely 
marked.  It  will  be  noticed  that  the  C02  per  hour  sinks  continuously  with 
rising  temperature  up  to  32°  C.  When  the  temperature  of  the  chamber  was 
raised  to  35°,  the  temperature  of  the  animal  rose  considerably,  i.  e.  the 
regulatory  mechanism  was  failing,  so  that  the  same  effect  was  produced  on 
metabolism   as  is  observed  in   working  with  cold-blooded   animals.     Tin' 


io°  so1 

« *■  Extt   Cemp.  a/e<5.  CenC. 

Fig.  558.     Effect  of  variations  in  the  external  temperature  on  the  C02  output 
(per  1000  cm.'-  body  surface)  of  warm-blooded  animals.     (C.  3.  Martin.) 

same  change,  though  less  marked,  is  observed  on  exposing  the  rabbit  to  a 
gradually  rising  temperature.  Here  however  the  process  of  regulation  is 
aided  by  alterations  in  the  heat  loss  as  well  as  in  the  heat  production  (Fig. 
558).  If  the  animals  be  observed  whilst  subjected  to  changes  of  tempera- 
ture, it  will  be  evident  to  any  one  that  the  regulation  is  associated  with 
changes  in  muscular  activity.  At  30°  to  35°  C.  the  animals  will  lie  perfectly 
flaccid,  breathing  rapidly,  or  may  go  to  sleep.  On  cooling  they  at  once 
become  more  vigorous  and  perform  active  movements  in  their  cage.  The 
same  effects  of  changes  in  the  external  temperature  are  familiar  in  our- 
selves. The  slackness  and  extreme  disinclination  to  violent  exercise  ob- 
served in  hot  moist  weather,  contrasted  with  the  stringing  up  of  the  tone 
of  the  muscles  which  follows  exposure  to  cold,  and  which  may  be  associated 
with   voluntary  exercise   to   keep  ourselves  warm,   arc   indications   of   the 


1226  PHYSIOLOGY 

important  part  played  by  the  muscles  in  determining  the  heat  production 
of  the  body.  As  a  rule  the  immersion  of  a  man  in  a  cold  bath  for  a  minute 
or  two  increases  considerably  his  output  of  C02.  It  is  possible  however 
to  sit  in  a  bath  and  by  an  act  of  the  will  keep  all  the  muscles  in  a  state  of 
relaxation.  Under  these  circumstances  the  temperature  of  the  body  rapidly 
falls,  and  with  it  the  rate  of  metabolism,  as  judged  by  the  output  of  carbon 
dioxide. 

This  process  of  adjustment  of  the  body  temperature  by  variations  in  the 
heat  production,  so  long  as  it  represents  the  only  method,  is  extravagant  of 
energy  directly  the  difference  in  temperature  between  animal  and  environ- 
ment attains  any  considerable  degree.  In  the  very  perfect  adjustment  of 
the  temperature  which  is  present  in  the  higher  mammals,  regulation  of  the 
heat  loss  plays  a  greater  part  than  regulation  of  heat  production.  The 
economy  of  adjustment  by  heat  loss  is  well  shown  if  we  compare  in  echidna 
and  rabbit  respectively  the  percentage  alteration  in  C02  production,  when 
the  difference  in  temperature  between  animal  and  environment  varies  from 
10°  C.  to  20°  C.  This  is  for  echidna  72  per  cent.,  for  mammals  16  per  cent. 
In  echidna  variations  in  heat  loss  can  be  practically  neglected,  so  that  the 
whole  of  the  work  of  regulating  the  body  temperature  falls  on  the  heat 
production.  As  soon  as  the  external  temperature  falls  below  a  certain 
degree,  the  mechanism  fails,  the  animal's  temperature  falls,  and  it  passes  into 
a  state  of  hibernation. 

THE   REGULATION   OF   HEAT   LOSS 

In  all  temperate  clirnates,  and  in  fact  in  all  climates  except  under  cer- 
tain exceptional  conditions,  the  temperature  of  the  warm-blooded  animal 
is  higher  than  that  of  his  environment,  so  that  there  must  be  a  constant 
loss  of  heat  from  the  surface  of  the  body.  In  the  warm-blooded  animals 
in  the  arctic  regions,  and  in  those  which  have  adopted  an  aquatic  exist- 
ence, the  thick  layer  of  fat  which  underlies  the  skin  protects  the  active 
portions  of  the  body,  the  muscles  and  internal  organs,  from  excessive  loss 
of  heat  to  the  surrounding  medium.  In  most  terrestrial  animals  the  loss 
of  heat  is  also  diminished  by  fur  and  feathers  with  which  these  animals  are 
clothed,  and  in  ourselves  the  same  office  is  performed  by  clothes,  which  are 
capable  of  voluntary  graduation  to  external  conditions.  The  value  of  these 
different  coverings  depends  on  the  fact  that  air  is  a  very  bad  conductor 
of  heat.  In  the  case  of  a  naked  man  the  layer  of  air  immediately  in  contact 
with  the  surface  of  the  body  is  warmed,  becomes  fighter,  and  rises,  its  place 
being  taken  by  fresh  cold  air.  Loss  of  heat  is  increased  by  a  draught, 
which  quickens  the  rate  at  which  the  layers  of  air  in  contact  with  the  surface 
are  renewed.  In  the  case  of  clothes  the  material  encloses  layers  of  air  and 
hinders  it  from  free  circulation,  and  it  is  the  air  enclosed  in  the  meshes  of 
the  garments  and  between  the  different  layers  of  garments  that  plays  the 
greater  part  in  preventing  loss  of  heat.  The  rapid  cooling  effect  of  wet 
clothes  is  partly  due  to  the  replacement  of  layers  of  air  by  water,  which  is  a 
much  better  conducting  fluid. 


TEMPERATURE   OF  THE   BODY  AND   ITS  REGULATION    1227 

In  addition  to  the  loss  of  heat  by  convection,  i.  e.  by  warming  the  layers 
of  air  in  contact  with  the  body,  heat  is  also  lost  by  radiation,  i.  e.  by  an 
exchange  of  heat  between  the  surface  of  the  body  and  that  of  surrounding 
cooler  objects.  This  loss  is  also  prevented  by  clothing.  Since  the  material 
of  which  clothes  are  made  does  not  allow  the  passage  of  radiant  heat,  they 
absorb  the  heat  leaving  the  body  and  become  warm.  This  warm  article  of 
clothing  may  in  its  turn  act  as  a  centre  for  the  loss  of  radiant  heat,  which 
may  again  be  prevented  by  putting  on  another  layer.  It  is  a  familiar 
experience  that  a  multiplication  of  garments  is  more  effective  in  retaining 
the  heat  of  the  body  than  merely  increasing  the  thickness  of  the  individual 
garments.  The  rate  of  loss  of  heat  by  radiation  is  diminished  by  a  rise  of 
the  amount  of  watery  vapour  in  the  air,  since  this  makes  the  air  more 
opaque  to  the  passage  of  radiant  energy.  Since  the  loss  of  heat  depends  on 
the  difference  of  temperature  between  the  surface  of  the  body  and  the 
surrounding  air  or  objects,  it  will  be  largely  affected  by  the  temperature 
of  the  skin,  and  therefore  by  the  amount  of  blood  flowing  through  the 
skin.  The  blood  flow  through  the  skin  is  under  the  control  of  the  central 
nervous  system,  through  the  vaso-motor  and  vaso-dilator  nerves,  and  it  is 
by  altering  the  size  of  the  cutaneous  vessels  that  the  central  nervous  system 
chiefly  acts  in  regulating  heat  loss.  In  cold  weather  or  when  the  heat  pro- 
duction in  the  body  is  low,  the  vessels  are  constricted,  the  skin  is  cold,  and 
the  heat  loss  is  small.  On  the  other  hand,  if  the  temperature  of  the 
surrounding  air  is  high,  or  a  large  amount  of  heat  is  being  produced  in 
consequence  of  muscular  exercise,  the  vessels  are  dilated  and  the  skin  is 
hot.  In  hot  weather  the  dilatation  in  the  cutaneous  vessels  is  associated 
with  muscular  inactivity,  so  that  there  is  a  derivation  from  the  muscles, 
where  the  blood  is  not  required,  to  the  skin,  where  a  considerable  circulation 
is  necessary. 

Loss  of  heat  by  radiation  and  convection  can  happen  only  when  the 
temperature  of  the  surrounding  air  is  lower  than  that  of  the  body.  The 
body  temperature  can  however  be  maintained  at  its  normal  height  in  an 
atmosphere  with  a  temperature  much  higher  than  37-5°  C,  and  this  in  spite 
of  the  fact  that  the  production  of  heat  in  the  body  is  still  going  on.  In  this 
case  there  is  a  profuse  secretion  of  sweat  on  the  surface  of  the  body.  In  the 
evaporation  of  the  sweat,  especially  if  aided  by  a  draught  of  air,  a  large 
amount  of  heat  becomes  latent  and  is  abstracted  from  the  body,  which  is 
therefore  kept  at  a  temperature  below  that  of  the  surrounding  atmosphere. 
If  the  secretion  of  sweat  is  checked  by  depriving  an  animal  or  man  of  water, 
or  if  its  evaporation  be  impeded  by  placing  him  in  an  atmosphere  already 
saturated  with  aqueous  vapour,  the  temperature  of  the  body  runs  up  rapidly 
and  death  ensues  from  hyperpyrexia  or  heat-stroke.  Although  a  man  can 
stand  exposure  to  a  temperature  of  200°  or  even  250°  F.  for  a  considerable 
time  provided  that  the  air  is  dry,  a  temperature  of  89°  F.  is  rapidly  fatal  if 
the  air  be  saturated  with  moisture.  The  same  mechanism  corfles  into  play 
when  the  heat  production  in  the  body  is  very  largely  increased,  as  by 
violent  exercise.  Under  these  conditions  a  man  may  sweat  profusely  when 
the  temperature  of  the  surrounding  atmosphere  is  at  0°  C. 


1228  PHYSIOLOGY 

The  main  regulation  of  heat  loss  thus  takes  place  by  the  control  of 
the  nervous  system  over  the  cutaneous  circulation  and  the  sweat  glands. 
Besides  these  channels  of  heat  loss,  others  may  play  an  important  part  under 
certain  conditions.  Heat  is  lost  to  the  body  in  warming  the  food  and 
air  which  are  taken  in.  It  is  also  lost  in  respiration,  in  the  evaporation  of 
water,  and  the  setting  free  of  C02  from  watery  solution  into  the  expired  air. 
The  following  estimate  by  Tigerstedt  represents  the  proportion  of  losses 
in  an  adult  man  by  these  different  ways  : 

A.     Warming  the  Food  and  Air 

(1)  1500  g.  water  drunk  at  15°  C.  and  warmed  to  37-5° — raised  therefore  Cal. 

22-5° =   33-75 

(2)  1500  g.  food  eaten  at  25°  C.  (mean)  and  warmed  to  37-5° — raised  therefore 

12-5;  specific  heat  0-8 =    15-00 

(3)  15,000  g.  (=  11,500   1.)  air  respired  at  15°  C.  and  warmed  to  37-5°— 

raised  therefore  22-5° ;  specific  heat  0-237 =   79-95 


128-70 


B.    Loss  of  Water  and  CO,  in  the  Breath 

(4)  Tt  is  assumed  that  the  inspired  air  is  half  saturated  with  watery  vapour 

at  15°  C.  and  that  the  expired  air  is  fully  saturated  at  37-5°  C.  Ap- 
proximately 450  g.  of  water  would  be  given  off  therefore  in  the  form  of 
vapour  from  the  respiratory  passages ;  the  latent  heat  of  the  water 
vapour  is  0-537  Cal =     241-70 

(5)  The  absorption  of  heat  in  the  liberation  of  CO,  from  the  lungs  (800  g.); 

0134  Cal.  per  g " =    107-20 

348-90 
From  above 128-70 


Total 477-60 

The  sum  of  heat  losses  specified  under  these  five  headings  amounts  to 
477-60  Cal.  Estimating  the  total  heat  loss  of  an  adult  man  at  2400  Cal., 
this  sum  represents  only  about  20  per  cent,  of  the  total.  The  remaining  80 
per  cent,  (in  round  numbers)  takes  place  through  the  skin. 

If  we  estimate  the  total  heat  loss  of  an  adult  man  at  2400  Calories,  we 
may  say  that  about  5  per  cent,  of  the  total  heat  loss  takes  place  by  warming 
the  food  and  air,  about  15  per  cent,  by  the  evaporation  of  water  and  C02  in 
respiration,  and  about  80  per  cent,  by  radiation  and  convection  and  the 
evaporation  of  sweat  from  the  skin.  The  proportion  represented  by  the 
last  factor  will  increase  very  largely  in  the  presence  of  a  high  external  temper- 
ature, or  of  an  excessive  heat  production  in  consequence  of  violent  muscular 
exercise. 

THE  NERVOUS  MECHANISM  FOR  HEAT  REGULATION 

The  accurate  balance  between  heat  production  and  heat  loss,  which  is 
responsible  for  the  nearly  constant  temperature  of  man,  indicates  the  active 
co-operation  of  the  central  nervous  system  in  every  step  of  the  process. 
Whether  this  function  of  temperature  regulation  can  be  specially  localised  at 


TEMPERATURE   OF  THE   BODY  AND   ITS  REGULATION     1229 

any  part  of  the  central  nervous  system,  so  that  it  would  be  possible  to  speak 
of  a  heat  centre  in  the  same  way  as  we  speak  of  a  respiratory  or  vaso-motor 
centre,  is  doubtful.  Many  observers  have  found  that  injury  to  the  corpus 
striatum  causes  a  rise  of  temperature  associated  with  increase  both  in  heat 
production  and  in  heat  loss.  On  the  other  hand,  injury  to  or  pathological 
lesions  cf  the  pons  Varolii  often  lead  to  an  increased  production  of  heat  in  the 
body,  which  is  not  compensated  for  sufficiently  by  heat  loss,  and  so  causes 
death  by  hyperpyrexia.  It  has  been  suggested  that  the  thermogenic 
centre,  i.  e.  that  responsible  for  regulating  heat  production,  is  situated  at  a 
lower  level  in  the  nervous  system  than  the  thermotaxic  system,  i.  e.  that 
which  presides  over  and  determines  the  balance  between  heat  production  and 
heat  loss.  The  observations  of  Meyer  and  Barbour,  that  local  cooling  of  the 
corpus  striatum  causes  increased  respiratory  exchanges  and  heat  production, 
while  warming  has  the  reverse  effect,  certainly  point  to  a  localisation  of  the 
thermotaxic  centre  in  this  part  of  the  central  nervous  system.  The  centres 
for  heat  loss  must  be  placed  in  the  medulla,  at  any  rate  so  far  as  concerns 
control  of  heat  loss  by  alterations  in  the  blood  supply  to  the  skin  or  in  the 
secretion  of  sweat.  The  facts  at  our  disposal  are  however  too  meagre  to 
warrant  any  definite  localisation  of  the  heat-regulating  function  in  the 
central  nervous  system,  or  any  such  accurate  analysis  of  the  regulating 
function  as  has  been  just  suggested. 

In  many  warm-blooded  animals  the  ability  to  maintain  a  constant  tem- 
perature  is  not  fully  developed  until  some  time  after  birth.  Pembrey  has 
shown  that  in  the  guinea-pig  and  chick,  in  which  the  nervous  system  is 
fully  functional  at  birth,  the  heat-regulating  mechanism  is  also  completely 
adequate,  whereas  animals  such  as  rats,  pigeons,  or  the  human  child,  which 
are  born  in  a  helpless  condition,  only  acquire  the  power  of  regulating  their 
own  temperature  some  time  after  birth.  As  we  should  expect,  the  develop- 
ment of  the  power  of  regulating  heat  production  runs  pari  passu  with  the 
acquisition  of  control  by  the  nervous  system  over  the  muscles  of  the  body. 


CHAPTER  XX 
THE   DUCTLESS   GLANDS 

INTERNAL   SECRETIONS 

In  unicellular  organisms,  as  in  the  rest  of  the  living  world,  activity  consists 
in  adaptation  to  external  conditions.  The  changes  in  the  environment 
which  determine  the  reactions  of  these  organisms  may  occur  at  their  surface 
or  at  some  distance.  Among  the  stimuli  which,  acting  from  a  distance, 
evoke  the  reaction  of  unicellular  organisms,  probably  the  most  important  are 
those  accompanied  by  chemical  changes.  The  interrelation  of  micro- 
organisms with  one  another  is  determined  almost  entirely  by  such  chemical 
stimuli.  Thus  the  antherozoids  of  ferns  are  attracted  to  the  ovule  in  con- 
sequence of  the  production  in  the  tissue  surrounding  the  latter  of  substances 
such  as  nialic  acid.  Among  micro-organisms  we  find  some  which  leave 
places  rich  in  oxygen,  while  others  move  towards  any  spot  in  their  environ- 
ment where  oxygen  is  most  plentiful.  These  reactions  of  unicellular  organ- 
isms to  chemical  stimuli  are  classed  together  under  the  term  chemiotaxis. 
When  the  cells  are  united  to  form  cell  colonies  or  when,  as  in  the 
metazoa,  the  multicellular  aggregate  is  formed  by  the  failure  of  the  products 
of  division  of  the  ovum  to  separate  one  from  another,  the  interrelations 
between  the  different  cells  of  the  organism  are  still  largely  determined 
by  chemical  stimuli.  In  fact,  in  the  lowest  metazoa  such  as  the  sponge,  we 
know  of  no  other  means  of  correlating  the  reactions  of  different  parts  of  the 
cell  aggregate.  If  a  foreign  substance  be  introduced  into  the  living  tissue  of 
a  sponge,  it  becomes  speedily  surrounded  with  a  collection  of  wandering 
phagocytic  cells,  called  from  the  surrounding  parts  by  the  diffusion  of 
chemical  substances  from  the  seat  of  the  lesion  into  the  fluids  of  the  body. 
The  same  chemical  sensibility  determines  the  aggregation  of  leucocytes 
around  bacteria  or  dead  tissue,  which  forms  the  essential  feature  of  the 
process  of  inflammation  in  higher  animals. 

When  the  reaction  of  distant  parts  of  the  body  to  a  change  occurring  in 
any  one  part  depends  on  the  diffusion  of  some  substance  from  a  stimulated 
part,  the  total  reaction  must  require  a  considerable  time  for  its  full  develop- 
ment. A  much  more  effective  method  of  correlation  was  acquired  by  the 
evolution  of  a  nervous  system,  by  means  of  which  the  consensus  partium  could 
be  maintained  by  the  rapid  propagation  of  molecular  changes  along  differen- 
tiated paths  in  the  protoplasm.    The  development  of  this  second  mode  of 


THE  DUCTLESS  GLANDS  1231 

correlation  of  activities  did  not  however  do  away  with  the  necessity  for  the 
more  primitive  method.  Even  in  the  higher  animals,  where  rapidity  of 
reaction  is  not  required,  we  find  adaptations  carried  out  in  response  to  some 
change  in  distant  parts  of  the  body,  the  message  having  been  chemical 
and  not  nervous  in  character  {e.g.  the  secretin  mechanism  for  pancreatic 
secretion). 

When  we  speak  of  the  chemical  correlation  of  the  activities  of  the  different 
parts  of  the  body,  it  is  important  not  to  confuse  processes  which  have  little 
or  nothing  in  common.  In  one  sense  we  may  say  that  every  cell  in  the  body 
is  chemically  connected  with  and  dependent  on  all  the  other  cells  in  the  body. 
This  interdependence  is  a  necessary  consequence  of  the  differentiation  of 
function  associated  with  increased  complexity  of  the  organism.  Thus  the 
foodstuffs  are  digested  and  absorbed  by  the  cells  lining  the  alimentary 
canal  and  are  then  transmitted,  more  or  less  changed  by  these  cells,  to  all  the 
other  tissues  of  the  body.  The  liver  stores  up  glycogen  and  is  ready  to  give 
of  its  store  to  any  tissue  in  need  of  carbohydrate.  All  the  tissues  probably 
produce  urea,  which  passes  to  the  kidneys  and  is  there  excreted.  All  tissues 
produce  carbon  dioxide,  which  passes  to  the  lungs  to  be  eliminated,  but  as  it 
traverses  the  respiratory  centre  it  arouses  respiratory  movements,  which  are 
exactly  proportioned  to  the  tension  of  the  carbon  dioxide  and  therefore  to 
the  need  of  the  whole  body  to  get  rid  of  this  waste  product.  The  liver 
receives  ammonia  from  the  alimentary  canal  and  converts  it  into  urea,  thus 
shielding  all  the  other  tissues  from  the  poisonous  effects  which  would  be 
produced  by  the  entrance  of" the  ammonia  into  the  general  circulation.  Thus 
one  organ  may  receive  and  modify  any  substance  or  foodstuff  so  as  to  prepare 
it  for  more  ready  assimilation  by  other  tissues.  It  may  shield  these  other 
tissues  from  the  poisonous  effects  of  certain  waste  products,  either  by  con- 
verting these  into  harmless  substances  or  by  excreting  them  from  the  body. 
In  all  these  cases  the  tissues  are  dealing  with  some  substance  which  is  utilised 
in  bulk  or  which,  by  its  accumulation,  could  exert  a  toxic  influence  on  other 
tissues.  We  are  probably  justified  in  treating  apart  a  group  of  phenomena 
in  which  the  substance  transmitted  from  one  part  of  the  organism  to  another 
is  significant  almost  entirely  as  an  excitatory  agent,  and  has  little  or  no 
value  as  a  source  of  energy.  When  the  adaptation  to  a  change  of  a  consists 
in  the  activity  of  an  organ  B,  the  activity  of  B  can  be  evoked  either  by  a  nerve 
impulse  passing  from  A  to  the  central  nervous  system  and  from  this  to  B, 
or  by  the  production  at  a,  as  a  direct  consequence  of  the  stimulus,  of  a  specific 
chemical  substance,  which  passes  into  the  circulating  blood  to  B,  where  in  its 
turn  it  will  excite  the  required  state  of  action.  Such  chemical  messengers 
are  designated  hormones,  from  OQfxdai,  '  I  excite.'  We  have  already  met 
with  several  examples  of  such  bodies.  It  may  be  interesting  here  to  consider 
what  must  be  their  general  character  if  they  are  to  fulfil  the  part  of  chemical 
messengers. 

(1)  In  the  first  place,  they  must  not  be  antigens,  i.e.  their  injection 
into  the  blood  stream  must  not  evolve  the  production  of  an  anti-body. 
If  this  w«re  the  case,  the  hormone,  on  entering  the  blood  stream,  would  meet 


L232  PHYSIOLOGY 

its  anti-body  and  would  be  unable  to  exert  any  effect  on  the  appropriate 
reacting  organ.  Practically  all  the  complex  colloid  bodies  allied  to  the 
proteins,  e.  g.  ferments,  egg  albumin,  peptone,  sera  of  different  animals,  when 
injected  into  the  blood  stream,  cause  the  production  of  the  corresponding 
anti-body.  The  hormones  must  be  simpler  in  character  than  such  substances 
and  probably  have  a  precise  and  comparatively  simple  chemical  or  mole- 
cular constitution. 

(2)  Since  they  must  be  carried  by  the  blood  stream  to  the  reacting  organ, 
1  hey  must  in  most  cases  be  susceptible  to  easy  passage  through  the  walls  of 
the  blood  vessels  if  they  are  to  excite  a  reaction  within  a  fairly  short  space 
of  time.  This  consideration  would  also  tend  to  keep  their  molecular  weight 
comparatively  low. 

(3)  As  a  rule  the  chemical  messenger  must  excite  a  state  of  activity  in 
response  to  a  change  in  some  other  part  of  the  body.  When  the  primary 
change  passes  away,  the  action  of  the  hormone  should  also  disappear.  On 
this  account  it  is  necessary  that  the  hormone  should  either  be  susceptible 
of  easy  destruction,  by  oxidation  or  otherwise,  in  the  fluids  of  the  body, 
or  be  readily  excreted,  so  that  its  action  may  not  be  continued  indefinitely. 

In  previous  chapters  we  have  already  come  across  several  examples  of 
correlated  activities  of  different  tissues  effected  by  chemical  means.  It  is 
perhaps  questionable  whether  we  should  regard  carbon  dioxide,  or  the  lactic 
acid  produced  by  a  contracting  muscle,  as  a  hormone  in  the  strict  sense  of 
the  term,  since  both  these  substances  are  produced  in  large  quantities  as  the 
final  product  of  oxidation  or  disintegration  of  the  foodstuffs.  Carbon 
dioxide  is  however  rapidly  eliminated  from  the  body,  and  lactic  acid  is 
equally  rapidly  oxidised  in  the  body  ;  and  there  is  no  doubt  that  the  activity 
of  the  respiratory  centre  is  determined  by  the  presence  of  this  substance  in 
the  blood  and  is  thereby  perfectly  co-ordinated  with  the  activities  of  the 
whole  of  the  rest  of  the  organism.  In  the  alimentary  canal  the  secretion  of 
pancreatic  juice,  at  the  precise  moment  when  it  is  required  in  the  duodenum 
for  the  digestion  of  the  food  arriving  there  from  the  stomach,  is  evoked  by 
the  production  in  the  cells  of  the  intestinal  mucous  membrane  under  the 
agency  of  the  acid  of  the  gastric  juice  (the  specific  stimulus)  of  a  substance, 
secretin.  This  substance,  which  is  heat  stable  and  diffusible  but  is  easily 
destroyed  by  oxidation,  is  absorbed  into  the  blood  and  carried  to  the  pan- 
creas, where  it  acts  as  a  specific  stimulus  for  the  secretory  cells.  The  same 
substance  excites  also  the  secretion  of  bile  by  the  fiver  cells  and  the  secretion 
of  intestinal  juice  by  the  glands  of  the  small  intestine.  These  are  perhaps 
the  two  best  examples  of  chemical  reflexes,  i.  e.  adaptations  effected  by 
chemical  means  rather  than  by  impulses  passing  along  the  nerve  channels. 
There  are  however  many  other  examples  of  a  chemical  influence  exerted 
by  one  organ  on  another,  in  which  the  interaction  probably  depends  on  the 
production  of  minute  quantities  of  some  substance  acting  in  virtue  of  its 
excitatory  qualities  rather  than  of  its  value  as  a  source  of  energy.  For 
many  of  the  organs  of  the  body  we  know,  in  fact,  no  other  function  than  the 
production  of  some  substance,  the  presence  of  which  in  the  blood  is  a  necessary 


THE  DUCTLESS  GLANDS  1233 

condition  for  the  carrying  out  of  the  normal  functions  either  of  growth 
or  activity  of  many  other  parts  of  the  body.  Li  other  cases  an  organ  may 
have  a  twofold  f miction.  Thus  the  pancreas  gives  au  external  secretion 
which  is  used  for  the  preparation  of  the  food  for  absorption,  and  an  internal 
secretion  which,  passing  into  the  blood,  exercises  an  important  influence  on 
the  metabolism  of  the  foodstuffs  after  absorption.  Other  instances  of 
these  chemical  correlations  may  be  cited.  The  secretion  of  gastric  juice, 
which  results  from  the  presence  of  peptones  or  other  substances  in  the 
stomach,  has  been  ascribed  by  Edkins  to  the  production  in  the  pyloric 
mucous  membrane  of  a  gastric  hormone,  which  travels  by  the  blood  to  the 
glands  of  the  fundus,  where  it  excites  secretion  of  gastric  juice.  According 
t< .  Fri  miii  t  he  injection  of  boiled  succus  entericus,  free  from  secretin,  provokes 
the  secretion  of  intestinal  juice.  In  the  reproductive  system  we  have 
many  examples  of  such  chemical  correlations.  The  pancreas,  by  its  internal 
secretion,  probably  influences  not  only  the  oxidation  of  the  carbohydrates 
but  also  the  assimilation  of  the  foodstuffs  by  all  parts  of  the  small  intestine. 
All  these  examples  are  discussed  in  fuller  detail  in  other  parts  of  this  book. 
There  is  one  class  of  organs  in  which  a  chemical  influence  exerted  on  the 
rest  of  the  body  is  the  only  function  with  which  we  are  acquainted.  These 
are  included  under  the  term  ductless  glands.  As  examples,  we  may  cite  the 
suprarenal  bodies,  the  thyroid  and  parathyroids,  the  thymus  and  the 
pituitary  body. 

THE   SUPRARENAL   BODIES 

The  suprarenal  capsules  in  mammals  are  two  small  masses  lying  on  the  upper  or  oral 
side  of  the  kidneys.  They  consist  of  two  parts,  the  cortex  and  the  medulla.  The 
cortex  is  composed  of  cells  arranged  in  columns  or  in  a  reticular  fashion.  The  outermost 
layer  of  cells  often  presents  an  alveolar  structure,  the  lumen  however  being  but  little 
marked. .  According  to  the  arrangement  of  the  cells  the  cortex  is  divided  into  three 
zones,  the  zona  glomerulosa,  zona  fasciculata,  and  zona  reticulata.  The  cells  them- 
selves are  distinguished  by  the  large  amount  of  granules  they  contain,  which  give 
the  ordinary  reactions  for  fat  but  consist  probably  of  lecithin  compounds.  In  some 
animals  e.  g.  the  guinea-pig,  the  cells,  especially  towards  the  inner  part  of  the  gland, 
contain  many  yellow  pigment  granules.  The  medulla,  much  less  extensive  than  the 
cortex,  presents  irregularly  shaped  cells,  the  outlines  of  which  are  but  slightly  marked. 
These  cells  contain  granules  which  stain  darkly  with  chromates  and  give  a  green  colour 
with  salts  of  iron.  It  is  hence  easy  to  delimit  the  area  of  the  cortex  in  any  section  of  a 
gland  which  has  been  hardened  in  a  fluid  containing  chromates.  The  substance  giving 
this  reaction  is  known  as  ckromophile  or  chromaffine  substance.  The  suprarenals  are 
richly  supplied  with  blood,  especially  in  the  medullary  part,  the  cells  of  which  impinge 
directly  on  the  endothelial  lining  of  dilated  capillaries.  They  also  receive  an  abundant 
nerve  supply  from  the  sympathetic  system,  the  nerves  forming  a  thick  meshwork, 
especially  in  the  medulla,  and  presenting  at  intervals  ganglion  cells  which  may  be 
isolated  or  combined  to  form  small  ganglia. 

A  study  of  the  development  of  the  suprarenal  glands  shows  that  we  have  here  to  do 
with  two  distinct  tissues,  probably  differing  in  the  part  they  play  in  the  animal  economy. 
Whereas  the  cortex  is  derived  from  that  portion  of  the  mesoblast,  the  '  intermediate 
cell  mass,'  from  which  the  mesonephros  is  also  developed,  the  medulla  is  produced 
by  an  outgrowth  from  the  sympathetic  system  and  may  be  said  indeed  to  consist  of 
profoundly  modified  nerve  cells.  In  many  fishes  these  two  elements  of  the  suprarenal 
gland  remain  separated  throughout  life,  the  cortex  being  represented  by  a  series  of 
78 


L234  PHYSIOLOGY 

jiaired  interrenal  bodies  lying  on  the  front  of  the  spinal  column,  and  the  medulla  l>y  a 
number  of  collections  of  chromaffine  cells  lying  in  close  j  uxtapcsition  to  the  spinal  nerves. 
In  some  animals  accessory  suprarenals  are  not  infrequent  in  which  both  cortex  and 
medulla  may  be  represented.  In  all  animals  we  find  masses  of  tissue,'  the  so-called 
paraganglia,  in  close  association  with  the  sympathetic  system,  which  present  the  chro- 
maffine  reaction  typical  of  the  medulla.  Since  a  watery  extract  or  decoction  of  these 
bodies  has  the  same  influence  on  injection  into  the  blood  stream  as  an  infusion  of  the 
medulla  of  the  suprarenal  body  itself,  we  are  probably  justified  in  regarding  these  bodies 
as  equivalent  to  accessory  medullary  portions  of  the  suprarenal.  They  have  the  same 
origin,  the  same  staining  reactions,  and  the  same  physiological  effect  as  the  latter. 

The  functions  of  the  suprarenal  bodies  were  a  matter  of  pure  hypothesis 
before  Addison  in  1850  drew  attention  to  the  coincidence  of  degenerative 
destruction  of  these  bodies  witli  a  disease  which  has  been  known  since  that 
time  as  Addison's  disease.  The  three  cardinal  symptoms  ol  this  disorder 
are  (1)  bronzing  of  the  skin,  (2)  vomiting,  (3)  excessive  muscular  weakness 
and  prostration.  The  disease  is  almost  invariably  fatal.  Addison's  observa- 
tions have  been  amply  confirmed  since  that  time,  but  we  are  not  yet  in  a 
position  to  account  for  the  occurrence  of  all  these  symptoms  as  a  result  of 
interference  with  the  cortex  and  medulla  of  the  suprarenals.  The  experi- 
mental destruction  or  extirpation  of  these  bodies  has  naturally  been 
frequently  carried  out.  The  operation  always  leads  to  the  death  of  the 
animal  within  twelve  to  twenty-four  hours.  Even  when  the  destruction  is 
carried  out  by  degrees  it  has  been  impossible  to  reproduce  the  bronzing 
which  is  so  characteristic  of  Addison's  disease.  The  one  symptom  which 
is  observed  as  a  result  of  the  experimental  extirpation  is  the  excessive  pros- 
tration, which  is  attended  with  muscular  weakness  and  a  lowered  blood 
pressure.  In  a  few  cases  it  has  been  found  possible  to  keep  rats  alive  after 
total  extirpation  of  these  organs,  but  this  result  is  probably  due  to  the 
frequent  presence  in  these  animals  of  accessory  suprarenals. 

Schafer  and  Oliver  in  1894  found  that  a  watery  extract  or  decoction  of 
the  suprarenal  bodies,  when  injected  into  the  circulation,  caused  a  very  great 
rise  of  blood  pressure,  brought  about  chiefly  by  constriction  of  all  the  blood 
vessels  of  the  body.  The  active  substance  responsible  for  this  rise  was 
limited  entirely  to  the  medulla,  infusions  of  the  cortex  being  without  influence 
on  the  blood  pressure.  Later  on  Takamine  succeeded  in  isolating  the  active 
substance,  to  which  he  gave  the  name  of  adrenaline,  and  since  that  time 
physiological  chemists  have  succeeded  not  only  in  determining  the  consti- 
tution of  adrenaline  but  also  in  preparing  it  synthetically.  The  constitution 
of  adrenaline  is  shown  by  the  following  formula  : 

HO_ 
HO<^  J>— CH(OH)— CH2NHCH3 

Since  it  possesses  an  asymmetric  carbon  atom,  a  substance  of  this  formula 
may  be  either  lsevo-  or  dextrorotatory.  Both  forms,  as  well  as  the  racemic 
modification;  have  been  prepared  synthetically.  The  substance  which 
occurs  in  the  suprarenal  gland  is  the  Isevorotatory  modification,  and  Cushny 
has  shown  that  it  is  only  this  modification  which  is  active,  injection  of  the 


THE   DUCTLESS  (I LANDS  1235 

dextrorotatory  compound  having  only  one-twelfth,  the  effect  of  the  lsevo- 
rotatory.  Adrenaline  is  active  in  excessively  minute  doses,  injection  of 
one  four-hundredth  of  a  milligramme  per  kilo,  body  weight  sufficing  to  evoke 
a  definite  rise  of  blood  pressure.  On  injecting  it  into  the  circulation  there  is 
immediately  a  rise  of  blood  pressure  which,  if  the  vagi  are  intact,  is  only 
moderate  in  amount  but  is  accompanied  by  a  marked  slowing  of  the  heart. 
This  excitation  of  the  vagus  is  however  probably  secondary  to  the  rise 
of  blood  pressure  and  is  not  due  to  direct  action  of  the  drag  on  the  vagus 
centre.  If  the  vagi  be  divided,  the  injection  of  adrenaline  evokes  a  huge 
rise  of  pressure  which  may  amount  to  301)  nun.  Hg.  It  may  indeed  be  so 
great  that  the  animal  dies  from  heart  failure  or  from  pulmonary  oedema. 
The  rise  of  pressure  is  observed  even  after  destruction  of  the  central  nervous 
system.  The  action  is  not  limited  to  the  blood  vessels.  It  has  been 
shown  by  Langley  and  by  Elliott  that  adrenaline  injected  into  the  circu- 
lation arouses  every  activity  which  can  be  normally  excited  by  stimulation 
of  the  sympathetic  system.  A  list  of  the  actions  of  adrenaline  is  therefore 
identical  with  a  list  of  the  chief  functions  of  the  sympathetic  nervous 
system.  In  the  head  it  causes  dilatation  of  the  pupil,  secretion  of  saliva, 
and  erection  of  the  hairs.  On  the  heart  it  has  a  strong  augmentor  and 
accelerator  influence,  so  that  this  organ  beats  more  effectively  as  a  rule 
even  against  the  enormously  increased  resistance  offered  by  the  constricted 
arterioles.  Whereas  a  rise  of  blood  pressure  generally  causes  increased 
systolic  volume  of  the  heart,  we  may  rind  after  an  injection  of  adrenaline  and 
during  the  height  of  the  rise  of  blood  pressure  that  the  heart  empties  itself 
more  effectively  than  it  did  before  the  injection.  On  the  lung  vessels 
adrenaline  has  probably  a  slight  constrictor  influence.  With  regard  to  the. 
vessels  of  the  brain,  we  find  the  same  divergence  of  opinion  as  in  the  case  of 
excitation  of  possible  vaso-motor  nerves  to  this  organ.  Some  observers, 
mi  perfusing  the  brain  with  defibrinated  blood,  have  obtained  constriction 
on  adding  adrenaline  to  the  perfused  blood,  while  others  have  been  unable  to 
obtain  any  positive  results  in  this  direction.  In  the  abdomen  intravenous 
injection  of  adrenaline  causes  complete  relaxation  of  the  musculature  of 
the  stomach,  small  and  large  intestines,  but~contraction  of  the  ileocolic 
sphincter.  On  the  bladder  its  effect  varies  according  to  the  animal  studied, 
but  in  every  case  is  identical  with  that  obtained  by  stimulating  the  hypo- 
gastric nerves.  It  lias  been  shown  by  Dale  that  adrenaline  may  also  excite 
vaso-dilator  fibres  or  produce  vaso-dilator  effects  when  such  effects  are  also 
obtained  from  stimulation  of  the  sympathetic  nerves.  In  order  to  evoke 
these  results  it  is  necessary  to  paralyse  the  vaso-constrictors  by  the  injection 
i  if  ngotoxin,  one  of  the  active  principles  of  ergot.  This  drug,  when  injected, 
causes  first  active  vaso-constriction  and  rise  of  blood  pressure,  followed  by 
paralysis  of  the  vaso-constrictor  mechanism.  Excitation  of  the  splanchnic 
nerves  or  injection  of  adrenaline  will  now  bring  about  a  fall  of  blood  pressure 
due  to  dilatation  of  the  vessels  in  the  splanchnic  area. 

The   point  of  attack  of  the  adrenaline  appears  to   be  in  the  muscular 
or  glandular   tissues  themselves,  since  it   may  be  obtained  not  only  after 


1236  PHYSIOLOGY 

destruction  of  the  cord  and  sympathetic  plexuses  but  even  after  tune  has  been 
allowed  for  the  peripheral  (post-ganglionic)  fibres  to  degenerate  as  a  result  of 
extirpation  of  the  corresponding  ganglia.  Although  the  effect  is  not  altered 
under  these  circumstances,  and  it  may  still  produce  either  relaxation  or 
contraction  of  muscles  according  to  the  original  action  of  the  sympathetic 
on  these  fibres,  we  are  not  justified  in  regarding  it  as  acting  on  the  contractile 
material  of  the  cells  themselves.  Rather  must  we  assume  with  Langley  and 
Elliott  that  the  action  of  adrenaline  is  on  some  substance  mediating  between 
the  nerve  and  the  responsive  tissue.  We  may  speak  of  this  reactive  material 
as  the  receptor  substance  (Langley),  or  we  may  locate  it  in  the  situation 
where  the  nerve  joins  the  muscle  or  gland  cell,  and  describe  adrenaline  as 
acting  on  the  myoneural  junction. 

Each  suprarenal  receives  a  number  of  filaments  from  the  splanchnic 
nerve  on  its  own  side.  These  pass  to  the  medulla  where  they  end  apparently 
without  the  interposition  of  any  ganglion  cells  on  their  course  (Elliott),  the 
cells  of  the  medulla  having  themselves  been  developed  by  a  modification  of 
sympathetic  ganglion  cells.  Stimulation  of  the  peripheral  end  of  the 
splanchnic  nerve  causes,  as  we  have  already  seen,  a  discharge  of  adrenaline 
into  the  blood  stream.  This  discharge  accoimts  for  the  secondary  rise, 
often  accompanied  with  quickening  of  the  heart,  observed  on  a  blood- 
pressure  tracing  as  the  result  of  stimulating  the  splanchnic  nerve.  Through 
the  splanchnic  nerves  a  discharge  of  adrenaline  can  be  excited  by  many 
general  conditions,  such  as  pressure  on  the  brain,  puncture  of  the  fourth 
ventricle,  administration  of  anaesthetics,  mental  disturbances  such  as  excite- 
ment or  fright.  Such  a  discharge  is  an  important  element  in  the  adaptation 
to  environmental  stress  and  enables  the  animal  to  react  for  the  preservation 
of  its  life  either  by  offence  or  flight.  If  one  splanchnic  nerve  be  cut  before  the 
administration  of  anaesthetics  or  the  maintenance  of  a  condition  of  irritation 
or  fright,  the  suprarenal  gland  on  the  corresponding  side  will  be  found  to 
contam  two  or  three  times  as  much  adrenaline  as  the  gland  which  has  been 
left  in  coimection  with  the  central  nervous  system.  It  is  interesting  that 
no  such  condition  of  exhaustion  can  be  produced  by  electrical  stimulation  of 
the  peripheral  end  of  the  divided  splanchnic.  It  has  been  suggested 
therefore  that  the  splanchnic  nerve  contains  two  sets  of  fibres,  anabolic 
and  catabolic,  that  only  the  latter  are  stimulated  by  central  irritation, 
whereas  electrical  stimulation,  exciting  both  sets  of  fibres,  causes  an  increased 
production  of  adrenaline  in  the  gland,  which  exactly  keeps  pace  with  the 
increased  output. 

When  adrenaline  is  injected  into  the  blood  stream  the  effect  is  only 
temporary.  It  is  not  excreted  in  the  urine,  but  rapidly  disappears  from  the 
blood.  Since  it  is  easily  oxidised  and  is  extremely  unstable  in  alkaline 
solution,  we  may  conclude  that  after  performing  its  excitatory  function  it  is 
destroyed  by  oxidation  in  the  fluids.  Adrenaline  is  thus  a  typical  hormone, 
a  body  of  comparatively  low  molecular  weight,  having  a  drug-like  excitatory 
action  on  specific  tissues  of  the  body,  easily  diffusible,  and  rapidly  destroyed 
after  discharging  its  office. 


THE  DUCTLESS  GLANDS  1237 

Owing  to  the  rapid  destruction  of  adrenaline,  relatively  enormous  doses  have  to  be 
given  by  the  mouth  in  order  to  produce  any  effect  on  the  blood  pressure.  There  is 
however  a  whole  series  of  substances,  more  or  less  allied  to  adrenaline  in  chemical  con- 
stitution, which  undergo  less  rapid  destruction  and  can  therefore  be  administered 
as  drugs  in  the  usual  way.  Dale  and  Barger  have  recently  described  three  such  sub- 
stances as  occurring  in  infusions  of  putrid  meat  and  as  forming  the  most  important  of 
the  active  principles  of  ergot.  The  constitution  of  these  substances  is  shown  in  the 
following  formula?  : 

CH3\ 

)CHCH,CH2NH,  Isoamylamine 

CH3/ 

HO<^  \— CH,CII2NH2  p-hydroxyphenylethylaniine 


/  \ 

_/ 


CH,CH2NH,  phenylethylamine 

N / 

HO 


HO'  y— CH(OH)CH.,NHC'H3         adrenaline 

The  formula  of  adrenaline  is  placed  below  in  order  to  show  the  relation  of  these 
substances  to  the  natural  hormone.  These  bodies  are  produced  from  the  amino-acids 
of  proteins  by  a  process  of  decarboxylation.  Leucine  would  yield  isoamylamine, 
tyrosine,  hydroxyphenylethylamine,  and  phenylalanine  would  give  phenylethylamine. 
Such  substances  may  be  formed  in  minute  quantities  dining  the  normal  processes  of 
putrefaction  which  occur  in  the  alimentary  canal. 

There  seems  little  doubt  that  we  must  regard  adrenaline  as  a  true  internal 
secretion,  and  therefore  must  ascribe  to  the  medulla  of  the  suprarenal  capsules 
as  well  as  to  the  other  chromaffine  tissue  in  the  body,  the  function,  of  main- 
taining the  normal  constriction  of  the  arterioles  and  of  facilitating  hi  some 
way  or  other  the  functions  of  the  sympathetic  system  generally.  The 
absence  of  this  secretion  in  cases  of  destruction  by  disease  of  the  suprarenals 
would  serve  to  account  for  the  weakness,  prostration,  and  lowered  blood 
pressure  of  Addison's  disease.  The  two  other  symptoms  of  this  disease, 
namely,  bronzing  and  vomiting,  still  remain  to  be  accounted  for.  It  is 
possible  that  the  latter  may  be  due  to  some  involvement  by  the.  morbid 
process  of  the  numerous  fibres  of  the  solar  plexus,  which  run  in  close 
proximity  to  the  suprarenals.  We  have  no  knowledge  whatsoever  of  the 
functions  of  the  cortical  portion  of  these  organs.  It  is  possible  that  future 
work  may  show  some  connection  between  the  cortex  and  the  destruction  of 
pigment  in  the  body.  At  present  it  is  only  by  a  process  of  exclusion  that 
we  may  guess  at  a  causal  relationship  between  the  destruction  of  the  cortex 
and  the  bronzing  which  occurs  in  Addison's  disease. 

There  seems  little  doubt  that  the  rapidly  fatal  effects  of  extirpation  of 
both  suprarenals  is  to  be  ascribed  rather  to  the  removal  of  the  cortex  than  of 
the  medulla.  The  functions  of  the  latter  can  be  more  or  less  effectively 
maintained  by  the  other  chromaffine  tissues  found  at  the  back  of  the 
abdomen.  Tn  the  few  cases,  where  animals  have  survived  double  extirpation, 
small  masses  of  accessory  cortical  substance  have  been  found  embedded  in 


1238 


PHYSIOLOGY 


the  kidney  or  elsewhere  in  the  neighbourhood  of  the  suprarenals.  Hyper- 
trophy or  a  tumour  of  the  suprarenal  bodies,  involving  the  cortex,  has  been 
found  associated  in  children  with  premature  sexual  maturity. 


Fig.  559. 


Section  of  thyroid  gland  of  dog. 
(Swale  Vincent.) 


THE    THYROID    GLAND    AND    THE    PARATHYROIDS 

The  thyroid  gland  consists  of  two  oval  bodies  lying  on  either  side  of  the  trachea, 
joined  in  many  animals  across  the  trachea  by  an  isthmus.     Surrounded  by  a  capsule 

of  connective  tissue,  it  is  made  up  of 
an  aggregation  of  vesicles  varying  in 
size  from  15  to  150/4.  The  vesicles 
are  lined  by  a  single  layer  of  cubical 
epithelial  cells,  and  are  tilled  with  a 
translucent  material  known  as  colloid 
(Fig.  559),  Of  the  cells,  some  present 
granules  and  resemble  the  cells  of  a 
secreting  gland,  while  others  contain 
masses  of  colloid,  or  have  undergone 
colloidal  degeneration.  Between  the 
vesicles  may  be  seen,  here  and  there, 
solid  masses  of  cells  which  by  some 
observers  are  regarded  as  destined  to 
replace  vesicles  the  epithelium  of  which 
has  undergone  complete  degeneration. 
The  colloid  matter  can  be  traced  be- 
tween the  cells  into  the  lymphatics 
lying  between  the  vesicles.  Since  the 
gland  possesses  no  duct,  it  is  supposed  that  the  cells  furnish  an  internal  secretion, 
which  makes  its  way  into  the  blood  along  the  lymphatic  efferents  of  the  gland. 
The  thyroid  is  richly  supplied  with  blood  by  the  superior,  middle,  and  inferior 
thyroid  arteries,  and  is  surrounded  with  a  plexus  of  veins  lying  immediately  under 
the  capsule.  In  development  the  thyroid  is  formed  by  an  outgrowth  from  the  fore- 
gut,  but  the  connection  with  the  gut  disappears  long  before  the  end  of  foetal  life. 
In  rare  eases  part  of  the  duct  may  persist  and,  becoming  gradually  filled  with  fluid, 
give  rise  to  a  hyoid  cyst  which  lies  below  the  tongue  and  may  require  excision  by 
the  surgeon. 

As  in  the  case  of  the  other  ductless  glands,  clinical  observations  have 
contributed  materially  to  our  knowledge  of  the  functions  of  the  thyroid. 
Although  the  gland  had  been  extirpated  in  animals  by  Astley  Cooper  and 
by  SchifEj  the  attention  of  physiologists  and  medical  men  was  especially 
directed  to  the  importance  of  this  organ  by  the  observations  of  surgeons, 
especially  Kocher,  on  the  untoward  and  even  fatal  effects  following  its 
complete  removal  in  man  in  operations  for  extirpation  of  goitre.  In  this 
country  attention  had  already  been  called  to  the  connection  of  a  disturbed 
condition  of  metabolism  known  as  mvxoedema  with  atrophy  of  the  thyroid. 
A  patient  affected  with  mvxoedema  presents  a  gradually  increasing  blunting 
of  his  or  her  mental  activities;  speech  is  slow,  cerebration  delayed.  With 
this  nervous  defect  are  associated  changes  in  the  connective  tissues,  the 
subcutaneous  connective  tissue  becoming  thickened,  so  that  the  face  and 
hands  appear  swollen  and  puffy,  looking  at  first  sight  as  if  oedema  were 
present.     The  swelling  is  however  due  to  newly  formed  connective  tissue 


THE  DUCTLESS  GLANDS  1239 

and  not  to  the  presence  of  an  excess  of  interstitial  fluid  in  the  tissues.  The 
patient  often  has  a  yellow  waxy  appearance  with  a  patch  of  colour  on 
the  cheeks.  The  hair  falls  out,  the  pulse  is  slowed,  and  the  temperature 
tends  to  be  subnormal  owing  to  the  diminution  of  the  rate  of  metabolism  in 
the  body.  The  intake  of  food  and  the  excretion  of  urea  are  diminished. 
If  the  atrophy  of  the  thyroid  occurs  in  early  life  during  the  period  of  growth, 
e.g.  in  young  children,  the  growth  of  the  skeleton  practically  ceases.  The 
bones  of  the  limbs  may  grow  in  thickness  but  not  in  length.  There  is 
early  synostosis  of  the  bones  of  the  skull  and  complete  cessation  of  develop- 
ment of  mental  powers.  Children  so  affected  may  live  for  many  years,  but 
when  twenty-five  or  thirty  present  still  a  childish  appearance  (Fig.  560,  c). 
Stunted,  pot-bellied,  and  ugly,  they  have  the  intelligence  of  a  child  of  four 
or  five.  They  often  present  fatty  tumours  above  each  clavicle,  and  similar 
subcutaneous  tumours  of  fat  or  loose  fibrous  tissue  are  found  in  cases  of 
myxoedema  in  the  adult. 

When  the  thyroid  is  extirpated  in  man  the  result  is  often  the  production 
of  typical  myxoedema.  In  some  cases,  especially  in  young  individuals,  the 
results  are  more  severe,  a  condition  of  tetany  being  set  up  in  which  there  an1 
tunic  spasms  of  the  muscles  of  the  body,  especially  of  the  extremities.  When 
the  thyroid  gland  is  extirpated  in  animals  the  results  more  closely  resemble 
these  acute  cases.  In  certain  instances  a  chronic  condition  of  malnutrition  is 
set  up.  but  a  tvpical  myxoedema  with  thickening  of  the  subcutaneous  tissues 
by  new  growth  of  connective  tissue  has  been  described  by  Horsley  only  in 
monkeys.  The  effects  are  more  pronounced  in  carnivora  than  in  hcrbivora. 
In  the  former  a  condition  of  tetany  is  produced,  accompanied  with 
muscular  tremors  and  clonic  convulsions  which  come  on  at  intervals  and 
may  be  accompanied  with  severe  dyspnoea  leading  to  death  within  fourteen 
davs.  In  herbivora,  wasting,  diminution  of  respiratory  exchange,  and 
disorders  of  nutrition  are  often  the  most  prominent  symptoms.  These 
results  were  ascribed  by  Munk  to  interference  with  the  recurrent  laryngeal 
nerves  during  the  operations,  but  the  observations  on  man  leave  very 
little  doubt  that  they  are  due  entirely  to  the  removal  of  the  chemical 
influence  of  the  thyroid  gland.  Many  authorities  were  at  first  inclined  to 
ascribe  these  results  in  man  and  animals  to  the  circulation  in  the  blood  of 
toxic  substances  which  would  normally  undergo  destruction  in  the  thyroid 
gland.  This  theory  is  put  out  of  court  by  the  results  of  administration  of 
thyroid  eland  to  patients  with  myxoedema  or  to  animals  deprived  of  their 
thyroids.  Schiff  first  showed  that  the  effects  of  extirpation  of  the  thyroid 
might  be  prevented  if,  at  the  same  time,  the  thyroid  from  another  animal 
were  transplanted  into  the  subcutaneous  tissue  to  take  the  place  of  the  one 
removed.  On  removing  the  transplanted  thyroid,  the  typical  symptoms 
of  thyroid  destruction  at  once  ensued.  It  was  later  found  that  similar 
good  results  could  be  obtained  by  subcutaneous  injection  of  the  expressed 
juice  of  the  thyroid,  and  later  that  even  this  was  not  necessary,  and  that  it 
was  sufficient  to  administer  the  thyroid  gland,  either  fresh,  dried,  or  partially 
cooked,  by  the  mouth.     The  administration  of  the  thyroid  gland  in  this  way 


1240 


PHYSIOLOGY 


is  indeed  one  of  the  therapeutic  triumphs  of  the  last  twenty  years.  An  ugly 
and  idiotic  cretin  can  be  converted  by  this  means  into  a  child  of  ordinary 
intelligence  with  normal  powers  of  growth  (Fig.  560).  Given  to  myxcedemic 
patients,  the  thyroid  gland  reduces  the  swelling  of  the  subcutaneous  tissues, 
causes  a  new  growth  of  hair,  and  restores  the  patient  to  his  or  her  former 
state  of  mental  health.  Nor  is  the  thyroid  gland  without  influence  on  the 
healthy  individual.  If  given  in  large  doses  either  to  man  or  animals,  it 
quickens  the  pulse,  even  causing  violent  palpitation,  and  increases  the  meta- 
bolic activities  of  the  body,  so  that  the  appetite  is  increased,  the  nitrogenous 
output  rises  above  the  intake,  and  the  subcutaneous  fat  is  diminished  01 


Fig.  560.  a,  a  cretin,  23  months  old.  E,  the  same  child,  34  months  old,  after  ad- 
ministration of  sheep's  thyroids  for  11  months,  c,  a  cretin,  untreated,  15  years 
Old.      (W.  OSLBB.) 

disappears.  It  is  possible  that  a  moderate  degree  of  thyroid  inadequacy  is 
not  infrequent  and  that  the  beneficial  effects  on  general  health,  in  removing 
excessive  corpulence  and  in  promoting  the  growth  of  hair,  which  are  observed 
on  administering  the  drug  to  people  of  middle  life,  may  be  due  to  the 
actual  replacement  of  a  function  which  is  being  insufficiently  discharged. 
The  symptoms  caused  by  excessive  doses  of  thyroid  gland  are  strikingly 
similar  to  those  occurring  in  the  disease  known  as  exophthalmic  goitre, 
where  there  is  a  true  hypertrophy  of  the  gland  associated  with  cardiac 
palpitation,  proptosis  (bulging  of  the  eyes),  wasting,  and  muscular  weakness. 
All  these  facts  warrant  us  in  including  the  thyroid  body  among  the 
glands  with  an  internal  secretion,  the  presence  of  which  in  the  blood  stream 
is  a  necessary  condition  for  the  normal  growth  and  functions  of  almost  all 
the  tissues  of  the  body.  If  this  secretion  is  lacking  we  obtain  the  condition 
known  as  mvxoedema  in  adults,  as   cretinism  in  young  children.     If  it  be 


THE  DUCTLESS  GLANDS  1241 

present  in  excess  the  symptoms  of  exophthalmic  goitre  are  produced. 
The  exact  character  of  the  internal  secretion  cannot  be  regarded  yet  as 
definitely  established.  It  seems  possible  that  it  is  identical  with  a  substance 
containing  iodine  in  organic  combination,  which  was  isolated  by  Baumann 
from  the  thyroid  gland  and  is  known  as  iodothyrin.  Li  certain  experiments 
the  results  of  administration  of  iodothyrin  were  found  to  be  identical  with 
those  obtained  by  giving  the  whole  gland.  Doubt  has  been  thrown  on  the 
specific  nature  of  this  body  on  account  of  the  fact  that  iodine  may  be 
wanting  in  the  thyroid  gland  in  certain  animals,  though  Reid  Hunt  has 


end 


'<■  \     ft    *  *     ,' 


Fro.  561.     Section  of  parathyroid.     (Koiin.) 
i  j>.  secreting  epithelium :  pig,  cells  containing  pigment;  cap,  sinus-like 
capillaries;  end,  endothelial  cells. 

shown  that  the  physiological  effects  of  thyroid  extract  are  proportional  to 
the  amount  of  iodine  contained  therein. 

SIGNIFICANCE  OF  THE  PARATHYROIDS.  The  parathyroids  are  small 
bodies,  varying  in  number,  situated  on  the  border  of  the  thyroid  gland 
or  actually  embedded  in  its  substance.  In  histological  appearance  they 
differ  widely  from  the  thyroid,  and  consist  of  solid  masses  or  columns  of 
epithelial  cells  surrounded  with  connective  tissue  and  richly  supplied  with 
blood  vessels  (Fig.  561).  Considerable  divergence  of  opinion  still  exists  as  to 
the  significance  of  these  bodies.  In  some  animals  e.g.  in  the  dog,  where 
they  are  embedded  in  the  gland,-  they  will  be  necessarily  removed  in  any 
operation  for  the  extirpation  of  the  thyroid.  In  others  such  as  the  rabbit, 
where  they  lie  outside  the  gland,  it  is  easy  to  avoid  them  in  the  excision  of 
the  thyroid.  To  this  varying  distribution  of  the  parathyroids  have  been 
ascribed  the  different  results  of  extirpation  of  the  thyroid  in  camivora  and 


Il'l-J 


PHYSIOLOGY 


herbivora  respectively.  Forsyth  has  shown  that,  in  man,  the  situation  of 
tlic  parathyroids  corresponds  almost  exactly  with  the  places  in  which  arc 
found  occasionally  accessory  thyroids;  and  according  to  Edmunds,  after 
excision  of  the  thyroid,  the  parathyroids  undergo  histological  alteration  and 
are  converted  into  thyroid  tissue,  the  cells  taking  on  an  alveolar  arrangement 
and  producing  colloid  material.  According  to  this  view  the  parathyroids 
would  represent  simply  immal  ure  t  liyvoid  i  issue.  ( )n  1  he  oi  her  hand,  il  has 
been  suggested  (Biedl)  that  the  parathyroids  have  a  function  entirely  dis- 
tinct from  that  of  the  thyroid  gland,  removal  of  the  thyroids  producing 
simply  a  condition  of  cachexia  and  the  changes  associated  with  myxoedema, 


Fig.  562.  Mesial  sagittal  section  through  the  pituitary  body  of  an  adult  monkey 
(semi-diagrammatic).     (After  Herring.) 

a,  optic  ehiasma;  b,  third  ventricle;  c,  tongue-like  process  of  pars  intermedia; 
d,  epithelial  investment  of  posterior  lobe;  r,  anterior  lobe;  /,  epithelial  cleft; 
</,  pars  intermedia;  h,  posterior  lobe. 

while  removal  of  the  parathyroids  is  responsible  for  the  nervous  disturbances 
and  tetany  observed  after  total  extirpation  of  these  organs.  The  matter 
cannot  yet  be  regarded  as  definitely  settled. 


THE    PITUITARY    BODY 

The  pituitary  body  consists  of  two  parts  which  have  separate  modes  of  origin.  An 
outgrowth  from  the  buccal  cavity  in  the  embryo  meets  a  hollow  extension  of  the  anterior 
cerebral  vesicle.  The  buccal  ectoderm  gives  rise  to  the  anterior  lobe  and  pars  intermedia 
of  the  pituitary,  while  the  neural  epiblast  becomes  developed  into  the  posterior  lobe 
(Fig.  562).  In  some  animals  the  posterior  lobe  remains  hollow  and  retains  its  primitive 
connection  with  the  third  ventricle  of  the  brain,  but  in  man  it  becomes  entirely  solid. 
The  anterior  lobe  in  the  adult  consists  of  nests  of  epithelial  cells  (Fig.  503),  many  of 
which  are  filled  with  granules,  and  is  richly  supplied  with  large  thin-walled  capillary 
blood  vessels.  The  anterior  lobe  is  separated  from  the  posterior  lobe  by  a  cleft  which 
is  the  remains  of  the  original  hollow  outgrowth  from  the  buccal  cavity.  The  epithelial 
tissue  immediately  surrounding  this  cleft  differs  somewhat  from  that  constituting  the 


THE   DUCTLESS  GLANDS 


1243 


anterior  lobe.  The  cells,  which  present  but  few  granules,  are  arranged  in  islets,  separated 
b\  an  intervening  tissue  continuous  with  the  main  mass  of  the  posterior  lobe.  Many 
of  the  islets  are  hollow  and  enclose  a  colloid  material.  The  colloid  material  has  been 
traced  by  Herring  into  the  intcralveolar  connective  tissue  and  into  the  prolongation 
of  the  infundibuluni  which  enters  the  posterior  lobe.  One  must  therefore  conclude  that 
the  colloid  material  secreted  by  the  cells  of  this  part  passes  directly  into  the  third 
ventricle.  The  amount  of  colloid  material  increases  in  animals  which  have  undergone 
extirpation  of  the  thyroid  gland. 

Our  first  clue  to  the  importance  of  this  organ  in  the  normal  processes 
of  the  body  was  furnished  by  the  observations  of  Pierre  Marie,  who  found 


-■-£.■••"    5-  :-  ? 


Fiq.  563.     Section  of  cat's  pituitary  body,  passing  through  the  cleft  in  the  gjand. 

(P.'T.  Herring.) 
a.  pars  anterior:  b,  clef!  ;  c,  para  intermedia;  d,  pars  nervosa  (posterior  lobe). 

that  the  morbid  condition  of  acromegaly  is  associated  with  tumours  of  the 
pituitary  gland.  This  disease  consists  in  an  increased  growth  of  certain 
parts  of  the  skeleton,  especially  the  lower  jaw  and  the  extremities  of  the 
limbs.  Headache  is  often  present,  and  there  may  be  polyuria  and  affection 
of  the  eyesight.  When  this  disease  occurs  during  the  period  of  active  growth, 
there  may  be  an  increase  in  length  both  of  the  limb-bones  and  of  the  trunk, 
and  most  of  the  giants,  which  are  shown  from  time  to  time,  are  examples  of 
this  pathological  condition  of  'gigantism.'  It  seems  probable  that  this 
condition  is  due  to  an  over-action  of  the  gland.  In  cases  of  acromegaly  the 
tumour  is  generally  an  adenoma,  i.e.  an  enlargement  of  the  ordinary  gland 
tissue.  It  lias  no1  been  possible  by  transplantation  to  replace  a  removed 
pituitary  body,  since  the  transplanted  organ  has  hitherto  always  undergone 


1244  PHYSIOLOGY 

degeneration.  Li  a  certain  number  of  cases  animals,  especially  if  young, 
have  survived  extirpation  of  the  pituitary  body.  In  these  the  operation  was 
followed  by  arrest  of  development— the  animals  remaining  in  an  infantile 
condition,  small,  with  an  excess  of  fat,  and  absence  of  sexual  development. 

The  most  definite  evidence  we  have  as  to  the  mode  of  action  of  the 
different  parts  of  the  pituitary  gland  has  been  furnished  by  experiments  on 
administration  or  injection  of  the  dried  gland  or  its  extracts.  The  posterior 
lobe  seems  to  be  practically  inactive,  extracts  made  from  this  lobe  having 
the  same  influence  as  extracts  from  nervous  tissue  generally.  If  however 
the  intermediate  epithelial  substance  is  included  in  the  posterior  lobe, 
marked  effects  may  be  obtained  from  the  intravenous  injection.  An 
extract  of  the  posterior  lobe  (including  pars  intermedia)  produces,  as  was 
shown  by  Schafer,  a  rise  of  blood  pressure  and  diuresis.  The  latter  result 
also  follows  administration  of  the  posterior  lobes  by  the  mouth.  Dale  has 
shown  that  the  active  principle  exercises  a  direct  excitatory  effect  on  all 
unstriated  muscle,  the  effect  being  unaltered  whether  the  nerve  supply  to  the 
muscle  be  present  or  not.  Thus  it  produces  contraction  of  the  blood  vessels, 
of  the  intestinal  muscle,  and  of  the  uterus,  and  will  act  upon  muscular 
tissues,  such  as  the  arteries  of  the  lungs  or  heart,  which  do  not  receive  con- 
strictor impulses  from  the  sympathetic  system.  The  active  principle  is 
much  more  stable  than  the  other  hormones  we  have  already  studied.  It 
is  not  destroyed  by  boiling,  and  after  injection  into  the  blood  stream  can  be 
recovered  from  the  urine.  It  is  possible  that  the  polyuria,  which  is  not 
infrequently  observed  in  association  with  head  injuries  or  tumours  of  the 
brain,  may  be  occasioned  by  an  increased  escape  of  this  material  into  the 
general  circulation. 

Extracts  from  the  anterior  lobe  have  no  definite  effect  when  injected 
into  the  blood  stream.  Schafer  found  that  the  addition  of  the  anterior 
lobe  of  the  pituitary  body  to  the  food  of  young  growing  animals  caused 
an  increased  rate  of  growth.  In  this  experiment  eight  rats  of  a  litter 
were  taken  :  four  were  fed  with  bread  and  milk  to  which  the  anterior  lobes 
of  pituitary  bodies  had  been  added,  while  the  other  four,  which  served  as 
controls,  received  bread  and  milk  with  a  corresponding  quantity  of  testis 
or  ovary.  Later  experiments  have  not  however  confirmed  these  results. 
According  to  Mackenzie  extracts  of  the  pituitary  body  have  a  marked 
excitatory  effect  on  the  secretion  of  milk  by  the  mammary  glands. 

It  is  evident  that  much  further  work  is  necessary  before  we  can  regard 
the  functions  of  the  pituitary  body  as  definitely  ascertained.  The  evidence 
we  have  at  present  would  seem  to  point  to  the  following  conclusions  : 

(a)  The  anterior  lobe  furnishes  some  substance  to  the  circulation  which 
promotes  growth,  especially  of  the  bony  and  connective  tissues  of  the  body. 

(b)  The  intermediate  part  surrounding  the  cleft  between  anterior  and 
posterior  lobes,  in  addition  to  the  production  of  some  substance  which  is  a 
general  excitant  for  unstriated  muscle  and  produces  diuresis,  also  furnishes 
a  colloid  secretion  which  passes  directly  into  the  ventricles  of  the  brain  and 
may  be  assumed  to  have  some  influence  on  the  growth  or  functions  of  the 


THE  DUCTLESS  GLANDS  1245 

central  nervous  system.  Schafer  regards  the  principle  giving  rise  to  diuresis 
as  distinct  from  that  causing  contraction  of  unstriated  muscle,  since  diuresis 
may  occur  without  corresponding  rise  of  blood  pressure.  The  independence 
of  the  two  phenomena,  renal  and  vascular,  cannot  be  regarded  as  proved. 

(c)  The  posterior  lobe  consists  mainly  of  neuroglia.  We  have  no  clue  to  its 
functions  apart  from  the  masses  of  intermediate  cells  which  it  may  contain. 

Very  little  can  be  said  as  to  the  other  ductless  glands.  The  thymus 
forms  two  large  masses  in  the  anterior  mediastinum,  which  in  man  grow  up 
to  the  second  year  of  life  and  then  rapidly  diminish,  so  that  only  traces 
are  to  be  found  at  puberty.  It  contains  a  large  amount  of  lymphatic  tissue 
and  is  therefore  often  associated  with  the  lymphatic  glands  as  the  seat  of 
formation  of  lymph  corpuscles.  The  epithelial  remains  of  Hassell's  cor- 
puscles found  in  the  medullary  part  of  its  globules  have  not  had  any  function 
assigned  to  them.  In  certain  cases  of  arrested  development  or  of  general 
weakness  in  young  people,  the  thymus  has  been  found  to  be  persistent. 
The  effect  of  extracts  made  from  the  thymus  do  not  differ  from  those  of 
extracts  made  from  any  other  cellular  organ. 

The  pineal  gland  has  so  far  not  been  proved  to  have  any  f miction  in 
metabolism.1  It  is  interesting  as  a  vestigial  remnant  of  a  primitive  dorsal 
eye.  In  certain  lizards  this  organ  still  presents  traces  of  its  original  structure, 
and  is  found  to  conform  to  the  invertebrate  type  of  eye.  It  is  doubtful 
whether  at  any  time  in  the  history  of  vertebrates  the  pineal  eye  has  been 
functional. 

The  carotid  and  coccygeal  glands  have  often  been  grouped  with  the 
collections  of  chromaffine  cells  already  described  as  associated  with  the 
sympathetic  system.  Their  structure  resembles  more  nearly  that  of  the 
parathyroid  bodies  or  the  anterior  lobe  of  the  pituitary  gland.  They  con- 
sist of  a  small  collection  of  columns  or  masses  of  cells  bound  together  by 
connective  tissue  with  a  rich  supply  of  blood  capillaries.  Nothing  is  known 
as  to  their  function. 

The  lymph  and  luvmolymph  glands,  and  the  spleen,  are  often  grouped 
with  these  ductless  glands.  The  essential  activity  of  these  bodies  however 
lies  in  the  production,  not  of  a  diffusible  chemical  substance,  but  of  formed 
elements  e.g.  lymph  corpuscles,  and  they  do  not  properly  fall  within  the 
scope  of  this  chapter.  As  a  matter  of  convenience,  we  may  deal  shortly 
here  with  the  functions  of  the  spleen. 

THE   SPLEEN 

This  organ  is  similar  in  many  respects  to  a  lymphatic  gland.  It  is 
formed  of  a  framework  of  connective  tissue  and  unstriated  muscular  fibres, 
in  the  interstices  of  which  is  contained  the  splenic  pulp.  This  consists  of  a 
fine  fibrillar  network,  on  the  fibrils  of  which  lie  endothelial  cells.  The 
meshes  contain  the  cells  of  the  splenic  pulp,  which  are  fairly  large  polygonal 

1  Cases  have  been  recorded  in  which  tumours  of  the  pineal  body  have  been  associated 
with  obesity,  premature  sexual  development  and  early  maturity. 


1246  PHYSIOLOGY 

cells,  and  leucocytes.  Just  as  in  a  lymphatic  gland  the  cellular  elements  of 
i  In- tissues  arc  bathed  bj  the  lymph  which  flows  through  the  gland,  so  in  the 

spleen  the  walls  of  the  capillaries  become  discontinuous,  and  the  blood  is 
poured  out  into  the  interstices  of  the  tissue.  The  spleen  is  therefore  the 
only  tissue  in  the  body  where  the  blood  comes  in  actual  contact  with  the 
tissue  elements  themselves.  The  blood  from  the  splenic  pulp  is  collected 
into  large  venous  sinuses,  which  run  along  the  trabeculse  to  the  hilum,  where 
they  unite  to  form  the  splenic  vein.  The  arteries  to  the  spleen  are  beset  in 
their  course  along  the  trabecule  with  small  nodules  of  lymphoid  tissue,  which 
are  known  as  the  Malpighian  follicles. 

It  is  evident  that  the  blood  must  meet  with  considerable  resistance  in 
passing  through  the  close  meshwork  of  the  splenic  pulp.  In  order  to  ensure 
a  constant  circulation  through  the  gland,  the  muscular  tissue  of  the  capsule 


Carotid  _  •'  •-.>■•.'■;■.-■■'. 


Fig.  5r>4.     Plethysuiu;jr.i|jlii<-  tracing  of  spleen  (upper  curve)  from  a  dog,  showing  the 
spontaneous  contractions  of  this  organ.    (Reduced  from  a  tracing  by  Sciiafeu.) 

and  trabeculse  has  the  property  of  rhythmic  contraction.  If  the  spleen  be 
enclosed  in  a  plethysmograph  or  splenic  oncometer,  and  its  volume  be 
recorded  by  connecting  this  with  an  oncograph,  it  will  be  seen  to  be  subject 
to  a  series  of  large  slow  variations,  each  contraction  and  expansion  lasting 
about  a  minute  and  recurring  with  great  regularity  (Fig.  564).  Superposed 
on  these  large  waves  are  smaller  undulations  due  to  the  respiratory  variations 
of  the  blood  pressure,  and  on  these  again  the  little  excursions  corresponding 
to  each  heai"t  beat.  The  contractile  power  of  the  spleen  is  under  the 
control  of  the  nervous  system,  and  a  rapid  contraction  may  be  induced  by 
stimulation  of  the  splanchnic  nerves. 

FUNCTIONS   OF   THE   SPLEEN 

The  structure  of  this  organ  suggests  that  the  splenic  cells  must  exercise 
a  constant  influence  on  the  blood  which  surrounds  them,  and  that  this 
influence  is  not  purely  of  a  chemical  nature.  In  the  liver  and  kidneys, 
which  exercise  so  powerful  an  effect  on  the  composition  of  the  blood  passing 
through  them,  the  proper  cells  of  the  organs  are  separated  from  the  blood 
stream  by  the  capillary  wall.  Microscopic  examination  of  the  cells  of  the 
splenic  pulp  shows  us  that  these  are  full  of  particles  of  brown  pigment 
or  fragments  of  red  corpuscles  (Fig.  565).      In  many  cases  of  infectious 


THE   DUCTLESS  CLANKS 


1247 


disease,  such  as  recurrent  fever,  the  splenic  cells  are  observed  towards  the 
end  of  the  attack  to  be  full  of  the  organism — spirillum — which  is  the  cause  of 
the  disease.  In  fact  these  cells  are  so  arranged  that  they  can  take  up  solid 
particles  held  in  suspension  in  the  blood  plasma.  We  must  indeed  look 
upon  the  spleen  as  the  great  blood  filter,  purifying  the  blood  in  its  passage  by 
taking  up  particles  of  foreign  matter  and  effete  red  corpuscles.  The  process 
of  phagocytosis,  which  was  described  under  the  cellular  mechanisms  of 
defence  (p.  1071).  is  in  the  spleen  a  normal  occurrence. 


.it. 


*, 


Fig.  565.     Cells  from  ;i  scraping  of  the  spleen.     (Kullikeu.) 
a.  splenic  pulp  cell  containing  red  blood  corpuscles,  b  (k  -    nucleus):  b,  leucocyte 
with  polymorphous  nucleus;  c,  pulp  cell  containing  disintegrated  red  corpuscles; 
i).  lymphocyte;  E,  giant-  cell:  F,  nucleated  red  corpuscles;  o,  normal  red  corpuscle; 
ji,  multinuclear  leucocyte;  .>.  eosinophils  coll. 


A  function  has  also  Keen  assigned  to  the  spleen  in  the  formation  of  red 
blood  corpuscles,  but  the  evidence  is  not  sufficient  to  determine  whether 
such  a  process  occurs  normally. 

Chemical  analysis  of  the  spleen  n  veals  the  presence  of  a  large  number  of 
what  ate  called  extractives,  such  as  succinic,  formic,  butyric,  and  lactic 
acids,  inosit,  leucine,  xanthine,  hypoxanthine,  and  uric  acid.  There  is  also 
a  protein  combined  with  iron,  as  well  as  several  pigments  probably  derived 
from  the  haemoglobin  of  the  red  corpuscles  destroyed  by  the  cells  of  the 
splenic  pulp.  The  fact  that,  in  cases  where  the  spleen  is  pathologically 
enlarged  as  in  leucocythaemia,  the  uric  acid  in  the  urine  is  largely  increased 
points  to  a  connection  between  the  spleen  and  the  formation  of  uric  acid 
in  the  body.  The  numerous  extractives  which  are  found  probably  owe  1  beir 
origin  to  the  destructive  changes  effected  on  the  effete  constituents  of  the 
blood  by  the  agency  of  the  splenic  pulp  cells. 


BOOK   IV 

REPRODUCTION 


79 


CHAPTER  XXI 

THE    PHYSIOLOGY    OF    REPRODUCTION 

SECTION   I 

THE  ESSENTIAL  FEATURES  OF  THE  SEXUAL  PROCESS 

TiiK.  two  fundamental  characteristics  of  protoplasm,  which  distinguish  it 
above  all  others  from  unorganised  matter,  are  growth  and  activity.  Growth 
occurs  at  the  expense  of  surrounding  non-living  material,  while  activity  is 
in  every  case  an  adapted  reaction  to  changes  in  the  environment.  The 
.second  characteristic  would  seem  to  involve  a  limitation  of  the  first,  and 
docs  in  fact  determine  the  conditions  under  which  it  may  occur.  In  the 
process  of  growth  of  a  minute  spherical  mass  of  protoplasm,  its  bulk  and 
mass  increase  as  the  cube,  while  the  surface  increases  only  as  the  square,  of 
the  radius.  Thus  the  proportion  of  surface  to  mass  diminishes  with  in- 
creased size  of  the  protoplasmic  unit  and,  since  activity  is  a  function  of  the 
surface,  the  larger  the  unit  t  lie  smaller  must  be  its  activity.  It  follows  that 
there  must  be  a  limiting  size  bo  the  living  protoplasmic  unit,  and  it  is  on 
this  account  that  practically  no  unicellular  animal  or  plant  exceeds  a  fraction 
of  a  millimetre  in  diameter.  II'  an  organism  is  to  attain  any  larger  size,  this 
can  only  be  by  a  multiplication  of  units,  each  presenting  the  same  relative 
amount  of  surface  as  a  complete  unicellular  organism,  though  the  surface 
rnav  be  exposed  to  an  internal  and  not  to  an  external  medium.  Another 
factor,  limiting  the  size  of  the  unicellular  organism  or  of  the  unit  of  the 
multicellular  organism,  is  the  necessity  for  maintaining  a  certain  proportion 
between  the  size  of  the  nucleus  and  that  of  the  cytoplasm  composing  the 
body  of  the  cell.  Observations  on  artificial  division  of  cells  have  shown 
us  that  the  functions  of  digestion,  assimilation,  and  growth  depend  upon  the 
presence  of  a  nucleus.  Hence,  when  for  any  reason  it  is  advantageous  that 
a  cell  should  attain  a  large  size,  such  a  cell  is  almost  always  found  to  contain 
main-  nuclei.  All  the  '  giant  cells  '  found  in  the  body  of  man  under  normal 
or  pathological  conditions  are  also  multinuclear. 

Thus  the  continuous  display  of  the  functions  of  assimilation  and  dis- 
similation, of  growth  and  activity,  is  possible  only  so  long  as  cell  division 
keeps  pace  with  growth.  In  unicellular  organisms,  under  favourable  con- 
ditions, this  growth  and  multiplication  occur  with  prodigious  rapidity.  It 
has  been  computed  that  a  paramoecium,  freely  supplied  with  food  material, 
would,  by  growth  and  division,  in  the  course  of  a  year  represent  a  mass  of 
protoplasm  the  size  of  the  earth,  assuming  of  course  that  no  accidents  or 

1251 


1252  PHYSIOLOGY 

destructive  agencies  intervened  to  destroy  the  pararnoecia  which  were  being 
formed.  This  computation,  which  may  seem  a  fanciful  one,  is  useful  as 
indicating  the  enormous  number  of  individuals  brought  under  the  action  of 
natural  selection,  which  very  few  survive.  In  unicellular  organisms  such  as 
paramcecium  or  amoeba, death  cannot  be  regarded  as  a  natural  process.  They 
may  be  eaten  by  higher  organisms  or  serve  as  food  to  vegetable  parasites, 
but  so  long  as  conditions  are  favourable  and  food  supply  sufficient,  they 
will  continue  to  grow  and  reproduce  themselves  eternally.  In  the  course 
of  its  existence  each  individual  may  be  brought  under  many  varieties  of 
conditions ;  some  of  these  may  be  so  harmful  that  the  individual  is  destroyed 
and  its  race  comes  to  an  end.  Other  individuals,  under  circumstances  of 
less  severity,  may  undergo  modifications  in  their  molecular  structure  which 
will  serve  to  neutralise  the  effect  of  the  injurious  environment.  Any  such 
modification  in  structure,  morphological  or  molecular,  must  be  transmitted  to 
the  next  generation,  so  that  with  slowly  varying  external  conditions  there  is 
a  possibility  of  a  corresponding  slow  variation  in  type,  which  may  finally 
attain  a  form  altogether  different  from  that  with  which  it  set  out.  A  new 
species  may  in  this  way  be  formed  by  gradual  alteration  of  environment. 
It  is  not  therefore  difficult  to  understand  in  the  case  of  such  organisms  either 
the  maintenance  of  type  by  heredity  under  constant  conditions,  or  the 
change  of  type  with  gradually  varying  conditions. 

Reproduction  by  continuous  growth  and  division  is  not  however  the 
only  means,  even  in  the  unicellular  animals,  by  which  new  generations  may 
be  produced.  If  protozoa  such  as  pararnoecia  be  kept  for  a  long  time  in 
nutrient  solutions,  their  rapidity  of  reproduction  after  a  time  falls  off,  while 
many  die,  and  others  become  the  easy  prey  to  infectious  diseases.  Under 
these  conditions  a  new  phenomenon  makes  its  appearance,  viz.  '  conjuga- 
tion,' which  is  the  analogue  of  the  sexual  reproduction  of  the  higher  animals. 
Infusoria  contain  two  kinds  of  nuclei,  a  large  and  a  small,  known  as  the 
macro-nucleus  and  the  micro-nucleus  respectively.  During  conjugation  the 
macro-nucleus  breaks  up  and  disappears  in  two  cells,  which  become  closely 
applied  together,  while  in  each  the  micro-nucleus  divides  twice  to  form  four 
spindle-shaped  bodies.  Three  of  these  degenerate,  (like  the  polar  bodies  of 
trie  ovum),  while  the  fourth  divides  into  two.  This  is  followed  by  an 
exchange  of  micro-nuclei,  one  micro-nucleus  from  a  passing  into  b,  while 
one  micro-nucleus  from  B  passes  into  A.  The  two  cells  then  separate,  a  single 
micro-nucleus  being  formed  in  each  by  the  amalgamation  of  the  two.  This 
micro-nucleus  then  divides  three  times,  so  that  eight  nuclei  are  formed,  while 
the  cell  itself  divides  into  four,  two  nuclei  passing  into  each  of  the  daughter 
cells.  Of  these  one  enlarges  to  form  the  macro-nucleus,  while  the  other 
remains  as  the  micro-nucleus.  After  conjugation  has  occurred,  the  colony  of 
infusoria  takes  on,  so  to  speak,  a  new  lease  of  life,  and  there  is  a  rapid 
production  of  new  generations  by  simple  division  of  the  cells,  in  which  both 
macro-nucleus  and  micro-nucleus  take  part.  Conjugation  apparently  occurs 
only  in  the  presence  of  adverse  conditions,  and  may  be  prevented  almost 
indefinitely   by   maintaining  the   colonies  in  as  favourable  conditions   as 


ESSENTIAL  FEATURES  OF  THE    SEXUAL  PROCESS    1253 


possible.  In  certain  organisms,  especially  in  Algae,  in  which  similar  pheno- 
mena take  place,  each  organism  after  conjugation  may  surround  itself  with 
a  thickened  wall  and  remain  for  a  considerable  length  of  time  in  a  state  of 
suspended  animation.  It  is  very  difficult  to  understand  the  advantage  of 
this  interchange  of  nuclear  material  either  to  the  individual  or  to  the  race. 
It  has  been  suggested  that,  as  soon  as  each  individual  concerned  in  the  pro- 
eess  receives  the  nuclear  material  from  organisms  which  may  have  been 


Second  fission 

First  fission,  after  separation 

Differentiation  of  micro-  and 
macro-nuclei 

Separation  of  the  gametes 
Division  of  the  cleavage-nucleus 

Cleavage-nucleus 

Exchange  and  fusion  of  the  germ- 
nuclei 

Germ-nuclei 

Formation  of  the  polar  bodies 
Union  of  the  gametes 


Fio.   566.     Diagram  showing   the  history  of  the  micro-nuclei  during  the 
conjugation  of  paramcecium.     (From  Wilson  after  Matjpas.) 
X  and  y  represent  the  opposed  macro-  and  micro-nuclei  in  the  two  gametes ; 
circles  represent  degenerating  and  black  dots  persisting  nuclei. 

exposed  to  slightly  different  circumstances,  cones  ponding  changes  will  be 
int  induced  into  the  tendencies  to  growth  of  the  product  of  the  union.  Some 
of  these  tendencies  may  be  more  advantageous  than  before,  while  others  may 
be  the  reverse.  Increased  possibility  of  variation  is  however  introduced 
by  this  admixture  of  nuclear  material,  and  this  may  be  the  advantage 
of  the  process  to  the  race.  It  should  be  noted  that  the  half  of  the  nucleus 
lost  by  each  conjugating  organism  is  qualitatively  different  from  that  which 
it  retains  and  probably  from  that  which  it  receives.  A  gamete  in  which 
the  nucleus  can  be  represented  by  ab,  and  which  by  simple  division  will 
produce  similar  organisms  with  nucleus  ab.  conjugates  with  an  organism 
of  slightly  different  structure,  and  therefore  with  a  nucleus  which  can  be 
represented  as  cd.  After  conjugation,  the  ab  gamete  will  contain  a  nucleus 
represented  by  ac,  while  the  cd  gamete  will  contain  a  nucleus  represented 


1254  PHYSIOLOGY 

by  bil;  ac  01  bd  may  be  better  or  worse  combinations  than  ab  or  cd.  If 
either  of  them  is  better,  that  organism  will  survive  under  the  less  favourable 
conditions,  and  the  race  will  continue  with  a  slight,  and  to  us  inappreciable, 
change  of  type. 

REPRODUCTION   IN   THE   METAZOA 

The  numberless  cells  forming  the  bodies  of  the  higher  animals  are  all 
produced  by  a  scries  of  divisions  from  a  single  cell,  the  fertilised  ovum. 
This  cell  is  the  result  of  a  process  of  conjugation  between  two  cells  derived 
from  different  individuals.  With  the  multiplication  of  cells  forming  a  single 
organism  there  is,  of  course,  an  increased  size  of  the  organism.  It  is  doubtful 
whether  this  of  itself  would  be  of  any  advantage,  were  it  not  that  the 
multiplication  of  cells  goes  hand  in  hand  with  differentiation,  groups  of 
cells  being  modified  structurally  and  set  aside  for  one  or  other  function  of  the 
body.  Differentiation  of  function  implies  higher  functional  capacity. 
As  a  motor  organ  or  as  a  means  of  locomotion,  the  differentiated  muscle 
cells,  with  their  attached  parts,  must  be  more  effective  than  the  undif- 
ferentiated protoplasm  of  the  amoeba.  Specialisation  of  function  involves 
changes  of  type  in  the  cells  resulting  from  the  division  of  the  primitive  un- 
differentiated ovum.  In  most  cases  this  change  of  type  is  permanent.  An 
epithelial  cell  such  as  that  forming  the  epidermis  or  the  liver,  when  it  divides, 
produces  another  cell  of  the  same  kind.  One  might  almost  speak  of  the 
evolution  of  a  new  species  of  cell,  but  that  it  takes  place  within  the  short 
period  of  the  development  of  the  multicellular  individual,  instead  of  occupy- 
ing a  long  space  of  time  and  involving  the  destruction  of  countless  indi- 
viduals, as  is  the  case  when  a  change  of  type  gradually  occurs  in  unicellular 
organisms.  Differentiation  necessarily  brings  with  it  a  limitation  of  the 
powers  of  reproduction.  Any  one  of  the  descendants  of  a  unicellular 
organism  is  in  all  respects  equivalent  to  its  ancestor,  and  can  reproduce  the 
same  type  of  individual.  The  specialised  liver  or  muscle  cell  can  produce 
only  a  cell  of  the  same  type,  one,  that  is  to  say,  incapable  of  independent 
existence  or  of  forming  the  divergent  series  of  types  necessary  for  the  pro- 
duction of  an  individual.  Differentiation  of  function  therefore  involves  the 
setting  aside  of  certain  cells,  germ  cells,  which  retain  their  primitive  character 
and  are  capable  of  indefinite  division  to  form  new  generations  each  able 
to  develop  into  a  complete  individual.  These  germ  cells  can  often  be 
recognised  from  the  very  earliest  divisions  of  the  fertilised  ovum,  which  lead 
to  the  production  of  the  mature  individual.  Tims  in  Ascaris,  the  progenitor 
of  the  germ  cells  differs  from  the  somatic  cells  both  by  the  greater  size  of 
its  nucleus  and  in  its  mode  of  division  (Fig.  567).  In  the  cells  destined  to 
produce  the  somatic  cells,  a  portion  of  the  chromatin  is  cast  out  into  the 
cytoplasm,  where  it  degenerates,  so  that  only  in  the  germ  cells  is  the  sum 
total  of  the  chromatin  retained.  Thus  in  the  two-celled  stage,  in  one  cell 
all  the  chromatin  is  preserved,  while  in  the  other  cell  the  thickened  ends  of 
the  chromosomes  are  cast  off  into  the  cytoplasm  and  degenerate,  only  the 
thinner  central  portions  being  preserved.     When  these  divide  again,  the 


ESSENTIAL  FEATURES  OF  THE   SEXUAL  PROCESS    1255 

same  process  is  repeated  in  only  one  of  the  daughter  cells  derived  from  a 
germ  cell,  and  this  recurs  during  five  or  six  divisions,  after  which  the 
chromatin  elimination  ceases  and  the  two  primordial  germ  cells  thence- 
forward give  rise  only  to  other  germ  cells  in  which  the  entire  chromatin  is 
preserved.  Thus  "  the  original  nuclear  constitution  of  the  fertilised  egg  is 
transmitted,  as  if  by  a  law  of  primogeniture,  only  to  one  daughter  cell,  and 


~*  fJO'  s 


Fig.  567.  Origin  of  the  primordial  gorni  cells  and  casting  out  of  chromatin  in 
the  somatic  cells  of  Ascaris.     (Wilson  and  Boveri.) 

a.  two-cell  stage  dividing;  8,  stem  cell,  from  which  arise  the  genu  cells.  B,  the 
same  from  the  side,  later  in  the  second  cleavage,  showing  the  two  types  of  mitosis 
and  tho  casting  out  of  chromatin  (c)  in  the  somatic  cell.  O,  resulting  four-cell 
stage;  the  eliminated  chromatin  at  c.  D,  the  third  cleavage,  repeating  the  foregoing 
process  in  the  twTo  upper  cells. 

by  this  again  to  one.  and  so  on,  while  in  other  daughter  cells  the  chromatin 
in  part  degenerates,  in  part  is  transformed,  so  that  all  of  the  descendants 
of  these  side-branches  receive  small  reduced  nuclei"  (Boveri,  quoted  by 
Wilson). 

The  immortality,  which  was  the  property  of  all  the  unicellular  ancestors 
of  the  metazoa,  has  in  the  latter  descended  only  to  the  germ  cells.  All  the 
other  cells  of  the  body,  which  form  the  nervous  and  muscular  tissues, 
glands,  skin,  etc.,  are  mortal.  They  pass  through  a  certain  number  of 
divisions  ;  hut  although  this  number  is  large,  it  is  limited,  and  on  the  number 
of  divisions  which  are  possible  depends  the  normal  duration  of  life  of  the 
organism  to  which  the  cells  belong.  We  may  thus  regard  the  egg  (-ell  as 
dividing  into  two  parts.     From  one  part  will  be  formed  by  differentiation 


125G  PHYSIOLOGY 

all  the  complex  somatic  mechanisms  of  the  adult  animal;  the  other  part 
will  divide,  but  will  remain  in  an  undifferentiated  form,  until  its  descendants 
can  conjugate  with  germ  cells  from  other  individuals  and  form  fertilised 
egg  cells,  destined  to  undergo  the  same  series  of  changes. 

The  rnetazoan  individual  thus  consists  of  a  mortal  host  holding  within  itself  the 
immortal  sexual  cells  or  gonads.  Gaskell  has  pointed  out  that  the  development  of 
the  fertilised  ovum  involves  two  parallel  processes — on  the  one  hand,  the  elaboration 
of  the  elements  forming  the  host;  on  the  other,  of  those  derived  from  the  tree-living 
independent  germ  cells.  From  the  very  beginning  the  somatic  part  of  the  organism, 
the  host,  is  a  reacting  individual  in  which  the  nervous  system  acts  as  the  integrator  of 
all  the  activities  of  the  body  and  as  the  middleman  between  the  internal  and  externa] 
epithelial  surfaces  and  the  muscular  system.  The  host  may  thus  be  regarded  as  a 
neuro- epithelial  syncytium,  eveiy  step  in  its  evolution  and  differentiation  being  attended 
by  increased  control  of  all  the  units  by  a  central  nervous  system. 

The  gonads  were  placed  at  first  within  the  interstices  of  this  syncytium,  and  escaped 
to  form  a  new  generation  only  after  the  death  and  disintegration  of  the  host.  But 
differentiation  and  division  of  labour  affect  also  the  free-living  gonads.  Some  of  these 
form  a  germ  epithelium  surrounding  the  body  cavity,  of  which  a  few  only  of  the  elements 
pass  out  of  the  host  as  perfect  germ  cells,  while  the  others  are  subordinated  to  the 
metabolic  needs  of  these  germ  cells  and  are  transformed  into  various  elements,  such  as 
nurse  cells,  wandering  mesoderm  cells  or  phagocytes,  yolk  cells,  and  so  on.  Gaskell 
regards  the  greater  part,  if  not  the  whole,  of  the  connective-tissue  framework  of  the 
body,  as  well  as  the  wandering  corpuscles  of  the  blood  and  tissue  fluids,  as  derived  from 
these  primitive  germ  cells.  All  these  tissues,  though  useful  to  the  host  as  well  as  to 
the  finally  successful  germ  cells,  present  the  common  feature  of  an  absolute  independence 
of  the  central  nervous  system.  Thus  the  evolution  of  the  animal  kingdom  means 
essentially  the  evolution  of  the  host,  and  must  therefore  be  closely  connected  with  the 
evolution  of  the  central  nervous  system,  the  ruling  element  in  the  neuro- muscular 
syncytium.  On.  these  grounds  Gaskell  has  used  the  comparative  morphology  of  the 
central  nervous  system  as  a  means  of  tracing  the  origin  of  the  vertebrate  from  the  in- 
vertebrate type,  and  has  come  to  the  conclusion  that  the  immediate  ancestor  of  the 
vertebrate  must  be  sought  in  the  invertebrate  group  presenting  the  most  highly  developed 
central  nervous  system,  namely,  the  Arthropoda. 

All  the  complex  mechanisms  which  are  concerned  in  maintaining  the 
life  of  the  individual  have  apparently  been  developed  in  order  to  give  the 
potentially  immortal  germ  cells  a  better  chance  of  survival  in  the  struggle 
for  existence.  From  the  broad  biological  standpoint,  as  Foster  points  out, 
all  the  toil  and  turmoil  of  human  existence  may  be  regarded  simply  as  the 
by-play  of  an  ovum-bearing  organism.  From  the  same  standpoint  one  must 
acknowledge  that  the  mortality  of  the  individual,  resulting  from  the  absence 
of  an  indefinite  power  of  multiplication  among  the  somatic  cells,  must  be 
an  advantage  to  the  race.  Throughout  the  living  world  the  welfare  of  the 
individual  is  subordinated  to  that  of  the  species.  With  each  new  genera- 
tion there  are  possibilities  of  variation  and  of  the  production  of  individuals 
better  or  worse  fitted  for  the  maintenance  of  the  race  than  those  of  the 
previous  generation.  Immortality  of  the  individual  would  handicap  the 
survival  of  the  younger  generations,  and  we  should  have  the  same  retardation 
of  progress  in  a  race  that  we  see  in  many  civilised  communities,  where  the 
power  and  the  conduct  of  affairs  are  in  the  hands  of  the  older  members. 


ESSENTIAL  FEATURES  OF  THE   SEXUAL  PROCESS    1257 

THE   FORMATION   OF   GERM   CELLS 

In  multicellular  organisms  the  cells  which  conjugate  to  form  a  new  cell, 
capable  of  developing  into  an  individual,  are  of  two  kinds.  One,  which 
has  generally  a  certain  amount  of  reserve  material  stored  up  in  its  cytoplasm, 
is  the  female  element  and  is  called  the  ovum.  The  other  cell,  which  consists 
of  little  more  than  nuclear  material,  is  the  male  element  and  is  called  the 
spermatozoon.  Both  kinds  of  cells  are  derived  from  a  mass  of  undifferentiated 
cells,  the  »cmi  epithelium  which,  as  we  have  seen,  can  often  be  traced  directly 
back  to  the  first  divisions  of  the,  fertilised  egg.  The  use  of  the  reserve 
material  in  the  ovum  is  to  serve  as  food  for  the  developing  individual.  The 
ovum  and  spermatozoon  cannot  be  regarded  as  corresponding  to  complete 
cells  Before  their  union  or  conjugation  both  male  and  female  germ,  cells 
undergo  certain  important  changes  which  differentiate  them  from  the. 
ordinary  somatic  cells  of  the  individual.  The  essential  differences  between 
a  genu  cell  and  a  somatic  cell  can  be  best  seen  by  a  study  of  the  nuclear 
changes  w  hich  precede  their  formation.  In  division  the  nuclei  of  all  somatic 
cdls.  whether  of  plants  or  animals,  undergo  a  series  of  changes  which,  in 
their  broad  outlines,  are  similar  throughout  both  animal  and  vegetable 
doms  (Fig.  568),  and  result  in  the  production  of  qualitatively  identical 
daughter  nuclei. 

The  nucleus  of  the  resting  cell  in  its  vegetative  condition  is  generally  separated 
from  the  cytoplasm  by  a  nuclear  membrane,  and  contains  irregular  masses  of  a  material 
staining  deeply  with  basic  dyes,  and  known  as  chromatin.  In  the  cytoplasm  of  most 
animal  cells  mav  be  seen  a  small  particle  known  as  the  centrosome.  When  division 
is  about  to  take  place,  the  clumps  of  chromatin  arrange  themselves  into  a  filament  which 
a  continuous  skein,  the  '  spireme  stage.'  This  then  breaks  up  into  a  number 
of  segments,  often  V-shaped,  the  chromatin  filaments  or  chromosomes.  Each  of  the 
filaments,  in  large  nuclei,  may  often  be  seen  to  be  composed  of  rows  of  granules.  While 
this  change  has  been  occurring,  the  nuclear  membrane  in  most  cases  disappears,  and 
the  centrosome  outside  the  nucleus  divides  into  two  parts,  which  travel  to  opposite 
ends  of  the  nucleus.'  Round  each  centrosome  the  cytoplasm  is  modified  and  presents 
iile  appearance,  the  asler,  while  joining  the  two  centrosomes  is  a  spindle  of  fine 
fibres,  the  achromatic  spindle.  The  V-shaped  segments  of  chromatin  arrange  themselves 
in  a  circle  at  the  equator  of  the  spindle  midway  between  the  two  centrosomes.  Each 
of  the  loops  then  splits  longitudinally,  and  each  half  travels  towards  one  or  other  of  the 
centrosomes,  thus  forming  two  daughter  nuclei.  The  half-loops  then  join  to  form  a 
skein,  and  may  return  to  the  c.  mditi<  >n  of  a  resting  nucleus.  These  different  phases  in 
division  are  presented  by  all  somatic  cells,  and  have  received  the  following  names : 

(1)  Prophase  (the  formation  of  the  spireme  and  of  the  achromatic  spindle,  and  the 
breaking  up  of  the  spireme  into  chromatin  loops  or  chromosomes). 

(2)  Metaphase  (the  splitting  of  the  chromosomes). 

(3)  A  naplui.se  (the  travelling  of  each  half-chromosome  to  the  extremity  of  the  spindle). 

(4)  Telophase  (the  retrogressive  changes,  leading  to  the  conversion  of  the  chromatin 
filaments  into  an  ordinary  resting  nucleus,  which  are  accompanied  or  preceded  by  a 
division  of  the  cytoplasm  across  the  equatorial  part  of  the  spindle). 

When  the  spireme  has  broken  up  into  separate  chromatin  loops,  it  is  possible  to 
count  them,  and  it  is  found  that  the  number  present  in  any  cell  is  constant  f<  <i  the  species. 
Thus  every  human  somatic  cell  has  sixteen  chromosomes  in  its  nucleus.  The  same 
number  is  found  in  types  so  far  apart  as  the  ox,  the  guinea-pig,  and  the  onion.  In 
the  mouse,  the  salamander,  and  the  lily  the  number  is  twenty-four.  Olh.-i  type  ,  ncli 
as  the  crustacean  Anemia,  are  said  to  have  as  many  as  168  chromosomes,  while  in  Ascaris 


1 258 


PHYSIOLOGY 


tin'  cells  contain  only  two  or  four  chromosomes.  All  these  changes,  which  arc  included 
under  the  term  mitosis  or  kuri/nkiiiesis,  seem  to  he  adapted  to  ensuring  an  equal  qualita- 
tive :is  well  as  quantitative  distribution  of  the  nuclear  chromatin  among  the  daughter 
cells  resulting  from  the  division  of  any  cell.  As  we  have  seen  in  an  earlier  chapter, 
the  nucleus,  by  its  interaction  with  the  cytoplasm,  determines  the  processes  of  assimila- 


W    \      6 


Fig.  568.     Diagram  showing  the  changes  which  occur  in  the  centrosomes 

and  nucleus  of  a  cell  in  the  process  of  mitotic  division.     (Schafer.) 

The  nucleus  is  supposed  to  have  four  chromosomes. 

tion  and  growth  of  the  whole  cell.  For  the  preservation  of  type  in  cell  division  it  is 
therefore  essential  that  the  nuclei  of  the  daughter  cells  shall  be  identical  in  all  respects 
with  the  nucleus  of  the  mother  cell. 

Sexual  reproduction  involves  the  conjugation  of  two  cells,  with  union 
of  their  nuclei.  If  each  of  these  nuclei  consisted  of  the  normal  number  of 
chromosomes,    the   fertilised    egg  cell  would  contain    double   the    number 


ESSENTIAL  FEATURES  OF  THE   SEXUAL  PROCESS     1259 

characteristic  of  the  species,  and  since  these  chromosomes  would  divide  by 
splitting,  the  number  of  chromosomes  in  each  cell  would  be  doubled  with 
each  generation.  This  doubling  is  obviated  by  the  fact  that,  in  the  forma- 
tion of  the  germ  cells,  the  ovum  and  spermatozoon  nuclei  undergo  a  special 
type  of  division,  which  leads  to  the  reduction  of  the  chromosomes  in  the 
lly  mature  cell  to  one-half  of  the  number  characteristic  of  the  species. 
This  mode  of  cell  division  is  often  called  'division  by  reduction."  or 
'  heterotype  '  mitosis.  01  '  meiosis '  (Fig.  569). 

We  may  take  as  an  example  the  development  of  spermatozoa.  The  mother  cells 
of  the  spermatozoa,  the  spermatocytes,  divide  twice,  giving  rise  to  four  daughter  cells, 
1  he  spermatids,  eaeh  of  which  develops  into  a  functional  spermatozoon.     In  the  nuclear 


Fie.   569.     Three  stages  of  heterotype  mitosis  in  spermatocyte  of  triton.     (Moore.) 
„.  germinal  condition  of  chromosomes;    b,  gemini  arranged  in  quadrate  loops  or 
tetrads;    c,  separation  of  tetrads  into  the  duplex  chromosomes  of  the  daughter 
nuclei. 

changes  preparatory  to  the  first  division,  the  spireme,  when  it  breaks  up,  gives  rise 
to  only  hall  the  normal  number  of  chromosomes.  Thus  if  the  somatic  number  of  chro- 
mosomes were  four,  we  should  find  in  the  spermatocyte,  after  the  breaking  up  of  the 
spireme,  only  two  chromosomes.  These  take  up  their  position  at  the  equator  of  the 
achromatic  spindle  and  then  divide :  the  division  is  effected  however,  not  by  splitting  of 
the  double  chromosome,  but  by  t  ransverse  division.  Each  chromosome  breaks  into  half, 
one  half  going  to  each  daughter  cell.  Since  each  of  the  reduced  number  of  chromosomes 
can  be  regarded  as  made  up  of' two  normal  chromosomes  placed  end  to  end  or  joined 
to  form  a  ring,  as  in  Fig.  569,  6,  the  division  in  the  middle  provides  for  a  qualitative 
difference  between  the  two  daughter  cells.  If  we  indicate  the  tour  normal  chromosomes 
as  0,6,  e,  d,io  ordinary  somatic  division,  each  daughter  cell  will  also  contain  chromosomes 
which' may  be  represented  as  ol,  61,  el,  dl,  and  «2,  62,  c2,  d2.  In  the  spermatocyte 
the  two  chromosomes  may  be  represented  as  ab  and  cd.  When  they  divide,  one  daughter 
cell  receives  a  and  c,  while  the  other  daughter  cell  receives  6  and  d.  The  second  division 
of  these  daughter  cells  takes  place  generally  by  splitting  of  the  filaments,  so  that  finally 
four  spermatids  are  produced  (Fig.  570),  eaeh  with  two  chromosomes,  two  of  them 
containing  a  and  c,  while  the  other  two  contain  6  and  d.  In  the  ovum,  during  matura 
tion,  analogous  changes  take  place.  Two  successive  cell  divisions  occur  as  in  the  forma 
tion'of  spermatozoa,  but  the  daughter  cells  are  of  verj  unequalsize.     In  the  first  division, 


1200 


PHYSIOLOGY 


the  heterotypical  division,  the  chromosomes  fuse  in  pairs  and  then  divide  as  in  the  sper- 
matocytes, so  that  each  of  the  daughter  cells  contains  one  half  the  somatic  number  of 
chromosomes.  The  larger  of  the  two  resulting  cells,  which  retains  most  of  the  cyto- 
plasm, is  still  called  the  ovum,  while  the  smaller  one  is  spoken  of  as  the  '  first  polar 

Primordial  germ  cell 


Primary  spermatocyl 


Secondary  spermatocy 


Maturation  period. 


Fig.  570. 

body.'  The  ovum  now  divides  again  and  throws  off  a  socond  polar  body,  the  division 
being  of  the  homotypical  variety.  The  first  polar  body  may  also  divide,  so  that  from 
the  original  ovum  three  cells  are  produced,  one  of  which  retains  the  greater  part  of  the 
cytoplasm,  while  the  others  are  extruded,  and  degenerate  (Fig.  571).  The  mature 
ovum  has  however  only  half  the  normal  number  of  chromosomes,  so  that  its  nucleus 
is  equivalent  to  the  nucleus  forming  the  head  of  the  spermatozoon.     The  only  difference 


Primordial  germ  cell. 


Primary  oocyte 


Secondary  oocytes  (egg  and 

first  polar  body) 


:  egg  and   three   polar   bodti 


Division  period  I  the  number  of  divi- 
sions is  much  greater). 


,   Growth  period. 


.   Maturation-period. 


Fig.  571. 


therefore  between  the  formation  of  ovum  and  spermatozoon  is  that  in  the  former  case 
three  of  the  cells  formed  by  the  division  of  the  primitive  ovum  are  abortive,  whereas 
in  the  spermatozoon  all  four  daughter  cells  produced  from  the  spermatocyte  remain 
functional.  The  production  of  these  two  kinds  of  sexual  cell  is  represented  in  Figs.  570 
and  571. 

Since  the  nuclei  of  the  mature  ovum  and  spermatozoon  contain  only  half  the  normal 
number  of  chromosomes,  they  are  generally  spoken  of  as  pro-nuclei. 


ESSENTIAL  FEATURES  OF  THE  SEXUAL  PROCESS     1261 


FERTILISATION 

The  essential  features  of  fertilisation,  i.  e.  the  union  of  the  sexual  cells, 
are  best  studied  in  some  of  the  lower  invertebrates,  such  as  ascaris  or  echino- 
derms.     In  the  latter  fertilisation  takes  place  in  the  sea-water,  into  which 


FlG.  572.  Fertilisation  and  first  division  of  ovum  of  Ascaris  megalocephala.  (Slightly 
modified  from  Boveiu  and  Wilson.) 
a,  second  polar  globule  just  formed;  tho  head  of  tho  spermatozoon  is  becoming 
changed  into  a  reticular  nucleus  (  J  ),  which  howevor  shows  distinctly  two  chromo- 
somes ;  just  above  it,  its  archoplasm  is  shown  :  the  egg  nucleus  (  9  )  also  shows  two 
chromosomes,  b,  both  pro-nuclei  aro  now  reticular  and  onlarged;  a  double  cen- 
trosomo  («)  is  visible  in  the  archoplasm  which  lies  between  thorn,  r,  the  chromatin 
in  each  nucleus  is  now  converted  into  two  filamentous  chromosomes;  the  contro- 
somes  are  separating  from  one  another.  D,  tho  chromosomes  are  more  distinct  and 
shortened;  tile  nuclear  membranes  have  disappeared;  the  attraction  spheres  are 
distinct.  E,  mingling  and  splitting  of  tho  four  chromosomes  (c);  the  achromatic 
spindle  is  fully  formed.  F,  separation  (towards  the  poles  of  tho  spindle)  of  tho 
halves  of  the  split  chromosomes,  and  commencing  division  of  the  cytoplasm.  Each 
of  the  daughter  cells  now  has  lour  chromosomes;  two  of  these  have  been  derived 
from  the  ovum  nucleus,  two  from  the  spermatozoon  nucleus. 

both  ova  and  spermatozoa  are  extruded.  The  ovum  of  the  echinoderm 
consists  of  a  naked  mass  of  protoplasm.  Of  the  countless  hordes  of  sperma- 
tozoa which  may  be  in  the  neighbourhood  of  a  given  ovum,  only  one  as  a 


L262  PHYSIOLOGY 

rale  enters.  Aw  scion  as  the  spermatozoon  lias  entered  the  ovum,  a  tough 
membrane  is  rapidly  formed  round  the  latter,  so  preventing  the  entrance  of 

any  further  spermatozoa.     The  head  of  the  spermatozoon  enters  the  i 

while  the  tail  atrophies  and  disappears.  The  head  of  the  spermatozoon 
enlarges  and  assumes  the  character  of  a  nucleus,  the  dense  mass  of  chromatin 
breaking  up  first  into  a  thread  and  then  into  the  characteristic  number 
of  chromosomes  (Pig.  572).  The  egg  now  contains  two  nuclei  or  pro-nuclei, 
exactly  similar  in  appearance,  one  derived  from  the  male  and  the  other 
belonging  to  the  egg  itself.  The  two  nuclei  approach  one  another  and  join: 
In  many  cases  there  is  an  apparent  fusion  of  the  substance  of  the  two 
nuclei.  In  others  the  chromatin  filaments  of  male  and  female  simply  lie 
side  by  side,  forming  a  complete  nucleus  with  the  somatic  number  of  chromo- 
somes. Fertilisation  is  rapidly  followed  by  cell  division.  Each  of  the 
chromosomes  splits  longitudinally,  half  going  to  each  of  the  daughter^ cells, 
and  this  process  is  repeated  throughout  the  succeeding  divisions  which  result 
in  the  formation  of  the  new  individual.  Thus  every  cell  of  the  body  con- 
tains a  nucleus  of  which  exactly  one  half  is  paternal  and  the  other  maternal  in 
origin.  In  ascaris  it  is  often  possible,  in  the  first  few  divisions  of  the  fertilised 
ovum,  to  distinguish  in  the  daughter  nuclei  the  chromatin  filaments  derived 
from  the  male  from  those  derived  from  the  female. 

The  strong  impetus  to  cell  division  given  by  the  process  of  fertilisation 
has  naturally  aroused  much  curiosity  as  to  its  intimate  character.  It  might 
be  thought  that  for  cell  division  to  take  place  a  normal  number  of  chromo- 
somes is  essential.  As  against  this  explanation  may  be  adduced  the  fact 
that  in  many  animals  parthenogenesis  occurs.  The  female  pro-nucleus 
may,  under  certain  conditions  of  environment  or  nutrition,  start  dividing 
and  give  rise  to  an  embryo,  each  cell  of  which  contains  only  half  the  normal 
number  of  chromosomes.  In  other  cases  of  parthenogenesis  only  one 
polar  body  is  extruded,  or  the  second  polar  body  joins  again  with  the  female 
pro-nucleus.  In  either  case  the  ovum  contains  a  nucleus,  with  a  normal 
number  of  chromosomes,  which  divides  and  produces  an  individual  resembling 
that  resulting  from  the  union  of  ovum  and  spermatozoon.  It  has  been 
suggested  that  the  impetus  to  division  is  given  by  the  entry  of  the  sperma- 
tozoon itself.  In  the  series  of  divisions  which  precede  the  formation  of  the 
female  pro-nucleus, the  centrosome  of  the  ovum  generally  disappears,  whereas, 
in  the  formation  of  the  spermatozoon,  the  centrosome  persists  and  forms  the 
middle  part  of  the  spermatozoon.  In  many  cases  the  centrosomes  divide 
in  the  spermatozoon  itself,  so  that  this  contains  two  centrosomes  when  it 
enters  the  egg.  These  two  centrosomes  then  become  the  centres  of  attrac- 
tion spheres.  They  diverge,  and  between  them  is  formed  an  achromatic 
spindle,  along  the  equator  of  which  the  chromatin  filaments  of  male  and 
female  pro-nuclei  arrange  themselves.  It  is  doubtful  however  how  far 
the  centrosome  can  be  regarded  as  a  permanent  cell  structure.  In  echino- 
derrn  eggs,  various  modes  of  treatment  will  lead  to  the  appearance  of  attrac- 
tion spheres  in  the  cytoplasm,  and  even  to  division  of  the  non-fertilised 
egg.     Loeb  has  suggested  that  the  action  of  the  spermatozoon  is  essentially 


ESSENTIAL   FEATURES   OE   THE   SEXUAL   PEOCESS     1263 

chemical  in  character.  By  alteration  of  the  medium  in  which  the  eggs  are 
contained.  Loeb  has  succeeded  in  imitating  exactly  the  changes  which 
normally  need  the  entrance  of  a  spermatozoon  for  their  occurrence.  On 
immersing  the  eggs  in  a  weak  solution  of  formic  or  lactic  acid,  a  membrane 
is  formed.  The  eggs  are  then  taken  from  the  acid,  placed  in  concentrated 
sea-water  for  a  short  tune,  and  then  removed  to  ordinary  sea-water.  Division 
rapidly  occurs  with  the  production  of  a  normal  larva.  He  suggests  that  the 
spermatozoon  brings  with  it  ferments  or  other  chemical  substances,  which 
excite  the  egg  nucleus  and  cytoplasm  in  the  same  way  as  the  chemical 
measures  adopted  for  this  artificial  induction  of  segmentation. 


SECTION  II 

-    DEVELOPMENT   AND    HEREDITY 

There  is  perhaps  no  phenomenon  which  is  so  impressive  as  the  development 
from  a  minute  speck  of  protoplasm,  the  fertilised  egg,  of  an  individual 
partaking  of  the  minutest  characteristics  of  both  its  parents.  An  egg  cell 
has  much  the  same  appearance  whether  it  belong  to  an  echinoderm,  a  fish, 
or  a  man.  In  the  process  of  development,  by  a  simple  repetition  of  a  series 
of  cell  divisions,  this  undifferentiated  protoplasm  is  formed  into  the  complex 
organs  with  the  potentialities  and  habits  which  distinguish  the  type  from 
which  the  protoplasm  has  been  derived.  We  cannot  wonder  that  the 
intimate  nature  of  this  process  has  been  the  subject  of  speculation  from  the 
very  birth  of  science.  Running  through  these  speculations  are  two  main 
ideas,  which  have  been  labelled  the  theories  of  '  evolution  '  and  of  '  epi- 
genesis.'  By  the  '  evolutionists '  the  egg  was  believed  to  contain  an 
embryo  fully  formed  in  miniature,  as  the  bud  contains  the  flower  or  the 
chrysalis  the  butterfly.  Development  was  therefore  only  the  unfolding  of 
something  already  existing.  If  however  this  theory  be  pushed  to  its  utmost 
and  if  the  egg  contain  a  complete  embryo,  this  must  itself  contain  eggs  for 
the  next  generation,  and  so  on  ad  infinitum,  a  conclusion  which  is  of  course 
absurd.  According  to  the  theory  of  epigenesis,  the  structure  of  the  egg  is 
wholly  different  from  that  of  the  adult,  its  development  consisting  in  the 
continual  formation  one  after  the  other  of  new  parts  previously  non-existent 
as  such.  There  is  no  doubt  that  this  view  is  fundamentally  correct.  The 
difficulty  with  which  we  have  to  contend  is  the  understanding  of  the  orderly 
sequence  and  correlation  of  the  cell  divisions  and  differentiations  which  result 
in  an  adult  individual  of  the  same  type  as  the  parents.  The  fact  that,  under 
approximately  identical  conditions,  one  mammalian  ovum  will  give  rise  to 
a  mouse  and  the  other  to  a  man  indicates  that  there  must  be  some  difference 
in  structure,  organisation,  or  composition  of  the  primitive  egg  cell  in  each 
case,  and  the  theory  of  '  evolution  '  has  reappeared  in  later  days  in  a  some- 
what modified  form,  according  to  which  the  differentiation  of  the  ovum 
is  causally  connected  with  a  preformed  differentiation  in  the  nuclear  struc- 
tures c.  g.  chromosomes,  of  the  ovum  itself.  We  have  already  seen  that  the 
germ  cells  in  some  types  are  separated  off  from  the  rest  of  the  embryo  at  a 
fairly  early  stage.  If,  in  the  two-celled  stage  of  the  frog's  egg,  one  cell  be 
destroyed  by  means  of  a  hot  wire,  the  other  cell  develops  to  form  half  an 
embryo,  thus  suggesting  that  each  cell  of  the  two-celled  embryo  could  give 
rise  only  to  the  corresponding  half  of  the  body.  This  limitation  of  develop- 
ment however  occurs  only  if  the  intact  cell  be  left  in  connection  with  the 

1264 


DEVELOPMENT  AND  HEREDITY  1265 

cell  that  has  been  injured.  If,  in  echinoderm  larvae,  the  cells  be  entirely 
separated,  even  as  late  as  the  eight-celled  stage  of  division,  each  cell  will  give 
rise  to  a  whole  embryo,  differing  from  a  normal  embryo  only  in  respect  of 
size.  This  difference  suggests  that  the  number  of  divisions  that  each  cell  can 
undergo  is  predetermined  in  the  egg  cell  itself,  but  shows  also  that  the  cells 
into  which  the  egg  divides  are,  at  first  at  any  rate,  equi potential.  We  must 
assume  therefore  that  the  reason  why  one  cell  under  ordinary  circum- 
stances forms  only  one  half  of  the  embryo  is  that  its  development  is  regu- 
lated and  determined  by  the  presence  of  the  other  cell  in  connection  with  it 
and  forming  the  other  half  of  the  embryo.  That  is  to  say,  the  development 
of  the  egg  involves  the  adaptation  to  environment  of  a  protoplasm  of  certain 
properties  and  powers  of  reaction.  The  final  product  of  development 
depends  (1)  on  the  nature  of  the  protoplasm  (including  the  nucleus)  of  which 
the  egg  is  composed,  and  (2)  on  the  environmental  conditions  to  which  the 
egg  is  subjected  during  the  rapid  growth  and  multiplication  attending  its 
development.  We  could  therefore  speak  of  a  morphology  of  inheritance, 
but  the  morphology  would  be  ultra-microscopic  and  have  relation  to  the 
molecular  structure  of  the  protoplasm  of  which  the  egg  was  composed. 

In  the  transmission  of  the  potentialities  of  development  from  parent 
to  fertilised  egg  we  must  regard  the  nucleus  as  the  essential  structure.  In 
ordinary  development  the  spermatozoon  furnishes  only  a  nucleus  and 
centrosome,  the  ovum  supplying  the  whole  of  the  cytoplasm.  There  seems 
however  no  grounds  for  assigning  any  directive  power  to  the  latter  struc- 
ture. In  echinoderm  ova  it  is  possible  to  get  rid  of  the  nucleus  and  then  by 
the  introduction  of  spermatozoa  to  have  an  individual  entirely  paternal  in 
origin,  which  on  development  produces  a  larva  of  the  paternal  character. 
In  division  of  the  egg  the  only  part  of  the  cell  which  divides,  so  that  each 
daughter  cell  shall  include  an  equal  part  of  both  parental  germs,  is  the 
nucleus.  The  constant  number  of  the  chromosomes  in  each  species,  and 
their  accurate  division  on  mitosis,  suggest  that  the  hereditary  transmission 
of  the  potentialities  of  the  cell  is  bound  up  with  the  chromosomes.  It  has 
been  suggested  that  every  character  is  located  in  a  chromosome  or  part  of 
a  chromosome.  If  this  be  the  case  one  might  regard  the  differentiation 
into  various  tissues,  which  occurs  in  the  process  of  development,  as  occa- 
sioned by  an  actual  loss  or  degeneration  of  the  constituent  parts  of  one  or 
more  chromosomes.  There  is  no  doubt  that  many  tissues  do  become  thus 
differentiated  at  a  fairly  early  period  in  development,  having  undergone  in 
the  process  an  absolute  modification  of  their  potentialities,  which  must  be 
at  any  rate  shared  by  the  chromosomes  of  their  constituent  cells.  The 
extent  to  which  this  limitation  of  powers  of  development  occurs  varies 
widely  in  different  animals.  In  the  higher  animals  such  as  man,  epithelium 
will  reproduce  epithelium  and  liver  cells  will  reproduce  liver  cells,  while 
nerve  cells  are  absolutely  incapable  of  multiplication.  On  the  other  hand, 
in  crustacea  a  whole  limb  may  be  torn  off  and  be  regenerated  from  the 
tissues  of  the  stump.  Destruction  of  the  optic  lens  in  the  salamander  is 
followed  by  its  regeneration  from  the  anterior  part  of  the.  optic  cup,  a  tissue 
80 


L266  PHYSIOLOGY 

which  had  no  part  in  its  primary  formation.  Worms  will  form  a  new  bead 
after  decapitation.  In  these  animals  therefore,  the  cells  in  many  parts  of 
the  body  possess  the  power  of  directed  growth,  if  need  arise  in  case  of 
injury,  and  are  able  to  form  tissues  of  many  different  kinds. 

I  have  mentioned  the  small  size  of  the  larva  formed  from  isolated  cells 
of  the  segmenting  egg  as  a  proof  that  the  number  of  cell  divisions  of  the 
somatic  part  of  the  developing  animal  is  predetermined  and  limited .  This 
conclusion  must  not  be  taken  too  absolutely.  Many  of  the  tissues,  even  of 
the  highest  animals,  possess  the  power  of  almost  unlimited  regeneration  by 
cell  multiplication  as  a  response  to  injury.  Under  normal  conditions  the 
growth  of  snch  tissues  is  limited,  not  by  absence  of  power  to  divide,  but  as 
a  result  of  a  mutual  interaction  between  them  and  the  surrounding  tells. 
We  might  almost  speak  of  a  struggle  for  existence  between  the  various  tissues 
of  the  body,  which  in  the  healthy  organism  results  in  an  equilibrium  or 
balance  of  multiplicative  powers.  If  this  balance  is  upset  by  any  means, 
such  as  stimulation  of  certain  cells  by  the  presence  of  intracellular  parasites, 
or  their  destruction  by  irritants  or  other  abnormal  conditions  (e.  g.  exposure 
to  X-rays),  one  tissue  may  enter  into  active  growth  at  the  expense  of  the 
surrounding  tissues,  and  the  result  is  a  morbid  growth  such  as  cancer.  It  is 
possible  that  in  the  latter  case  a  new  factor  comes  into  play.  All  tissues 
of  the  body,  as  we  have  seen,  begin  to  die  from  the  time  that  they  are  born. 
They  have  a  certain  span  of  hfe,  a  certain  limitation  to  their  generations, 
which  results  in  the  phenomenon  of  senescence,  such  as  occurs  in  a  culture 
of  protozoa.  Li  protozoa  this  phenomenon  is  the  signal  for  rejuvenation 
by  conjugation.  It  is  possible  that  in  cancer  something  of  the  same  nature 
occurs.  It  is  at  any  rate  significant  that  in  a  rapidly  growing  cancer  many 
of  the  dividing  cells  present  the  phenomenon  of  heterotype  mitosis,  a 
phenomenon  which  is  otherwise  found  only  in  the  sexual  cells  preparing 
for  conjugation  and  for  the  production  of  a  new  individual.  Given  adequate 
conditions  of  nutrition,  there  seems  to  be  no  limit  to  the  growth  of  cancer 
cells.  In  mice  a  cancer  may  be  transferred  from  one  individual  to  another 
by  inoculation,  and  this  process  may  apparently  go  on  indefinitely,  so  that 
finally  a  mass  of  cancer  cells  may  have  been  produced  equal  in  volume  to 
many  thousands  of  mice,  and  persisting  long  after  the  mouse  from  which 
it  was  first  taken  would  have  died  under  natural  conditions. 

In  sexual  reproduction  the  new  individual  partakes  of  characteristics 
of  both  its  parents.  It  therefore  resembles  neither  of  its  parents  in  all 
details.  The  conjugation  of  the  two  parent  cells,  from  which  it  is  derived,  has 
been  preceded  by  a  throwing  out  of  half  the  chromosomes  from  each  parent 
cell-  It  is  therefore  natural  to  ascribe  the  variations,  which  occur  among  the 
members  of  one  family,  to  a  qualitative  difference  in  the  chromosomes  which 
have  been  eliminated  in  the  formation  of  their  respective  egg  cells.  Can 
we  regard  the  chromosomes  as  representing  separate  qualities  of  the  individual, 
or  must  we  assume  that  all  qualities  are  represented  to  a  greater  or  less 
extent  in  every  chromosome  ?  In  the  case  of  many  qualities,  especially 
those  which  distinguish  the  species  as  apart  from  the  individual  variation 
or  family  characteristic,  we  must  probably  accept  the  latter  idea  as  correct. 


DEVELOPMENT  AND  HEREDITY  1267 

In  i  his  rase  the  child  can  be  regarded  as  representing  an  arithmetical  mean 
of  both  its  parents.  In  certain  respects  however,  a  cpiality  seems  to  be 
transmitted  from  parent  to  offspring  either  completely  or  not  at  all.  This 
is  specially  applicable  to  those  characters  which  have  been  rapidly  produced 
by  artificial  selection,  characters  which,  if  artificial  selection  be  abandoned, 
rapidly  disappear,  with  reversion  to  the  type  from  which  the  special  strain 
was  ultimately  produced. 

The  way  in  which  these  characteristics  are  transmitted  was  first 
studied  by  Mendel  and  has  been  formulated  as  Mendel's  law.  Mendel's 
first  experiments  were  carried  out  on  peas.  On  crossing  a  tall  plant 
with  a  dwarf  plant,  seeds  were  obtained  from  which  all  the  plants  were 
tali.  On  recrossing  the  plants  of  this  generation  among  one  another,  a 
third  generation  was  obtained  in  which  25  per  cent,  of  the  plants  were 
dwarfs  and  75  per  cent,  were  tall.  Crossing  the  dwarf  plants  among 
themselves  led  to  the  production  of  dwarf  plants  through  successive 
generations.  Of  the  75  per  cent,  tail  plants  one-third  and  all  their  descend- 
ants continued  to  produce  tall  plants  when  self -fertilised,  whereas  of  the 
remaining  two-thirds  of  the  tali  plants  25  per  cent,  produced  dwarfs  and 
75  per  cent,  produced  tail  plants.  On  continuing  the  process  of  breeding,  the 
dwarf  plants  when  self-fertilised  always  produced  dwarfs,  whereas  of  the 
tall  plants  25  per  cent,  produced  tall  plants  which  bred  true,  while  the 
remaining  50  per  cent,  produced  the  same  percentage  of  tall  and  dwarf  as  in 
the  preceding  generations.  Mendel  explained  these  results  by  the  assump- 
tion that  a  character  could  be  dominant  or  recessive.  If  both  characters 
were  present  together  in  one  plant  it  would  partake  of  the  dominant  type ; 
the  fact  that  this  plant  possessed  the  recessive  character  would  be  shown  only 
by  the  results  of  breeding.  In  the  case  of  the  peas  the  tall  character  was 
dominant  over  the  dwarf.  Thus  when  the  tall  and  dwarf  pea  were  crossed 
the  first  generation  of  plants  would  exhibit  the  dominant  character  and  be 
tall.  In  the  second  generation  however,  25  per  cent,  of  the  individuals 
would  be  pure  dominants  (D  -\-  D),  25  per  cent,  would  be  pure  recessive 
(1!  -I-  R)i  while  50  per  cent,  would  be  mixed  (D  +  R)-  The  pure  dominants 
bred  together  would  always  give  rise  to  nothing  but  pure  dominants,  the 
recessive  to  recessive,  while  the  mixed  type  would  always,  as  before,  give 
rise  to  25  per  cent,  pure  dominants,  50  per  cent,  mixed,  and  25  per  cent. 
pure  recessives.  These  results  may  perhaps  be  made  clearer  by  the  following 
Table  : 

D+  R 

I 
DR 


D                                     t ,,DR  25%  R 

I  !              I 

I  !                    I  I  I 

J)  25%  l>                   50%  DR  25%  It  R 


D    25%  D  50%  DR      25%  R  R 


1268  PHYSIOLOGY 

It  has  been  suggested  that  a  very  large  number,  if  not  all,  of  the  characters 
of  an  individual  might  be  brought  under  this  law.  This  might  be  done 
by  indefinitely  subdividing  the  characters,  but  the  question  would  then 
become  beyond  the  limits  of  analysis  or  experimental  investigation.  There 
is  no  doubt  that  many  qualities  are  subject  to  Mendel's  law,  and  that  their 
study  will  be  of  considerable  assistance  in  guiding  the  efforts  of  our  breeders 
and  horticulturists  in  the  formation  of  new  varieties  desirable  for  their 
value  to  man.  In  respect  of  many  qualities  the  Mendelian  law  seems  to 
fail.  Thus  in  man  the  progeny  of  a  cross  between  a  white  and  black  race 
are  more  or  less  intermediate  between  the  two  and  vary  according  to  the 
amount  of  black  and  white  blood  introduced  in  succeeding  generations. 
Definite  black  and  white  individuals  are  not  produced,  but  merelyindividuals 
of  various  degrees  of  brownness. 


SECTION   III 
REPRODUCTION    IN    MAN 
THE    DEVELOPMENT   OF   THE    REPRODUCTIVE   ORGANS 

The  most  marked  example  of  chemical  correlation  is  found  in  the  influence 
exerted  by  the  genital  glands  upon  the  other  parts  of  the  reproductive 
apparatus  and  upon  the  body  generally.  Thus  castration,  i.  e.  removal  of 
the  testes  or  ovaries,  if  carried  out  before  the  time  of  puberty,  prevents  the 
development  of  the  secondary  sexual  characters,  which  normally  occurs 
at  this  epoch  in  both  sexes.  Puberty  denotes  the  period  at  which  ripe 
spermatozoa  and  ova  are  produced  in  the  testis  and  ovary  respectively.  In 
the  human  species  this  period  is  marked  or  preceded  in  the  male  by  increased 
growth  of  the  skeleton,  by  growth  of  the  larynx,  leading  to  a  lowering 
in  pitch  of  the  voice,  by  the  growth  of  hair  on  the  face  and  pubes,  and 
by  the  development  of  sexual  desire.  In  the  female  we  find  at  puberty 
enlargement  of  the  breasts,  attended  by  some  growth  of  the  mammary 
glands  and  by  a  moulding  of  the  whole  form,  making  it  more  fit  for  the 
bearing  of  children.  The  chief  sign  of  puberty  in  the  female  consists  in  the 
periodic  changes  in  the  uterus,  which  give  rise  to  menstruation,  i.  e.  a  flow 
of  blood  and  mucus  from  the  genital  organs,  lasting  three  to  five  days  and 
repeated  every  four  weeks.  Menstruation  persists  so  long  as  the  ovary  is 
functional,  and  is  producing  ripe  ova.  The  activity  of  the  ovary  comes  to 
an  end  between  the  forty-fifth  and  fiftieth  year  ('  the  climacteric  '  or 
'  change  of  life  ').  With  the  cessation  of  its  activity  menstruation  also 
stops,  and  the  uterus  undergoes  a  process  of  atrophy.  These  secondary 
sexual  characters  must  be  ascribed  to  the  influence  of  chemical  substances 
produced  in  the  ovary  and  testis  respectively.  Castration  after  puberty, 
though  not  causing  any  change  in  the  skeleton,  which  has  already  assumed 
its  permanent  form,  brings  about  retrogressive  changes  in  the  other  genital 
organs,  analogous  to  those  occurring  in  the  female  at  the  climacteric.  In 
animals  the  phenomena  of  '  coming  on  heat '  or  '  rat '  seem  to  be  analogous 
with  menstruation  in  the  human  female,  and  like  this  depend  on  the  normal 
activity  of  the  ovary.  They  are  permanently  abolished  by  extirpation  of 
the  ovaries,  but  may  be  reinduced  by  implantation  in  the  peritoneum  of 
an  ovary  from  another  animal  of  the  same  species.  This  fact  shows  that 
the  changes  in  the  uterus  responsible  for  rut,  as  well  as  for  menstruation, 
are  independent  of  any  nervous  connections  between  the  ovaries  and  the 
rest  of  the  body,  and  must  therefore  be  brought  about  by  the  circulation  in 
the  blood  of  specific  chemical  substances  produced  in  the  ovaries.     According 

L269 


1270  PHYSIOLOGY 

in  some  authors,  the  essential  factors  for  the  production  of  these  genital 
hormones  are  the  'interstitial  cells'  found  both  in  the  testes  and  ovaries 
of  various  animals.  These  interstitial  cells  are  not  however  universally 
present.  It  has  been  shown  that,  by  means  of  the  Rontgen  rays,  it  is 
possible  to  destroy  the  germ  cells  in  either  testes  or  ovaries,  so  rendering 
the  animal  sterile.  The  interstitial  cells,  when  present,  are  not  destroyed 
by  these  rays,  yet  the  effects  on  the  accessory  genital  organs  are  stated  to 
be  as  marked  as  after  complete  extirpation  of  either  ovaries  or  testes. 

The  chemical  correlations  between  the  ovaries  and  the  other  organs 
concerned  in  reproduction  are  perhaps  best  marked  in  the  changes  which 
attend  pregnancy.  In  this  case  the  fertilisation  of  the  ovum  by  a  sperma- 
tozoon is  followed  by  a  great  development,  first  of  the  mucous  membrane 
and  later  on  of  the  muscular  wall  of  the  uterus.  The  mucous  membrane 
thickens,  apparently  in  order  to  form  a  bed  for  the  developing  fertilised 
ovum.  With  this  growth  of  the  uterus  there  is  a  corresponding  growth 
of  the  other  parts  of  the  genital  tract,  e.  g.  the  vagina.  At  the  same  time 
rapid  changes  take  place  in  the  mammarv  glands.  These  changes  may  be 
studied  experimentally  in  the  rabbit,  in  which  gestation  lasts  only  about 
twenty-nine  days.  In  a  virgin  rabbit  of  a  year  old  it  is  difficult  with  the 
naked  eye  to  see  any  trace  of  the  mammary  gland  in  the  tissue  lying  under 
the  nipples.  Each  gland  is  limited  to  an  area  not  more  than  1  cm.  broad, 
and  consists  entirely  of  ducts  lined  with  a  single  layer  of  flattened  epithelial 
cells.  With  the  occurrence  of  conception  a  marked  change  takes  place. 
Four  or  five  days  after  fertilisation,  when  it  is  still  impossible  with  the 
naked  eye  to  discover  any  embryos  in  the  swollen  uterine  horns,  on  reflecting 
the  skin  from  the  abdomen  each  mammary  gland  appears  as  a  circular  pink 
area,  about  3  cm.  in  diameter.  On  section  the  gland  consists  of  ducts 
which  are  in  an  active  state  of  proliferation,  their  epithelial  lining  being 
two  or  three  cells  thick  and  presenting  numerous  mitotic  figures.  By  the 
ninth  day  the  whole  abdomen  is  covered  with  a  thin  layer  of  glandular 
tissue ;  by  the  twenty-fifth  day  this  tissue  is  \  cm.  in  thickness  and  consists 
for  the  greater  part  of  secreting  alveoli,  lined  with  cells  containing  numerous 
fat  globules.    At  full  term  the  alveoli  contain  ready-formed  milk. 

This  hypertrophy  of  the  mammary  glands  occurs  during  pregnancy 
after  complete  divisionof  all  possible  nervous  paths  between  the  glands  of 
the  ovaries  or  uterus.  In  the  guinea-pig  a  mammary  gland  has  been  actually 
transplanted  to  another  part  of  the  body,  thus  severing  all  its  normal  nervous 
connections,  and  yet  it  enlarged  as  usual  during  a  subsequent  pregnancy. 
Ancel  and  Bouin  have  brought  forward  evidence  that  the  corpus  luteum — 
the  tissue  produced  in  the  ovary  as  a  result  of  the  discharge  of  an  ovum- 
is  intimately  concerned  with  the  growth  of  the  mammary  glands,  and  may 
indeed  cause  a  certain  degree  of  hypertrophy  of  these  glands  in  the  entire 
absence  of  any  product  of  conception  within  the  uterus.1      The  limited 

1  According  to  Ancel  and  Bouin,  in  the  rabbit  discharge  of  an  ovum  and  formation 
of  a  corpus  luteum  occur  only  as  a  result  of  copulation.  The  same  effect  may  be  pro- 
duced by  artificial  rupture  of  a  ripe  follicle,  whereupon  there  is  a  development 
of  the  mammary  glands.     If  no  impregnation  has  taken  place  (e.  rj.  if  the  buck  has 


REPRODUCTION  IN  MAN  1271 

growth  of  the  glands,  which  occurs  at  puberty,  can  certainly  not  be  ascribed 
to  the  presence  of  a  foetus  in  the  uterus,  and  must  be  connected  with  the 
growth  of  ripe  ova  or,  as  suggested  by  the  two  French  authors,  with  the 
growth  of  the  tissue  of  the  corpus  luteuni,  resulting  from  the  discharge 
of  ova. 

There  seem  also  to  be  obscure  relationships  between  the  activity  of  the 
sexual  organs  and  that  of  certain  so-called  ductless  glands.  Thus  castra- 
tion at  an  early  age  leads  to  persistence  of  the  thymus  gland,  whereas 
normally  this  gland  atrophies  just  before  the  sexual  organs  commence  their 
functional  activity.  The  existence  of  a  connection  between  the  thyroid 
and  the  ovaries  has  been  a  popular  belief  for  2000  years.  In  many  individuals 
the  thyroid  is  perceptibly  enlarged  at  each  menstrual  period.  On  the  other 
hand,  extirpation  of  the  thyroid  before  puberty  brings  about,  among  the 
other  signs  of  cretinism,  failure  of  development  of  the  ovaries,  so  that 
puberty  is  delayed  partially  or  completely. 

We  must  thus  regard' the  germ  cells  not  only  as  representing  the  cells 
from  which  the  individuals  of  the  new  generation  may  be  developed,  but 
also  as  concerned  in  the  formation  of  chemical  substances  which,  dis- 
charged into  their  hosts,  affect  many  or  all  of  the  functions  of  the  latter, 
with  the  object  of  finally  subordinating  the  activities  of  the  individual  to 
the  preservation  and  perpetuation  of  the  species. 

THE   MALE   REPRODUCTIVE   ORGANS 

In  all  the.  higher  animals  we  may  divide  the  reproductive  organs  into 
the  essential  organs,  which  form  the  germ  cells,  the  spermatozoa  and  ova 
respectively,  and  the  accessory  organs,  which  have  as  their  office  the  facilita- 
tion of  the  access  of  the  spermatozoa  to  the  ova  (fertilisation),  and  in  the 
female  the  nutrition  of  the  product  of  fertilisation  during  the  early  period 
of  its  development. 

The  essential  sexual  organ  of  the  male  is  represented  by  the  testis. 
This  is  made  up  of  a  collection  of  convoluted  tubules,  the  seminal  tubules, 
which  are  contained  in  a  number  of  compartments  separated  by  fibrous 
septa.  The  tubules  present  few  or  no  branches,  each  one  being  about 
500  mm.  long.  The  testis  is  formed  in  the  first  instance  in  the  peritoneal 
cavity  from  the  germinal  epithelium,  but  early  in  life  leaves  the  abdominal 
cavity  by  the  abdominal  ring  to  lie  in  a  pouch  of  skin — the  scrotum.  Several 
tubules  unite  to  form  a  straight  tubule,  which  leads  by  a  series  of  com- 
municating spaces,  the  rete  testis,  into  the  vasa  efferentia  (Fig.  573).  These 
join  to  form  the  duct  of  the  epididymis,  coiled  into   a  mass  lying  at  the 

been  sterilised  by  ligature  of  the  vas  deferens),  the  glands  develop  for  fourteen  days 
and  then  begin  to  atrophy.  This  period  corresponds  to  the  period  of  active  growth 
of  the  corpus  luteum.  The  continued  growth  during  the  latter  half  of  pregnancy  these 
authors  ascribe  to  the  production  of  another  hormone  by  a  special  glandular  tissue 
('  myoruetrial  gland  ')  which  makes  its  appearance  about  the  fourteenth  day  in  the  wall 
of  the  uterus,  at  the  site  of  implantation  of  the  placenta,  and  lasts  until  the  end  of 
pregnancy. 


1272 


PHYSIOLOGY 


back  of  the  testis.  The  epididymis  is  composed  of  the  convolutions  of  this 
single  duct,  which  is  about  20  feet  long.  From  the  lower  end  of  the  epi- 
didymis the  vas  deferens,  a  tube  with  thick  muscular  walls,  leads  by  the 
abdominal  ring  to  the.  base  of  the  bladder,  where  it  opens  into  the  beginning 
of  the  urethra  in  its  prostatic  part.  Just  before  it  joins  the  urethra  each  vas 
deferens  presents  a  diverticulum,  the  seminal  vesicle,  which  lies  along,  and 
is  attached  to,  the  base  of  the  bladder.  The  prostate  itself,  which  surrounds 
the  first  part  of  the  urethra,  is  composed  of  a  matrix  of  unstriated  muscular 
fibres,  enclosing  numerous  branched  racemo-tubular  glands.  From  the 
point  of  entry  of  the  vasa  deferentia  to  its  orifice,  the  urethra  represents 


Tunica  vaginalis 

Tunica  albuginea 

Septum 

Seminal  tubule? 

Lobule 


Fro.  573. 


—    Vas  deferens 


Vasa  efferentu 


_  Yas  aberrans 


mmatic  representation  of  the  course  of  the  seminal  tubules  in  the 
testis  and  epididymis.     (After  Nagel.) 


a  common  passage  for  the  urine  and  for  the  sexual  products-— the  semen. 
It  passes  therefore  through  tissues,  forming  the  penis,  which  are  especially 
adapted  for  the  purpose  of  intromission,  i.  e.  the  introduction  of  the  semen 
containing  the  spermatozoa  into  the  female.  In  the  urethra  we  distinguish 
the  prostatic,  the  membranous,  and  the  penile  portions.  Into  the  beginning 
of  the  penile  portion,  the  bulb  of  the  urethra,  open  the  ducts  of  the  two 
glands  of  Cowper.  In  the  penis  itself  the  urethra  is  surrounded  with 
erectile  tissue,  forming  the  corpus  spongiosum,  and  lies  between  the  two 
corpora  cavernosa,  which  consist  of  the  same  kind  of  tissue.  The  erectile 
tissue  is  a  spongy  meshwork  of  elastic  and  unstriated  muscle  fibres,  enclosing 
spaces  in  free  communication  with  the  efferent  veins  of  the  organ.  The 
arterioles  also  open  into  these  spaces,  but  under  normal  circumstances  both 
the  arterioles  and  the  muscle  tissues  of  the  framework  are  contracted,  so 
that  the  blood  trickles  very  slowly  from  the  arterioles  into  the  spaces, 
whence  it  escapes  readily  by  means  of  the  veins.     If  the  muscle  fibres  be 


REPRODUCTION   IN  MAN  1273 

relaxed,  so  that  blood  can  pass  rapidly  into  and  distend  the  spaces,  the 
tissue  swells  and  becomes  harder,  causing  '  erection  '  of  the  organ. 

In  the  immature  testis,  i.  e.  from  birth  up  to  puberty,  the  seminal  tubules 
are  filled  with  cells  with  large  nuclei.  Some  of  these  are  the  spermatogonia, 
the  mother  cells  of  the  future  spermatozoa,  while  the  others  form  the  cells 
of  Sertoli,  whose  function  it  is  to  act  as  nurse  cells  to  the  developing  sper- 
matozoa. The  actual  formation  of  spermatozoa  begins  at  puberty,  when 
the  spermatogonia  divide  many  times  to  form  the  spermatocytes,  which 
in  their  turn  undergo  heterotype  mitosis  to  form  the  spermatids,  as  already 
described.  By  a  modification  of  the  latter  the  fully  formed  spermatozoa 
are  formed.  These,  when  mature,  pass  by  the  tubules  of  the  testis  and  of 
the  epididymis  into  the  vas  deferens,  whence  they  make  their  way  into  the 
seminal  vesicles.  Their  movement  is  probably  facilitated  by  the  cells  fining 
the  tubule  of  the  epididymis  as  well  as  by  the  secretion  of  the  fining  mem- 
brane of  the  seminal  vesicles.  It  has  been  noted  that  the  spermatozoa  are 
practically  motionless  while  in  the  seminiferous  tubules  of  the  testis,  but 
become  actively  motile  in  the  vas  deferens,  or  when  mixed  with  prostatic 
secretion.  It  is  difficult  to  understand  how  the  spermatozoa  are  conveyed 
through  the  resistance  which  must  be  offered  by  the  huge  length  of  the 
tubule  of  the  epididymis,  unless  their  onward  motion  is  facilitated  by  the 
cilia-like  structures  attached  to  some  of  the  cells  lining  this  tubule.  The 
formation  of  the  spermatozoa  is  continuous,  though  the  rate  at  which  this 
occurs  is  variable  and  regulated  by  the  sexual  activity  of  the  individual.  In 
the  fully  formed  semen  the  spermatozoa  originating  in  the  testis  are  mixed, 
not  only  with  the  fluid  secreted  by  the  fining  membrane  of  the  epididymis 
and  of  the  seminal  vesicle,  but  also  with  the  mucous  secretions  of  the  prostatic 
glands  and  of  Cowper's  glands.  Nevertheless  it  contains  spermatozoa  in 
enormous  numbers,  the  semen  emitted  at  a  single  act  of  coitus  containing 
as  many  as  226,000,000  spermatozoa.  Though  the  vast  majority  of  these 
are  probably  capable  of  fertilising  an  ovum,  this  act  is  carried  out  by  only 
one — a  fact  characteristic  of  the  prodigality  of  nature  when  dealing  with 
the  perpetuation  of  the  type. 

THE   FEMALE   REPRODUCTIVE   ORGANS 

The  essential  organ  of  reproduction  in  the  female  is  the  ovary,  the  seat 
of  production  of  the  ova.  The  accessory  organs  include  the  oviducts  or 
Fallopian  tubes,  the  uterus,  in  which  the  fertilised  ovum  is  retained  during 
the  first  nine  months  of  its  development,  and  the  vagina,  which  is  especially 
adapted  for  the  reception  of  the  male  organ  in  the  act  of  impregnation. 

Among  the  accessory  organs  we  may  also  reckon  the  mammary  glands, 
which  undergo  a  special  development  during  pregnancy,  and  serve  for 
the  nourishment  of  the  young  individual  during  the  first  period  of 
extra  -uterine  life, 

OVULATION.  At  birth  the  ovary  consists  of  a  stroma  of  spindle-shaped 
cells,  and  is  covered  by  a  layer  of  cubical  epithelium  (the  germ  epithelium) 
continuous   with    the  endothelium  lining  the    general   peritoneal   cavity. 


1274 


NIYSIOLOdY 


Embedded  in  the  stroma  but  especially  numerous  just  underneath  the  epithe- 
lium, are  a  vast  number  of  '  primordial  follicles.'  These  are  formed  during 
foetal  life  by  down  growths  of  the  germinal  epithelium.  Of  the  cells  pro- 
longed in  this  way  from  the  germinal  epithelium,  some  undergo  enlargement 
to  form  the  primordial  ova,  while  the  others  are  arranged  in  a  single  layer 
of  flattened  nucleated  cells,  the  '  follicular  epithelium,'  as  a  sort  of  capsule 
to  the  ovum.  Of  the  primordial  follicles,  about  70,000  are  to  be  found  in 
the  ovary  of  the  newborn  child.    During  the  first  twelve  to  fourteen  years  of 


Fig.  574.     Graafian  follicle  of  mammalian  ovary.     (Prenant  and  Bouin.) 

ov,  ovum;   dip,  discus  proligerus;   Iq.f,  liquor  folliculi;   ch,  theoa; 

gr,  membrana  granulosa. 


life  they  remain  in  a  quiescent  condition.  With  the  onset  of  puberty  one  or 
more  of  the  primordial  follicles  begin  to  develop.  Indeed,  this  development 
may  be  regarded  as  the  causative  factor  in  the  various  phenomena  which 
are  characteristic  of  puberty  in  the  female  (v.  p.  1269).  The  first  stage  in 
the  growth  of  the  follicle  is  a  proliferation  of  the  follicular  epithelium,  the 
cells  of  which  become  cubical  and  are  arranged  in  Iseveral  layers  round  the 
ovum.  At  one  point  in  the  mass  of 'cells  surrounding  the  ovum,  a  cavity 
appears  rilled  with  fluid,  the  liquor  folliculi.     The  epithelium  thus  becomes 


REPRODUCTION  IN  MAN         -  1275 

separated  into  two  parts,  i.  e.  the  membrana  granulosa,  several  layers  thick, 
lining  the  whole  follicle,  and  the  discus  proldgerus,  a  mass  of  cells  attached  to 
one  side  of  the  follicle,  in  which  is  embedded  the  ovum  (Fig.  574).  Round 
the  growing  follicle  the  stroma  assumes  a  concentric  arrangement  and  forms 
a  capsule,  of  which  the  internal  layer  consists  chiefly  of  spindle-shaped  cells 
richly  supplied  with  blood  vessels,  while  the  outer  layer — the  theca  externa 
— is  made  up  of  a  tough  fibrous  tissue.  With  the  growth  of  the  follicle 
the  ovum  also  becomes  larger  and  surrounds  itself  with  a  distinct  membrane, 
known  as  the  zona  pellvcida.  This  membrane  presents  a  fine  radial  striatum, 
which  is  supposed  to  indicate  the  existence  of  canals  through  which  the 
ovum  can  obtain  sustenance  from  the  surrounding  cells  of  the  follicular 
epithelium.  The  nucleus  also  becomes  larger,  and  forms  the  germinal 
vesicle  containing  one  or  two  well-marked  nucleoli — the  germinal  spot.  The 
mature  Graafian  follicle  projects  from  the  surface  of  the  ovary  as  a  trans- 
parent vesicle  about  the  size  of  a  pea.  (Its  diameter  is  about  15  mm.)  In 
the  process  of  growth  the  ovum  has  increased  from  a  diameter  of  25/x  to 
200jW..  Before  the  ovum  can  undergo  fertilisation,  the  double  division  of 
the  nucleus  or  germinal  vesicle  has  to  take  place,  which  leads  to  the  forma- 
tion and  extrusion  of  the  two  polar  bodies.  This  process  probably  occurs 
just  before  or  just  after  the  discharge  of  the  ovum  from  the  ovary. 

With  increasing  size  of  the  Graafian  follicle  the  membrane  covering  it 
becomes  progressively  thinner.  At  certain  periods,  or  under  certain  con- 
ditions, the  membrane  ruptures,  and  the  ovum  is  discharged  in  the  liquor 
fbllicidi,  still  surrounded  by  an  adherent  mass  of  the  cells  of  the  discus 
proligerus.  Li  some  animals  this  process  of  ovulation  occurs  at  definite 
periods  of  the  year.  In  others  such  as  the  rabbit,  the  occurrence,  of  ovula- 
tion depends  upon  coitus  taking  place  during  the  period  of  sexual  activity. 
We  shall  have  later  to  discuss  the  relation  of  ovulation  in  the  human  female 
to  the  periodic  changes  occurring  in  the  other  parts  of  the  reproductive 
apparatus. 

After  the  discharge  of  the  ovum  the  remaining  portions  of  the  follicle 
undergo  a  characteristic  series  of  changes,  svhich  result  in  the  production 
of  the  corpus  luteum.  Immediately  after  the  rupture  the  follicle  becomes 
filled  with  blood,  apparently  resulting  from  the  sudden  release  of  the  pressure 
on  the  capillaries  in  the  walls  of  the  follicle.  The  cells  of  the  membrana 
granulosa  rapidly  increase  in  size,  a  few  of  them  undergoing  mitotic  division, 
so  that  a  dense  mass  of  cells  is  formed,  nearly  filling  the  original  follicle.  At 
the  same  time  the  cells  of  the  internal  theca  proliferate,  with  the  formation 
of  connective  tissue,  which  grows  in  among  the  cells  filling  the  Graafian 
follicle.  These  cells  finally  attain  a  size  four  or  five  times  that  of  the  cells 
of  the  membrana  granulosa  in  the  mature  follicle.  Blood  vessels  grow  from 
the  external  theca  towTards  the  centre  of  the  follicle.  The  cells  within  the 
follicle  then  undergo  fatty  degeneration  and  present  a  yellow  colour  due 
to  a  fatty  pigment  known  as  lutein.  The  corpus  luteum,  as  the  body  so 
formed  is  called,  attains  its  greatest  size  about  a  week  after  ovulation,  and 
then    gradually    undergoes    regressive    changes.      If    however    the    ovum, 


1270 


PHYSIOLOGY 


which  has  been  discharged,  undergoes  fertilisation,  and  pregnancy  results, 
the  corpus  luteum  continues  to  grow  for  a  considerable  time  and  attains  its 
largest  size  at  about  the  third  month  of  pregnancy.  It  does  not  entirely 
disappear  until  after  the  end  of  pregnancy.  The  big  corpus  luteum  found 
in  pregnancy  is  often  spoken  of  as  the  '  true '  corpus  luteum,  and  is 
distinguished  from  the  corpus  luteum  spurntm  of  menstruation  or  of 
ovulation  without  fertilisation.  There  is  no  essential  difference  other  than 
that  of  size  between  these  two  kinds  of  corpus  luteum.  It  must  not  be 
imagined  that  all  the  70,000  primordial  follicles  found  in  the  ovary  of  a 
newborn  child  undergoes  this  series  of  changes ;  it  is  probable  that  in  the 
human  female  ovulation  occurs,  as  a  rule,  once  every  four  weeks  during  the 


Fig.  575.     Fully  developed  corpus  luteum  o£  the  mouse.     (Sobotta.) 

thirty-five  years  of  sexual  life.  A  vast  number  of  the  Graafian  follicles, 
after  developing  to  a  certain  extent,  undergo  regressive  changes,  both  during 
childhood  and  during  adult  life.  The  cellular  elements  degenerate,  leuco- 
cytes wander  into  the  follicle  and  attack  the  degenerating  ovum,  so  that 
finally  the  follicle  is  replaced  by  connective  tissue,  without  the  formation 
of  any  corpus  luteum. 

MENSTRUATION.  Puberty  in  the  girl  is  marked  by  the  onset  of 
menstruation.  Under  this  term  is  understood  a  flow  of  blood  and  mucus 
from  the  uterus,  which  recurs  every  four  weeks  and  lasts  each  time  from  four 
to  five  days.  Before  the  first  menstrual  period,  other  signs  of  puberty,  i.  e. 
of  approaching  sexual  maturity,  are  usually  observed.  These  include 
rapid  growth,  with  changes  in  the  skeleton,  leading  to  the  typically  feminine 
type  of  pelvis,  a  development  of  the  mammary  glands,  and  the  growth  of 
hair  on  the  pubes.  At  the  same  time  there  is  increased  development  of  the 
mental  characteristics  which  are  typical  of  the  sex.     The  amount  of  blood 


REPRODUCTION  IN   MAN  1277 

lust  at  each  menstrual  period  varies  between  luo  and  300  grm.  During  the 
'  period  '  there  are  often  disturbances  of  other  functions  of  the  body,  which 
are  so  common  that  to  be  '  unwell '  is  the  recognised  polite  description  of 
the  menstrual  period.  Thus  it  is  often  attended  with  pains  in  the  abdomen, 
a  feeling  of  weight  and  fulness,  disturbance  of  digestion,  headache,  and 
neuralgias  of  various  distribution.  At  the  same  time  there  is  a  general 
disinclination  for  exertion. 

Menstruation  is  due  to  periodic  changes  in  the  uterine  mucous  membrane. 
During  the  few  days  previous  to  the  period  the  mucous  membrane  undergoes 
a  rapid  hypertrophy,  increasing  in  thickness  from  2  mm.  to  6  mm.  At  the 
same  time  there  is  increased  vascularity  of  the  membrane  in  consequence  of 
dilatation  of  its  blood  vessels.  At  the  commencement  of  the  menstrual 
period  there  is  an  escape  of  the  red  blood  corpuscles,  chiefly  by  diapedesis, 
but  partly  by  actual  rupture  of  the  blood  capillaries  into  the  spaces  between 
the  uterine  glands.  At  this  period  sections  of  the  uterine  mucous  mem- 
brane show  numerous  collections  of  red  blood  corpuscles,  lying  immediately 
under  the  superficial  epithelium.  In  some  cases  this  stage  is  followed  by 
an  almost  complete  desquamation  of  the  superficial  epithelium.  Generally 
the  desquamation  is  only  partial,  but  in  either  case  the  blood  escapes  into 
the  cavity  of  the  uterus,  where  it  becomes  mixed  with  the  increased  secre- 
tion from  the  uterine  glands  and, is  discharged  into  and  from  the  vagina  as 
t  lie  menstrual  fluid.  With  the  occurrence  of  the  menstrual  flow  the  mucous 
membrane  begins  to  diminish  in  thickness.  The  vascularity  decreases,  and 
much  of  the  blood  in  the  deeper  parts  of  the  mucosa  becomes  reabsorbed. 
The  desquamated  epithelium  is  replaced  by  proliferation  of  the  cells  which 
remain  intact,  so  that  finally  the  mucosa  is  completely  regenerated  and 
brought  back  to  its  original  condition.  This  period  of  regeneration  lasts 
about  fourteen  days.  During  the  next  few  days  the  condition  of  the  mem- 
brane is  stationary,  but  this  period  of  rest  lasts  but  a  short  time,  since  signs 
of  the  pre-menstrual  swelling  can  be  detected  as  early  as  three  days  before 
the  onset  of  the  next  menstrual  period. 

THE    RELATION    OF    OVULATION    TO    MENSTRUATION 

There  is  no  doubt  that  menstruation  depends  on  the  functional  activity 
of  the  ovary.  Its  onset  coincides  with  the  first  production  of  ripe  ova  in  the 
ovary,  and  it  ceases  with  the  cessation  of  ovulation  at  the  climacteric  or 
menopause.  In  cases  where  the  ovaries  have  been  removed  before  puberty 
menstruation  never  occurs.  Removal  of  both  ovaries  during  adult  life 
generally  brings  about  a  premature  menopause.  It  seerns  probable  that 
the  ripening  of  the  ova  in  the  human  ovary  occurs  at  periods  corresponding 
to  those  of  menstruation.  But  there  has  been  much  division  of  opinion  as  to 
the  exact  relation  between  the  two  processes.  Fairly  definite  clinical  and 
■post-mortem  evidence  has  1 n  brought  forward  for  the  theory  that  ovula- 
tion precedes  the  menstrual  flow.  On  this  theory  the  degeneration  of 
the  uterine  mucous  membrane,  which  occurs  at  each  period,  represents,  so 


1278  PHYSIOLOGY 

to  speak,  the  undoing  of  a  preparation  for  the  reception  of  a  fertilised  ovum. 
The  ovum  has  been  discharged,  the  mucous  membrane  has  been  prepared 
for  its  reception,  but  fertilisation  not  having  taken  place,  ovum  and  mucous 
membrane  are  cast  out  together  in  the  menstrual  flow.  Unfortunately 
almost  equally  definite  cluneal  evidence  has  been  adduced  for  the  view  that 
ovulation  occurs  during  or  after  the  menstrual  period.  Light  is  thrown 
upon  the  question  by  the  study  of  the  phenomena  of  '  rut '  or  '  heat '  in  the 
lower  animals.  In  most  mammals  impregnation  and  conception  can  only 
occur  at  certain  definite  periods  of  the  year.  At  these  seasons  the  female 
presents  a  swelling  of  the  mucous  membrane  of  the  external  genitals,  and 
often  a  flow  of  blood  or  mucus.  As  a  rule  it  is  only  when  in  this  condition 
that  it  will  permit  the  approach  of  the  male.  Thus  the  bitch  '  comes  on 
heat '  as  a  rule  twice  in  the  year ;  the  cat  three  or  four  times ;  most  car- 
nivora  only  once  a  year.  At  these  periods  the  uterus  shows  well-marked 
histological  changes,  which  may  be  divided  into  the  following  periods  : 

(1)  The  period  of  rest.  During  this  time,  which  extends  over  the  greater 
part  of  the  year,  the  mucous  membrane  is  thin  and  pale.  The  period  of 
heat  being  known  as  the  oestrus,  this  first  period  is  denoted  by  Heape  the 
anoBstrum. 

(2)  The  period  of  growth  or  congestion.  This  corresponds  to  the  pre- 
menstrual thickening  of  the  mucous  membrane  of  the  human  female. 

(3)  Period  of  destruction,  associated  with  haemorrhages  into  the  mucous 
membrane,  desquamation  of  the  superficial  epithelial  cells,  and  occasionally 
discharge  of  blood  and  mucus  from  the  vagina.  These  two  periods  are 
grouped  together  as  the  pro-oeslrum. 

(4)  Period  of  recuperation  corresponding  to  the  post-menstrual  regenera- 
tion of  the  mucous  membrane.  It  is  during  the  first  part  of  this  period  or  at 
the  very  end  of  the  last  period  that  ovulation  occurs  in  those  animals  where 
ovulation  is  independent  of  coitus.  It  is  at  this  time  too  that  the  animal 
exhibits  sexual  desire  and  permits  the  approaches  of  the  male.  If  fertilisa- 
tion occurs,  the  mucous  membrane  undergoes  rapid  hypertrophy,  much 
more  marked  than  that  occurring  during  the  pro-oestrum.  In  the  absence 
of  impregnation  the  mucous  membrane  returns  to  the  condition  of  rest,  the 
stage  of  return  being  known  as  the  metcestram. 

These  results  have  been  found  by  Heape  and  Marshall  to  apply  to  a 
large  number  of  different  mammals.  We  are  therefore  justified  in  con- 
cluding that  menstruation  is  the  physiological  homologue  of  the  pro-oestrum 
in  the  lower  mammals,  and  that  ovulation  occurs,  or  at  any  rate  that  the 
ova  attains  maturity,  after  or  at  the  very  end  of  the  menstrual  flow.  If  we 
consider  that  the  ovum  may  take  some  days  to  pass  down  the  Fallopian 
tube  to  the  uterus,  and  that  the  spermatozoa  may  retain  their  vitality  for 
ten  days  or  more  in  the  Fallopian  tubes  or  uterus,  it  is  evident  that  in  man 
impregnation  may  take  place  at  any  time  between  two  menstrual  periods. 
Sexual  desire  is  thus  not  limited  to  certain  seasons,  as  is  the  case  with  most 
of  the  lower  animals. 


REPRODUCTION  IN  MAN  1279 


FERTILISATION 


The  act  of  impregnation  consists  in  the  introduction  of  spermatozoa 
into  the  female  genital  tract,  where  they  may  come  in  contact  with  and 
fertilise  the  ovum,  which  is  discharged  from  the  ovary  by  bursting  of  a 
Graafian  follicle.  This  is  effected  in  the  act  of  coitus  or  sexual  congress  by 
the  insertion  of  the  penis  into  the  vagina  of  the  female.  Before  this  can 
occur  erection  of  the  male  organ  must  take  place.  The  mechanism  of 
erection  is  twofold.  The  most  important  factor,  as  was  shown  by  Eckhard 
and  Loven.  is  an  active  dilatation  of  the  vessels  of  the  penis,  especially  of  the 
medium-sized  and  smaller  arteries.  If  the  penis  be  cut  across  while  in  the 
flaccid  condition,  venous  blood  merely  trickles  away  from  the  cut  surface, 
whereas,  if  erection  be  excited,  the  flow  of  blood  from  the  cut  surface  is 
increased  eight  to  ten  times,  and  the  blood  becomes  bright  arterial  in  colour. 
It  is  thus  possible  to  excite  erection  in  an  animal,  in  whom  the  second  factor 
has  been  abolished  by  paralysing  the  muscles  by  means  of  curare.  This 
second  factor  is  the  contraction  of  the  ischio-ca/oe/rnosus  or  erector  penis 
muscle,  certain  fibres  of  which  pass  over  the  dorsal  vein  of  the  penis  and 
compress  this  vessel  when  they  contract.  Since  ligature  of  the  veins 
coming  from  the  penis  does  not  produce  erection,  the  contraction  of  this 
muscle  must  be  regarded  as  simply  aiding  the  effects  of  the  arterial 
dilatation. 

Before  or  at  the  beginning  of  coitus  analogous  changes  occur  in  the 
female  organs,  leading  to  erection  of  the  clitoris  and  of  the  erectile  structures 
of  the  vulva.  The  glands  of  the  vulva,  especially  the  glands  of  Bartholini, 
secrete  a  mucous  fluid,  thus  lubricating  the  passage  into  the  vagina.  The 
friction  between  the  clans  penis  and  the  wall  of  the  vagina  causes  a  reflex 
discharge  of  motor  impulses  in  both  male  and  female  (the  '  orgasm  ').  hi 
the  former  the  muscular  walls  of  the  vasa  deferentia  and  seminal  vesicles 
enter  into  rhythmic  contractions,  thus  forcing  the  spermatozoa  they  contain 
into  the  urethra.  The  spermatozoa,  mixed  with  the  secretions  of  the 
epididymis,  the  seminal  vesicles,  the  prostatic  glands,  and  the  glands  of 
Cowper,  form  the  semen,  which  is  pressed  along  the  urethra  by  rhythmical 
contractions,  from  behind  forwards,  of  the  bulbo-  and  ischio-cavernosi 
muscles.  It  has  been  stated  that  movements  take  place  coincidently  in  the 
uterus,  so  that  its  axis  more  nearly  corresponds  to  that  of  the  vagina.  The 
movement  of  the  semen  along  the  uterus  and  Fallopian  tubes  is  ascribed  by 
certain  observers  to  an  antiperistaltic  contraction  of  these  organs.  A  more 
important  factor  is  probably  the  movement  of  the  spermatozoa  themselves. 
As  we  have  already  seen,  these  are  introduced  into  the  female  passage  in 
countless  numbers.  They  will  be  chemiotactically  attracted  by  the  alkaline 
mucus,  secreted  by  and  filling  the  cervix  of  the  uterus.  When  they  have 
entered  this  organ  they  will  meei  the  downward  stream  of  mucus  impelled 
by  the  action  of  the  cilia  lining  tin'  uterus  and  Fallopian  tubes.  It  seems 
probable  that  their  reaction  to  tins  carrenl  is  to  swim1  against  it  (positi/ve 

1  Spermatozoa  move  in  a  straight  line,  at  (lie  rate  of  2  to  3  mm.  per  minute.     Thus 


1280  PHYSIOLOGY 

•rheotaxis),  so  that  they  reach  the  upper  part  of  the  Fallopian  tubes  or  the 
surface,  of  the  ovary  itself.  Fertilisation  of  the  ovum  occurs  in  most  cases 
in  the  Fallopian  tube,  and  the  fertilised  ovum  is  then  earned  slowly  down 
the  tube  into  the  uterus. 

NERVOUS  MECHANISM  OF  IMPREGNATION.  Although,  in  both  sexes, 
coitus  is  attended  by  a  high  degree  of  psychical  excitement,  yet  it  is 
essentially  a  spinal  reflex,  and  can  be  carried  out  when  all  impulses  from  the 
higher  centres  are  cut  off  by  section  of  the  cord  in  the  dorsal  region.  The 
centre  presiding  over  the  act  is  situated  in  the  lumbar  spinal  cord.  The 
external  generative  organs,  like  the  bladder,  are  supplied  from  two  sets  of 
nerve  fibres — from  the  lumbar  nerves  through  the  sympathetic,  and  from 
the  sacral  nerves.  The  fibres  from  the  lumbar  nerves  arise  in  the  cat  from 
the  second,  third,  and  fourth,  or  the  third,  fourth,  and  fifth  lumbar  nerve 
roots,  and  in  the  dog  from  the  thirteenth  thoracic,  and  the  first  to  the  fourth 
lumbar  roots.  They  run  in  the  white  rami  conimunicantes  to  the  sympathetic 
chain,  whence  they  may  take  two  paths. 

(a)  The  great  majority  of  the  fibres  rim  down  the  sympathetic  chain  to 
the  sacral  ganglia,  whence  fibres  are  given  off  in  the  grey  rami  conimunicantes 
to  the  sacral  nerves ;  their  further  course  is  by  the  pudic  nerves,  none 
running  in  the  nervi  erigentes. 

(b)  A  few  fibres  go  by  the  hypogastric  nerves  to  the  pelvic  plexus. 
Excitation  of  these  fibres  causes  contraction  of  the  arteries- of  the  penis, 

and  of  the  unstriated  muscles  of  the  tunica  dartos  of  the  scrotum.  In  animals 
which  possess  a  retractor  penis  muscle,  excitation  of  the  lumbar  nerves 
causes  strong  contraction  of  the  muscle. 

The  fibres  from  the  sacral  nerves  can  be  divided  into  two  classes — 
visceral  and  somatic.  The  visceral  branches  run  in  the  pelvic  nerves,  or 
nervi  erigentes.  Stimulation  of  these  fibres  produces  active  dilatation  of  the 
arteries  of  the  penis  or  vulva,  and  also  inhibition  of  the  unstriated  muscle  of 
the  penis,  of  the  retractor  muscle  of  the  penis,  when  present,  and  of  the  vulva 
muscles.  The  somatic  branches  supply  motor  nerves  to  the  ischio-  and 
bulbo-cavernosi,  as  well  as  to  the  constrictor  urethrse.  In  the  female  they 
supply  the  analogous  muscles,  namely,  the  erector  clitoridis  (ischio-caver- 
nosus)  and  the  sphincter  vaginae  (bulbo-cavernosus).  Both  these  sets  of 
fibres  are  therefore  involved  in  the  erection  of  the  generative  organs  which 
accompanies  coitus. 

The  internal  organs,  i.  e.  the  uterus  and  vagina  in  the  female,  and  vasa 
deferentia,  seminal  vesicles,  and  uterus  mascuhnus  in  the  male,  differ  from 
the  external  organs  in  receiving  no  efferent  nerve  fibres  from  the  sacral  nerves, 
as  has  been  pointed  out  by  Langley  and  Anderson.  They  are  supplied  with 
fibres,  which  pass  out  through  the  anterior  roots  of  the  third,  fourth,  and 
fifth  lumbar  nerves  (in  the  rabbit  and  cat),  and  run  through  the  sympathetic 

they  might  traverse  the  distance  of  16  to  20  cm.  between  the  os  uteri  and  the  trumpet- 
shaped  orifice  of  the  Fallopian  tubes  in  three-quarters  of  an  hour.  In  animals  sper- 
matozoa have  been  found  at  the  peritoneal  end  of  the  Fallopian  tubes  within  an  hour 
or  two  after  coitus. 


REPRODUCTION  IN  MAN  1281 

to  the  inferior  mesenteric  ganglia,  whence  they  proceed  by  the  hypogastric 
nerves.  On  stimulating  these  fibres,  two  effects  are  produced  on  the  uterus 
and  vagina,  namely,  a  contraction  of  the  small  arteries  leading  to  palior 
of  the  organs,  and  a  strong  contraction  of  the  muscular  coats.1  In  the 
vagina  the  contraction  can  usually  be  seen  to  start  from  one  end  and  spread 
to  the  other.  The  whole  then  remains  for  a  time  in  a  state  of  powerful 
tonic  contraction,  which  affects  both  longitudinal  as  well  as  circular  muscles. 
In  the  male  stimulation  of  these  nerves  excites  contraction  of  the  whole 
musculature  of  the  vasa  deferentia  and  seminal  vesicles,  which  may  be 
strong  enough  to  cause  emission  of  semen  from  the  penis.  These  effects  on 
the  utems  and  seminal  vesicles  are  not  abolished  by  injection  of  atropine. 

The  course  of  the  sensory  fibres  from  the  generative  organs  to  the 
lumbosacral  cord  has  not  yet  been  fully  made  out,  but  it  seems  probable 
that  it  corresponds  to  the  course  taken  by  the  efferent  fibres. 

An  accessory  genital  muscle,  the  retractor  penis,  which  is  found  in  the  dog,  cat,  horse, 
donkey,  hedgehog  (not  in  the  rabbit  or  man),  presents  considerable  physiological 
interest.  It  was  first  described  by  Eckhard  as  the  Afterruthenband,  and  consists  of  a 
thin  band  of  longitudinally  arranged  unstriated  muscle  (15  to  20  cm.  long  in  a  spaniel 
weighing  about  15  kilos.),  which  is  inserted  at  the  attachment  of  the  prepuce,  and  is 
continued  backwards  in  a  sheath  of  connective  tissue  to  the  bulb,  when  it  divides  into 
two  slips  which  pass  on  either  side  of  the  anus.  A  few  striated  fibres  are  found  in  the 
back  part  of  this  muscle,  derived  from  the  external  sphincter  of  the  anus  and  the  bulbo- 
cavernosus  muscles.  This  muscle  is  extremely  sensitive  to  changes  of  temperature, 
and  is  at  the  same  time  very  tenacious  of  life.  Thus  it  may  be  cut  out  of  the  body  and 
kept  in  serum  or  blood  in  a  cool  place  for  two  days.  At  the  end  of  this  time  it  will, 
on  warming,  relax  and  enter  into  spontaneous  rhythmic  contractions.  At  about  40°  C. 
the  muscle  is  quite  flaccid.  On  cooling  slightly  (to  35°)  it  will  shorten,  and  at  the  same 
time  may  enter  into  slow  rhythmic  contractions.  If  cooled  to  15°  C.  the  muscle  will 
contract  to  about  a  quarter  of  its  previous  length.  The  same  shortening  may  be 
produced  on  exciting  the  muscle  with  strong  interrupted  currents. 

The  muscle  is  innervated  from  two  sources,  the  two  nerves  having  antagonistic 
actions  (cp.  p.  247).  The  motor  fibres  to  the  muscle  are  derived  from  the  lumbar  sympa- 
thetic (i.  e.  the  upper  set  of  nerve  roots),  and  run  to  the  muscle  in  the  internal  pudic 
nerve.  The  pelvic  nerves,  on  the  other  hand,  carry  inhibitory  impulses  to  the  muscle, 
thus  enabling  the  concomitant  vascular  dilatation  to  take  effect  in  producing  erection 
of  the  penis. 

1  Under  some  circumstances  stimulation   of  the  sympathetic   nerves   may   cause 
ition  of  the  uterus. 


SI 


SECTION  IV 

PREGNANCY   AND    PARTURITION 

PREGNANCY 

Fertilisation  of  the  ovum  takes  place,  as  a  rule,  in  the  Fallopian  tube. 
Directly  one  spermatozoon  has  penetrated  into  the  ovum,  a  membrane  is 
formed  round  the  yolk,  which  prevents  the  entrance  of  any  other  sperma- 
tozoa. The  fusion  of  the  male  and  female  pronuclei  is  followed  immediately 
by  division  of  the  fertilised  ovum,  so  that,  by  the  time  it  arrives  in  the  uterus 
(about  eight  days  after  fertilisation),  it  consists  of  a  mass  of  cells  known  as 
the  morula.  At  this  time  the  ovum  has  a  diameter  of  about  0-2  mm. 
Pregnancy  in  the  human  being  lasts  about  nine  months,  birth  generally 
taking  place  280  days,  i.  e.  ten  periods  after  the  last  menstrual  period. 
During  pregnancy  menstruation  is  absent. 

With  the  arrival  of  the  fertilised  ovum  in  the  uterus,  extensive  changes 
begin  in  this  and  the  neighbouring  organs  of  generation.  The  virgin  uterus 
is  pear-shaped,  and  its  cavity  amounts  to  about  2-5  c.c.  Just  before  birth 
the  volume  of  the  uterus  is  about  5000-7000  c.c,  and  the  walls  of  the  organ 
are  thickened  in  proportion.  In  the  hypertrophy  of  the  uterine  wall  all 
its  elements  are  involved,  but  especially  the  muscle  cells.  It  is  doubtful 
whether  there  is  an  actual  new  formation  of  muscle  fibres,  but  each  fibre 
glows  in  length  and  thickness,  becoming  finally  between  seven  and  eleven 
times  as  long  and  three  to  five  times  as  thick  as  in  the  unimpregnated 
uterus  (Fig.  576).  There  is  at  the  same  time  a  great  growth  of  the  blood 
vessels,  which  have  to  supply  not  only  the  growing  wall  of  the  uterus  but 
also  by  means  of  a  special  organ — the  placenta — the  nutritional  needs  of 
the  developing  foetus. 

CHANGES  IN  THE  UTERINE  MUCOUS  MEMBRANE.  At  the  moment 
of  conception  the  uterine  mucous  membrane  begins  to  undergo  hyper- 
trophy. Within  fourteen  days  it  has  attained  a  thickness  of  \  cm.,  and 
by  the  end  of  the  second  month  f  cm.  On  section  it  shows  a  compact 
layer,  lining  the  cavity  of  the  uterus,  and  beneath  this,  abutting  on  the 
muscular  tissue,  is  a  spongy  layer  three  times  as  thick  as  the  compact 
layer.  The  superficial  epithelium  becomes  flattened,  loses  its  cilia,  and  de- 
generates. In  the  spongy  layer  the  uterine  glands"  proliferate,  the  stroma 
cells  are  enlarged,  and  the  blood  capillaries  are  widely  dilated.  The  stroma 
cells  become  converted  into  the  large  decidual  cells.  By  the  time  the 
fertilised  ovum  arrives  in  the  uterus,  the  process  of  Ivypertrophy  of  the 

1282 


PREGNANCY  AND  PARTURITION 


1283 


layers  of  the  mucous  membrane  has  already  made  some  progress.  As  it 
lies  on  the  mucous  membrane,  the  outermost  cells  of  the  developing  ovum 
exercise  a  destructive  influence  on  the  adjacent  cells  of  the  mucous  mem- 
brane, apparently  through  some  sort  of  digestion,  so 
that  the  ovum  sinks  in  the  membrane  and  reaches  the 
sub-epithelial  connective  tissue.  Round  the  margins 
of  the  depression  which  the  ovum  has  made  for  itself, 
the  mucous  membrane  grows  over  the  protruding 
part  of  the  ovum  (Fig.  577).  When  this  has  taken 
place,  the  different  parts  of  the  mucous  membrane 
receive  different  names.  Since  (in  man)  they  are  all 
to  be  cast  off  with  the  foetus  at  birth,  each  part  is 
spoken  of  as  the  decidua,  that  lining  the  main  body 
of  the  uterus  being  known  as  the  decidua  vera,  that 
covering  the  protruding  part  of  the  egg  as  the  decidua 
rejlexa,,  while  that  to  which  the  egg  is  immediately 
attached  is  the  decidua  serotina  or  basalis.  It  is  from 
the  latter  that  the  placenta  is  formed.  By  the  end 
of  the  second  week  the  blood  vessels  in  this  situa- 
tion are  considerably  enlarged.  This  enlargement 
proceeds,  affecting  especially  the  capillaries  and 
veins,  until  these  form  venous  sinuses  at  the  junc- 
tion between  the  mucous  membrane  and  the  muscular 
coat.  Changes  take  place  at  the  same  time  in  the 
embryo.  When  it  sinks  into  the  mucous  membrane 
it  has  a  diameter  of  1  mm.  The  blastoderm  is  fully 
formed  with  its  three  layers;  the  yolk  sac,  the 
body  cavity,  and  the  amnion  are  present.  The 
outermost  layer  of  the  epiblast  becomes  specially 
modified  to  serve  for  the  nutrition  of  the  embryo, 
and  gives  rise  to  the  production  of  numerous  villi,  the 
chorionic  villi,  so  that  the  whole  ovum  has  a  shaggy 
appearance.  Since  this  tissue  takes  no  part  in  the 
further  development  of  the  embryo,  but  serves  simply 
for  its  nutrition,  it  is  often  spoken  of  as  the  tropho- 
blast.  With  the  formation  of  festal  blood  vessels, 
these  penetrate  into  the  villi,  together  with  mesoblast. 
The  villi  grow  into  the  venous  spaces,  especially  in 
the  basal  part  of  the  decidua,  so  that  at  this  period  the  foetal  villi  are 
immersed  in  maternal  blood,  the  foetal  blood  vessels  being  separated  from 
the  maternal  blood  by  a  double  layer  of  epithelium,  one  layer  of  which  is 
maternal  and  the  other  festal  in  origin.  Later  these  cells  become  reduced 
to  a  single  layer. 

NUTRITION  OF  THE  EMBRYO.  At  the  earliest  period  of  its  develop- 
ment the  fertilised  ovum  is  dependent  for  its  nourishment  on  the  remains 
of  the  cells  of  the  discus  proligerus  adhering  to  it,  or  on  the  thud  of  the 


Fjg.  576.  Isolated  mus- 
cle    cells    from    the 
uterus,  showing  the 
hypertrophy   during 
pregnanc3'. 
a,  fibre  from  uterus 
in  ninth  month  of  preg- 
nancy ;  b,  fibre  from  a 
non-gravid  uterus. 
(After  Bumm.) 


1284 


LMIYSlOLOCY 


Fallopian  tube  in  which  it  is  immersed.  The  first  blood  vessels  which  are 
formed  serve  to  take  up  nourishment  from  the  yolk  sac.  In  man  this 
source  of  supply  is  insignificant,  and  from  the  second  week  onwards  blood- 
vessels traversing  the  chorionic  villi  come  into  close  relation  with  the 
maternal  blood,  from  which  henceforth  the  whole  growth  of  the  foetus  is  to 
be  maintained  by  a  special  development  of  these  connections  in  the  placenta. 
In  the  fully  formed  foetus  blood  passes  from  the  foetus  to  the  placenta 
by  the  umbilical  artery,  and  is  returned  by  the  umbilical  veins.  There  is 
no  communication  between  foetal  and  maternal  circulations.  The  placenta 
represents  the  foetal  organ  for  respiration,  nutrition,  and  excretion.     Thus 


^e^B 


Fig.  577.  Diagram  to  illustrate  the  imbedding  of  the  ovum  in  the  deeidua,  and  the 
first  formation  of  the  foetal  villi  in  the  form  of  a  syncytial  trophoblast  (derived 
from  the  outer  layer  of  the  ovum)  which  is  invading  sinus-like  blood  spaces  in  the 
deeidua.     ( After  T.  H.  Bryce.  ) 

the  umbilical  artery  carries  to  the  placenta  a  dark  venous  blood,  which  in 
this  organ  loses  carbonic  acid  and  takes  up  oxygen,  so  that  the  blood  of  the 
umbilical  vein  is  arterial  in  colour.  The  oxygen  requirements  of  the  foetus 
are  however  but  small.  It  is  protected  from  all  loss  of  heat,  movements  are 
sluggish  or  for  the  most  part  absent,  and  the  only  oxidative  processes  are 
those  required  in  the  building  up  of  the  developing  tissues.  On  the  other 
hand,  the  foetus  has  need  of  a  rich  supply  of  foodstuffs,  which  it  must 
obtain  through  the  placental  circulation.  It  is  imagined  that  the  epithelium 
covering  the  villi  serves  as  an  organ  for  passing  on  the  necessary  foodstuffs 
from  the  maternal  to  the  foetal  blood  in  the  form  best  adapted  for  the 
requirements  of  the  fcetus.  We  know  however  practically  nothing  as  to 
the  changes  or  mechanism  involved  in  this  transference.  Although  most  of 
the  organs  of  the  fcetus  are  fully  formed  some  time  before  birth,  they  are 
for  the  most  part  in  a  state  of  suspended  activity.  The  nitrogenous  excreta 
are  turned  out  by  the  placenta,  so  that  the  foetal  secretion  of  urine  is  minimal 


PREGNANCY  AND   PARTURITION  1285 

or  absent.  The  alimentary  apparatus  is  for  the  most  part  ready.  Thus 
pepsin  can  be  extracted  from  the  foStal  gastric  mucous  membrane.  The 
pancreas  contains  tripsinogen  and  the  intestinal  mucous  membrane  pro- 
secretin. Amy lo lytic  ferments  seem  however  to  be  absent  both  from 
the  salivary  glands  and  the  pancreas.  The  liver  stores  up  glycogen  and 
secretes  bile,  -which  accumulates  in  the  small  intestine,  forming  the  meco- 
nium.   This  is  generally  voided  by  the  child  shortly  after  birth. 

THE  FCETAL  CIRCULATION.  In  the  foetus,  from  the  middle  of  intra- 
uterine life,  we  find  certain  arrangements  of  the  circulation  which  are 
directed  to  providing  the  forepart  of  the  body,  especially  the  rapidly  growing 
brain,  with  oxygenated  blood,  while  the  less  important  tissues  of  the  limbs 
and  trunk  receive  venous  blood  (Fig.  578).  The  arterial  blood  coming  from 
the  placenta  along  the  umbilical  vein  can  pass  directly  into  the  liver.  The 
greater  part  of  it  however  traverses  the  ductus  venosus  to  enter  the  inferior 
vena  cava,  by  which  it  is  carried  to  the  right  auricle.  Here  it  impinges  on 
the  Eustachian  valve,  and  is  directed  thereby  through  the  foramen  ovale  into 
the  left  auricle,  whence  it  passes  into  the  left  ventricle  to  be  driven  into  the 
aorta.  As  this  arterial  blood  passes  into  the  inferior  cava,  it  is  of  course 
mixed  with  the  venous  blood,  returning  from  the  lower  limbs  and  lower  part 
of  the  trunk.  By  the  aorta  this  mixture,  containing  chiefly  arterial  blood, 
is  carried  to  the  head  and  fore  limbs.  The  venous  blood  from  these  parts  is 
carried  by  the  superior  vena  cava  to  the  right  auricle,  and  thence  to  the 
right  ventricle,  by  which  it  is  driven  into  the  pulmonary  artery.  Only  a 
small  part  of  the  blood  passes  through  the  lungs,  the  greater  part 
traversing  the  patent  ductus  arteriosus  to  be  discharged  into  the  aorta 
below  the  arch,  whence  it  flows  partly  to  the  lower  limbs  and  trunk,  but 
chiefly  to  the  placenta  by  the  umbilical  arteries.  In  the  foetus  therefore 
the  work  of  the  circulation  is  largely  carried  out  by  the  right  ventricle.  The 
greater  thickness  of  the  left  ventricular  walls,  which  is  so  characteristic  of 
the  adult,  does  not  become  evident  until  shortly  before  birth. 

With  the  first  breath  taken  by  the  newborn  child  all  the  mechanical 
conditions  of  the  circulation  are  modified.  The  resistance  to  the  blood  flow 
through  the  lungs  being  diminished,  the  blood  passes  from  the  pulmonary 
arteries  through  the  lungs  into  the  left  auricle.  The  pressure  in  the  left 
auricle  is  thus  raised,  while  that  in  the  right  auricle  falls,  so  that  the  foramen 
ovale  is  maintained  closed.  Even  before  birth  proliferation  of  the  lining 
membrane  may  be  seen  both  in  the  ductus  arteriosus  and  in  the  ductus 
venosus ;  and  with  the  mechanical  relief  of  the  vessels  afforded  by  respira- 
tion and  the  changed  conditions  of  the  foetus,  this  proliferation  goes  on  to 
complete  obliteration  of  the  vessels. 

PARTURITION 

As  the  uterus  increases  in  size  and  becomes  more  distended,  its  irritability 
becomes  greater,  so  that  it  is  easily  excited  to  contract.  The  stimulus  may 
be  supplied  from  adjacent  abdominal  organs,  from  the  brain,  as  by  emotions, 
or  by  direct  excitation  of  the  internal  surface  of  the  litems,  in  consequence 


286 


PHYSIOLOGY 


of  movements  of  the  foetus.     Tn  many  cases  no  antecedent  stimulus  can  be 
discovered,  and  the  automatic  contraction  of  the  uterus  seems  to  be  analo- 


FlQ.  578.     Diagrammatic  outline  of  the  organs  of  circulation  in  the 
foetus  of  six  months.     (After  Allen  Thomson.) 
ha,  right  auricle  of  the  heart;  rv,  right  ventricle;  la,  left  auricle;  ev,  Eustachian 
valve ;  LV,  left  ventricle ;  L,  liver ;  E,  left  kidney ;  I,  portion  of  small  intestine ;  a,  arch 
of  the  aorta ;  a',  its  dorsal  part ;  a",  lower  end ;  vcs,  superior  vena  cava ;  vci,  inferior 
vena  where  it  joins  the  right  auricle;  vci',  its  lower  end;  s,  subclavian  vessels; 
j,  right  jugular  vein ;  c,  common  carotid  arteries ;  four  curved  dotted  arrow-lines  are 
carried  through  the  aortic  and  pulmonary  opening  and  the  auriculo-ventricular  ori- 
fices ;  da,  opposite  to  the  one  passing  through  tho  pulmonary  artery  marks  the  place 
of  the  ductus  arteriosus ;  a  similar  arrow-line  is  shown  passing  from  the  inferior  vena 
cava  through  the  fossa  ovalis  of  the  right  auricle  and  the  foramen  ovale  into  the  left     • 
auricle ;  hv,  the  hepatic  veins ;  vp,  vena  portse ;  x  to  vci,  the  ductus  venosus ;    uv, 
the  umbilical  vein;  va,  umbilical  arteries;  vc,  umbilical  cord  cut  short;  %%',  iliac 
vessels. 

gous  to  that  which  occurs  in  the  distended  bladder.  These  contractions 
ordinarily  give  rise  to  no  sensations,  and  are  felt  only  when  they  are  aug- 
mented in  consequence  of  reflex  stimulation.     During  the  greater  part  of 


PREGNANCY  AND   PARTURITION  1287 

pregnancy  they  have  little  or  no  effect  on  the  contents  of  the  uterus.  During 
the  last  weeks  or  days  of  pregnancy  however,  these  contractions,  which  have 
now  become  more  marked,  have  a  distinct  physiological  effect.  Not  only 
do  they,  by  pressing  on  the  foetus,  cause  it  in  most  instances  to  assume  a 
suitable  position  for  its  subsequent  expulsion  but,  affecting  the  whole  body 
of  the  uterus  including  the  longitudinal  muscular  fibres  surrounding  its 
neck,  they  assist  the  general  enlargement  of  the  organ  in  dilating  the 
internal  os  uteri,  so  that  the  upper  part  of  the  cervix  is  obliterated  and 
drawn  up  into  the  body  of  the  uterus  some  little  time  before  labour  has 
commenced. 

With  these  changes  hi  the  uterus  are  associated  changes  in  the  round 
ligaments  and  in  the  vagina  and  vulva.  The  muscular  fibres  of  the  round 
ligaments  become  much  hypertrophied  and  lengthened,  and  these  structures 
can  therefore  aid  appreciably  the  uterine  contractions  in  the  subsequent 
expulsion  of  the  foetus.  The  vaginal  walls  become  thickened  and  of  looser 
texture,  so  as  to  afford  less  resistance  to  distension  during  the  passage  of 
the  foetal  head. 

Considerable  discussion  has  taken  place  as  to  the  cause  for  the  onset  of 
the  processes  comprised  under  the  heading  of  labour  or  parturition  at  a  nearly 
constant  period  of  two  hundred  and  seventy -two  days  after  conception. 
Most  of  the  explanations  which  have  been  suggested,  such  as  the  great  irrita- 
bility of  the  uterus  at  the  termination  of  pregnancy,  the  loosening  of  the 
foetal  membranes,  the  return  of  the  menstrual  congestion  after  ten  months, 
thrombosis  of  the  placental  sinuses,  simply  replace  one  question  by  another. 
According  to  Spiegelberg  the  phenomena  accompanying  the  birth  of  twins, 
which  are  often  bom  at  a  considerable  interval  from  each  other,  the  onset  of 
contractions  of  the  uterus  at  the  right  time  in  extra-uterine  as  well  as  in 
normal  fcetation,  the  fact  that  the  extra-uterine  foetus  dies  when  it  has 
become  mature,  all  go  to  show  that  the  reason  why  labour  occurs  at  a 
definite  time  must  be  sought  for  in  foetal  rather  than  in  uterine  changes. 
This  author  suggests  that  some  substances  which  had  previously  been  used 
up  by  the  foetus  gradually  accumulate  in  the  maternal  blood  as  the  foetus 
becomes  mature,  and  provoke,  by  their  direct  action  on  the  uterus  or  spinal 
cord,  the  uterine  contractions  which  give  rise  to  labour. 

Actual  parturition  in  the  woman  is  generally  divided  into  two  stages. 
In  the  first  stage  the  contractions  are  confined  to  the  uterus,  and  chiefly  act 
in  dilating  the  os  uteri.  In  this  dilatation  two  factors  are  involved,  namely, 
the  active  dilatation  brought  about  by  the  contraction  of  the  longitudinal 
muscular  fibres  which  form  the  chief  constituent  of  the  lower  part  of  the 
uterine  wall ;  and  in  the  second  place,  a  passive  dilatation  by  the  pressure 
of  the  foetal  bag  of  membranes,  which  is  filled  with  amniotic  fluid,  and  forced 
down  as  a  fluid  wedge  into  the  os  by  the  contractions  of  the  uterine  fundus. 
The  uterine  contractions  are  essentially  rhythmical,  being  feeble  at  first,  and 
increasing  gradually  in  intensity  to  a  maximum  which  endure;  a  certain 
time,  and  then  gradually  subsides.  The  frequency  and  duration  of  the 
contractions  increase  as  labour  advances. 


1238  PHYSIOLOGY 

As  soon  as  the  os  uteri  is  fully  dilated  and  the  foetal  head  has  entered 
the  pelvis,  the  contractions  change  in  character,  being  much  more  prolonged 
and  frequent,  and  attended  by  more  or  less  voluntary  contractions  of  the 
abdominal  muscles.  This  action  of  the  abdominal  muscles  is  associated 
with  fixation  of  the  diaphragm  and  closure  of  the  glottis,  so  that  pressure  is 
brought  to  bear  on  the  whole  contents  of  the  abdomen,  including  the  uterus. 
No  expelling  force  can  be  ascribed  to  the  vagina,  since  it  is  too  greatly 
stretched  by  the  advancing  foetus.  In  this  way  the  foetus  is  gradually 
thrust  through  the  pelvic  canal,  dilating  the  soft  parts  which  impede  its 
progress,  and  is  finally  expelled  through  the  vulva,  the  head  being  bom 
first.  The  membranes  generally  rupture  towards  the  end  of  the  first  stage 
of  parturition. 

A  third  stage  of  labour  is  generally  described.  .  This  consists  in  a  re- 
newal of  uterine  contractions  about  twenty  to  thirty  minutes  after  the 
birth  of  the  child,  and  results  in  the  expulsion  of  the  placenta  and  decidual 
membranes. 

NERVOUS  MECHANISM.  We  possess  little  experimental  knowledge  of 
the  nervous  mechanism  of  parturition.  The  most  important  observation 
on  this  point  is  the  already  quoted  experiment  by  Goltz,  in  which  this 
physiologist  observed  the  normal  performance  of  menstruation  (heat), 
impregnation,  and  parturition  in  a  bitch  whose  spinal  cord  had  been  com- 
pletely divided  in  the  dorsal  region  during  the  previous  year.  On  the  other 
hand,  destruction  of  the  lumbo-sacral  cord  completely  abolishes  the  normal 
uterine  contractions  of  parturition,  so  that  this  act  must  be  regarded  as 
essentially  reflex,  presided  over  by  a  controlling  '  centre  '  in  the  grey  matter 
of  the  cord.  The  activity  of  the  centre  can  be  inhibited  or  augmented  by 
impulses  arriving  at  it  from  the  peripheral  parts  of  the  body,  as  by  the 
stimulation  of  sensory  nerves,  or  from  the  brain,  as  under  the  influence  of 
emotions.  The  nerve  paths  from  the  centre  to  the  uterus  have  been  already 
described. 


SECTION  V 
THE   SECRETION   AND    PROPERTIES   OF   MILK 

LACTATION 

During  pregnancy  the  foetus  obtains  the  whole  of  its  nourishment  from  the 
mother  by  means  of  the  placenta.  After  birth  the  quality  of  the  nutriment 
supplied  to  the  young  child  depends  on  the  activity  of  the  cells  of  the 
mammary  glands.  Now  however  nutrition  involves  further  activity  on 
the  part  of  the  young  animal,  the  alimentary  canal  being  concerned  in  the 
digestion  of  the  milk  supplied  by  the  mother,  and  the  excretory  organs, 
especially  the  kidneys,  being  made  use  of  for  getting  rid  of  waste  material. 
The  preparation  of  the  mammary  glands  for  the  subsequent  nourishment 
of  the  newborn  child  begins  in  the  first  month  of  pregnancy,  and  is  marked 
by  swelling  of  the  glands,  rapid  proliferation  of  the  duct  epithelium,  and 
production  of  many  new  secreting  alveoli.  The  development  of  these 
glands  in  the  rabbit  has  been  already  described,  and  there  is  no  doubt 
that  in  the  human  species  the  process  follows  very  much  the  same  course, 
being  however  spread  over  nine  months  instead  of  four  weeks,  as  is  the 
case  with  the  rabbit.  During  the  latter  half  of  pregnancy  a  watery  fluid 
can  generally  be  expressed  from  the  nipple.  In  certain  mammals  this 
watery  secretion  gives  place  to  a  secretion  of  true  milk  at  the  end  of  gesta- 
tion or  during  the  process  of  parturition  itself.  In  the  woman  the  secretion 
does  not  begin  as  a  rule  until  the  second  or  third  day  after  birth,  though 
the  formation  of  milk  may  be  anticipated  if  a  child  has  been  put  to  the 
breasts  during  the  latter  part  of  pregnancy.  Secretion  begins  on  the 
second  or  third  day,  even  if  the  child  has  been  born  dead  and  no  attempt 
at  suckling  has  taken  place.  For  the  maintenance  of  the  secretion  the 
process  of  suckling  is  absolutely  necessary.  If  the  woman  does  not  nurse 
her  child,  the  swelling  of  the  breasts  gradually  passes  off,  the  milk  disappears, 
and  the  glands  undergo  a  process  of  involution.  Under  normal  conditions 
the  secretion  of  milk  lasts  for  six  to  nine  months  and  may  in  rare  cases 
extend  over  more  than  a  year.  The  amount  secreted  increases  at  first  with 
the  growth  and  size  of  the  child.  The  Table  on  p.  1290  represents  the 
average  amount  of  milk  secreted  during  the  thirtyrseven  weeks  after  birth. 
It  will  of  course  be  greater  with  strong  big  children,  and  smaller  with 
weakly  children. 

COLOSTRUM.     Refore  the  secretion  of  true  milk  begins,  the  fluid  which 
1289 


1290 


PHYSIOLOGY 


is  obtained  from  the  breast  is  known  as  colostrum.  It  may  be  expressed 
from  the  breasts  immediately  after  birth  and  is  ingested  by  the  child  during 
the  first  two  days  after  birth.  The  colostrum  is  formed  only  in  slight 
quantities.  It  is  an  opalescent  fluid,  often  somewhat  yellowish,  containing 
fat  globules  which,  if  the  fluid  be  allowed  to  stand,  form  a  yellowish  layer 
on  the  top.  Under  the  microscope,  in  addition  to  the  fat  globules,  may  be 
seen  the  so-called  colostrum  corpuscles,  which  consist  of  multinucleated  cells 
loaded  with  particles  of  fat.  They  are  probably  leucocytes  or  phagocytes 
which  have  wandered  into  the  alveoli  and  have  taken  up  fat  globules.  Some 
of  the  corpuscles  may  be  desquamated  secretory  cells.  Colostrum  is  distin- 
guished from  true  milk  by  containing  little  or  no  caseinogen.  It  contains 
about  3  per  cent,  of  proteins,  namely,  lactalbumen  and  lactoglobulin,  which 
coagulate  on  boiling.  Lactose  and  salts  are  present  in  the  same  proportions 
as  in  ordinary  milk.  It  is  popularly  supposed  to  have  a  laxative  effect 
on  the  child. 

Table  Showinq   Amount  of  Milk  Secreted  by  a   Nursing  Woman. 


increase 


Time 
1st  day 
2nd.,' 
3rd  .. 
4th  ,. 
5th  „ 
6th  „ 
7th  „ 
2nd  week 
3rd— 4th  week 
5th-8th  .. 
9th-12th  ., 
13th-16th  .. 
17th-20th  „ 
21st-24th  „ 
25th-28th  ,.. 


Milk  secreted 
20  grm. 
97 
211 
326 
364 
4(12 
478 
502 
572 
736 
797 
836 
867 
944 
963 


l'i:cl;i;\s[.: 


29th-32nd  week 
33rd-36th      ., 
37  th  week      ,. 


'.illi  'Jim. 
909     „ 
885     „ 


PROPERTIES   OF   MILK 

Fully  formed  milk  presents  certain  features  which  are  common  to  all 
mammals.  These  have  been  chiefly  studied  in  the  case  of  cows'  milk.  We 
may  therefore  deal  with  the  composition  of  cows'  milk  and  point  out  later 
in  what  respects  human  milk  differs  therefrom.  Milk  is  an  opaque  white 
fluid  with  characteristic  odour  and  sweetish  taste.  Its  specific  gravity 
varies  between  1028  and  1034.     Its  reaction  to  litmus  is  neutral,  to  lacmoid 


THE   SECRETION  AND  PROPERTIES  OF  MILK         1291 

it  reacts  alkaline,  and  to  phenolphthalein,  acid.  One  hundred  cubic  centi- 
metres of  fresh  milk,  when  treated  with  lacmoid,  require  41  c.c.  w/10  acid 
for  neutralisation.  When  treated  with  phenolphthalein  the  same  amount 
requires  19-5  »/l0  alkali  for  neutralisation.  When  exposed  to  the  air.  milk 
rapidly  undergoes  changes  in  consequence  of  infection  by  micro-organisms. 
The  most  common  of  these  changes  is  the  formation  of  lactic  acid  bv  the 
bacillus  lacticus.  In  some  cases  the  milk  may  undergo  a  species  of  alcoholic 
fermentation,  as  in  the  formation  of  kephir,  which  is  made  by  the  fermenta- 
tion of  mares'  milk. 

The  opaque  appearance  of  milk  is  due  chiefly  to  the  presence  of  multi- 
tudes of  fine  fatty  particles.  On  allowing  the  milk  to  stand,  the  particles  rise 
to  the  surface,  forming  cream,  and  by  mechanical  agitation,  especially  if  the 
milk  is  slightly  sour,  they  may  be  caused  to  run  together  with  the  formation 
of  butter.  Much  discussion  has  arisen  as  to  the  reason  why  the  fat  globules 
do  not  run  together  naturally.  By  many  authors  it  has  been  imagined  that 
they  are  clothed  with  a  special  protein  membrane  (liaptogen  membrane) 
originating  from  the  protoplasm  of  the  cell  in  which  the  fat  globules  were 
originally  formed.  It  must  be  remembered  that  in  any  protein  solution, 
such  as  that  in  which  the  globules  are  suspended,  the  protein  tends  to  aggre- 
gate, with  the  formation  of  a  pellicle,  at  the  surface,  so  that  an  emulfion 
once  produced  in  such  a  fluid  will  tend  to  be  more  or  less  permanent.  There 
seems  no  reason  to  assume  the  presence  of  a  distinct  membrane  differing 
in  composition  from  the  proteins  present  in  the  surrounding  fluid.  The 
fats  of  milk  consist  for  the  greater  part  of  the  neutral  glycerjdes,  tripal- 
initin,  tristearin,  and  triolein.  In  smaller  quantities  it  contains  the  tri- 
glycerides of  myristic  acid,  butyric  acid  (?),  and  capronic  acid,  with  traces 
of  caprylic,  capric,  and  lauric  acids. 

The  milk  plasma,  the  fluid  in  which  the  fat  globules  are  suspended, 
contains  various  proteins,  a  carbohydrate  (lactose),  and  inorganic  salts, 
with  a  small  amount  of  lecithin  and  nitrogenous  extractives. 

THE  PROTEINS  OF  MILK.  The  chief  protein  of  milk  is  cmeinogen, 
belonging  to  the  class  of  phosphoproteins.  Like  other  bodies  of  this  class 
it  presents  distinct  acid  characteristics,  being  precipitated  by  acids  and 
soluble  in  dilute  alkalies.  It  may  be  prepared  from  separated  milk  by  the 
addition  of  weak  acids.  A  convenient  method  is  to  dilute  one  litre  of  milk 
with  ten  litres  of  distilled  water  and  add  to  the  mixture  10  c.c.  of  glacial 
acetic  acid.  The  precipitate  which  is  formed  rapidly  sinks  to  the  bottom 
and  may  be  washed  two  or  three  times  by  decantation.  It  may  be  purified 
by  solution  in  dilute  ammonia  and  precipitation  by  acetic  acid  two  or  three 
times.  The  precipitate  finally  obtained  is  extracted  with  alcohol  and 
ether,  and  the  dried  caseinogen  prepared  in  this  way  forms  a  snow-white 
powder  which  is  practically  insoluble  in  water  and  dilute  salt  solutions.  It 
is  easily  dissolved  on  the  addition  of  a  little  alkali,  when  it  yields  solutions 
which  are  acid  to  litmus.  When  rubbed  up  with  chalk  it  dissolves,  displacing 
the  carbonic  acid  and  forming  a  calcium  caseinogenate.  A  solution  of  case- 
inogen in  soda  or  potash  is  transparent  and  passes  easily  through  a  clay  cell. 


1292  PHYSIOLOGY 

The  calcium  caseinogenate  forms  only  opalescent  solutions.  Apparently 
the  compound  is  dissociated  by  water  with  the  formation  of  caseinogen  acid 
which  is  in  a  state  of  partial  solution  as  swollen-up  aggregates.  It  is 
impossible  therefore  to  filter  calcium  caseinogenate  through  a  clay  cell.  It 
is  mainly  in  this  form  that  caseinogen  is  contained  in  milk,  hence  the 
opalescent  appearance  of  the  milk  plasma.  When  calcium  caseinogenate 
solution  is  boiled,  it  forms  a  pellicle  on  the  surface  in  the  same  way  as  milk 
does.  On  treating  the  caseinogen  with  rennet  ferment  it  is  converted  into  a 
modification  known  as  paracasein,  which  in  the  presence  of  lime  salts  is 
thrown  out  as  insoluble  casein.  To  this  process  is  due  the  clotting  of  whole 
milk  by  rennet,  which  is  made  use  of  in  the  preparation  of  cheese,  the  curd 
consisting  of  a  network  of  casein  enclosing  fat  globules  in  its  meshes.  On 
allowing  the  clot  to  stand  it  shrinks,  pressing  out  a  milk  serum. 

From  the  milk  serum  or  whey  may  be  obtained  two  other  proteins, 
known  as  lactalbumen  and  lactoglobulin.  These  resemble  very  nearly  the 
albumen  and  globulin  of  blood  serum.  They  are  coagulated  on  heating. 
According  to  some  authors  a  third  protein  is  present  in  the  whey,  to  which 
the  name  whey  protein  has  been  given,  and  which  is  supposed  to  be  split  off 
from  the  caseinogen  under  the  action  of  the  rennet  ferment. 

•Milk  can  be  boiled  without  undergoing  any  coagulation.  If  it  be 
allowed  to  stand  and  become  sour  by  the  formation  of  lactic  acid,  at  a  certain 
degree  of  acidity  boiling  the  milk  causes  its  complete  coagulation.  Later  on 
the  acid  produced  is  sufficient  in  itself  to  precipitate  the  caseinogen.  Both 
these  processes,  namely,  coagulation  of  half-sour  milk  by  heating,  and 
spontaneous  clotting  of  milk  by  the  production  of  acid,  are  made  use  of  in 
different  countries  for  the  manufacture  of  cheese. 

MILK  SUGAR.  The  sugar  of  milk,  or  lactose,  is  most  easily  obtained 
from  whey  which,  after  separation  of  the  clot,  is  boiled  to  precipitate  the 
remaining  proteins.  On  filtering  and  evaporating  slowly,  the  milk  sugar 
crystallises  out..  Lactose  is  a  disaccharide  and  has  the  formula  C12H2201:l. 
It  is  only  known  to  occur  in  milk.  It  may  be  found  in  the  urine  of  nursing 
women  when  the  breasts  are  not  kept  empty,  so  that  there  is  reabsorption 
of  the  lactose  formed  in  the  mammary  glands.  It  is  unaltered  by  ordinary 
yeast,  so  that  the  yeast  test  is  the  best  means  of  distinguishing  lactose  from 
dextrose  in  the  urine.  It  gives  the  ordinary  tests  for  reducing  sugar.  The 
salts  of  milk  include  insoluble  salts,  soluble  calcium  salts,  sodium  and 
potassium,  phosphates  and  chlorides. 

Mere  enumeration  of  the  constituents  of  milk  presents  but  little  interest 
unless  we  realise  how  closely  the  composition  of  this  fluid  is  adapted  to  the 
needs  of  the  growing  animal.  Li  the  first  place,  we  find  a  proportionality 
between  the  total  solids  of  the  milk  and  the  rate  at  which  the  young  animal 
grows.  It  must  be  remembered  that  the  milk  taken  by  the  animal  serves 
only  in  part  for  the  production  of  energy  in  its  body,  a  great  proportion  of 
it  being  required  for  the  building  up  of  new  tissue.  Li  no  respect  is  this 
correspondence  seen  better  than  in  the  comparative  analyses  of  the  ash  of 
milk  and  of  the  young  animal  of  the  same  species  which  were  made  by 


THE   SECRETION  AND  PROPERTIES   OF  MILK 


1293 


Bunge.  The  following  Table  shows  the  composition  of  the  ash  of  a  rabbit 
fourteen  days  old,  of  the  milk  which  it  was  receiving  from  its  mother,  of 
the  ash  of  rabbit's  blood  and  blood  serum.  Nothing  could  be  more  striking 
than  the  marvellous  way  in  which  the  cells  of  the  mammary  gland  have 
picked  out  from  the  salts  of  the  circulating  plasma  exactly  those  salts  which 
are  needed  for  the  growing  animal  and  in  the  same  proportion  : 


Rabbit 

Rabbit's 

Babbit's 

Rabbit's 

1  i  days  old 

milk 

blood 

blood  serum 

Potash   ....                    .           10-8 

101 

23-8 

3-2 

Soda 

6-0 

7-9 

31-4 

54-7 

Lime 

350 

35-7 

0-8 

1-4 

Magnesia 

2-2 

2-2 

0-6 

0-6 

Iron  oxide 

0-2.'! 

0-08 

<;•'.) 

0 

Phosphoric  acid 

41-9 

39-9 

hi 

30 

Chlorine 

4-9 

5-4 

32-7 

47-8 

This  close  correspondence  is  necessary  only  where  growth  is  very  rapid, 
so  that  the  greater  part  of  the  constituents  of  the  milk  have  to  be  utilised 
in  the  building  up  of  the  animal  tissues.  As  Bunge  has  shown,  the  slower 
the  growth  of  the  animal  the  greater  the  divergence  between  the  composition 
of  the  milk  and  that  of  the  new-born  animal .  We  may  compare  for  instance 
the  rabbit,  which  doubles  its  weight  in  six  days,  with  the  dog,  which  doubles 
its  weight  in  ninety -six  days,  and  the  human  infant,  which  takes  one  hundred 
and  eighty  days  to  double  its  weight  at  birth. 

The  last  column  of  the  following  Table  represents  the  composition  of  the 
ash  of  cow's  milk,  and  shows  how  very  inefficiently  this  milk  can  be  regarded 
as  replacing  human  milk,  the  natural  food  of  the  infant. 


Rabbit  14 
days  old 

Rabbit's 
milk 

• 
Puppy  few- 
hours  old 

Bitch's 
milk 

Infant 

some 

minutes 

alter  birth 

Human 
milk 

35-2 

Cow's 
milk 

Potash 

10-8 

101 

11-4 

150 

8-9 

221 

Soda  . 

60 

7-9 

10-6 

8-8 

100 

10-4 

13-9 

Lime 

350 

35  T 

29-5 

27-2 

33-5 

14-8 

20-0 

Magnesia 

2-2 

2-2 

1-8 

1-5 

1-3 

2-9 

2-6 

Iron  oxide  . 

0-23 

0-08 

0-72 

012 

1-0 

0-18 

0-04 

Phosphoric  acid 

41!» 

39-9 

39-4 

34-2 

37-7 

21-3 

24-8 

Chlorine 

4-9 

5-4 

8-4 

16-9 

8-8 

19-7 

21-3 

Thr  relation  between  rate  of  growth  and  protein  content  of  fond  is  well 
illustrated  by  a  comparison  of  the  composition  of  the  milk  in  different 
animals.  In  the  following  Table  (Proscher)  it  will  be  seen  that  the  more 
rapidly  an  animal  urows  the  greater  is  the  protein  content  of  the  milk  with 
which  it  is  supplied  : 


L294 


I'llYSIOLOGY 


Time  in  which 

100  parts  of  Milk  contain 

the  body  weight 
of  the  newborn 

animal  was 

doubled. 

1  lays 

Protein 

Ash 

Lime 

Phosphoric 
acid 

Man 

ISO 

10 

0-2 

0-328 

0-473 

Horse 

60 

20 

0-4 

1-240 

1-310 

Cow 

47 

3-5 

0-7 

1-600 

1-970 

Goat 

19 

4-3 

0-8 

2100 

3-220 

Pig. 

18 

5-9 

— 

— 

— 

Sheep 

10 

6-5 

0-9 

2-720 

4-120 

Dog. 

8 

71 

1-3              4-530 

4-930 

Cat  . 

7 

9-5 

—                 — 

— 

We  should  expect  that  the  milk,  which  is  the  sole  food  of  the  growing  infant, 
should  contain  a  relatively  greater  proportion  of  protein  than  is  necessary  in  the  case 
of  the  adult.  In  an  experiment  by  E.  Feer,  quoted  by  Bunge,  a  child  weighing  8226  grm. 
at  the  thirtieth  week  took  951  grm.  of  milk.     Human  milk  contains  : 


Protein 
Pat      . 


1-6  per  cent. 
3-4       „ 
61      „ 
0-2       „ 


The  child  was  therefore  receiving  daily  : 

Protein 

Fat      . 

Sugar  .... 

Ash     . 


15-2  grm. 
32-3    „ 

58-0    „ 
1-9    „ 


According  to  the  same  proportions  a  man  of  70  kilos,  would  take  in : 


Protein 
Fat  . 
Sugar  . 
Ash     . 


129  grm. 

275    „ 

494    „ 

16    „ 


It  is  interesting  to  note  that  the  protein  of  this  diet  differs  but  little  from  that  in 
the.  diets  ordinarily  accepted  as  standard,  but  there  is  a  large  excess  in  the  fat  and  in 
the  total  caloric  value,  as  would  be  expected  from  the  more  rapid  metabolism  and  the 
relatively  larger  body  surface  of  the  young  child. 


The  fitness  of  caseinogen  for  building  up  the  tissues  of  the  body  is  evident 
when  we  compare,  as  in  the  Table  on  page  89,  the  products  of  its  hydrolysis 
with  those  of  all  the  proteins  in  other  foodstuffs.  It  will  be  seen  that 
practically  every  ammo-acid  and:  allied  substance  employed  in  the  building 
up  of  the  various  proteins  is  represented  in  caseinogen.  The  only  exception 
is  glycine,  which  can  be  easily  formed  from  other  amino-acids. 

In  another  point  we  find  an  adaptation  of  the  milk  to  the  growth  of  the 
young  animal,  and  that  is  in  its  lecithin  content.  Lecithin  is  probably 
employed  to  the  largest  extent  in  the  building  up  of  the  central  nervous 
system,  where  it  forms  the  most  important  constituent  of  the  medullary 


THE  SECRETION  AND   PROPERTIES  OF  MILK 


1295 


sheaths  of  the  nerve  fibres.     There  is  a  corresponding  proportionality  between 
the  lecithin  content  of  milk  and  the  relative  brain  weight  of  the  young 

Chemical  Constitution  of  Different  Proteins 


3 

1 

3 

a 

5 

B 

t 

1 

JJ 

| 

I 
ft 
W 

a 

3 
05 

a 

3 
03 

S 
1 

3 

•3 
.2 

3 

J3 

.a 

3 

a 

o 

Glycine 

0 

3-5 

0-4 

0-1 

1-0 

16-5 

360 

20 

Alanine 

4-19 

2-1 

2-2 

0-9 

20 

2-0 

2-5 

0-8 

21-0 

3-7 

Valine  . 

4-3 

+ 

10 

0-3 

1-0 

1-0 

0-9 

Leucine 

29-04 

20-0 

18-7 

105 

8-0 

5-6 

15-0 

2-1 

1-5 

111 

Isoleucine 

Phenylalanine 

4-24 

31 

3-8 

3-2 

3-7 

2-4 

3-2 

04 

1-5 

3-1 

Tyrosine 

1-33 

2-1 

2-5 

4-5 

1-5 

1-2 

1-5 

10-5 

2-2 

Serine  . 

7-8 

0-56 

0-6 

0-2 

0-5 

0-2 

0-4 

1-6 

Cystine 

0-31 

2-5 

0-7 

0-6 

0-5 

0 

Proline 

110 

2-34 

1-0 

2-8 

31 

3-2 

7-0 

5-4 

5-2 

+ 

5-1 

Oxyprolrne    . 

1-04 

0-2 

3-0 

Aapartic  acid 

4-43 

31 

2-5 

1-2 

5-3 

0-6 

4-0 

0-6 

+ 

41 

Glutamic  acid 

1-73 

7-7 

8-5 

11-0 

13-8 

37-4 

18-4 

o-!i 

151 

Tryptophane 

+ 

+ 

+ 

1-5 

+ 

+ 

0 

+ 

Arginine 

87-4 

5-42 

4-8 

101 

3-2 

7-6 

10 

7-1 

Lysine  . 

0 

4-28 

5-8 

4-3 

0-0 

2-8 

+ 

7-1 

Histidine 

0 

10-96 

2-5 

25 

1-0 

0-4 

+ 

1-1 

Ammonia 

1-6 

2-0 

51 

0-4 

10 

animal.  Thus  in  the  calf  the  brain  is  only  vAi>  of  the  whole  animal.  In 
cow's  milk  lecithin  is  present  in  the  proportion  of  1-4  per  cent,  of  the  total 
protein.  In  the  puppy  the  brain  is  -:i\  of  the  whole  body  and  the  proportion 
of  lecithin  to  protein  in  the  milk  is  2-11  per  cent.  In  the  infant  the  brain 
forms  \  of  the  body  weight,  while  the  lecithin  is  3-05  per  cent,  of  the  protein 
of  human  milk. 


Calf 

Puppy 

Infant 

Kelative  brain  weight       ..... 
Lecithin  content  of  milk  in  percentage  of  protein 

1:370 
1-40 

1:  30 
2-lL 

1  :  7 
3-05 

We  thus  see  that  under  normal  conditions  the  young  animal  is  supplied 
through  its  natural  food  with  all  the  foodstuffs  in  the  proportions  which  it 
requires  for  its  normal  nourishment  and  growth.  It  is  impossible  therefore 
satisfactorily  to  replace  the  natural  milk  of  an  animal  by  that  of  another 
species.  In  civilised  communities  it  is  becoming  more  and  more  the  custom 
to  endeavour  to  feed  the  child  with  cow's  milk,  more  or  less  modified,  in  the 
vain  endeavour  to  reproduce  the  properties  of  human  milk.  Among  all 
classes  this  involves  the  administering  of  a  milk  differing  in  its  qualities 
and  in  the  relative  proportions  of  its  proteins,  fats,  carbohydrates,  and 
salts,  from  human  milk.  So-called  '  humanised  '  milk  is  only  a  rough  imita- 
tion of  the  natural  mother's  milk.  Among  the  poorer  classes  this  artificial 
feeding  means  the  replacement  of  a  natural  sterile  food,  throwing  very  little 


1296  PHYSIOLOGY 

work  on  the  digestive  organs  of  the  child,  by  a  foreign  milk,  very  difficult 
to  digest  and  often  teeming  with  micro-organisms.  There  is  no  doubt  that 
of  the  children  dying  during  the  first  year  of  life  four-fifths  are  murdered  by 
this  unnatural  method  of  feeding.  In  some  cases  it  is  necessary  to  adopt 
artificial  feeding  because  the  mother  is  abnormal,  and  there  is  an  insufficient 
secretion  of  milk.  It  is  therefore  important  to  lcnow  what  are  the  main 
differences  in  composition  between  human  and  cow's  milk.  In  human  milk 
the  caseinogen  is  not  only  absolutely  but  also  relatively  less  than  in  cow's 
milk,  while  the  latter  is  relatively  poorer  in  milk  sugar.  Human  milk  is 
poorer  in  salts,  especially  in  lime,  containing  only  one-sixth  of  the  amount 
present  in  cow's  milk.  Human  milk  is  also  said  to  be  poorer  in  citric  acid. 
The  main  differences  may  be  summarised  as  follows  : 


Water 

Proteins 

Fat 

Milk  sugar 

Salts 

0-2 

0-7 

Caseinogen 

Albumin 

Human  milk  . 
Cow's  milk 

88-5 
87-1 

1-2 

302 

0-5 
0-53 

3-3 
3-7 

60 

4-8 

The  caseinogen  of  human  milk  presents  several  points  of  difference  from 
the  caseinogen  of  cow's  milk.  It  is  less  easily  precipitated  by  acids.  When 
coagulated  by  rennet  it  does  not  form  a  firm  clot,  but  is  thrown  out  in  a 
flocculent  form.  It  is  thus  much  more  susceptible  to  the  action  of  gastric 
juice.  Whereas  the  caseinogen  of  cow's  milk  generally  gives  a  precipitate 
of  '  pseudonuclein  '  on  digestion  with  pepsin  and  hydrochloric  acid,  a  smaller 
or  no  precipitate  is  formed  with  human  caseinogen. 

Another  important  advantage  of  human  milk  for  the  infant  lies  in  the 
presence  of  antitoxins.  It  has  been  shown  by  Ehrlicb  that,  when  a  female 
animal  has  been  immunised  against  any  toxin  and  has  produced  in  conse- 
quence antitoxins  in  its  blood,  these  antitoxins  will,  if  it  has  young,  pass  over 
into  the  milk.  The  same  passage  of  anti-bodies  into  the  milk  has  been 
proved  in  the  case  of  various  infective  disorders.  The  ingestion  of  human 
milk  will  therefore  not  only  nourish  the  infant,  but  will  provide  it  with  a 
certain  measure  of  passive  immunity  against  possible  infection  by  diseases 
to  which  its  species  is  liable. 

THE  SECRETION  OF  MILK.  When  fully  formed,  each  mammary  gland 
consists  of  fifteen  to  twenty  lobes  embedded  in  connective  tissue.  Each  lobe 
is  made  up  of  a  mass  of  secreting  alveoli  which  lead  by  narrow  ducts  into  one 
large  lactiferous  duct.  These  lactiferous  ducts,  one  from  each  lobe,  open  on 
the  nipple,  undergoing  in  the  nipple  itself  an  oval  enlargement.  Before  secre- 
tion begins,  the  alveoli  as  well  as  the  ducts  are  lined  with  a  cubical  epithe- 
lium. When  secretion  commences  a  marked  difference  develops  between  the 
epithelium  of  the  alveoli  and  that  of  the  ducts.  While  that  of  the  latter 
retains  its  previous  character,  the  cells  of  the  secreting  epithelium  grow  in 
length  and  project  into  the  lumen  of  the  gland.    In  the  innermost  part  of  the 


THE   SECRETION  AND  PROPERTIES   OF  MILK         1297 

protoplasm  numerous  fat  globules  make  their  appearance.  If  sections  be 
made  of  the  gland  during  the  various  stages  of  its  activity  and  stained 
bv  Altmann's  method  (acid  fuchsia  and  picric  acid),  it  will  be  seen  that  the 
commencement  of  activity  is  marked  by  the  growth  of  the  innermost  part  of 
the  cells  and  the  development  in  these  of  a  number  of  granules  (Fig.  579). 
These  granules  finally  lengthen  into  shapes  like  spirilla,  while  others  of  them 
form  fat  and  become  metamorphosed  into  fat  granules.  The  nuclei  of  the 
cells  also  divide,  apparently  in  preparation  for  the  replacement  of  some  cells 
which  undergo  complete  degeneration  and  are  cast  off  into  the  secretion. 
We  know  verv  little  about  the  mechanism  of  milk  secretion.    It  seems 


Fig.  579.  Sections  of  mammary  gland  of  guinea-pig  (fat  granules 
stained  black  with  osmic  acid). 
A,  during  rest.  r..  during  active  secretion.  It  will  be  noticed  that  in  this  case 
the  active  formation  of  products  of  cell  metabolism  (granules,  etc.)  begins  with 
the  commencement  of  secretion,  and  does  not  occur  almost  exclusively  during  rest, 
as  in  the  salivary  glands.  In  the  mammary  gland,  the  active  growth  of  protoplasm, 
the  formation  of  granules  from  the  protoplasm,  and  the  discharge  of  these  granules 
in  the  socretion  appear  to  go  on  at  one  and  the  same  time. 

impossible  at  present  to  explain  the  very  close  adaptation  between  the 
activity  of  the  secretory  cells  and  the  needs  of  the  infant  or  young  animal. 
Two  at  least  of  the  constituents  of  milk,  caseinogen  and  lactose,  are  peculiar 
to  this  secretion.  It  has  been  assumed  that  the  caseinogen  is  produced  by 
some  sort  of  alteration  in  the  nucleo-proteinsof  the  gland  cells,  and  that  the 
lactose  is  derived  in  the  same  way  from  some  sort  of  gluco-protein  or  gluco- 
nucleoprotein ;  but  the  evidence  for  either  of  these  assumptions  is  very  scanty. 
The  growth  of  the  mammary  glands  during  pregnancy  is  largely  determined 
by  some  form  of  chemical  stimulation,  the  specific  hormone  being  produced  in 
the  corpus  luteum  of  the  ovary  and  possibly  also  in  the  growing  foetus.  It 
has  been  suggested  by  Hildebrandt  that  this  stimulus  is  inhibitory  in  character 
— inhibitory,  that  is  to  say,  of  secretion- — and  therefore  tending  to  the  con- 
tinuous growth  of  the  gland  cells.  With  the  expulsion  of  the  fcetus  at  birth 
82 


1298  PHYSIOLOGY 

the  source  of  the  inhibitory  stimulus  is  removed  and  the  overgrown  gland 
cells  enter  into  a  condition  of  spontaneous  activity.  However  this  may  be, 
there  is  no  doubt  that  the  secretion  of  the  gland,  once  formed,  is  continued 
independently  of  the  foetus  or  indeed  of  any  of  the  pelvic  organs.  The 
onset  of  a  new  pregnancy  brings  the  secretion  to  a  close.  Removal  of 
the  ovaries  in  a  cow  is  sometimes  employed  as  a  means  of  prolonging  the 
secretion  of  milk.  The  only  condition  in  the  human  being,  which  is 
necessary  for  secretion  to  continue  during  six  to  nine  months  after  birth, 
is  the  repeated  emptying  of  the  gland,  i.  e.  the  removal  of  the  secreted 
milk.  The  process  of  suckling  not  only  removes  the  milk  already  secreted 
but' excites  the  secretion  of  more  milk.  The  secretion  is  certainly  subject 
to  nervous  influences,  but  physiologists  have  not  succeeded  in  either  pro- 
ducing secretion  by  stimulation  of  the  nerves  going  to  the  glands,  or  in 
stopping  secretion  by  section  of  these  nerves.  Moreover  the  food  of  the 
animal  may  be  varied  within  very  wide  limits  without  altering  the  composi- 
tion or  amount  of  the  milk  secreted,  provided  that  the  food  is  sufficient 
in  amount.  The  only  constituent  of  the  milk  for  which  we  have  direct 
evidence  of  alteration  by  changes  in  the  food  supply  of  the  mother  is  the  fat. 
It  is  well  known  that  the  composition  of  butter  may  be  affected  according  to 
the  food  supplied  to  the  cow.  A  large  supply  of  oilcake,  for  instance,  may 
result  in  the  production  of  a  butter  which  is  deficient  in  the  higher  fatty  acids 
and  is  therefore  oily  at  ordinary  temperatures.  Abnormal  fats  and  fatty 
acids  such  as  iodised  fats  or  erucic  acid,  when  administered  to  an  animal  in 
lactation,  may  appear  among  the  fats  of  the  milk.  Not  only  can  the  secretion 
and  composition  of  the  milk  be  affected  reflexly  through  the  nervous  system, 
as  e.  g.  under  the  influence  of  emotions,  but  the  influence  may  be  reciprocal. 
This  is  especially  marked  in  the  case  of  the  pelvic  organs.  The  act  of 
suckling  excites  tonic  contractions  of  the  uterus.  Putting  the  child  to  the 
breast  shortly  after  birth  is  therefore  an  important  means  of  causing 
contraction  of  the  uterus  and  stopping  any  tendency  to  haemorrhage  from 
the  veiious  sinuses  opened  by  the  separation  of  the  placenta  and  fcetal 
membranes.  The  nursing  of  the  child  is  thus  an  important  means  of 
procuring  a  proper  involution  of  the  uterus  after  labour.  Many  uterine 
troubles  among  women  may  be  ascribed  to  the  previous  neglect  of  this 
elementary  duty. 


INDEX 


Absobftiox  of  fats,  784 

of  foodstuffs,  779 
intestinal,  779 
through  membranes,  131 
from  tissues,  1068 
Acapnia,  1151 
Accelerator  nerves,  470 
Accessory  food  substances,  693 
Accommodation,  amplitude  of,  527 

effect  of  drugs  on,  52  8 

of  old  age  on,  528 
of  eye,  496,  524 
in  birds,  504 
innervation  of,  527 
in  man,  504 
mechanism  of,  526 
spasm  of,  538 
theories  of,  524 
Acetone  in  uriDe,  1173 
Acid  albumin,  96 

intoxication,  S10 
Acidosis,  810 
A  aids,  organic,  48 
Acroodextrine,  68 
Acrose,  62 

Acrylic  acid  scries,  .",4 
Activity  associated  with  disintegration,  4 
Adaptation,  r>.  177 

dark,  556 
sensory.  4  s:> 
visual,  608, 570 
Addison's  disease.  1234 
Adenine,  100 
Adrenaline,  51 

action  of,  1234 

on  heart,  1020 
on  nerve  endings,  278 
on  pupil,  509 
influence  of,  1046 
in  muscular  exercise,  1055 
production  of  glycosuria  by,  840 
Adsorption,  145 

by  protein.  72 
^rotonometer,  1107 
Afferent  impulses,  345 
After  image,  567 

cause  of,  574 
fate  of,  570 
utility  of,  574 
Alanine,  80 
Albumin,  crystallisation  of,  73 

in  plants,  1 1 
Albuminoids,  104 
Albumins,  95 
Alcaptonuria,  814 
Alcohol  as  food,  702 
Alcohols,  46 


Aldehydes,  17 

Aldol  condensation,  118 

Aldoses,  60 

Aleurone  crystals,  72 

Alexia,  456 

Allantoin,  822 

'  All  or  none  '  law,  205 

Alveolar  air,  analysis  of,  1101 

Amboceptor,  1085 

Amines,  49 

formation  from  amino-acids,  76,  154 
Amino-aeetic  acid,  80 
Amino-acids,  48,  75-95 

action  of  bacteria  on,  76 
aromatic,  83 
containing  sulphur,  85 
conversion  into  sugar,  845 

into  urea,  803 
distribution  in  albumoids,  106 

in  proteins,  89 
energy  value  of,  805 
fate  after  absorption,  795 
formation  of,  154 

in  plants,  37 
heterocyclic,  84 
intestinal  absorption  of,  793 
linkage  of,  87 
optical  activity  of,  78 
pancreatic  digestion  of,  7-r>0 
properties  of,  77 
separation  of,  79 
synthesis  of,  808 

in  plant,  112 
transformation  of,  116 
value  as  food,  690 
Amino-propionic  acid,  80 
Ammonia,  effects  on  muscle,  186 

estimation  in  urine,  1177 
excretion  of,  809 
formation  of  purines  from,  11«> 
of  urea  from,  803 
Amoeba,  removal  of  nucleus  in,  28 

structure  of,  14 
Amoeboid  movements,  248 
Amphoteric  nature  of  amino-acids,  7!) 

of  colloids,  147 
Amylodextrin,  68 
Anacrotic  pulse,  971 
Anaesthesia,  454 
Anaesthetics,  influence  on  peripheral  nerves, 

260 
Anelectrotonus,  265 
Anisometropia,  539 
Anode,  187 

excitation  at,  263 
Antidromic  impulses,  323,  1041 
Antigens,  1085 


1300 


INDEX 


\ni  illirornbin,  889 
Antitoxins,  1080 

of  milk,  L296 
\ [ 1 1 1 . i  ia.  454 
Apncea,  1145 

Appetite,  influence  on  gastric  secretion,  7:S'> 
Aqueous  humour.  516 
Arabinose,  (>1 
Archipallium,  41<> 
Arcuate  fibres,  366 
Arginine,  fate  of,  810 
Aromatic  compounds.  49 

groups,  metabolism  of,  81  I 
sulphates,  813 

in  urine,  1170 
Arteries,  blood  flow  through,  962 
pressure  in,  916 
structure  of,  915 
Asparagine,  81 

in  seedlings,  112 
Aspartic  acid,  81 
Asphyxia,  1129 

influence  on  circulation,  1027 
Assimilation,  2,  25 

by  cells,  mechanism  of,  24 
relation  of  nucleus  to,  31 
Associated  fibres  of  brain,  424 
Association  processes  in  brain.  451 
Asthma,  1099 
Astigmatism,  538 

radial,  532 
Ataxia,  346 
Auditory  ossicles,  602 

sensations,  611 
Auricles,  pressure  in,  945 
Auriculo-vcntricular  bundle,  9:iii,  993 
Axis  cylinder,  electrolytes  in,  172 
Axon,  295,  301,  309 

-reflexes,  323,  475 

'  Bahntog,'  305 
Basal  metabolism,  675 

Batteries,  electrical,  186 
Beats  (sound),  613 
Benzene  derivatives,  49 
Bidwdl's  experiment.  572 
Bile,  759-763 

composition  of,  760 
digestive  functions  of,  762 
secretion  of,  762 
Binocular  vision,  588-594 
Biogen  molecule,  20 
Biophore,  20 

Biuret  reaction,  92  • 

Bladder,  functions  of,  1206 

in  spinal  animal,  332 
innervation  of,  1211 
in  man,  after  transection  of  cord,  337 
Blindness,  577 
Blindspot,  549 
Blood,  853-912 

characters  of,  854 
circulation  of,  913-1060 
coagulation  of,  882 
conductivity  of,  906 
-corpuscles,  854 

destruction  of,  1085 
enumeration  of,  901 
hemolysis  of,  23 
red,  861 


Blood  eorpuscles,  red,  life  history  of,  874 
white,  856 
functions  of,  34 
gases  of,  1103 
general  composition  of,  907 
osmotic  pressure  of,  906 
oxygen  capacity  of,  901 
-pigment  of  cephalopoda,  44 
-plasina,  absorption  of,  891 
collection  of,  882 
composition  of,  909 
properties  of,  885 
protein  of,  909 
relative  amount  of,  900 
-platelets,  879 

in  coagulation,  887 
-pressure,  916 

dependence  on  heart  output, 

929 
diastolic,  919 
in  different  vessels,  922 
distribution  of,  919 
effect  of  asphyxia  on,  1027 
of  spinal  centres  on, 
1032 
influence  on  heart,  1023 

of  capacity  on,  927 
measurement  of,  916 

in  man,  920 
in  spinal  shock,  331 
systolic,  919 
venous,  922 
quantity  of,  897 
reaction  of,  904 
regeneration  of,  874 
serum,  composition  of,  910 

proteins  of,  910 
specific  gravity  of,  903 
tension  of  gases  in,  1 107 
velocity  of,  931 

methods  of  measuring,  932 
-vessels,  chemical  control  of,  1045 
nervous  control  of,  1025 
tone  of,  1033 
-volume,  estimation  of,  897 
Body,  material  basis  of,  36-120 
Bone,  composition  of,  105 
Brain.     See  Cerebral  hemispheres, 
chemical  composition  of,  58 
development  of,  360 
nerve  cells  of,  426 

path  of  motor  impulses  in,  389,  422 
-pressure,  464 
-stem,  conduction  in,  381 

descending  tracts  of,  389 
functions  of,  390-394 
structure  of,  360-394 
tracts  of,  384 
structure  of,  416 

vertebrate,  comparative  structure  of, 
363 
Broca's  convolution,  454 
Bronchi,  innervation  of,  1096 
Brown-Seqnard  paralysis,  359 
Bulbo-spinal  animal,  391 
Burch's  experiment,  573 
Butyric  fermentation,  119 

Caffeine,  101 
Calcium,  43 


INDEX 


1301 


Calcium,  importance  for  blood  clotting,  884 
Calorie  value  of  normal  diet,  695 
Calorimeter,  construction  of,  668 
Cane  Bugar,  67 

ies,  blood  flow  through,  1048 
circulation  through,  973 

in  muscles,  1054 
inflammatory  changes  in,  1074 
measurement  of  pressure  in,  974 
Capillary  electrometer,  173,  227 
Capsule,  internal,  375,  423 
Carbamino-acids.  7ii 
Carbohydrates,  45 

absorption  of,  789 
chemistry  of,  59-70 
as  constituent  of  protein,  86 
of     nueleins, 
102 
conversion  into  fat,  830 
digestion  of,  767 
influence  on  metabolism,  081 
metabolism  of,  839 

lor,  in  proteins,  93 
Carbon,  assimilation  of,  107—111 
by  plants,  37 
as  a  constituent  of  protoplasm,  3ti 
dioxide,  a  ssimilation  by  green  plants, 
108 
in  atmosphere,  38 
condition  in  blood,  1015 
effect  on  circulation,  1047 
elimination  in  lungs,  1121 
influence    on    nervous    con- 
duction, 261 
production  in  isolated  mus- 
cle, 216 
reduction  in  plants,  37 

of  respiration, 
1137 
!  monoxide,  influence  oa  blood,  1153 
Cardiac  cycle,  93$ 

1  points,  522 
i  ardiograph,  948 
( '.milometer,  957 

Cartilage,  chemical  composition  of,  104 
n,  9s,  73o.  752,  1291 
■  n.  influence  of,  1269 
Catacrotic  pulse,  971 
Catalysis,  158 

mechanism  of,  159 
.   specificity  of,  159 
i  latelectrotonus,  265 
Cathode,  187 

excitation  at,  263 
Cell  organs,  32 

as  structural  unit,  13 
structure  of,  10 
-wall.  22 
Cells,  chemical  reactions  in,  153 
division  of,  31,  35 
histological  differentiation  of,  31 
galvanic,  186 
osmotic  phenomena  in,  22 
of  plants.  1.'! 
surface  layer  of,  21 
vital  phenomena  of,  25 
i  '•  llulose,  22 

properties  of,  69 
use  in  food,  BOO 
Central  nervous  system,   2SS-311 


Central  nervous  system,  continuity  in,  309 
Centres,  cortical,  arrangement  of,  431     ' 
motor,  439 
sensory,  443 
Cereals,  proteins  of,  96 
Cerebellar  functions  in  man,  403 

tracts  of  cord,  354 
Cerebellum,  370 

functions  of,  395-404,  451 
influence  on  muscular  tone,  336, 

398 
removal  of,  4(12 
stimulation  of.  401 
structure  of,  398 
tracts  of,  387,  400 
Cerebral  cortex,  connection  with  cord,  35(1 
functions  of,  394 
influence  on  equilibrium,  654 
localisation  of  functions  in, 

433 
stimulation  of,  435 
structure  of,  41(i,  42(1 
hemispheres,  415-460 

afferent  tracts  of,  421 
association    fibres    in. 

424 
commissural  fibres  in, 

425 
effects  of  removal  of, 

439 
efferent  tracts  of,  422 
evolution  of,  419 
functions  of,  433 
general     character    of 

functions  of,  449 
higher  associative  func- 
tions of,  451 
localisation  in,  434 
minute    structure    of, 

426 
motor  functions  of,  435 
projection  fibres  of,  42! 
sensory    functions    of, 

443 
stimulation  of,  435 
structure  of,  415 
time  relations  of,  457 
tracts  of,  420 
Cerebral  vesicles,  361 
Ccrebrin,  58 

Cerebro-spinal  fluid,  4(52 
Cetyl  alcohol,  47 
Charpentier' s  bands,  566 
Chemical    energy   of   dissohed    substances, 
128 
sense,  639 
Chemiotaxis,  27,  639,  1075 
Cheyne-Stokes'  breathing,  1111' 
Chitin,  composition  of,  65 
Chlorides  of  urine,  1162 
Chlorine,  43 
Chloroform,  influence  on  nervous  conduction, 

261 
Chlorophyll,  function  of.  6,  37,  107 

necessity   of  iron  in  formation 
of,  43 
Chloroplasts,  17,  107 
'in,  47 

i     i  in  i  it  ui'iit  of  surface  layer, 
23 


1302 


INDEX 


Cholesterol,  significance  of,  56 

esters,  56 
Choline,  composition  of,  57 
Chondroitin,  104 

-sulphuric  acid,  104 
Chorda  tympani  nerve,  412 

effect  on  secretion,  710 
Choroid,  500 

structure  of,  506 
Chromatic  aberration,  530 
Chromatin,  17 
Chromoproteins,  99 
Chromosomes,  31,  33 
Cilia,  33 

Ciliary  body,  structure  of,  506 
movement,  248 
muscle,  action  of,  526 
nerves,  functions  of,  511. 
Circulation,  physiology  of  the,  913-1000     — 
action  of  heart  on,  935 
through  arteries,  919,  962 
capacity  of,  925 
through  capillaries.  973 
capillary,  regulation  of,  1048 
cerebral,  464 

chemical  relation  of,  1045 
coronary,  1010 
influence  of  anaemia  on,  1060 
on  lymph,  1066 
of     nervous     system 

on,  1025 
of  plethora  on,  1058 
in  invertebrates,  913 
during  muscular  exercise,  1051 
pulmonary,  979 
through  veins,  976 
Circulatory  system,  evolution  of,  34 
Clark's  column,  325 
Clonus,  241,  336 

Clotting  of  blood.     See  Coagulation. 
Coagulation  of  blood,  855,  882-896 
of  colloids,  148 
heat,  93,  148 
history  of,  892 
intravascular,  889 
mechanism  of,  149 
of  muscle  plasma,  212 
of  protein,  72,  93 
theory  of,  891 
of  transudations,  892 
Cochlea,  606 
Cochlear  nerve,  411 

central  connections  of,  379 
Ccelenterata,  differentiation  in,  33 

nervous  system  of,  289 
Ccelomata,  33 
Coelum,  34 
Coil,  induction,  188 
Coitus,  physiology  of,  1279 
Collagen,  digestion  in  stomach,  732 
Colloidal  compounds,  influence  on  diffusion, 
135 
properties  of  protoplasm,  '20 
solution  of  metal,  138 
Colloids,  72,  137-151 

adsorption  by,  145 
amphoteric  nature  of,  147 
classification  of,  137 
coagulation  of,  148 
combination  between,  148 


Colloids,  definition  of,  137 

electrical  charges  on,  147 

properties  of,  144 
imbibition  by,  149 
molecular  weight  of,  138 
optical  properties  of,  143 
osmotic  pressure  of,  140 
precipitation  of,  145 
properties  of,  137-151 
surface  phenomena  in,  145 
Colostrum,  1289 
Colour  blindness,  578 
mixing,  562 
triangle,  486 

vision,  effect  of  intensity  on,  5SI 
peripheral,  581 
theories  of,  583 
Colours,  complementary,  487 

mixture  of,  487 
Combination  tones,  616 
Comma  tract,  353 
Commissural  fibres  in  brain,  425 
Complement,  1085 
Complemental  air,  1095 
Complementary  colours,  571 
Concentration  battery,  170 
Conchiolin,  106 
Condenser,  191 
Conditioned  reflexes,  453 
Conduction  in  brain  stem,  381 

irreciprocal,  in  synapse,  275 
in  spinal  cord,  351 
Cones,  function  of,  583 
Conjugated  proteins,  98 

sulphates,  813 
Conjugation  in  metazoa,  1254 
in  protozoa,  1252 
Consciousness,  9,  451,  481 
Conservation  of  energy  in  living  beings,  2 

of  mass  in  living  beings,  2 
Consonance,  614 
Consonants,  625 
Contractile  stress  of  voluntary  muscle,  200 

tissues,  177-249 
Contractility  of  muscle,  179 
Contraction  of  muscle,  194-204,  234-238 
arrested,  200 
isometric,  197 
isotonic,  197 
osmotic     theory     of, 

235 
surface  tension,  theorv 

of,  235 
energy  of,  236 
in  relation  to  surface  tension,  24 
secondary,  233 
-wave  in  muscle,  228 
Contrast,  effect  on  sensation,  483 
simultaneous,  571 
successive,  571 
Co-ordination  of  eye  movements,  495 

of  movement  in  spinal  animal, 

331 
muscular,  395 

influence     of     eyes 
on,  406 
part   played   by   afferent  im- 
.    pulses  in,  345 
Copper  as  necessary  constituent  of  certain 
plants  and  animals,  44 


INDEX 


1303 


Cornea,  500 

structure  of,  504 
Coronary  circulation,  1010 
Corpora  quadrigemina,  373,  392,  405 
Corpus  luteum,  1275 

striatum,  functions  of,  442 
Cortex,  cerebral.     See  Brain. 
Cramptori  8  muscle,  504 
Cranial  nerves,  connections  and  functions  of, 

414 
Creatine  metabolism,  811 
Creatinine,  origin  of,  si  1 

in  urine,  1106,  1178 
Cretinism,  1239 
Crusta,  373 
Crystallin,  95 
Cuorin,  58 
Curare,  effect  of,  1S5,  259 

on  nerve  endings,  277 
Currents,  galvanic,  186 
induced,  188 
Cutaneous  sensations,   Head's  classification 

of,  635 
Cystine,  74,  85 
Cytase,  70 
Cytolysins,  1085 

Cytoplasm  contrasted  with  nucleus,  30 
Cytosine,  102 

Dark  adaptation,  .".."id 
Deaminisation,  153,  803 

of  amino-acids,  798 
Death,  0 
Decarboxylation,  154 

of  amino-acids,  T t ; 
brate  rigidity,  392 
Defalcation,  777 

Defence,  cellular  mechanisms  of,  1070-1078 
chemical     mechanisms     of,     1079- 
1087 
Degeneration  of  nerve  fibres  in  cord,  320 

retrograde,  320 
Deglutition,  721-727 

nervous  mechanism  of,  720 
Delirium  cordis,  1011 
Demarcation  current,  225,  233 
Dendrites,  301 
Depressor  impulses,  1044 

nerves,  1022 
Depth  perception,  hypothesis  of,  593 
Development  of  egg,  1264 
Dextrorotatory  compounds,  52 
Dextrose,  63 
Diabetes,  838,  843,  831 

glycogen  in.  Sis 
Diabetic  puncture,  S43 
Dialysis,  134 
Diamino-acids,  82 

in  histones,  95 
Diamino-trioxydodecoic  acid,  83 
Diapedesis,  1073 
Diaphragm,  1090 
Dicrotic  notch,  969 
Diet,  distribution  of  foodstuffs  in,  698 

influence  on  urinary  composition,  802 
of  man.  695 
Diffusibility  in  relation  to  electrical  potential, 

171 
Diffusion,  122.  129-136 
Digestion,  25,  703-800 


Digestion,  course  in  dog,  797 

intestinal,  74S-75S.  707 

loss  of  food  in,  698 

in  mouth,  706-720 

of  protein,  76 

in  stomach,  728-741 
Dilemma,  460 
Diphasic  variation,  229 
Disaceharides,  61,  67 
Discrimination,  tactile,  631 
Dissimilation,  located  in  cytoplasm,  31 
Dissociation  of  colloidal  salts,  135 
Dissonance,  613 
Diuretics,  action  of,  1201 
Diving,  respiration  in.  1153 
Ductless  glands,  1230-1247 

interaction  between,  849 

Ear,  internal,  600,  606 
middle,  601 
structure  of,  600 
Eck's  fistula,  804 
Edestin,  74 
Edridge    Green's    theory    of    colour    vision 

566 
Efficiency,  mechanical,  of  body,  684 
Egg  albumin,  95 

molecular  weight  of,  74 
Elastin,  106 

Electrical  changes,  in  voluntary  contraction, 
241 
in  living  tissues,  169-173 
in  muscle,  169,  224-233 
in  retina,  545 
Electrodes,  187 
Electrotonic  current,  280 
Electrotonus,  264,  280 
Elements  essential  to  life.  36 
Embryo,  nutrition  of,  1283 
Emulsions,  formation  of,  56 
Emulsoids,  139 
Endocardiac  pressure,  942 
Endplate,  275 

fatigue  situated  in,  276 
Energetic  basis  of  body,  121-173 
Energy  balance  sheets,  666 

chemical,   of   dissolved   substances, 

128 
evolved  in  fermentative  changes,  155 
income  and  output,  3 
of  muscular  contraction.  201 
muscular,  effects  of,  169 
source  of,  686 
origin  in  cells,  25 

from  fat,  830 
value  of  amino-acids,  805 
Enterokinase,  751 
Epiblast,  33 

Epicritic  sensibility,  636 
Epilepsy,  437 

analysis  of  spasms  in,  24 1 
Equilibration,  397 
Equilibrium,  maintenance  of,  654 
Erepsin,  766 
Erythroblasts,  876 

Erythrocytes.     See  Blood  corpuscles,  red. 
Erythrodextrin,  68 

Ether,  influence  on  nervous  conduction,  261 
Eustachian  tube,  604 
Excitability,  26 


1304 


INDEX 


Excitation,  propagation  in  invertebrate  ner- 
vous system,  296 
•in  involuntary  mus- 
cle, 24(1 
Excitatory  process,  nature  of,  284 
Eye,  abnormal  refraction  of,  534 
accommodation  of,  524-528 
anatomy  of,  500 
central  connections  of,  405 
chromatic  aberration  of,  530 
comparative  anatomy  of,  502 
diffraction  in,  529 
development  of,  501 
malnutrition  of,  518 
minute  anatomy  of,  504 
movements,  409,  493^199 
muscles,  nuclei  of,  406,  409 
nourishment    and   protection   of,   514- 

518 
optical  constants  of,  521 
defects  of,  533 
system  of,  519-528 
peripheral  aberrations  of,  532 
reduced,  524 

refraction  in,  522,  529-539 
refractive  indices  of,  522 
spherical  aberration  of,  531 
Eyeball,  muscles  of,  494 

nerve  supply  to,  505 
structure  of,  500-513 
EyeUds,  anatomy  of,  514 

closure  of,  514 
Eyes,  conjugate  deviation  of,  496 
fixation  of,  589 

Facial  herve,  412 

Facilitation,  305 

Fajces,  799 

False  image,  produced  by  squint.  498 

Faraday -Tyndall  phenomenon,  143 

Fasting,  influence  on  metabolism,  666 

Fatigue  of  muscle,  208 

of  nerves,  259,  285 
of  reflex  arc,  304 
of  sense  organs,  4sj 
situated  in  endplates,  276 
in  synapse,  343 
Fats,  45 

absorption  of,  784 
chemistry  of,  53—58 
formation  of,  155,  828 

in  plants,  37 
sugar  from,  837 
history  in  body,  826-838 
identification  of,  56 
influence  of  bile  on  digestion  "1,  7i>:i 

on  metabolism,  681 
metaboUsm  of,  826,  838 
of  milk,  55 
origin  of,  827 
oxidation  of,  155,  835 
properties  of,  55 
significance  in  diet,  699 
synthesis  of,  117-120,  168 
Fatty  acids,  48 

formation  of,  118 
list  of,  54 
Fatty  degeneration,  832 
Fechner's  law,  485 
Ferment  action,  152-168 


Ferment  action,  influence    of    concentration 
on,  162-165 
mechanism  of,  160 
methods     of    investigation, 

163 
reversibility  of,  166 
Ferments,  action  of,  148 

as  catalysts,  158 

chemical    character    of    changes 

effected  by,  153 
colloidal  character  of,  157,  167 
definition  of,  156 
list  of,  157 

as  synthetic  agents,  167 
Fertilisation  in  man,  1279 
nature  of,  1262 
nervous  mechanism  of,  1280 
Fibrin,  884 

-ferment,  885 
Fibrinogen,  95,  884 

tissue-,  99 
Fibroin,  106 
Fillet,  367 

Filtration-angle  of  eye,  516 
Fischer's  methods  of  separating  amino-acids, 

79 
Flicker,  568 

-method,  565 
Fluorine,  44 
Focus,  depth  of,  530 
Foetus,  circulation  in,  1285 
Food,  changes  during  digestion,  704 
effect  on  metabolism,  677 
fsecal  residue  from,  800 
in  normal  diet,  695 
passage  from  mouth  to  stomach,  712 
requirements  of  man,  696 
of  woman,  696 
Foodstuffs,  absorption  of,  779 

distribution  in  normal  diet,  698 
fate  in  body,  3 
heat  value  of,  667 
history  in  body,  801-852 
inorganic,  692 
significance  of,  688 
as  source  of  energy,  2 
Foramen  of  Monro,  375 
Fore  brain,  373 

connection  with  cord,  356 
structure  of,  373 
Formaldehyde,    formation    of     amino-acids 
from,  114 
from  carbon  dioxide,  109 
as  stage  in  carbon  assimila- 
tion, 109 
Fornix,  375 
Fovea,  543 

vision  by,  548 
Fructose,  63 

formation  in  plant,  111 

Galactose,  64 

as  constituent  of  phospholipids, 

58 
structure  of,  66 
Galactosides,  58 
Ganglia,  293 

functions  of,  474 

inhibition  in  peripheral,  475 

root  development  of,  298 


INDEX 


1305 


Gastric  digestion,  728-741 
juice,  728 

acidity  of,  730 

action  on  albuminoids,  7;{2 

on  carbohydrates,  734 
on  food,  730 
on  milk,  733 
effect  of  vagus  on,  737 
secretin,  740 
secretion  of,  734 

chemical   mechan- 
isms in,  73S 
Gauss'  theorem,  522 
Gelatin,  105 

diffusion  through,  140 
as  food,  081 
Gels,  137 

properties  of,  139 
Gemmules,  20 

Geniculate  bodies,  373,  375,  386 
Geotaxis,  27 

Germ-cells,  formation  of,  1257 
Glands,  ductless,  1230-1247 

mammary.  333,  1270,  1289 
Glaui  oma,  509,  517 
Gliadins,  96 
Globin,  868 
Globulin,  74 

precipitation  of,  95 
Glomeruli,  functions  of,  1192 
Glossopharyngeal  nerve,  413 
Glucosamine,  65 

from  proteins,  86 
Glucose,  67 

conversion  into  lactic  acid,  113 
formation       from         ammo-acids, 
808 
in  plants.  II I 
tests  for,  62 
Glucosides,  formation  of,  65 
hydrolysis  of,  10(1 
methyl-,  66 
i  Uutamic  acid,  81 
Glutelins,  96 
Glycerides,  53,  59 
Glycerin,  effects  on  muscle,  186 

origin  of,  119,  831 
Glycerol,  53 
Glycine,  80,  114 
Glycocoll.  Si) 

Glycogen  in  diabetes,  84S 
formation  of,  840 
in  muscle.  218 
preparation  of,  839 
properties  of,  69 
Glj  coproteins,  103 
Glycosuria,  843 
Glycuronic  acid,  65 

in  urine.  I  173 
Glyoxilic acid  in  plants,  114 
Golgi  method,  300 
network,  309 
Gout,  nature  of,  824 
Gracilis  experiment  (Kiihnc  ,  254 

nucleus,  365 
Grape  sugar,  63 
Growth,  4 

relation  of  nucleus  to,  31 
of  tissues,  681 
Guanine,  100 


H.KMATIX,  S68 

chemical  relations  of,  870 
Hrernatoblasts,  854 
Hematocrit,  900 

Haematocytes  (blood  platelets),  879 
Haematoporphyrin,  870 
Hseniin,  868 
Haemochromogen,  870 
Haemocyanin,  44 
Haemoglobin,  99.  8113 

crystallisation  of.  73 
derivatives  of,  868 
dissociation  curve  of,  1109 
fate  of,  877 

molecular  weight  of,  '.III 
osmotic  pressure  of,  75 
properties  of,  864 
Haemolymph  glands,  1245 
Haemolysis,  23,  1085 

osmotic  pressure  of  electrolites, 
126 
Haemopyrroles,  872 
Haemorrhage,  effects  of,  1060 
Halogen-proteins,  96 

Hausmann's  method  of  protein  analysis,  90 
Hearing,  physiology  of,  595-617 
central  paths  of,  411 
cortical  localisation  of,  448 
Heart,  933-961 

apex  beat  of,  947 

arrangement  of  muscle  fibres  in,  '.135 

-beat,  causation  of,  982 

-block,  988 

blood  pressure  in.  04(1 

changes  in  form  of,  946 

compensation  in.  lout 

contraction  wave  in,  990 

effects  of  potassium  on,  1018 

of  salts  on  muscle  of,  1005 
of  sympathetic  on,  1018 
electrical  changes  in,  230,  990  996 
-failure  in  asphyxia,  1027 
filling  of,  953        _ 
frog's,  anatomy  of,  982 
influence  of  length  of  muscle  fibre  on 
contraction.  1001 
of  reaction  of  blood  on.  Ions 
of  temperature  on,  1005 
of  tension  of,  1001 
of  vagus  on,  1013 
inhibition  of,  1017 
law  of,  1003 
of  Limulus,  988 
mammalian,  contraction  of,  992 

origin  of  rhythm  in,  994 
mechanical  measurement  of,  935 
methods  of  determining  output,  955 
-murmurs,  950 

-muscle,  excitation  time  of.  272 
-nerves,  circulation  of,  1012 
nutrition  of,  1009 
output  of,  954 

during  exercise,  1052 
physiological  properties  of  mil 
-pressure  curves,  '.112 
propagation  in,  986 
reflexes  from,  L02I 
refractory  period  in,  999 
rhythm  of,  983 
sequence  of  contraction  in.  935 


1306 


INDEX 


Heart  sounds,  949 

'staircase  phenomena  '  in,  999 
tone  of,  1004 
valves  of,  938 
work  of,  959 

during  exercise,  1054 
Heat-formation  in  muscle,  219-223,  237 
-loss,  regulation  of,  1226 

in  isolated  muscle,  291 
in  nerve,  285 
-production  in  body,  3,  668,  1223 
-value  of  foods,  607 
Hdler's  test,  94 

Hiimholtz,  theory  of  hearing,  611 
Helweg's  tract,  353 
Hemiansesthesia,  445 
Heminanopia,  553,  577 
Hemiplegia,  445 
Heredity,  1264-1268 
Bering's  theory  of  colour  vision,  583 
Herpes  zoster,  349 
Hexonc  bases,  82 
Hexoses,  61 

derivatives  of,  64 
in  nucleins,  102 
Hibernation,  837 

Hind  brain,  connection  with  cord,  354 
Hippuric  acid  in  urine,  1169 
Hippus,  512 
His,  bundle  of,  936,  993 
Histidine,  85 

metabolism  of,  816 
Histological  differentiation,  7 
Histones,  95 
Hojmanris  test,  83 
Homogentisic  acid,  51,  814 
Homoiothermic  animals,  1221 
Hopkins'  reactions  for  tryptophane,  92 
Hormones,  1230-1247 
food-,  693 
Horopter,  590 

Hunger,  influence  of  gastric  movements  on, 746 
Hyaloplasm,  18 
Hydenia,  1058 
Hydrocarbons,  45 
Hydrogels,  138 
Hydrogen,  sources  of,  39 

peroxide,  production     in     green 
plant,  110 
effect  of  platinum   on, 
158 
Hydrolysis  of  protein,  97 
Hydrosols,  137 

properties  of,  140 
Hypernietropia,  534,  536 
Hypoblast,  33 
Hypoglossal  nerve,  414 
Hypoxanthine,  100 

Imbibition  by  colloids,  149 

Iminazol,  84,  101 

synthesis  of,  115 

Immunity,  1079 

Ehrlich's  theory  of,  1083 

Incisure,  969 

Indol,  813 

Inflammation,  1073 

Inhibition,  26 

in  central  nervous  system,  306 
of  cord,  effect  of  strychnine  on,  347 


Inhibition  of  heart,  1017 
nature  of,  1017 
in  peripheral  ganglia,  475 
of  reflexes,  306 
of  voluntary  muscles,  339 
Inhibitory  functions  of  cortex,  450 

nerves,  248 
Innervation,  reciprocal.  See  Reciprocal  inner- 
vation. 
Inogen,  237 
Inosite,  116 
Insanity,  457 

Intellectual  processes  in  brain,  457 
Intercostal  muscles,  1092 
Internal  capsule,  375,  423 

secretion,  1230-1247 
Intestinal  juice,  764 

villi,  functions  of,  780 
Intestines,  large,  functions  of,  768 
movements  of,  775 
law  of,  773 
small,  movements  of,  771 

peripheral  nervous  system 

of,  469 
secretion  by,  704 
Intraocular  fluid,  516 

pressure,  517,  526 
Introduction,  1—9 
Inulin,  69 

Involuntary  muscle,  243-248.    See  Muscle, 
influence  of  temperature 

on,  247 
propagation   of   excita- 
bility in,  246 
Iodine,  in  living  mechanisms,  44 

in  thyroid  gland,  1241 
Iris,  functions  of,  507 
innervation  of,  510 
structure  of,  505 
Iron,  excretion  of,  43 
in  haemoglobin,  74 
oxidative  functions  of,  43 
sources  of,  42 
Irradiation  in  cord,  339 
Irreciprocal  conduction  in  nervous  system,302 

in  synapse,  275 
Irritability  of  muscle,  184 
of  nerves,  265 
Isoleucine,  81 

Isomerism  in  amino-acids,  77 
Isometric  method,  197 
Isotonic  method,  197 

Kerasin,  58 

Keratin,  105 

'  Kernleiter,'  281 

Keto-acids,  49 

Ketonic    acids,    formation    of    amino-acids 

from,  115 
Ketose,  60 
Keys,  electrical,  178 
Kidneys,  function  of,  1160-1213 

structure  of,  1181 
Kjeldahl's  method,  90,  1175 
Knee  jerk,  333,  451 

Labyrinth,  anatomy  of,  652 

auditory,  606 

functions  of,  396 
Lactation,  1289 


INDEX 


1307 


Lacteal,  780 
Lactic  acid,  804 

formation  in  muscle,  215.  237 

of   amino-acids  from, 
113 
as  stage  in  fat  synthesis,  117 
tests  for,  215 
Lactose  hydrolysis,  104 

time  relations  of,  104 
Lsevorotatory  compounds,  51 
Lsevulose,  64 
Langerhans'  islets,  850 
Lanoline,  50 
Lardaceous  tissue,  104 
Larynx,  anatomy  of,  618 
Latent  period  of  muse  1<,  198 
Lateral  nucleus,  369 

Law  of  contraction  in  human  nerves.  269 
Pjliiger's,  267 
of  the  minimum,  30 
Lecithin,  composition  of,  57 
formation  of,  43 
in  surface  layer,  23 
Lens,  crystalline,  519 

composition  of,  95 
influence  on  refraction  of  eye,  533 
refraction  by,  520 
Leucine,  81 
Leucinide,  87 
Leucocytes,  858 

action  in  inflammation,  1073 
classification  of,  1076 
formation  of,  858 
functions  of,  859 
Lcucocytosis  after  ingestion  of  nucleins,  824 
Leucoplasts,  109 

Liebermanri  s  reactions  for  proteins,  92 
Life,  conditions  of,  6 
definition  of,  4 

fundamental  phenomena  of,  2 
evolution  of,  5 
without  oxygen,  26 
Light,  absorption  of,  488 

chemical  changes  due  to,  490 
diffraction  of.  489 
physical  properties  of,  486 
-reflexes,  512 
refraction  of,  490 
white,  composition  of,  486 
Liminal  stimulus.  1!»3.  482 
Limulus,  heart  of,  988 
Linoleic  series,  54 
Lipsemia  in  diabetes,  849 
Lipase,  168 

Lipoid  character  of  protoplasm  surface,  23 
Liver,  formation  of  urea  in,  803 
secretory  functions  of,  759 
Localisation,  cerebral,  433 

tactile,  032 
Lock's  fluid,  1006 
Locomotion  in  spinal  animal,  -•'>! 
Lungs,  circulation  through,  979 

exchangoofoxygenin.lll  1,1 120,1 1-  I 
movements  of,  1089 
Lymph  and  tissue  fluids,  1061-1069 
absorption  of,  1068 
movement  of,  1066 
Lymphagogues,  1065 
Lymphatics  of  brain,  464 
Lysine,  82 


McDoUOALLS     THEORY     OB     COLOUK     VISION, 

587 
Magnesium,  43 

Maltase,  influence  on  glucosides,  I  66 

Maltose,  structure  of,  66 

Mammary  glands,  development  of,  1270 

growth  in  spinal  animal, 

333 
secretion  by,  1289 
Mannose,  64 
Marey's  law,  1023 
Marginal  bodies,  291 
Marie,  tract  of,  353 
Meat,  value  of,  701 
Mechanical  efficiency  of  body,  084 
Mechanism,  8 
Medulla  oblongata.  364 

centres  in,  414 
functions  of,  390 
respiratory  functions  of, 
1127 
Medusa,  nervous  system  of,  290 
Membrana  tympani,  601 
Membranes,  electrical  differences  at  surface 
of,  171 
passage  of  dissolved  substances 
through,  129-136 
Mendel's  law,  1267 
Menstruation,  1269,  127.~> 
Metabolism,  659 

of  aromatic  groups,  814 
basal,  675 

of  carbohvdrates,  839-852 
of  fat,  826-838 

influence    of    fats    and    carbo- 
hydrates on,  681 
of  food  on,  677 
of  muscular  work  on, 

683 
of  proteins  on,  677 
methods  employed  in  investi- 
gating, 660 
of  nuclein,  818-825 
of  protein,  801-817 
of  purine,  818-825 
during  starvation,  670-676 
of  sulphur,  813 
tissue-,  801 
Methyl  glucosides,  66 
Micella;,  20 

Micturition,  1205-1213 
Mid  brain,  connection  with  cord,  350 

structure  of,  364,  372 
Milk,  action  of  gastric  juice  on;  733 
composition  of,  1290 
fats  of,  55 
secretion  of,  1289,  1290 

in  spinal  animal,  333 
sugar  of,  67 
Milton's  reaction.  S3,  92 
I/--/..,/,','  test,  63,  93 
Monosaccharides,  61 
Moore's  test,  63 
Motor  cent  res,  43!) 

end  plate  of  muscle,  182 
functions  of  nervous  system,  434 
impulses,  path  in  brain,  3S'j,  422 
nerve  roots,  322 
es,  1149 
Movement,  ciliary,  248 


1308 


INDEX 


Movement,  dependent  on  differences  of  sur- 
face tension,  2-1 
mechanisms  of,  177-287 

of  co-ordinated,  338- 
348 
sense  of,  648 
Movements  of  eye,  409,  493^99    - 
Mucins,  86,  103 
Mucoids,  104 
Mailer's  law,  255,  481 
Muscle,  action  of  salts  on,  210 
of  drugs  on.  2]  1 
afferent,  impulses  from,  :!:!4 
arrangement  in  frog's  leg,  189 
break-excitation  of,  192 
chemical  changes  in,  212-218 
ciliary,  action  of,  526 
conditions   affecting   mechanical   re- 
sponse of,  205-211 
contraction,  194-204 

arrested,  200 
isometric.  197 
isotonic,  197 
osmotic  theory  of,  235 
surface  tension,   theory 
of,  235 
effects  of  ammonia  on,  186 

of  constant  current  on,  192 

of  glycerin  on,  186 

of  length  on  contraction  of, 

201 
of  load  on,  200-203 
on  polarised  light,  182 
of  temperature  on,  207 
electrical  changes  in,  169,  224—233 
energy  of  contraction  of,  236 
excitation  of ,  185-193 

time  of,  271 
extensibility  of,  203 
fatigue  in,  208 
heart-,  178,  272 
of  insects,  1S2 
intimate   nature   of   contraction    of, 

234-238 
involuntary,  178,  243-248 

'  all  or  none  '  law    in, 

205 
double   innervation   of, 

247 
influence    of     tempera- 
ture on,  247 
inhibition  of,  248 
propagation   of   excita- 
bility in,  246 
rhythmic      contraction 

in,  244 
stimulation  of,  244 
structure  of,  243 
summation  in,  245 
irritability  of,  184 
latent  period  of,  198 
make  excitation  of,  192 
mechanical  changes  during  contrac- 
tion, 194-204 
methods  of  stimulating,  186-192 
motor  end-plate  of,  182 
oxidative  changes  in,  237 
oxygen  supply  to,  1013 
-plasma,  212 
production  of  heat  in,  219-223 


Muscle,  production  of  lactic  acid  in,  215,  237 
of  tension  in,  202,  222 
propagation  of  contraction  in,  203 
relation   of   energy   of    response    to 
energy  of  stimulus,  27 
of  tension  to  length,  202 
rigor  of,  20s.  214 
sartorius,  Is'.i 
-sound,  241 
-spindles,  334,  648 
summation  in.  21  Hi 
'  threshold  '  or  liminal  stimulus,  193 
tone  of,  654 
-twitch,  194-201 

methods  of  recording,  194-198 
mxstriated.     See  involuntary. 
varieties  of,  178 

voluntary,  chemical  composition  of, 
212 
contraction  of,  239-242 
propagation  in,  204 
refractory  period  of,  206 
structure  of,  177-184 
Muscular  energy,  source  of,  686 

exercise,  effect  on  circulation,  1051 
sense,  647 
sensibility,  346 
tone,  333 

effect  of  cerebellum  on,  336, 
398 
work,  effect  on  metabolism,  683 

on  respiratory  quotient, 
686 
Musical  scale,  615 
Myelin,  58,  251 

Myelination  in  central  nervous  system,  319 
Myogen,  213 
Myographs,  194 
Myopia,  534,  537 
Myosin,  96,  212 
Myosinogen,  212 
Myxoedema,  1239 

Naoeli's  theory    op    protoplasm   struc- 
ture, 20 
Negative  variation,  226 
Neopallium,  416 
Nerve,  physiology  of,  250-287 
characteristics  of,  271 
chemical  changes  in,  256 
conduction  in,  253 
degeneration  in,  274 
effect  of  temperature  on,  258,  262,  273 
electrical  changes  in,  172,  256 

stimulation  of,  270-274 
electrotonic  changes  in,  264 
-endings,  delay  in,  27ii 

effect  of  curare  on,  277 
function  of,  276 
excitability  of,  261 
excitation  of,  262-269 

influence      of      Lutrapolar 

length,  268 
-time  of,  271 
fatigue  in,  285 
-fibre,  degeneration  in  cord,  320 

regeneration  of,  30 
human,  electric  stimulation  of,  268 
-impulse,  253 
influence  of  anesthetics  on,  260 


INDEX 


1309 


Nerve,  influence  of  constant  current  on,  263 
of  curare  on,  185.  259 
of  drugs  on,  260 
of  fatigue  on,  259 
of  injury  on.  274 
-junction  with  muscle  fibres,  27S 
law  of  excitation  in,  266 
medullated,  251 

methods  of  stimulating,  1S<>  r.'2 
nature  of  excitatory  process  in,  284- 

287 
non-rnedullated,  252 
oxygen  consumption  by,  256 
polarisation  of,  260,  280-283 
ttion  in,  253-255,  281 
rate  of  conduction  in,  258 
refractory  period  of.  273 
-roots,  distribution  in  cord,  3.">ii 
functions  of,  255 
motor,  322 
structure  of,  250-252 
summation  of  stimuli  in,  272 
Telocity  of  conduction  in,  253 
-Wives,  ciliary,  functions  of,  511 
grafting  of,  255 
inhibitory,  248 
irritability  of,  265 
V  i  \  e  cells,  automaticity  of,  314 
of  brain,  426 
effects  of  section  of   axon  on, 

321 
functions  of,  310,  312-314 
liberation  of  energy  in,  313 
structure  of,  300 
Nervous  impulse,  256 

conditions  affecting,  258- 
261 
processes,  energy  of,  464 
system,  blood  supply  of,  462 
central,  288-477 
of  Ccelenterata.  289 
conduction  in,  296,  301-389 
connection  with  periphery, 

299 
control      of      co-ordinated 
movements  by,   33S-34S 
of  cra3'fish,  294 
development  of,  297 

of  control  in, 
293 
evolution  of,  33,  2ss  296 
function  of  cells  in,  312—314 
higher  reflex  functions  of, 

340-408 
invertebrate,  288-296 
irreciprocal  conduction  in, 

302 
law  of  forward  direction  in, 

302 
motor  functions  of,  434 
of  medusa,  290 
nutrition  of,  461 
paths  in.  299 
psychical  functions  of,  433, 

451 
reflex  action  in,  303-311 
:i  iory  functions  of,  443 
-tincture  of,  360-389,  415- 

432 
trophic  functions  of,  349 


Nervous  system,  vascular  arrangements   of, 
461 
of  vertebrates,  297-302 
Nervus  erigens,  473 
Neural  groove,  297 
Neurilemma,  251 
Neurine,  composition  of,  57 
Neuro-blasts,  development  of,  298 
Neuro-epithelial  cells,  295 
Neuro-fibrils,  251,  296,  307 

of  vertebrates,  301 
Neuro-keratin,  105 
Neuro-muscular  function,  275 
Neurons,  definition  of,  295 

nature  of  connection  between,  307- 
311 
Neuro-pilem,  296 

Neutral  salts,  action  on  protein,  94 
Nicotine,  action  on  nerve  cells,  472 

on  nerve  endings,  277 
Nictitating  membrane,  515 
Night  blindness,  578 
Nissl  bodies,  301 
Nitrates,  fate  in  plants,  114 
Nitrification,  40 
Nitrogen,  assimilation  of,  40 
in  cells,  40 

distribution  in  protein  molecule,  90 
digestion  in  urine,  802 
-fixing  bacteria,  40 
source  of,  39 
Nucleic  acid,  99 

I.  .  i      i  " 

Nuclei  of  cranial  nerves,  376-380 
Nuclein,  99 

decomposition  of,  102 
fate  of,  821 
formation  of,  43 
metabolism  of,  818 
phosphoproteins  converted  into,  116 
Nucleoplasm,  17 
Nucleoprotems,  98,  99 

fate  in  stomach,  733 
Nucleotides,  103 
Nucleus,  14,  33 

of  Bechlerew,  379 
chemical  composition  of,  27 
cuneatus,  365 
of  Deiiers,  379.  389,  410 
functions  of,  27 
gracilis,  365 
red,  376 
structure  of,  16 
Nutrition,  influence  of  nervous  system  on, 
349 
mechanism  of,  657    1217 
Nystagmus,  656 

OCUXO-MOTOR  NEEVE,  409.   196 
(Esophagus,  action  of,  724 
Ohm's  law  (sound  analysis),  lilt; 
Old  age,  effect  on  accommodation,  :,i's 
Olfactometer,  645 
Olfactory  apparatus,  420 

bulb,  connection  of,  387 

lobe,  structure  of,  420 
Olivary  body,  366.  381 
I  llivo  spinal  tract,  363,  389 
Ophthalmoscope,  553 
Opsonins,  1086 


1310 


INDEX 


Optic  chiasina,  3SI>.  405 
cup,  502 
disc,  554 
radiations,  422 
thalamus,  373 

functions  of,  :{'.):( 
tracts,  386,  405,  551 
i  >p1  Leal  activity,  51 

in  sugars,   00 
Orbit,  anatomy  of,  493 
Organ  of  Corti,  609 

Organic  compounds,  chief,  of  body,  45 
Organs,  evolution  of,  34 
Ornithine,  82 
Osazones,  62 
Osmometer,  140 
Osmosis,  129-136 
Osmotic  machine,  123. 

phenomena  in  colls,  22 
pressure,    121 

of  blood,  906 
of  colloids,   14  0 
of  protein,  75 
effects  of,   134 
measurements  of,  123 

by  blood  corpuscle 

method,  125 
by    depression    of 
freezing  point, 
127 
by  plasmolysis,  125 
by  vapour  tension, 
127 
relation      to      electrical 
changes,  171 
Otolith  organ,  397 
Otoliths,  functions  of,  656 
Ova,  development  of,  1273 
Ovary,  changes  in,  1275 
Ovulation,  1275 
Oxidation  in  cells,  25 

of  fats,  155,  835 

of  fatty  acids,  805 

mechanism  of,  156 

relation  to  muscular  contraction, 

237 
in  tissues,  1155-1159 
Oxyacids,  49 

formation  in  plants,  1 11 
Oxygen  capacity  of  blood,  898 

consumption  by  nerve,  256 

functions  of,  25 

influence   on   muscular  contraction, 

217 
lack  of,  1138 
life  without,  26 
source  of,  39 
supply  to  muscle,  1013 
Oxyhemoglobin,  99 

molecular  weight  of,  74 
Oxyproline,  84 

Pacchionian  bodies,  463 
Pain,  cause  of,  634 
referred,  476 
in  spinal  animal,  331 
Pancreas,  effects  of  extirpation,  847 

histological  changes  in,  757 
Pancreatic  juice,  748-758 

activation  of,  750 


l'ancrea tic  juice,  action  on  carbohydrates.  7">:J 
on  fats,  753 
on    intestinal    secre- 
tion,  765 
on  milk,  752 
on  proteins,  749 
conditions  of  activity,  751 > 
secretion  of,  753 
Pangene,  20 

Paradoxical  contraction,  282 
Paraglobulin,  95 
Paralysis,  cortical,  439 
Paramucin,  104 
Paramyogen,  213 
Paramyosinogen,  95 
Paraplegia,  spastic,  336 
Parathyroids,  functions  of,  1241 
Parturition,  1285-1288 

nervous  mechanism  of,  1288 
Pelvic  visceral  nerves,  471 

action  on  bladder,  1212 
Pentose,  61 

in  nucleic  acid,  102 
tests  for,  61 
Pepsin,  action  of,  97 
Peptones  in  gastric  digest,  730 
Perimeter,  549 
Peripheral  aberration  of  eye,.  532 

nervous  system,  469 
Permeability  of  membranes,  134 

of  surface  layer  of  cells,  22 
Peroxides,  function  in  carbon  assimilation, 

110 
Pfluger's  law,  266 
Phagocytosis,  859,  1071 
Phenyl  alanine,  77,  83 
Phenyl  hydrazine  tests  for  sugars,  62 
Phloridzin  diabetes,  844 
Phosphates  of  urine,  1163 

estimation  of,  1179 
Phosphatides,  57 
Phospholipines,  57,  58 
Phosphoproteins,  98 

conversion  into  nuclein,  110 
digestion  in  stomach,  733 
Phosphoric  acid  in  nucleic  acid,  100 
Phosphorus,  sources  of,  43 
Phototaxis,  27 
Phrenosin,  58 

Physiology,  scope  of,  1,  7,  35 
Pilomotor  nerves,  469 
Pineal  gland,  504,  1245 
Pituitary  body,  1242-1245 
Placenta,  formation  of,  1284 
Plants,  assimilation  of  nitrogen  by,  11 

chemical  process  in,  38 
Plasma,  blood-,  854,  882 

muscle-,  212 
Plasmolysis,  22,  30,  125 
Plasome,  20 
Plastids,  17, 33 

permanence  of.  20 
Plethora,  1058 

Poikilothermic  animals,  1221 
Polarimeter,  51 
Polypeptides,  88 

isomerism  in,  88 
Polysaccharides,  62,  67 
Pons  Varolii,  368 

functions  of,  392 


INDEX 


1311 


Posterior    longitudinal    bundle,     380,    389, 

407 
Postural  tone,  450 
Potassium,  43 
Pregnancy, 1282 

in  spinal  animal,  333 
Pressor  impulses,  1044 
Pressure,  intrathoracic,  1094 
Principal  point  of  eye,  522 
Projection,  tactile,  633 
Proline,  84 

Proprioceptive  system,  395 
Propriospinal  fibres,  354 
Protamines,  94,  99 
Proteid,  98  (footnote) 
Proteins,  45,  71-106 

absorption  of,  790 

action  of  bacteria  on,  76 

of  intestinal  juice  on.  766 
of  neutral  salts  on,  94 
of  pancreatic  juice  on,  749 

alkaloidal  reaction  of,  93 

amino-acids  of,  80 

aromatic  constituents  of.  S3 

behaviour  with  acids  and  alkalies, 
147 

biological  value  of,  691 

of  blood  plasma,  909 

building  up  of,  86 

carbohydrates  contained  in,  80 

chemical  analysis  of.  ~'.i 

chemistry  of,  7!    L06 

coagulation  of,  93 

colour  reaction  of,  92 

compounds  with  salts,  93 

conjugated,  98 

crystallisation  of,  72 

derivatives  of,  96 

digestion  of,  76,  730,  749,  766 

disintegration  products  of,  80 

distribution  of  nitrogen  in.  90 

elementary  composition  of,  71 

empirical  formuli  of,  74 

formation  of  fat  from,  831 

gastric  digestion  of,  730 

hydrolysis  of,  75,  96 

isomerism  in,  88 

metabolism  of,  801-817 

influence   of   carbo- 
hydrates, S46 

molecular  structure  of,  75 
weight  of,  73,  90 

origin  of  aromatic  constituents,  111' 

osmotic  pressure  of,  75 

physical  structure  of,  72 

precipitation  of,  94 

putrefaction  of,  76 

significance  of,  888 

surface  phenomena  in,  21 

specific   dynamic   action   of.    681, 
688,  804 

sulphur  in,  85 

synthesis  of,  87 

in  plant,  111-117 

tests  for,  92 

transport  in  plant,  1 12 

varyins  constitution  of,  B9 

vegetable.  96 
Proteoses,  fractional  separation  of,  7:;o 
Protopathic  sensibility,  635 


Protoplasm,  14 

Altmann  s  granules  in,  17 

definition  of,  15 

elementary      constituents      of, 

36-44 
fibrillar  theory  of,  18 
granular  theory  of,  17 
physical  structure  of,  17 
proximate       constituents       of, 

45-106 
ultramicroscopic  structure  of,  20 
Pseudo-ions,  147 
Pseudomucins,  104 
Pseudopodia,  33 
Pulse,  arterial,  962 

causation  of  secondary  elevations  in, 

967 
-curves,  970 

abnormalities  in,  972 
effect  of  exercise  on,  1056 
-rate,  influence  of  altitude  on,  1151 

in  man,  1024 
velocity  of  transmission  of,  967 
Pupil,  Argyll  Robertson,  512 
contraction  of,  507 
dilatation  of,  509 
effect  of  drugs  on,  509,  513 
movement  of,  507 
reflex  paths  of,  553 
Purine  bases,  100 

origin  in  plants,  115 
metabolism  of,  818 
synthesis  of,  1 16 
Purlcinje's  fibres  of  heart,  994 

figures,  554 
Putrefaction  of  protein,  76 
Pyramidal  tracts,  352,  422 
decussation,  365 
Pyrimidine,  101 
Pyrrol,  84 

metabolism  of,  816 
origin  in  plants,  1 15 
Pyruvic  acid,  804 

as  stage  in  fat  formation,  119 

Quotient,  respiratory.     See  Respiratory. 

Racemic  compoxtnds,  52 
Rami  communicantes,  468 
Reaction  of  blood,  904 

chemical,  velocity  of,  159 
of  urine,  1161 

estimation  of,  1175 
based  on  consciousness,  4S2 
cerebral,  time  relations  of,  4.">7 
-time.  4.">7 
Receptor  cells,  295 

substance.  :277 

excitation  time  of.  -77 
Reciprocal  innervation,  339 

of    eye   mo\  i 

497 
in  iris,  511 

of  voluntary  muscles, 
335 
Recurrent  sensibility,  32:; 
Red  marrow,  875 
nucleus.  37n 
Reduced  eye,  52 1 
Reduct ion,  mechanism  of,  !■"><' 


1312 


INDEX 


Referred  pain,  476 
Reflex  action,  177 

characteristics     of,     303-306, 

344 
in  nervous  system,  303-311 
peripheral,  474 
'  stepping,'  332 
structural  basis  of,  299 
arc,   177 

of  brain  stem,  382 
evolution  of,  289 
fatigue  of,  304 

irreciprocal  conduction  in.  202 
of  muscle,  335 
axon-,  323 

functions  of  brain  stem,  393 
mass,  337 
Reflexes  from  heart,  1021 
inhibition  of,  306 
light-,  512 
segmental,  321 
spinal,  328 

structural  basis  of,  341 
visual,  405 
Refractory  period  of  heart,  muscle,  999 
of  muscle,  206 
of  nerves,  273 
Regeneration,  influence  of  nucleus  on,  29 
Renal  excretion,  1 160-1213 
Rennin,  action  of,  733 
Reproduction,  4 

physiology  of,  1251-1298 
in  man,  1264-1281 
Residual  air,  1095 
Resonance  in  ear,  (ill 
Resonators  (sound),  597 
Respiration,  2,  108S-1159 

action  of  vagi  on,  1139 
air  movements  in,  1095 
blood  changes  in,  1104 
changes  in  lungs,  1119 
chemical  regulation  of.  1129 
chemistry  of,  1100-1125 
Cheyne-Stokes ',  1146 
effect  of  altitude  on,  1150 

of  changes  in  air  breathed 
on.  1148 
in  diving,  1153 
lung  changes  in,  1089 
mechanics  of,  1088 
medulla  oblongata  in,  1127 
-murmurs,    1094 
of  muscles,  1113 
muscular  mechanism  of,  1090 
nervous  regulation  of,   1129 
underpressure,  1153 
rib  movements  in,  1092 
secretory  processes  in,  1124 
by  skin,'  1218 
-tissue,  1112,  1155-1159 
Respiratory  centre,  functions  of,  1127 

exchanges,  measurement  of,  662 
during       starvation, 

675 
during  work,  683 
movements,  influence  on  circu- 
lation, 980 
quotient,  685,  830,  1100 

effect  of  diet  on,  834 
Restiform  body,  367 


Retieulin,  105 

Retina,  abnormalities  of,  577 
development  of,  543 
central  connections  of,  551 
connections  with  brain,  445 
effect  of  light  on,  544 

of  periodical  stimuli  on,  569 
electrical  changes  in,  545 
fatigue  of,  570 
histology  of,  540 
pigments  of,  545 
Retinoscopy,  535 
Retractor  penis,  1281 
Reverser,  188 
Rheocord,  192 
Rheonome,  270 
Rheoseopic  frou'.  --'* 
Rhythm  of  bladder,  1209 
of  cortex,  241 
of  heart,  983 
of  intestinal  muscle,  771 
of  medusa,  292 
of  nerve  impulse.  241 
respiratory.  1128 
of  voluntary  muscle,  240 
of  ureters,  1205 
Ribose,  61,  103 
Rigidity,  decerebrate.  392 
'  Rigor  Mortis,'  208,  214 
Ringer's  fluid,  1006 
Ritter-  Valli  law,  274 
Rods,  function  of,  583 
Roof  nucleii  of  cerebellum,  381 
Rotation,  optical,  51 
Riibncr  on  heat  production  in  body,  3 
Rubro-spinal  tract.  353,  389 
Hut.  nature  of,  1269 
Rutherford's  theory  of  bearing,  613 

Saccharose,  67 
Saccule,  397 

Saliva,  different  forms  of,  708 
digestion  of  starch,  707 
secretion  of,  708 
uses  of,  707 
Salivary  glands,  708 

nerve  supply  to,  711 
significance  of  double  nerve 
"supply,  718 
Salmon,  formation  of  generative  glands  in, 

116 
Salts,  absorption  of,  7S1 

action  on  muscle,  210 
electrical  changes  in,  169 
precipitation  of  colloids  by,  144 
in  urine,  1165 
value  in  food ,  692 
Saponification,  46,  55 
Sarcolemma,  179 
Sarcomeres,  179 
Sarcoplasma,  179 
Sarcosine,  83 
Sarcostyles,  179 
Sarcous  elements,  1 80 
Sartorius  muscle,  189 
Sclera,  500 

structure  of,  506 
Scleroproteins,  104 
'  Scratch  '  reflexes,  331 
Sebaceous  glands,  secretion  of,  56 


INDEX 


1313 


Sebum,  1216 
Secretin,  gastric,  740 

pancreatic,  755 
Secretion,  electrical  changes  accompany  ing, 
169,  717 
energy  involved  in,  719 
histological  changes  during,  715 
internal,  1230-1247 
mechanism  of.  713 
of  milk.  333,  1289,  1296 
relation  of  nucleus  to,  31 
Seedlings,  occurrence  of  asparagine  in,  s2 
Semicircular  canal,  652 
Semipermeable,  definition  of,  123 
Sensation  bodies  in  brain.  42 1 

cortical  apprecial  Loo  of,  146 
disturbances  of,  441 
localisation  of,  443 
cutaneous,  626-638 
gustatory.  640 

histological  elements  involved,  637 
in  invertebrata,  293 
labyrinthine,  651 
localisation  of,  303 
measurements  of,  479 
of  movement,  646 
Jffiflcr'slaw  of,  4S1 
olfactory.  642 
pain-,  634 
paths  of,  324 

in  central  nervous  system, 

440 
in  cord,  357 
projection  of.  48] 
relation  to  stimulus,  478,  482 

in  eve,  555-568 
spatial.  65] 
static,  646 
tactile.  629 
temperature 
Weber's  law  of,  483 
Sense  organs,  plvysiology  of,  47 

classification  of,  479 
fatigue  of,  482 
projieient,  293 
of  skin,  637 
Sensibility,  recurrent,  323 
Sensoparalysis,  345 
Sensory  functions  of  cortex.  44:'. 
nerve  roots,  322 
tracts  in  brain  stem,  384 
Septo-marginal  bundle,  353 
Serine,  80 
Serum  albumin,  74,  95 

colloids,  molecular  weight  of,  142 
globulin,  95 
Sexual  process,  essential  functions  of,  12.~>l 

reproduction,  1254 
Shock,  nervous,  330 

in  man.  3!7 
Silicon,  significance  of,  44 
Skatol,  813 

Skin,  functions  of,  1214-1218 
innervation  of,  326 
structure  of.  121  1 
Sleep,  state  of  pupils  in,  508 
Smedley,  theory  of  fat  synthesis,  119 
Smell,  cortical  localisation  of,  4  19 
Soaps,  formation  of,  55 
Sodium,  43 


Sols,  137 

Solutions,  energy  of,  121 

Sound  analysis,  596 

in  ear.  theories  of,  609 
appreciation  of,  61  I 
conduction  of,  600 
localisation  of,  616 
muscle-,  241 
properties  of,  595 
Spastic  paraplegia,  336 

Specific  dynamic  action  of  protein,  681,688,804 
irritability,  law  of,  255,  480 
rotatory  power,  52 
Spei  I  ra  luminosity,  curves  of,  556 
Spectrum.  486 

energy  of,  489 
Speech,  central  mechanism  of,  453-457 

mechanism  of,  623-625 
Spermatozoa,  composition  of,  95,  99 
development  of.  1271 
formation  of,  1259 
Spherical  aberration  of  eye,  531 
Sphingosine,  58 
Sphygmograph,  965 
Spinal  animal,  329 

conduction,  344 
cord,  315-359 

anatomy  of,  351 

classification  of  nerve  cells  in,  318 
as  conductor,  351-359 
course  of  fibres  in,  319 
development  of,  297 
effect  of  poisons  on,  :U7 
of  transection,  330 

in  man,  330 
grey  matter  of,  324 
hemisection  of,  359 
methods  of  studying  tracts  in. 

319 
motor  functions  of,  327 
paths  in,  324 

of  impulses  in,  356 
reflex  functions  of,  322,  329 
structure  of,  315-321 
tracts  of,  352 
trophic  functions  of,  349 
visceral  functions  of,  327 
nerve  roots,  central  connection  of,  324 
dilator  functions  of.  323 
functions  of,  323-337 
reflex,  nervous  paths  of,  328 
reflexes,  structural  basis  of,  324 
shock,  330 
Spindles,  muscle-,  334,  648 
Spino-tectal  tract,  354 
Spinothalamic  tract,  354 
Spleen,  functions  of,  1245-1247 
Spongin,  106 
Spongioblasts,  298 
Spongioplasm.  18 
Squint,  497 

treatment  of,  499 
Stapedius  muscle,  603 
Starch,  digestion  by  saliva,  707 

formation  in  plant-,  6,  17.  .'>7.  107 
moleoula  c    I  net  ure  of,  69 
proper)  Les  of,  68 
Slarval  i.  i  lit  during,  071 

metabolism  during.  670 
nil  rogeiioiis  excretion  during,  074 


1314 


INDEX 


Stenopeic  aperture,  536 
'  Stepping  '  reflex,  332 
Stereoisomerism  in  the  sugars,  60 
Stimulation  of  muscle,  186-192 
of  nerve,  262-269 
of  sense  organs,  47 f) 
Stimulus,  definition  of,  26 
energy  of,  262 
influence  of  strength  on,  205 

of  stress  on,  205 
inhibitory,  26 
liminal,  193,  482 
relation  of  response  to,  26 
summation  of,  245,  272.  304 
Stomach,  digestion  in,  728-741 

influence  of  vagus  on,  737 
movements  of,  742-747 
Strabismus,  497 

from  myopia,  53S 
String  galvanometer,  227 
Stroma  of  red  corpuscles,  863 
Structural  basis  of  the  body,  13-35 
Strychnine,  effects  of,  347 
Substrate,  163 

Suckling,  importance  to  mothers,  1298 
Sugar  in  blood,  839 

conversion  into  fats,  117 

into  lactic  acid,  113 
formation  from  amino-acids,  845 

from  fat,  837 
of  milk,  67 
in  urine,  843,  1172 
synthesis  of,  62 
utilisation  of,  842 
value  of,  701 
Sugars,  assimilable,  61 

chemistry  of,  59-67 
reaction  of,  62 
Sulphates  of  urine,  1103 
Sulphur  in  amino-acids,  85 
in  keratin,  105 
metabolism,  813 
in  protein,  74 
sources  of,  42 
test  for  in  protein,  92 
Summation  in  muscle,  206,  245 
of  stimuli,  245,  272 

in      reflex      action, 
304 
Supplemental  air,  1095 
Suprarenal  bodies,  1233-1238 
Surface  action  in  emulsions, 

layer,  properties  of,  21 
phenomena  in  soap  solution,  56 
tension  in  cells,  20 

effect   of   electrical   changes 

on,  172 
in  protoplasm,  19 
Surfaces,  electrical  changes  on,  172 
Suspensoids,  139 
Swallowing,  721-727 
Sweat,  secretion  of,  1216-1218 
Sympathetic  action  on  heart,  1018 
ganglia,  465 

nerve,  effect  on  blood   vessels, 
1037 
on  salivary  glands, 
712 
-supply  to  eye-ball,  511 
system,  465 


Synapse,  fatigue  in,  343 
functions  of,  310 
between  nerve  and  muscle,  275 
structure  of,  298,  308 

Tactile  discrimination,  631 

sensibility,  629 
Taste,  cortical  localisation  of,  449 
nerves  of,  411 
sense  of,  640 
Tears,  secretion  of,  515 
Tecto-spinal  tract,  389 
Tegmentum,  373 
Teleology,  justification  of,  5 
Temperature  changes  in  muscle,  219 

effei  I  on  excitability,  273 

on  ferment  action,  159 
on  heart,  1005 
on  muscle,  207,  247 
nervous  mechanism  of,  1228 
regulation  of,  443,  1219-1229 
-sense,  626 
Tendon  phenomena,  333 

reflex,  333 
Tension  of  muscle,  202 

relation  to  heat  produc- 
tion, 222 
Tensor  tympani,  603 
Tetanus,  closing,  264 

involuntary  movement,  241) 
in  muscle,  206 
-toxin,  347 
Thalamo-spinal  tract,  353,  389 
Thalamus,  optic,  structure  of,  373 
functions  of,  393 
Theobromide,  101 
Thermopile,  219 
Thigmotaxis,  27 

Thorax  movements  in  respiration,  1091 
'  Threshold  value  '  of  sensation,  482 
Thrombin,  885 
Thrombogen,  887 
Thrombokinase,  887 
Thrombosis,  880,  888 
Thymine,  102 
Thyroid  gland,  123S-1241 
Tidal  air,  1095 
Timbre,  597 
Tissue  fibrinogen,  99,  S89 

metabolism,  811 
Tissues,  electrical  changes  in  living,  169-173 
Tone  of  muscle,  333,  654 
Tonus  cerebella,  398 
Touch,  sense  of,  629 
Toxins,  148 

influence  of,  1080 
Tracts  of  brain  stem,  384 
of  eord,  352 
optic,  386,  405,  551 
Training,  influence  of,  1055 
Traube  curves,  1031 
Triglycerides,  54 
Trammer's  test,  63 
Trophic  functions  of  5th  nerve,  411 
of  spinal  cord,  349 
Trypsin,  749 

action  of,  97 

action  of  polypeptides  on,  88 
velocity  of  reaction,  165 
Trypsinogen,  751 


INDEX 


1315 


Tryptophane,  84 

metabolism  of,  815 
Twilight  vision,  547,  583 
Twitch,  muscle-,  194-201 

methods     of      recording, 
194-198 
Tympanum,  functions  of,  604 
Tvrosin,  50.  83 

action  of  bacteria  on,  76 
metabolism  of,  814 

Uracil,  101 
Urates.  1168 
Urea,  estimation  of,  1176 
origin  of,  802 
production  from  arginine,  810 

from  creatine,  83 
in  urine,  1165 
Uric  acid,  100,  S19 

excretion  of,  S22 
formation  in  birds,  804 
origin  of,  821 
in  urine,  1 167 
Urinary  deposits.  1174 
Urine,  abnormal  constituents  of,  1171 
in  blood  plasma,  1181 
composition  of,  1160-1180 
inorganic  constituents  of,  1162 
phosphates  in.  1163 
pigments  of,  1170 
organic  constituents  of,  1155 
quantitative  estimation  of  chief  con- 
stituents of,  1175-1180 
salts  in,  1165 
secretion  of.  1181-1204 
sugar  in,  843,  1172 
Urobilin.  871 
Uterus,  changes  during  birth.  1287 

during  menstruation,  1275 
Utricule,  397 

Vagus,  action  ox  heakt,  1013 
on  intestines,  775 
on  oesophagus,  726 
on  respij  ition,  1139 
on  stom.ich,  746 
function-  of,  J. 3 
respiratory  til  res  of,  413 
Valves  of  heart,  93  S 

370 
Vaso-dilatation  in  ralivary  glands,  712 
Vaso-dilator  nerve? .  1039 
Vaso-motor  inipul  es,  path  in  cord,  359 
nerve  •,  469 

course  ot,  1033 
reflexes,  UM3 
I     em,  1025--1050 
Wins,  blood  flow  in,  976 

pulse  in,  977 
Ventricles.     j.'ee  Heart. 

1 1  essure  in,  940 
Veratrin,  action  on  muscles,  211 
Vertigo,  651 
\  esicular  murmur,  1094 


Vestibular  nerve,  379,  412 

functions  of,  396 
Vestibulo-spinal  tract,  353,  389 
Viscera,  sensibility  of,  476 
Visceral  nervous  system,  465—477 

afferent     functions 
of,  476 
Vision,  physiology  of,  486-594 
binocular,  r,88-594 
colour  threshold  for,  557 
cortical  localisation  of,  447 
different  thresholds  for,  561 

types  of.  502 
field  of,  549 

intensity  threshold,  555 
mechanism  of,  490 
monocular,  590 
paths  in  brain.  386,  405 
peripheral,  551 

colour-,  581 
psychic  cortex,  430 
sensation  curve  of,  566 
sensory  cortex.  430 
size  threshold  for,  558 
stereoscopic,  591 

subjective  phenomena  of,  566-576 
theories  of  colour-,  583 
Visual  acuity,  558 

determination  of,  535 
colour  threshold  for,  561 
add,  549  • 

impulses,  path  of,  406 
impressions,  I  IT 
persistence,  568 
purple,  545,  5S3 
Vital  force,  8 
Vitalism,  8 
Vitamines,  693 
Vocal  cords,  620 
Voice,  mechanism  of.  618 
production  of,  621 
Volition,  451 
Voluntary  contraction,  239-242 

electrical  changes  in, 
241 
movement,   effect  of  hemisection 

of  cord  on,  359 
muscle.   See  Muscle. 
Vomiting,  746 
\  owi  I    ound  .  624 

Walleeij-S  method,  320 
Waller's  theory  of  hearing.  613 
\\  ater,  as  oi  i. ition  to  life,  6 
Weber's  law,  483 

for  touch,  031 
Work  of  heart,  959 

during  exercise,  1054 
of  isolated  muscle,  202 

Xanthine,  100 
Xylose,  61 

Yquso'S  theory  of  colour  vision,  583 


Printed    in    Great    Britain    bt 
Richard  Clay  &  Sons,    Limited, 

BRUNSWICK  ST.,  STAMFORD  ST.,  S  E.  lt 
AND    BUNOAT,    SUFFOLK. 


Slcvv-l\nci  Q^iAJ  \ 


